Increased Level of Serum Hepcidin in Female Adolescent Athletes.
To determine the serum hepcidin concentration and standard hematological parameters in a group of female adolescent athletes, compared with a group of nonathlete females. A case-control study. A senior high school for athletes in Gothenburg, Sweden. All female athletes (70), at the school were offered to take part. Fifty-six athletes accepted. From a random sample of age-matched nonathletes, 71 students were recruited to the control group. Iron deficiency (ID) was determined by levels of serum iron, total iron-binding capacity, transferrin saturation (TS), and ferritin. Serum hepcidin was determined by a mass spectrometry method. All samples were taken at least 12 hours after training. The main result was the finding of a significantly elevated serum hepcidin level in the athlete group, 4.7 nmol/L compared with 3.3 nmol/L (P < 0.001) in the nonathlete group. In the athlete group, the serum iron concentration was significantly lower, 14.0 μmol/L compared with 17.6 μmol/L (P = 0.003) in the nonathlete group. No difference was found regarding TS, total iron binding capacity, and ferritin. There was no difference in the occurrence of ID or iron deficiency anaemia (IDA). These findings show an increase in serum hepcidin in a large group of female athletes. The elevated hepcidin levels may affect the iron balance of the athletes, adding to the traditional explanation of dietary intake/iron loss balance.


Designing Chemically Replaced Interfacial Layer via Unveiling the Influence of Zn Crystal Facets for Practical Zn-Metal Anodes.
Zn metal anodes (ZMAs) undergo irregular deposition and unfavorable side reactions, which hinders the practical application of aqueous rechargeable Zn metal batteries (ARZMBs). Chemical replacement reaction (CRR) strategies can achieve stable ZMAs, but the effect of the crystal facets of metallic Zn as reductants remains poorly understood. In this study, based on the observation that preferentially exposed Zn crystal facets affect the surface characteristics of chemically replaced layers in Sn-based CRR, a multifunctional Sn-based interfacial layer (ZnTCF@Sn) is designed on the Zn with textured crystal facets using a novel two-step CRR process. ZnTCF@Sn simultaneously provides abundant zincophilic sites and high surface energy and homogenizes the distribution of current/Zn2+ flux, resulting in fast electrochemical kinetics and dendrite-free deposition. Furthermore, the uniform Sn coverage on the ZnTCF@Sn surface inhibits side reactions and enhances reversibility during Zn deposition/dissolution. Thus, the ZnTCF@Sn achieves exceptional cyclability over 1200 h even under harsh operating conditions with a cumulative capacity of 24 Ah cm-2 . This study contributes to the development of practical ARZMBs by providing new insights into the effect of the Zn crystal facets on the surface modification of ZMAs through various CRRs.


Olfactory-based behavioral interactions among five species in the southern pine bark beetle group.
Olfactory-mediated behavioral interactions were investigated among the five scolytid species comprising the southern pine bark beetle group. Behavioral response, as determined from field trap catch data, showed that each species was attracted in greatest numbers to the pheromonal blend produced by conspecifies. Interspecifically,D. frontalis displayed no cross-attractancy toIps pheromonal blends, but was weakly attracted to the pheromonal blend of femaleD. terebrans. ThreeIps species displayed varying degrees of cross-attraction as well as to theDendroctonus pheromonal blends. More specifically,I. calligraphus was attracted toI. avulsus and, to a very limited extent, also to the maleD. terebrans pheromonal blend.I. avulsus was somewhat more cross-attractive thanI. calligraphus and showed attraction to the pheromonal blends of femaleD. frontalis, male and femaleD. terebrans, maleI. calligraphus, and maleI. grandicollis. I. grandicollis showed the greatest degree of cross-attraction, particularly in response to theDendroctonus pheromonal blends.


Effects of pre-sleep protein consumption on muscle-related outcomes - A systematic review.
The timing of protein intake over the day on muscle mass and strength gains have received interest in the literature. Thus, the aim of this systematic review is to analyze clinical studies that evaluated the acute effects of pre-sleep protein consumption on overnight muscle protein synthesis and the chronic effects on muscle mass and strength. Systematic review. A literature search was conducted up to June 2020 according to PRISMA statement and nine articles were included to analyze. The consumption of 20-40 g of casein approximately 30 min before sleep stimulates whole-body protein synthesis rates over a subsequent overnight period in young and elderly men (preceded or not by resistance exercise, respectively). In addition, pre-sleep protein consumption can augment the muscle adaptive response (muscle fiber cross-sectional area, strength and muscle mass) during 10-12 weeks of resistance exercise in young, but not in elderly men. Based on current evidence, the consumption of 20-40 g of casein approximately 30 min before sleep improves protein synthetic response during an overnight recovery period in healthy young adult men, with possible positive effects on muscle mass and strength following prolonged resistance exercise. In elderly, despite the initial evidence regarding the pre-sleep protein enhances overnight muscle protein synthesis rates, the current available evidence is limited precluding to conclude about the chronic effects on skeletal muscle mass or strength. These conclusions need to be taken with caution due to uneven protein intakes between experimental groups. Therefore, more data are needed before further considering pre-sleep protein as an effective nutritional intervention.


Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials).
Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer. Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9). For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items. The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer.


Affective responses to keeping and not keeping an activity product.
This study examined whether keeping or not keeping the products of a craft activity influences affective meaning and mood. Four groups of undergraduate (n = 23) and graduate (n = 20) students created block-printed stationery. Two groups were allowed to keep their stationery, and two groups were not. The measure of mood changes was the Bipolar Profile of Mood States, which subjects completed before and after the activity. After the activity, subjects also completed the Osgood 12-scale short-form semantic differential, which measured the affective meanings of the activity. Data analysis revealed significant differences between conditions on two out of nine variables. The subjects who could not keep their products became significantly more hostile and significantly more energetic than the subjects who kept their stationery. Implications for occupational therapy theory and further research possibilities are discussed.


Neural signals in the monkey ventral striatum related to motivation for juice and cocaine rewards.
1. The results of neuropsychological, neuropharmacological, and neurophysiological experiments have implicated the ventral striatum in reward-related processes. We designed a task to allow us to separate the effects of sensory, motor, and internal signals so that we could study the correlation between the activity of neurons in the ventral striatum and different motivational states. In this task, a visual stimulus was used to cue the monkeys as to their progress toward earning a reward. The monkeys performed more quickly and with fewer mistakes in the rewarded trials. After analyzing the behavioral results from three monkeys, we recorded from 143 neurons from two of the monkeys while they performed the task with either juice or cocaine reward. 2. In this task the monkey was required to release its grip on a bar when a small visual response cue changed colors from red (the wait signal) to green (the go signal). The duration of the wait signal was varied randomly. The cue became blue whenever the monkey successfully responded to the go signal within 1 s of its appearance. A reward was delivered after the monkey successfully completed one, two, or three trials. The schedules were randomly interleaved. A second visual stimulus that progressively brightened or dimmed signaled to the monkeys their progress toward earning a reward. This discriminative cue allowed the monkeys to judge the proportion of work remaining in the current ratio schedule of reinforcement. Data were collected from three monkeys while they performed this task. 3. The average reaction times became faster and error rates declined as the monkeys progressed toward completing the current schedule of reinforcement and thereby earning a reward, whereas the modal reaction time did not change. As the duration of the wait period before the go signal increased, the monkeys reacted more quickly but their error rates scarcely changed. From these results we infer that the effects of motivation and motor readiness in this task are generated by separate mechanisms rather than by a single mechanism subserving generalized arousal. 4. The activity of 138 ventral striatal neurons was sampled in two monkeys while they performed the task to earn juice reward. We saw tonic changes in activity throughout the trials, and we saw phasic activity following the reward. The activity of these neurons was markedly different during juice-rewarded trials than during correctly performed trials when no reward was forthcoming (or expected). The responses also were weakly, but significantly, related to the proximity of the reward in the schedules requiring more than one trial. 5. The monkeys worked to obtain intravenous cocaine while we recorded 62 neurons. For 57 of the neurons, we recorded activity while the monkeys worked in blocks of trials during which they self-administered cocaine after blocks during which they worked for juice. Although fewer neurons responded to cocaine than to juice reward (19 vs. 33%), this difference was not significant. The neuronal response properties to cocaine and juice rewards were independent; that is, the responses when one was the reward one failed to predict the response when the other was the reward. In addition, the neuronal activity lost most of its selectivity for rewarded trials, i.e, the activity did not distinguish nearly as well between cocaine and sham rewards as between juice and sham rewards. 6. Our results show that mechanisms by which cocaine acts do not appear to be the same as the ones activated when the monkeys were presented with an oral juice reward. This finding raises the intriguing possibility that the effects of cocaine could be reduced selectively without blocking the effects of many natural rewards.


Vomeronasal organ: critical role in mediating sexual behavior of the male hamster.
Sexual behavior in male hamsters is totally abolished by bilateral removal of the olfactory bulbs. This operation eliminates sensory input from both the olfactory and the vomeronasal systems. We previously demonstrated that peripheral destruction of the olfactory receptors caused anosmia but did not impair male hamster mating behavior. Here we demonstrate that peripheral deafferentation of the vomeronasal system produces severe sexual behavior deficits in approximately one-third of the treated animals. Combined deafferentation of both the vomeronasal and the olfactory systems eliminates copulation in 100 percent of the animals. This is the first experimental demonstration of a functional role for the vomeronasal organ in a mammalian species.


[The effect of neostigmine on the motor endplate in the intermediate syndrome of organophosphate poisoning].
A patient with severe organophosphate intoxication received Neostigmine 1 mg IV during the intermediate syndrome. This dose resulted clinically and neurophysiologically in a marked deterioration of neuro-muscular transmission. This effect of neostigmine on the neuromuscular block during the intermediate syndrome (deterioration) differs from its effect on a similar pattern (improvement), which is seen in the delayed neuropathy following organophosphate exposure. The administration of therapeutic doses of cholinesterase inhibitors in patients with a reduced safety margin due to inhibition of endplate acetylcholinesterase may be dangerous.


Health of America's newcomers.
Newcomer health and health care are policy issues with major outcomes of cost shifting and enormous consequences for newcomers and the community health nurses who promise them care. Newcomers are persons entering U.S. borders who could be asylees, refugees, immigrants, legal or illegal aliens, migrants, international adoptees, and others. Described in this article are the role federalism has played on the interplay among policymakers regarding newcomer health. Also addressed is newcomer health policy, including immigration policies, and newcomer health issues such as infectious diseases and questionable health care. Additional newcomer health issues such as newcomers at high risk for health problems, issues of access to care for newcomers, and welfare reform policies are discussed. Newcomer health and special interest group activities such as those from medicine and nursing are also addressed. Finally, meaningful options and possible solutions for newcomer health care concerns are identified and shared.


Vulvar carcinoma in situ.
Sixty-five patients with carcinoma in situ of the vulva were reviewed. Attention was focused upon the epidemiology, duration of symptoms, and location of lesions. The vulva and perineum were divided diagrammatically into 16 geographic compartments; lesion location and percentage of occurrence in each area were calculated. The most common site was the inferior border of the right labium majus. Eighty-four percent of patients under the age of 40 had multifocal disease. Sixty-five percent of patients over 40 had unifocal disease.


Functional evolution of mammalian odorant receptors.
The mammalian odorant receptor (OR) repertoire is an attractive model to study evolution, because ORs have been subjected to rapid evolution between species, presumably caused by changes of the olfactory system to adapt to the environment. However, functional assessment of ORs in related species remains largely untested. Here we investigated the functional properties of primate and rodent ORs to determine how well evolutionary distance predicts functional characteristics. Using human and mouse ORs with previously identified ligands, we cloned 18 OR orthologs from chimpanzee and rhesus macaque and 17 mouse-rat orthologous pairs that are broadly representative of the OR repertoire. We functionally characterized the in vitro responses of ORs to a wide panel of odors and found similar ligand selectivity but dramatic differences in response magnitude. 87% of human-primate orthologs and 94% of mouse-rat orthologs showed differences in receptor potency (EC50) and/or efficacy (dynamic range) to an individual ligand. Notably dN/dS ratio, an indication of selective pressure during evolution, does not predict functional similarities between orthologs. Additionally, we found that orthologs responded to a common ligand 82% of the time, while human OR paralogs of the same subfamily responded to the common ligand only 33% of the time. Our results suggest that, while OR orthologs tend to show conserved ligand selectivity, their potency and/or efficacy dynamically change during evolution, even in closely related species. These functional changes in orthologs provide a platform for examining how the evolution of ORs can meet species-specific demands.


On the involvement of mitochondrial intermembrane junctional complexes in apoptosis.
The voltage dependent anion channel and the adenine nucleotide translocase are the principal proteins found in the mitochondrial outer and inner membranes, respectively. The two proteins can associate to form a junctional complex that establishes contact sites between the two membranes. This complex in turn recruits a range of proteins depending on the function to be executed. Among these, the junctional complexes can bind Bax and other proapoptotic proteins. Bax regulates the involvement of mitochondria in the apoptotic signalling pathway by controlling the the release of apoptogenic proteins from the mitochondrial intermembrane space to the cytosol. Another protein recruited to ANT is cyclophilin-D. Cyclophilin-D is a peptidylprolyl cis-trans-isomerase located in the intramitochondrial (matrix) compartment which stabilizes a "deformed" conformation of ANT in which its native gating properties are lost. Although the deformed state, when extensive, is lethal, cells can tolerate this conformational change when it occurs transiently. There is now a large body of data that implicates the voltage dependent anion channel, the adenine nucleotide translocase and cyclophilin-D, both separately and together, in the mitochondrial reactions of apoptosis. But there is no consensus over how, or indeed if, they are involved. This article examines the data relevant to this question and considers why a complex of these three proteins may be essential for the action of Bax and other proapoptotic proteins in permeabilizing the outer membrane to intermembrane space proteins.


IFNT-independent effects of intrauterine extracellular vesicles (EVs) in cattle.
Extracellular vesicles (EVs) present in uterine lumen are involved in conceptus-endometrial interactions during the pre-implantation period. Despite numerous studies conducted on interferon tau (IFNT), a major protein of maternal recognition of pregnancy, the effect of intrauterine EVs on the endometrium during pre-implantation periods has not been well-characterized. To characterize conceptus-derived intrauterine EVs independent of IFNT, transcripts found from RNA-seq analysis in RNAs extracted from primary bovine endometrial epithelial cells (EECs) treated with cyclic day 17 (C17) EVs, pregnant day 17 (P17) EVs or IFNT were analyzed. These analyses identified 82 transcripts uniquely induced by IFNT-independent P17 EVs, of which a large number of transcripts were associated with 'the TNF signaling pathway' and 'Inflammatory response'. Moreover, high expression of CD40L, a member of the TNF superfamily, and its receptor CD40 were found in P17 EVs and in EECs, respectively. Furthermore, the expression of TNF signaling pathway-related genes was up-regulated by the treatment with P17 EVs, but these increases were down-regulated by NF-kB signaling inhibitor. These findings suggest that P17 EVs could induce a pro-inflammatory response in the endometrium, independent of IFNT, to regulate uterine receptivity, facilitating conceptus implantation.


Characterization of aluminium-containing adjuvants.
The approved aluminium-containing vaccine adjuvants have been shown to be poorly crystalline aluminium oxyhydroxide (AIO(OH)) and amorphous aluminium hydroxyphosphate of varying phosphate content. Adsorption of the antigen by the adjuvant is implied in many proposed mechanisms of antibody production enhancement caused by the adjuvants. The World Health Organization recommends adsorption of 80% or more of tetanus and diphtheria toxoid by the aluminium-containing adjuvants. Thus, one objective in the preparation of vaccines containing these adjuvants is to optimize adsorption of the antigen on the adjuvant. Production of a consistent adjuvant effect in vaccines would be facilitated by the thorough characterization of aluminium-containing adjuvants with reference to properties that affect adsorption and other colloidal behaviour. Such properties include surface area, surface charge, chemical composition, structure, and morphology. Techniques and measurements such as X-ray diffraction, infrared spectroscopy, transmission electron microscopy, energy-dispersive spectrometry, Doppler electrophoretic light scattering analysis, dissolution rates, and adsorption isotherms provide a basis for understanding and predicting interactions and behaviour in monovalent as well as multivalent vaccines. Such characterization would be crucial in vaccine standardization and quality control.


A Conserved cis-Regulatory Module Determines Germline Fate through Activation of the Transcription Factor DUO1 Promoter.
The development of the male germline within pollen relies upon the activation of numerous target genes by the transcription factor DUO POLLEN1 (DUO1). The expression of DUO1 is restricted to the male germline and is first detected shortly after the asymmetric division that segregates the germ cell lineage. Transcriptional regulation is critical in controlling DUO1 expression, since transcriptional and translational fusions show similar expression patterns. Here, we identify key promoter sequences required for the germline-specific regulation of DUO1 transcription. Combining promoter deletion analyses with phylogenetic footprinting in eudicots and in Arabidopsis accessions, we identify a cis-regulatory module, Regulatory region of DUO1 (ROD1), which replicates the expression pattern of DUO1 in Arabidopsis (Arabidopsis thaliana). We show that ROD1 from the legume Medicago truncatula directs male germline-specific expression in Arabidopsis, demonstrating conservation of DUO1 regulation among eudicots. ROD1 contains several short conserved cis-regulatory elements, including three copies of the motif DNGTGGV, required for germline expression and tandem repeats of the motif YAACYGY, which enhance DUO1 transcription in a positive feedback loop. We conclude that a cis-regulatory module conserved in eudicots directs the spatial and temporal expression of the transcription factor DUO1 to specify male germline fate and sperm cell differentiation.


Methodology and validation for identifying gait type using machine learning on IMU data.
With the rising popularity of activity tracking, there is a desire to not only count the number of steps a person takes, but also identify the type of step (e.g., walking or running) they are taking. For rehabilitation and athletic training, this difference is important to the prescribed regiment. Fourteen healthy adults walked, jogged and ran on a treadmill at three different constant speeds (1.21, 2.01, 2.68 m/s) for 90 s. An inertial measurement unit (IMU) with accelerometer and gyroscope was affixed to their left ankle. Collected acceleration and angular velocity data were partitioned into individual time-normalised strides. These data were used as features in the artificial neural network (ANN) that classified the type of stride. Several ANN models were tested: using only acceleration, only angular velocity and both. Using primarily acceleration data in the trained ANN yielded the best results (>94% correct stride-type identification) after cross-validation. The ANN models were able to accurately classify the gait type of each stride using a single wearable IMU. The accuracy of the method should improve further as more data is added to the ANN training.


Genetic susceptibility and environmental factors of esophageal cancer in Xi'an.
To analyse the role of genetic susceptibility and environmental factors in the process of esophageal cancer (EC) formation in Xi'an, China. A hospital based case-control study, combined with molecular epidemiological method, was carried out. A total of 127 EC cases and 101 controls were interviewed with questionnaires containing demographic items, habit of tobacco smoking, alcohol drinking, and family history of EC. Polymorphism of CYP1A1 and GSTM1 of 127 EC cases and 101 controls were detected by PCR method. The interactions between genetic susceptibility and environmental factors were also discussed. Tobacco smoking, alcohol drinking and a family history of EC were risk factors for EC with an OR of 2.04(95% CI 1.15-3.60), 3.45(95% CI 1.74-6.91), 3.14 (95% CI 1.28-7.94), respectively. Individuals carrying CYP1A1 Val/Val genotype compared to those with CYP1A1 Ile/Ile genotype had an increased risk for EC (OR 3.35, 95% CI 1.49-7.61). GSTM1 deletion genotype was a risk factor for EC (OR1.81, 95% CI 1.03-3.18). Gene-environment interaction analysis showed that CYP1A1 Val/Val genotype, GSTM1 deletion genotype had synergetic interactions with tobacco smoking, alcohol drinking and family history of EC. Tobacco smoking, alcohol drinking and a family history of EC are risk factors for EC. CYP1A1 Val/Val and GSTM1 deletion genotypes are genetic susceptibility biomarkers for EC. There are synergic interactions between genetic susceptibility and environmental factors.


Proline-rich region of non-muscle myosin light chain kinase modulates kinase activity and endothelial cytoskeletal dynamics.
Disruption of the pulmonary endothelial barrier and subsequent vascular leak is a hallmark of acute lung injury. Dynamic rearrangements in the endothelial cell (EC) peripheral membrane and underlying cytoskeleton are critical determinants of barrier function. The cytoskeletal effector protein non-muscle myosin light chain kinase (nmMLCK) and the actin-binding regulatory protein cortactin are important regulators of the endothelial barrier. In the present study we functionally characterize a proline-rich region of nmMLCK previously identified as the possible site of interaction between nmMLCK and cortactin. A mutant nmMLCK construct deficient in proline residues at the putative sites of cortactin binding (amino acids 973, 976, 1019, 1022) was generated. Co-immunoprecipitation studies in human lung EC transfected with wild-type or mutant nmMLCK demonstrated similar levels of cortactin interaction at baseline and after stimulation with the barrier-enhancing agonist, sphingosine 1-phosphate (S1P). In contrast, binding studies utilizing recombinant nmMLCK fragments containing the wild-type or proline-deficient sequence demonstrated a two-fold increase in cortactin binding (p<0.01) to the mutant construct. Immunofluorescent microscopy revealed an increased stress fiber density in ECs expressing GFP-labeled mutant nmMLCK at baseline (p=0.02) and after thrombin (p=0.01) or S1P (p=0.02) when compared to wild-type. Mutant nmMLCK demonstrated an increase in kinase activity in response to thrombin (p<0.01). Kymographic analysis demonstrated an increased EC membrane retraction distance and velocity (p<0.01) in response to the barrier disrupting agent thrombin in cells expressing the mutant vs. the wild-type nmMLCK construct. These results provide evidence that critical prolines within nmMLCK (amino acids 973, 976, 1019, 1022) regulate cytoskeletal and membrane events associated with pulmonary endothelial barrier function.


The Rules of the Game Called Psychological Science.
If science were a game, a dominant rule would probably be to collect results that are statistically significant. Several reviews of the psychological literature have shown that around 96% of papers involving the use of null hypothesis significance testing report significant outcomes for their main results but that the typical studies are insufficiently powerful for such a track record. We explain this paradox by showing that the use of several small underpowered samples often represents a more efficient research strategy (in terms of finding p < .05) than does the use of one larger (more powerful) sample. Publication bias and the most efficient strategy lead to inflated effects and high rates of false positives, especially when researchers also resorted to questionable research practices, such as adding participants after intermediate testing. We provide simulations that highlight the severity of such biases in meta-analyses. We consider 13 meta-analyses covering 281 primary studies in various fields of psychology and find indications of biases and/or an excess of significant results in seven. These results highlight the need for sufficiently powerful replications and changes in journal policies.


Proton-pump inhibitors: understanding the complications and risks.
Proton-pump inhibitors (PPIs) are the most effective therapy for the full spectrum of gastric-acid-related diseases. However, in the past decade, a steadily increasing list of complications following long-term use of PPIs has been reported. Their potent acid-suppressive action induces several structural and functional changes within the gastric mucosa, including fundic gland polyps, enterochromaffin-like cell hyperplasia and hypergastrinaemia, which can be exaggerated in the presence of Helicobacter pylori infection. As discussed in this Review, most associations of PPIs with severe adverse events are not based on sufficient evidence because of confounding factors and a lack of plausible mechanisms. Thus, a causal relationship remains unproven in most associations, and further studies are needed. Awareness of PPI-associated risks should not lead to anxiety in patients but rather should induce the physician to consider the appropriate dosing and duration of PPI therapy, including long-term monitoring strategies in selected groups of patients because of their individual comorbidities and risk factors.


Highly Enantioselective Production of Chiral Secondary Alcohols with Candida zeylanoides as a New Whole Cell Biocatalyst.
The increasing demand for biocatalysts in synthesizing enantiomerically pure chiral alcohols results from the outstanding characteristics of biocatalysts in reaction, economic, and ecological issues. Herein, fifteen yeast strains belonging to three food originated yeast species Candida zeylanoides, Pichia fermentans, and Saccharomyces uvarum were tested for their capability for asymmetric reduction of acetophenone to 1-phenylethanol as biocatalysts. Of these strains, C. zeylanoides P1 showed an effective asymmetric reduction ability. Under optimized conditions, substituted acetophenones were converted to corresponding optically active secondary alcohols in up to 99% enantiomeric excess and at high yields. The preparative scale asymmetric bioreduction of 4-nitroacetophenone (1m) by C. zeylanoides P1 gave (S)-1-(4-nitrophenyl)ethanol (2m) with 89% yield and > 99% enantiomeric excess. Compound 2m has been obtained in an enantiomerically pure and inexpensive form. Additionally, these results indicate that C. zeylanoides P1 is a promising biocatalyst for the synthesis of chiral alcohols in industry.


Bcl3-dependent stabilization of CtBP1 is crucial for the inhibition of apoptosis and tumor progression in breast cancer.
B-cell lymphoma 3 (Bcl3) is a proto-oncogene upregulated in a wide range of cancers, including breast cancer. Although Bcl3 is known to promote cell proliferation and inhibit apoptosis, the molecular mechanisms underlying the proto-oncogenic function of Bcl3 have not been completely elucidated. To gain insight into the oncogenic role of Bcl3, we applied a proteomic approach, which led to the identification of C-terminal binding protein 1 (CtBP1) as a binding partner of Bcl3. A PXDLS/R motif embedded in Bcl3 was found to mediate the interaction between Bcl3 and CtBP1, which caused the stabilization of CtBP1 by blocking proteasome-dependent degradation. Apoptotic stimuli-induced degradation of CtBP1 was significantly abolished by the upregulation of Bcl3, leading to the sustained repression of pro-apoptotic gene expression and subsequent inhibition of apoptosis. Intriguingly, a strong positive correlation between the protein levels of Bcl3 and CtBP1 was detected in breast cancer patient samples. Our study reveals a novel combinatorial role for Bcl3 and CtBP1, providing an explanation for the acquisition of resistance to apoptosis in cancer cells, which is a major requirement for cancer development.


Gender differences in food craving among overweight and obese patients attending low energy diet therapy: a matched case-control study.
This case-control study examined gender differences in food craving among a sample of overweight and obese patients attending low energy diet therapy. To disentangle the specific role of gender from the role of confounders, we paired groups for BMI, age and severity of binge eating as assed by the Binge Eating Scale (BES). The participants were 73 pairs of patients who were attending low energy diet therapy. All the participants were administered the State and Trait Food Cravings Questionnaire, trait version (FCQ-T) and the BES. Female patients had higher mean scores on six out of nine dimensions of the FCQ-T. When controlling for the effect of other variables, obese and overweight female patients were 1.1 times more likely to report higher anticipation of relief of negative states and feelings from eating than their male pairs. Obese and overweight female patients experience more cravings for food than their male pairs despite comparable severity of binge eating and obesity suggesting the need for tailored interventions.


Emergence of CTX-M-15 type extended-spectrum beta-lactamase-producing Salmonella spp. in Kuwait and the United Arab Emirates.
Cephalosporins are major antimicrobials used to treat serious Salmonella infections. However, their effectiveness is being compromised by the emergence of extended-spectrum beta-lactamases (ESBLs). The genetic determinants encoding ESBL in Salmonella spp. isolated from patients in Kuwait and United Arab Emirates (UAE) were studied over a 2 year period. Out of a total of 407 isolates, 116 isolates possessed the resistance phenotypes consistent with possible ESBL production. Of these, 69 (59.5 %) were ESBL positive. PCR and sequencing were used to determine the genetic determinant(s) responsible for ESBL phenotypes. A total of 14 (12.1 %) and 29 (24.6 %) isolates were CTX-M-15 ESBL producers and TEM producers, respectively. Ten CTX-M-15 producers carried the insertion sequence ISEcpI gene. PFGE analysis revealed identical profiles in 4 of the 13 Kuwaiti strains. This study reports the presence of the bla(CTX-M-15) gene in Salmonella spp. and Salmonella enterica serotype Typhi from Kuwait and UAE for what is believed to be the first time. This is of great concern as the gene is also found in association with the ISEcpI gene, which may easily facilitate its spread. These isolates originated mostly from non-Kuwaiti Arabs rather than from people of Asian origin.


Ultrasmall Abundant Metal-Based Clusters as Oxygen-Evolving Catalysts.
The oxygen evolution reaction is a crucial step in water electrolysis to develop clean and renewable energy. Although noble metal-based catalysts have demonstrated high activity for the oxygen evolution reaction, their application is limited by their high cost and low availability. Here we report the use of a molecule-to-cluster strategy for preparing ultrasmall trimetallic clusters by using the polyoxometalate molecule as a precursor. Ultrafine (0.8 nm) transition-metal clusters with controllable chemical composition are obtained. The transition-metal clusters enable highly efficient oxygen evolution through water electrolysis in alkaline media, manifested by an overpotential of 192 mV at 10 mA cm-2, a low Tafel slope of 36 mV dec-1, and long-term stability for 30 h of electrolysis. We note, however, that besides the excellent performance as an oxygen evolution catalyst, our molecule-to-cluster strategy provides a means to achieve well-defined transition-metal clusters in the subnanometer regime, which potentially can have an impact on several other applications.


Correlates of consistent condom use with main partners by partnership patterns among young adult male injection drug users from five US cities.
This paper examined correlates of consistent condom use with a main partner among heterosexual male injection drug users (IDUs). Using data from a multi-site sample of young IDUs, we identified 1770 sexually active men of whom 24% (429/1770) reported an exclusive main female sex partner and 49% (862/1770) reported both main and casual female sex partners. Consistent condom use with a main partner was low among men with an exclusive main partner and those with multiple partners (12% and 17%, respectively). In multivariate analysis, consistent condom use with a main partner across partnership patterns was directly associated with anticipating a positive response to requests for condom use and by partner support of condom use; consistent condom use was inversely associated with a main partner's pregnancy desires. Among men with an exclusive main partner, consistent condom use was also inversely associated with needle sharing with a main partner. Among men with multiple partners, consistent condom use with a main partner was inversely associated with injecting with a used needle and intimate partner violence. The low prevalence of consistent condom use with main female partners among heterosexually active male IDUs indicates an increased risk for HIV transmission between men and their primary sex partners. Interventions for heterosexual males that are geared toward increasing condom use in primary relationships are warranted.


Successful treatment of a child with fulminant liver failure and coma due to Amanita phalloides poisoning using urgent liver transplantation.
Intoxication due to eating wild mushrooms presents with a variety of signs, ranging from mild diarrhea to severe organ failure. We present the case of an 11-year-old boy with fulminant liver failure and hepatic coma due to Amanita phalloides poisoning treated with an urgent pediatric orthotopic liver transplantation. Successful treatment of patients with fulminant liver failure and hepatic coma caused by Amanita phalloides poisoning is possible using urgent orthotopic liver transplantation when conservative medical treatment modalities are ineffective.


Correlating first- and second-rib fractures noted on spine computed tomography with major vessel injury.
First- and second-rib fractures diagnosed on plain radiographs have been associated with traumatic aortic injury. We examined whether such fractures diagnosed on computed tomography (CT), which is of greater sensitivity than plain radiograms for rib fractures, are associated with traumatic vascular injury. We identified 1,894 patients who had undergone a chest CT angiogram with indication of trauma between 2005 and 2008. Among these, 185 patients were selected at random. The main mechanism of injury was motor vehicle accident or a fall. The patients were divided into two groups: patients with first- and/or second-rib fractures and those without. Proportions of patients with major vessel injury noted on CT angiography were compared between groups. Information regarding displacement of the fracture, location of the fracture, detection upon plain film, and gender of the patients was also evaluated and correlated with incidence of major vessel injury. Fisher's test and χ2 analysis were used to determine significance of the data. Incidence of major vessel injury was similar between patients with and without first- and/or second-rib fractures (7% vs. 9%, respectively; p = 0.59). No subset of type of rib fracture was associated with greater incidence of aortic injury. First- and second-fractures are not associated with greater incidence of aortic injury. Thus, the previous axiom that first- and second-rib fractures should result in increased examination for aortic injury may not hold true.


A new strategy to screen molecular imaging probe uptake in cell culture without radiolabeling using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
Numerous new molecular targets for diseases are rapidly being identified and validated in the postgenomic era, urging scientists to explore novel techniques for accelerating molecular probe development. In this study, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was investigated as a potential tool for high-throughput screening and characterization of molecular imaging probes. Specifically, MALDI-TOF-MS was used to screen a small library of phosphonium cations for their ability to accumulate in cells. C6 cells incubated with phosphonium cations at room temperature were collected and lysed for experiments. Calibration curves for the internal standard, methyltriphenyl phosphonium, and for tetraphenylphosphonium bromide (TPP) and other phosphonium cations were first established. The time course of TPP uptake by C6 cells was then quantified using both MALDI-TOF-MS and liquid scintillation counting with (3)H-TPP. In addition, MALDI-TOF-MS was used to screen a library of 8 phosphonium cations and subsequently rank their ability to penetrate membranes and accumulate in cells. Finally, the accumulation of 4-fluorophenyltriphenyl phosphonium (FTPP) in the membrane potential-modulated cells was also measured by MALDI-TOF-MS. MALDI-TOF-MS spectra clearly revealed that TPP was easily identified from cell lysates even as early as 10 min after incubation and that levels as low as 0.11 fmol of TPP per cell could be detected, suggesting the high sensitivity of this technique. The time course of TPP influx determined by both MALDI-TOF-MS and radioactivity counting showed no statistically significant difference (P > 0.05 for all time points). These data validated MALDI-TOF-MS as an alternative approach for accurately measuring uptake of phosphonium cations by cells. TPP and FTPP demonstrated greater accumulation in cells than did the other cations evaluated in this study. Furthermore, uptake profiles suggested that FTPP preserves the membrane potential-dependent uptake property of TPP in cell cultures. Taken together, these data justify further synthesis and evaluation of (18)F-FTPP as a molecular probe for imaging mitochondrial dysfunction. These results demonstrate that MALDI-TOF-MS is a powerful analytic tool for rapid screening and characterization of phosphonium cations as molecular probes. This technique can potentially be applied to the evaluation of other imaging probes or drugs and thus may facilitate their rational design and development.


Silent myocardial ischemia. A clinical perspective.
Silent myocardial ischemia has been shown to occur far more frequently than anginal episodes in patients with coronary artery disease. Both an increase in myocardial oxygen demand and abnormalities of coronary vasomotor tone appear to play a significant role in the genesis of silent ischemia. Recent data show that in excess of 40% of patients with stable angina have frequent episodes of silent ischemia. The presence of silent ischemia predicts an increased risk of coronary events and cardiac death. Based on these data, it has been proposed that anti-ischemic therapy should be directed toward control of total ischemic burden. Although several recent studies have demonstrated efficacy of various antianginal drugs in reducing the number and duration of silent ischemic episodes, none has demonstrated beneficial effect on the associated adverse prognosis.


Expanding the public health benefits of syringe exchange programs.
To provide a brief history of community syringe exchange programs (SEPs), describe the clinical profile of those who attend them, identify factors interfering with the transition of SEP participants to more comprehensive substance abuse treatment services, review studies designed to improve rates of treatment seeking, and offer practical suggestions to facilitate links between SEPs and substance abuse treatment. Relevant articles were identified using a PubMed literature search of English-language journals from 1997 to 2007. Studies were included that evaluated the effectiveness of SEPs or methods for increasing treatment enrolment in SEP participants or other out-of-treatment intravenous drug users. Relevant articles prior to 1997 were identified using reference lists of identified articles. SEPs have little impact on rates of drug use or injections. Substance abuse treatment reduces human immunodeficiency virus transmission through drug use reduction and psychosocial functioning improvement, yet SEP participants only infrequently engage in treatment. Psychological and pharmacological interventions delivered at the SEP setting can improve treatment seeking in SEP participants. Use of SEPs by substance abuse treatment programs can improve harm-reduction efforts at these settings. Efforts to improve the link between SEPs and substance abuse treatment should include interventions to enhance cooperation across programs, motivate treatment enrolment and SEP use, and expand access to treatment. A more fluent and bidirectional continuum of services can enhance the public health benefits of both of these health care delivery settings.


Michel's medium as a preservative for immunofluorescent staining of cutaneous biopsy specimens in dogs and cats.
Paired 3-mm skin biopsy specimens from 24 dogs and 11 cats with suspected autoimmune dermatopathies were stained with fluorescein-conjugated antisera. In each case, 1 specimen was immediately embedded in optimum cutting temperature compound, quick frozen to -30 C, processed, stained, and examined. The other sample was placed in Michel's transport medium, held for 7 days, and then processed, stained, and examined. The location, quality, and intensity of immunofluorescent staining (when positive) were then compared in the 2 specimens. There were no differences in the staining patterns between the specimens processed immediately and those held in Michel's medium, thus demonstrating the validity of preserving canine and feline skin biopsy specimens in Michel's medium for immunofluorescent examination.


The use of the Levenberg-Marquardt curve-fitting algorithm in pharmacokinetic modelling of DCE-MRI data.
The use of curve-fitting and compartmental modelling for calculating physiological parameters from measured data has increased in popularity in recent years. Finding the 'best fit' of a model to data involves the minimization of a merit function. An example of a merit function is the sum of the squares of the differences between the data points and the model estimated points. This is facilitated by curve-fitting algorithms. Two curve-fitting methods, Levenberg-Marquardt and MINPACK-1, are investigated with respect to the search start points that they require and the accuracy of the returned fits. We have simulated one million dynamic contrast enhanced MRI curves using a range of parameters and investigated the use of single and multiple search starting points. We found that both algorithms, when used with a single starting point, return unreliable fits. When multiple start points are used, we found that both algorithms returned reliable parameters. However the MINPACK-1 method generally outperformed the Levenberg-Marquardt method. We conclude that the use of a single starting point when fitting compartmental modelling data such as this produces unsafe results and we recommend the use of multiple start points in order to find the global minima.


Hookah smoking in high school students and its determinants in Iran: a longitudinal study.
Hookah smoking has increased worldwide, especially among youth, and has been identified as an emerging threat to public health. The aim of the present study was to estimate the prevalence and transition rates in hookah smoking statuses and predictors of transitions among a representative sample of Iranian high school students. In this longitudinal study, a representative sample (n = 5197) of students in the northwest of Iran was assessed thrice with a 6-month interval in 2010 and 2011. A self-administered questionnaire was used to measure hookah smoking, demographic characteristics, and personal and environmental factors. In total, the prevalence of hookah use (at least once a month) in this study was 6.0% (95% confidence interval [CI] = 5.1, 6.9). Results indicated that 44.9% (95% CI = 43.0, 46.7) of the students in the sample at least tried hookah smoking. During 1 year, 18.5% and 1.5% of students who have never used hookah before had transitioned to experimenter and regular hookah smoking, respectively, and notably, 7.8% of experimenters had transitioned to regular hookah smoking. Adjusted for other factors, being male, regular cigarette smoking, and positive attitude toward smoking were factors associated with students' transition to hookah smoking status. The incidence rate of hookah smoking in adolescents is notable. The findings identified the co-occurrence of risky behaviors that support programs aimed at reducing or preventing high-risk behaviors simultaneously.


Population fitness has a concave relationship with migration distance in Sanderlings.
In Focus: Reneerkens, J., Versluijs, T. S. L., Piersma, T., Alves, J. A., Boorman, M., Corse, C., … Lok, T. (2020). Low fitness at low latitudes: wintering in the tropics increases migratory delays and mortality rates in an Arctic breeding shorebird. Journal of Animal Ecology, 89, 691-703. A central question in migratory ecology has been to understand the fitness consequences of individual variation in migration distance among different species and populations. Reneerkens et al. (2020) investigated the demographic consequences of long-distance migration for Sanderlings Calidris alba, an Arctic-breeding species of sandpiper. Their study population has a remarkable geographic distribution with a breeding range that is concentrated in northeast Greenland and Ellesmere Island, Canada but a nonbreeding range that extends across 85° of latitude from Scotland to Namibia. The authors report on unexpected patterns of latitudinal variation in three demographic parameters: timing of passage on northward migration, probability of juvenile migration and apparent survival of adults. Sanderlings travelling 1,800-2,800 km to settle at north temperate sites during the nonbreeding season had earlier passage dates, and also higher probabilities of migration and apparent survival. In contrast, birds travelling 6,000-7,800 km to equatorial sites experienced later passage dates, delayed maturity and lower apparent survival. However, if Sanderlings migrated even farther and flew over 11,000 km to nonbreeding sites in Namibia, then their performance was restored to early passage dates and higher survival. Movement tracks from birds tagged with geolocators showed that birds wintering in Namibia make nonstop flights of 7,500 km that bypass West Africa during northward migration. Thus, all lines of evidence suggest that Sanderlings face adversity when spending the nonbreeding season at equatorial latitudes. Moreover, the central finding that components of fitness can have nonlinear relationships with migration distance is a novel discovery that leads to many additional questions. The new findings have broader implications for theoretical models of migration, and for understanding how different patterns of movements may arise or be maintained in migratory species.


Rare loss-of-function variants in matrisome genes are enriched in Ebstein's anomaly.
Ebstein's anomaly, a rare congenital heart disease, is distinguished by the failure of embryological delamination of the tricuspid valve leaflets from the underlying primitive right ventricle myocardium. Gaining insight into the genetic basis of Ebstein's anomaly allows a more precise definition of its pathogenesis. In this study, two distinct cohorts from the Chinese Han population were included: a case-control cohort consisting of 82 unrelated cases and 125 controls without cardiac phenotypes and a trio cohort comprising 36 parent-offspring trios. Whole-exome sequencing data from all 315 participants were utilized to identify qualifying variants, encompassing rare (minor allele frequency < 0.1% from East Asians in the gnomAD database) functional variants and high-confidence (HC) loss-of-function (LoF) variants. Various statistical models, including burden tests and variance-component models, were employed to identify rare variants, genes, and biological pathways associated with Ebstein's anomaly. Significant associations were noted between Ebstein's anomaly and rare HC LoF variants found in genes related to the matrisome, a collection of extracellular matrix (ECM) components. Specifically, 47 genes with HC LoF variants were exclusively or predominantly identified in cases, while nine genes showed such variants in the probands. Over half of unrelated cases (n = 42) and approximately one-third of probands (n = 12) were found to carry one or two LoF variants in these prioritized genes. These results highlight the role of the matrisome in the pathogenesis of Ebstein's anomaly, contributing to a better understanding of the genetic architecture underlying this condition. Our findings hold the potential to impact the genetic diagnosis and treatment approaches for Ebstein's anomaly.


P/Q Type Calcium Channel Cav2.1 Defines a Unique Subset of Glomeruli in the Mouse Olfactory Bulb.
Voltage-gated calcium (Cav) channels are a prerequisite for signal transmission at the first olfactory sensory neuron (OSN) synapse within the glomeruli of the main olfactory bulb (MOB). We showed previously that the N-type Cav channel subunit Cav2.2 is present in the vast majority of glomeruli and plays a central role in presynaptic transmitter release. Here, we identify a distinct subset of glomeruli in the MOB of adult mice that is characterized by expression of the P/Q-type channel subunit Cav2.1. Immunolocalization shows that Cav2.1+ glomeruli reside predominantly in the medial and dorsal MOB, and in the vicinity of the necklace glomerular region close to the accessory olfactory bulb. Few glomeruli are detected on the ventral and lateral MOB. Cav2.1 labeling in glomeruli colocalizes with the presynaptic marker vGlut2 in the axon terminals of OSNs. Electron microscopy shows that Cav2.1+ presynaptic boutons establish characteristic asymmetrical synapses with the dendrites of second-order neurons in the glomerular neuropil. Cav2.1+ glomeruli receive axonal input from OSNs that express molecules of canonical OSNs: olfactory marker protein, the ion channel Cnga2, and the phosphodiesterase Pde4a. In the main olfactory epithelium, Cav2.1 labels a distinct subpopulation of OSNs whose distribution mirrors the topography of the MOB glomeruli, that shows the same molecular signature, and is already present at birth. Together, these experiments identify a unique Cav2.1+ multiglomerular domain in the MOB that may form a previously unrecognized olfactory subsystem distinct from other groups of necklace glomeruli that rely on cGMP signaling mechanisms.


Mdm-2 phosphorylation by DNA-dependent protein kinase prevents interaction with p53.
In response to genotoxic stress, the p53 tumor suppressor protein exerts a G1 cell cycle arrest that is dependent on its ability to transactivate downstream target genes. This p53-dependent G1 block is reversed by the binding of Mdm-2 to p53, preventing further transactivation. Interestingly, following DNA damage, the mdm-2 gene is also transcriptionally activated by p53, and therefore, the question of how p53 can continue to transactivate genes in the presence of its own negative regulator has remained unanswered. Here, we provide evidence that phosphorylation of Mdm-2 protein by DNA-dependent protein kinase (DNA-PK) blocks its ability to associate with p53 and regulate p53 transactivation. The data support a model by which DNA-PK activation by DNA damage and phosphorylation of Mdm-2 renders the Mdm-2 protein unable to inhibit p53 transactivation, resulting in cell cycle arrest. Following DNA repair, the loss of DNA-PK activity results in newly synthesized Mdm-2 protein that is unphosphorylated and, therefore, capable of binding to p53, allowing cell cycle progression.


Dental caries and caries associated factors in Swedish 15-year-olds in relation to immigrant background.
The aim of the present study was to evaluate the prevalence of caries and caries associated variables in 15-year-olds in relation to foreign background and to examine differences in the prevalence of caries in immigrant adolescents according to their length of residence in Sweden. All 15-year-old adolescents (n=143) at one public school in the city of Jönköping, Sweden were asked to participate in the study. The adolescents were divided into two groups according to their background: immigrants and non-immigrants. Data on caries prevalence were extracted from the dental records of the examination made when the participants were 15 years old. The proportions of immigrants and non-immigrants free from carious lesions were equal. Immigrant adolescents, however, had on average more enamel carious lesions. Adolescents born in Sweden of immigrant parents or who had arrived before 1 year of age had a caries prevalence similar to those of non-immigrant adolescents, whereas children who had immigrated to Sweden after 7 years of age had a caries prevalence that was 2-3 times higher. As the caries carious lesions in immigrant adolescents is mainly restricted to the enamel, and possibly reversible, early introduction of preventive programmes seems essential.


Tonsil-derived mesenchymal stem cells ameliorate CCl4-induced liver fibrosis in mice via autophagy activation.
Liver transplantation is the treatment of choice for chronic liver failure, although it is complicated by donor shortage, surgery-related complications, and immunological rejection. Cell transplantation is an alternative, minimally invasive treatment option with potentially fewer complications. We used human palatine tonsil as a novel source of mesenchymal stem cells (T-MSCs) and examined their ability to differentiate into hepatocyte-like cells in vivo and in vitro. Carbon tetrachloride (CCl4) mouse model was used to investigate the ability of T-MSCs to home to the site of liver injury. T-MSCs were only detected in the damaged liver, suggesting that they are disease-responsive. Differentiation of T-MSCs into hepatocyte-like cells was confirmed in vitro as determined by expression of hepatocyte markers. Next, we showed resolution of liver fibrosis by T-MSCs via reduction of TGF-β expression and collagen deposition in the liver. We hypothesized that autophagy activation was a possible mechanism for T-MSC-mediated liver recovery. In this report, we demonstrate for the first time that T-MSCs can differentiate into hepatocyte-like cells and ameliorate liver fibrosis via autophagy activation and down-regulation of TGF-β. These findings suggest that T-MSCs could be used as a novel source for stem cell therapy targeting liver diseases.


The requirement for both DNA polymerase and 5' to 3' exonuclease activities of DNA polymerase I during Tn5 transposition.
By assaying transposition of Tn5 from lambda b221 cI857 rex::Tn5 (Berg 1977) in polA-proficient and deficient cells, both the polymerase activity and 5' to 3' exonuclease activity of DNA polymerase I have been shown to be required for transposition. This requirement could not be observed in three other systems in which the transposon donor replicon had existed in the PolA-proficient and deficient cells before the transposition event to be assayed occurred. By analogy to Tn3, this may indicate that the repressor encoded by Tn5 has already been expressed and hence become rate-limiting in the overall transposition process, even PolA-deficient cells still possessing a residual activity. One PolA mutant was found among more than 50 transposition deficient (tnp) mutants isolated by the use of lambda b221 cI857 rex::Tn5.


Progesterone and its downstream molecules as blastocyst implantation essential factors.
This review is to update the previous review (Am J Reprod Immunol, 63, 2010 and 413) on the research on blastocyst implantation essential factors (BIEFs). Focus of the current review is on progesterone and its downstream molecules in the process of blastocyst implantation. To understand the process of implantation, we need to know where and when the BIEFs are expressed and what they do. Progress in this research area is rapid, and its update is indeed necessary. The basic concept of BIEFs is that they have dual functions, one physiological and the other immunological (J Reprod Dev, 58, 2012 and 196). As we are still exploring the mechanism of implantation, available data are incomplete and human data are few. Thus, I will use information obtained through research on animal models, in vitro studies, cell lines, and some human studies where available. The ultimate goal of the review is to understand human blastocyst implantation.


Chromosomal aberrations in lymphocytes of healthy subjects and risk of cancer.
There is evidence that increased frequency of chromosomal aberration (CA) in peripheral blood lymphocytes is a predictor of cancer, but further data are needed to better characterize CA as marker of cancer risk. From the archives of 15 laboratories we gathered cytogenetic records of 11,834 subjects who were free of cancer at the moment of blood drawing and who underwent cytogenetic examination for preventive purposes in the Czech Republic during 1975-2000. We linked these records to the national cancer registry, revealing a total of 485 cancer cases. Subjects were classified according to the percentiles of CA distribution within each laboratory as low (0-33rd percentile), medium (34-66th percentile), and high (66-100th percentile). Subjects were further classified by occupational exposure and by subclass of CA. We found a significant association between the overall cancer incidence and the presence of chromosome-type aberrations [relative risk (RR) for high vs. low CA level = 1.24; 95% confidence interval (CI), 1.03-1.50] but not chromatid-type aberrations. Stomach cancer showed a strong association with frequency of total CA (RR = 7.79; 95% CI, 1.01-60.0). The predictivity of CA observed in subjects exposed to various classes of carcinogens did not significantly differ from the group of nonexposed subjects. This study contributes to validation of CA as a predictive marker of cancer risk, in particular, of stomach cancer; the association between CA frequency and cancer risk might be limited to chromosome-type aberrations.


Neuroimmune pharmacology as an emerging curriculum for pre-medical students.
As science continues to evolve and expand some major areas of interest are now crossing boundaries to become multi-disciplinary in nature closely reflecting the biological processes of the organism as a whole. The fields of neuroscience, immunology, and pharmacology are good examples of one such emerging inter-disciplinary area. This article is focused on developing a curriculum for undergraduate pre-medical students in the area of neuroimmune pharmacology (NIP) to empower them with the knowledge of neuroscience and its interaction with immune responses and drug interactions. This course is intended to amalgamate and put into perspective a large body of knowledge including: (1) brain function in health and disease, (2) cross talk between neural and immune responses, and (3) the pharmacology of drugs of abuse in the context of neurodegenerative diseases. The goal of this course is to expose pre-medical students to the field of NIP so that they are equipped with a solid foundation in these multidisciplinary fields for future clinical/academic careers.


[Community acquired pneumococcal pneumonia in hospitalized adult patients].
S pneumoniae is the most common cause of community-acquired pneumonia. To evaluate the clinical characteristics, antibiotic resistance, management and prognostic factors in pneumococcal pneumonia. Prospective evaluation in 46 adults (age +/- sd: 68 +/- 17 years) hospitalized with pneumococcal pneumonia confirmed by sputum, blood or pleural fluid cultures. Clinical and radiographic variables, risk factors for antibiotic resistance, and hospital mortality rate were recorded. Heart disease (39%), COPD/asthma (25%), and diabetes mellitus (18%) were the most frequent underlying diseases. None of the patients had previously received pneumococcal vaccine. Only 17% of the patients had the classic triad of chills, fever and productive cough. At admission, interestingly, 17% presented with congestive heart failure. Resistance of pneumococci to penicillin, cefotaxime or erythromycin was 15%, 6% and 11%, respectively. Antibiotic use prior to admission was significantly associated with antibiotic resistance (OR = 6; CI 95% = 1.1-32; p < 0.05). Fifty per cent of the patients were admitted to intermediate or intensive care units, 15% were mechanically ventilated, 20% developed septic shock, 20% developed acute renal failure and 13% died in the hospital. Clinical factors significantly associated with higher mortality were systolic hypotension (< or = 90 mmHg), ICU admission and BUN > 30 mg per dL. Our data suggest that pneumococcal pneumonia is still a severe infection with high mortality; hence, efforts should be made at prevention using pneumococcal immunization.


Trophic niches reflect compositional differences in microbiota among Caribbean sea urchins.
Sea urchins play a critical role in marine ecosystems, as they actively participate in maintaining the balance between coral and algae. We performed the first in-depth survey of the microbiota associated with four free-living populations of Caribbean sea urchins: Lytechinus variegatus, Echinometra lucunter, Tripneustes ventricosus, and Diadema antillarum. We compared the influence of the collection site, echinoid species and trophic niche to the composition of the microbiota. This dataset provides a comprehensive overview to date, of the bacterial communities and their ecological relevance associated with sea urchins in their natural environments. A total of sixty-samples, including surrounding reef water and seagrass leaves underwent 16S rRNA gene sequencing (V4 region) and high-quality reads were analyzed with standard bioinformatic approaches. While water and seagrass were dominated by Cyanobacteria such as Prochlorococcus and Rivularia respectively, echinoid gut samples had dominant Bacteroidetes, Proteobacteria and Fusobacteria. Propionigenium was dominant across all species' guts, revealing a host-associated composition likely responsive to the digestive process of the animals. Beta-diversity analyses showed significant differences in community composition among the three collection sites, animal species, and trophic niches. Alpha diversity was significantly higher among L. variegatus samples compared to the other species. L. variegatus also displayed an increased abundance of Planctomycetes and Cyanobacterial OTUs. The bacterial community of this herbivorous echinoid reflected similarities to the microfilm community found on Thalassia testudinum leaves; a very abundant seagrass and its main food resource. The results of this study elaborate on the microbial ecology of four important Caribbean echinoids, confirming that selection on the microbial community is trophic-niche dependent.


Pathogenicity of avian leukosis viruses related to fowl glioma-inducing virus.
Fowl glioma-inducing virus (FGV), which belongs to avian leukosis virus subgroup A, causes the so-called fowl glioma and cerebellar hypoplasia in chickens. In the present study, the complete nucleotide sequences of four isolates (Tym-43, U-1, Sp-40 and Sp-53) related to the FGV prototype were determined and their pathogenicity was investigated. Phylogenetic analysis showed that the 3'-long terminal repeat of all isolates grouped together in a cluster, while sequences of the surface (SU) proteins encoded by the env gene of these viruses had 85 to 96% identity with the corresponding region of FGV. The SU regions of Tym-43, U-1 and FGV grouped together in a cluster, but those of Sp-40 and Sp-53 formed a completely separate cluster. Next, C/O specific-pathogen-free chickens were inoculated in ovo with these isolates as well as the chimeric virus RCAS(A)-(FGVenvSU), constructed by substituting the SU region of FGV into the retroviral vector RCAS(A). The four variants induced fowl glioma and cerebellar hypoplasia and the birds inoculated with Sp-53 had the most severe lesions. In contrast, RCAS(A)-(FGVenvSU) provoked only mild non-suppurative inflammation. These results suggest that the ability to induce brain lesions similar to those of the FGV prototype is still preserved in these FGV variants.


Expression of two structurally distinct D-galactan O antigens in the lipopolysaccharide of Klebsiella pneumoniae serotype O1.
The lipopolysaccharide (LPS) molecule is an important virulence determinant in Klebsiella pneumoniae. Studies on the serotype O1 LPS were initiated to determine the basis for antigenic heterogeneity previously observed in the O1 side chain polysaccharides and to resolve apparent ambiguities in the reported polysaccharide structure. Detailed chemical analysis, involving methylation and 1H- and 13C-nuclear magnetic resonance studies, demonstrated that the O-side chain polysaccharides of serotype O1 LPS contained a mixture of two structurally distinct D-galactan polymers. The repeating unit structures of these two polymers were identified as [----3)-beta-D-Galf-(1----3)-alpha-D-Galp-(1----] (D-galactan I) and [----3)-alpha-D-Galp-(1----3)-beta-D-Galp-(1----] (D-Galactan II). D-Galactan I polysaccharides were heterogeneous in size and were detected throughout the sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) profile of O1 LPS. In contrast, D-galactan II was confined to the higher-molecular-weight region. The structures of the two D-galactans were not influenced by simultaneous synthesis of a capsular K antigen. Apparently, neither of the D-galactans constitutes a common antigen widespread in Klebsiella spp. as determined by immunochemical analysis. Examination of the LPSs in mutants indicated that expression of D-galactan I can occur independently of D-galactan II. Transconjugants of Escherichia coli K-12 strains carrying the his region of K. pneumoniae were constructed by chromosome mobilization with RP4::mini-Mu. In these transconjugants, the O antigen encoded by the his-linked rfb locus was determined to be D-galactan I, suggesting that genes involved in the expression of D-galactan II are not closely linked to the rfb cluster.


Total Joint Arthroplasty in a Stand-alone Ambulatory Surgical Center: Short-term Outcomes.
For decades, the average hospital stay following total joint arthroplasty (TJA) has been getting shorter. The historical standard was several weeks of hospitalization, yet improvements in perioperative care have reduced the average length of stay to a few days. Medicare recognizes a 3-day inpatient stay as the standard of care following hip or knee replacement. Yet continued advances in minimally invasive surgical techniques, short-acting general anesthetics, long-acting local anesthetics, and blood loss management have further improved the safety and recovery for TJA procedures. Thus, further reductions in postoperative hospitalization have been implemented around the country, with surgeons reporting successful same-day protocols, as defined by hospitalization discharge on the day of surgery. Although these studies have presented results of same-day TJA in the hospital setting, this study is the first to report on the perioperative adverse events and early outcomes of 51 consecutive TJA procedures performed in a stand-alone ambulatory surgical center (ASC). The ASC offers an ideal setting to perform such procedures in the properly selected patient population, obviating any form of postoperative hospitalization. Although 16 (31.4%) of 51 patients reported minor adverse events in the postanesthesia care unit, specifically nausea and/or pain, early intervention permitted 50 (98.0%) of 51 patients to be discharged home, on average 176 minutes after surgery, with 1 patient discharged to a rehabilitation facility as arranged prior to surgery. There were no major adverse events in the 90-day perioperative period, and although 1 (2.0%) patient was hospitalized for persistent incisional drainage, none required admission for pain. This study examines the strict eligibility criteria and perioperative analgesia protocols that permit successful outpatient TJA. [Orthopedics. 2016; 39(4):223-228.].


Unraveling the Physicochemical Determinants of Protein Liquid-liquid Phase Separation by Nanoscale Infrared Vibrational Spectroscopy.
The phenomenon of reversible liquid-liquid phase separation of proteins underlies the formation of membraneless organelles, which are crucial for cellular processes such as signalling and transport. In addition, it is also of great interest to uncover the mechanisms of further irreversible maturation of the functional dense liquid phase into aberrant insoluble assemblies due to its implication in human disease. Recent advances in methods based on atomic force microscopy (AFM) have made it possible to study protein condensates at the nanometer level, providing unprecedented information on the nature of the intermolecular interactions governing phase separation. Here, we provide an in-depth description of a protocol for the characterisation of the morphology, stiffness, and chemical properties of protein condensates using infrared nanospectroscopy (AFM-IR).


A longitudinal study of mental health in refugees from Burma: the impact of therapeutic interventions.
The present study seeks to examine the impact of therapeutic interventions for people from refugee backgrounds within a naturalistic setting. Sixty-two refugees from Burma were assessed soon after arriving in Australia. All participants received standard interventions provided by a resettlement organisation which included therapeutic interventions, assessment, social assistance, and referrals where appropriate. At the completion of service provision a follow-up assessment was conducted. Over the course of the intervention, participants experienced a significant decrease in symptoms of post-traumatic stress disorder, anxiety, depression and somatisation. Pre-intervention symptoms predicted symptoms post-intervention for post-traumatic stress, anxiety and somatisation. Post-migration living difficulties, the number of traumas experienced, and the number of contacts with the service agency were unrelated to all mental health outcomes. In the first Australian study of its kind, reductions in mental health symptoms post-intervention were significantly linked to pre-intervention symptomatology and the number of therapy sessions predicted post-intervention symptoms of post-traumatic stress. Future studies need to include larger samples and control groups to verify findings.


The substructure of three repetitive DNA regions of Schistosoma haematobium group species as a potential marker for species recognition and interbreeding detection.
Schistosoma haematobium is the causative agent of human urogenital schistosomiasis affecting ~112 million people in Africa and the Middle East. The parasite is transmitted by snails of the genus Bulinus, which also transmit other closely related human and animal schistosomes. The accurate discrimination of S. haematobium from species infecting animals will aid effective control and elimination programs. Previously we have shown the utility of different repetitive nuclear DNA sequences (DraI, sh73bp, and sh77bp) for the identification of S. haematobium-group species and inter-repeat sequences for discriminating S. haematobium from S. bovis. In this current study we clarify the structural arrangement and association between the three repetitive sequences (DraI, sh73bp, and sh77bp) in both S. haematobium and S. bovis, with a unique repeat linker being found in S. haematobium (Sh64bp repeat linker) and in S. bovis (Sb30bp repeat linker). Sequence data showed that the 3'-end of the repeat linker was connected to the DraI repetitive sequence array, and at the 5'-end of the repeat linker sh73bp and sh77bp were arranged in an alternating manner. Species-specific oligonucleotides were designed targeting the species-specific repeat linkers and used in a reverse line blot (RLB) hybridization assay enabling differentiation between S. haematobium and S. bovis. The assay was used to discriminate natural infections in wild caught Bulinus globosus. This research enabled the characterisation of species-specific DNA regions that enabled the design of species-specific oligonucleotides that can be used to rapidly differentiate between S. haematobium and S. bovis and also have the potential to aid the detection of natural hybridization between these two species.


O-buffer: a framework for sample-based graphics.
We present an innovative modeling and rendering primitive, called the O-buffer, as a framework for sample-based graphics. The 2D or 3D O-buffer is, in essence, a conventional image or a volume, respectively, except that samples are not restricted to a regular grid. A sample position in the O-buffer is recorded as an offset to the nearest grid point of a regular base grid (hence the name O-buffer). The O-buffer can greatly improve the expressive power of images and volumes. Image quality can be improved by storing more spatial information with samples and by avoiding multiple resamplings. It can be exploited to represent and render unstructured primitives, such as points, particles, and curvilinear or irregular volumes. The O-buffer is therefore a unified representation for a variety of graphics primitives and supports mixing them in the same scene. It is a semiregular structure which lends itself to efficient construction and rendering. O-buffers may assume a variety of forms including 2D O-buffers, 3D O-buffers, uniform O-buffers, nonuniform O-buffers, adaptive O-buffers, layered-depth O-buffers, and O-buffer trees. We demonstrate the effectiveness of the O--buffer in a variety of applications, such as image-based rendering, point sample rendering, and volume rendering.


Sedation practices for routine gastrointestinal endoscopy: a systematic review of recommendations.
Sedation is commonly used in gastrointestinal endoscopy; however, considerable variability in sedation practices has been reported. The objective of this review was to identify and synthesize existing recommendations on sedation practices for routine gastrointestinal endoscopy procedures. We systematically reviewed guidelines and position statements identified through a search of PubMed, guidelines databases, and websites of relevant professional associations from January 1, 2005 to May 10, 2019. We included English-language guidelines/position statements with recommendations relating to sedation for adults undergoing routine gastrointestinal endoscopy. Documents with guidance only for complex endoscopic procedures were excluded. We extracted and synthesized recommendations relating to: 1) choice of sedatives, 2) sedation administration, 3) personnel responsible for monitoring sedated patients, 4) skills and training of individuals involved in sedation, and 5) equipment required for monitoring sedated patients. We assessed the quality of included documents using the Appraisal of Guidelines for Research & Evaluation (AGREE) II tool. We identified 19 guidelines and 7 position statements meeting inclusion criteria. Documents generally agreed that a single, trained registered nurse can administer moderate sedation, monitor the patient, and assist with brief, interruptible tasks. Documents also agreed on the routine use of pulse oximetry and blood pressure monitoring during endoscopy. However, recommendations relating to the drugs to be used for sedation, the healthcare personnel capable of administering propofol and monitoring patients sedated with propofol, and the need for capnography when monitoring sedated patients varied. Only 9 documents provided a grade or level of evidence in support of their recommendations. Recommendations for sedation practices in routine gastrointestinal endoscopy differ across guidelines/position statements and often lack supporting evidence with potential implications for patient safety and procedural efficiency.


Economic values of rabbit traits in different production systems.
In animal breeding, genetic parameters along with economic weights (EWs) of traits are applied. Profit functions currently used to calculate rabbit traits' EWs do not consider nutrient requirements based on animal weight, growth rate and doe reproductive status. Therefore, the aim of this study was to develop a flexible bioeconomic model of rabbit-production systems and implement it in a computer programme in order to calculate economic values and relative EWs for rabbit traits. The bioeconomic model includes calculation of the doe age structure in the stationary state of a doe population; calculation of progeny structure; modelling growth, digestible energy, feed and water requirements for does in different reproductive statuses and for all progeny groups using a normative approach; calculation of the total feed and non-feed costs, revenues and profit per doe and per year; calculation of marginal economic values for up to 20 production and functional traits and estimation of the relative EWs of selected traits. The application of the programme is shown through an example calculation of trait economic values for a typical Czech commercial rabbit-production system. The trait economic value expresses the change in profit per doe and per year when the trait mean is increased by one unit. The programme developed is primarily useful for selection purposes in rabbit-breeding systems. Using this programme, some economic analyses of the impact of production, management and economic circumstances on the economic efficiency of various rabbit-production systems can also be performed.


Comparison of PhoP binding to the tuaA promoter with PhoP binding to other Pho-regulon promoters establishes a Bacillus subtilis Pho core binding site.
The phosphate-deficiency response in Bacillus subtilis is regulated by PhoP and PhoR, a pair of two-component regulatory proteins. PhoR is a histidine kinase and PhoP is a response regulator. Genetic evidence indicates that the Pho-regulon genes, which are induced or repressed under phosphate starvation conditions, are regulated by PhoP and PhoR at the transcriptional level. It has previously been shown that PhoP binds to four Pho-regulon promoters in both unphosphorylated and phosphorylated forms. This study demonstrates that another Pho-regulon gene promoter, the tuaA promoter preceding the operon which is responsible for cell wall teichuronic acid synthesis, is also transcriptionally regulated and is bound by PhoP. The binding affinity for phosphorylated PhoP was about 10-fold higher than that for unphosphorylated PhoP. Both unphosphorylated and phosphorylated PhoP bound upstream of the -20 region in the tuaA promoter. By aligning the PhoP-binding sites within the Pho-regulon promoters, a consensus core PhoP-binding region composed of four TT(A/T)ACA direct repeats, each separated by 5 +/- 2 non-conserved nucleotides was identified. PhoP, phosphorylated or unphosphorylated, binds to such a sequence in all Pho-regulon promoters studied. Phosphorylated PhoP binds to the core binding region with high affinity and to additional regions surrounding this region with similar or lower affinity.


The capacity of polyomavirus enhancer binding protein 2alphaB (AML1/Cbfa2) to stimulate polyomavirus DNA replication is related to its affinity for the nuclear matrix.
The nuclear matrix is thought to play an important role in the DNA replication of eukaryotic cells, although direct evidence for such a role is still lacking. A nuclear matrix-associated transcription factor, polyomavirus (Py) enhancer binding protein 2alphaB1 (PEBP2alphaB1) (AML1/Cbfa2), was found to stimulate Py replication through its cognate binding site. The minimal replication activation domain (RAD) was identified between amino acid (aa) 302 and aa 371 by using a fusion protein containing the GAL4 DNA binding domain (GAL4-RAD). In addition, the region showed affinity for the nuclear matrix and, on the basis of competition studies, binding activity for one or more proteins involved in the initiation of Py DNA replication. A leukemogenic chimeric protein, AML1/ETO(MTG8), which does not contain this region of PEBP2alphaB1/AML1, was also localized in the nuclear matrix fraction and competed for nuclear matrix association with PEBP2alphaB1 and GAL4-RAD. Moreover, AML1/ETO inhibited Py DNA replication stimulated by PEBP2alphaB1 and GAL4-RAD. The inhibition was specific for replication mediated by PEBP2alphaB1 and GAL4-RAD, and proportional to the degree of loss of these activators from the nuclear matrix, suggesting a requirement for nuclear matrix targeting in the stimulation of Py DNA replication by RAD. These results are the first to suggest a molecular link between the initiation of DNA replication and the nuclear matrix compartment.


Ten simple rules for starting FAIR discussions in your community.
This work presents 10 rules that provide guidance and recommendations on how to start up discussions around the implementation of the FAIR (Findable, Accessible, Interoperable, Reusable) principles and creation of standardised ways of working. These recommendations will be particularly relevant if you are unsure where to start, who to involve, what the benefits and barriers of standardisation are, and if little work has been done in your discipline to standardise research workflows. When applied, these rules will support a more effective way of engaging the community with discussions on standardisation and practical implementation of the FAIR principles.


Anaphylactoid reactions due to haemodialysis, haemofiltration, or membrane plasma separation.
A previously undescribed anaphylactoid reaction to haemodialysis, haemofiltration, or membrane plasma separation occurred in 15 patients receiving regular dialysis. The illness varied in severity from urticaria, sneezing, and watering of the eyes to severe bronchospasm and cardiovascular collapse, and began within a minute of blood being returned from the dialyser or filtration device to the patient. Reactions developed only when a dialyser sterilised with ethylene oxide was used for the first time and never after sterilisation with formalin. Several patients had more than one reaction while three had a reaction each time a new dialyser was used. Incorrect priming of the dialysers may be a partial explanation of these attacks, but the exact reason for their occurrence is unknown. This is a dramatic and potentially life-threatening syndrome that may not previously have been recognised as a reaction to dialysis.


Genus Pimenta: An Updated Comprehensive Review on Botany, Distribution, Ethnopharmacology, Phytochemistry and Biological Approaches.
Pimenta is a genus of flowering plants belonging to family Myrtaceae, native to the West Indies, Mexico, and South America. Numerous traditional uses were reported as anti-inflammatory, analgesic, antipyretic, sedative, diuretic, and sexual stimulant. This article aims to provide a comprehensive overview of the botany, traditional uses, phytochemical profile, and biological activities of genus Pimenta for future exploration of plant-based drugs and therapeutic approaches. The data were collected (up to date as of October 1, 2023) from several databases such as Web of Science, google scholar, science direct, Pubmed and Proquest. Pimenta species were reported to include various classes of phytochemicals like tannins, saponins, flavonoids, phenylpropanoids, monoterpenes, sesquiterpenes and essential oils. Quercetin glycosides and eugenol derivatives were the predominant compounds of this genus. Several biological activities have been reported such as antihypertensive, antioxidant, antimicrobial, antiviral, histidine decarboxylase inhibition, hypoglycemic, anticancer, anti-inflammatory, analgesic, antipyretic, acaricidal, anxiolytic, anti-depressant and anti-estrogenic. Several scientific reports have been published on various isolated phytochemicals and pharmacological properties of Pimenta species that confirm its ethnobotanical and traditional history. However, in vivo studies on different extracts and their phytoconstituents, alongside mechanistic analysis deserve more attention for drug researchers to provide better guidance to utilize Pimenta plants as medicinal resources for herbal formulations in different approaches.


Emerging role of vitamin D in colorectal cancer.
Colorectal cancer is a common cancer and the fourth leading cause of death in Korea. The incidence and mortality of colorectal cancer varies according to risk factors, such as age, family history, genetic history, food habits, and physical activities. Some studies have focused on the association between vitamin D and colorectal cancer. Today, there is growing evidence that high vitamin D intake and a plasma level of 25(OH)D(3) reduce the incidence of colorectal cancer by modifying cancer angiogenesis, cell apoptosis, differentiation, and proliferation. Taken together, these results suggest that vitamin D supplementation alone, or in combination with anti-cancer agents, might reduce the incidence of colorectal cancer. In this review, we discuss the function and mechanism of vitamin D including the effect of vitamin D on colorectal cancer.


Identification of Novel Human Serum Albumin (SA) Inhibitors from Scoparia Dulsis for Urolithiasis.
Urolithiasis is the process of forming stones in the kidney, bladder, and/or urinary tract. It has been reported that kidney stones are the third most common disorder among urinary diseases. At present, surgical procedures and Extracorporeal Shock Wave Lithotripsy (ESWL) are commonly employed for the treatment of Urolithiasis. The major drawback of these procedures is the recurrence of stones. This study aimed to identify potential natural inhibitors against human Serum Albumin (SA) from the plant Scoparia Dulsis for Urolithiasis. As protein-ligand interactions play a key role in structure- based drug design, this study screened 26 compounds from Scoparia Dulsis and investigated their binding affinity against SA by using molecular docking. The three dimensional (3D) structure of SA was retrieved from Protein Data Bank (PDB) and docked with PubChem structures of 26 compounds using PyRX docking tool through Autodock Vina. Moreover, a 3D similarity search on the PubChem database was performed to find the analogs of best scored compound and docking studies were performed. Drug-likeness studies were made using Swiss ADME and Lipinski's rule of five was performed for the compounds to evaluate their anti-urolithiatic activity. The results showed that citrusin c (Eugenyl beta-D-glucopyranoside) exhibited best binding energy of -8.1 kcal/mol with SA followed by aphidicolin, apigenin, luteolin and scutellarein. Two compounds (PubChem CID 46186820, PubChem CID 21579141) analogous to citrusin c were selected based on the lowest binding energy. This study, therefore, reveals that these compounds could be promising candidates for further evaluation for Urolithiasis prevention or management.


[Reliability of dengue mortality data in two national health information systems, Brazil, 2000-2005].
We analyze the crude and adjusted reliability of dengue mortality data from the Notifiable Diseases Information System and the Mortality Information System in Brazil from 2000 to 2005. An observational, cross-sectional, descriptive epidemiological study was conducted. Overall crude agreement and chance-adjusted agreement (kappa index) over the study period were 99.9% and 19.6%, respectively. In the year with the most dengue cases (2002), these values were 99.9% and 28.2%, respectively. The proportion of concordant dengue deaths by State varied from 0% to 33%, and the Central-West region showed the highest median. We discuss the importance of integrating and continuing to analyze health information systems and recommend improving and increasing the use of these systems for appropriate public health evaluations.


Sporadic insulinoma in a 10-year-old boy: a case report and literature review.
Insulinoma is an exceedingly uncommon pancreatic islet cell neuroendocrine tumor. Its estimated incidence is approximately four cases per million individuals per year. We report the case of sporadic insulinoma in an exceptionally very young 10-year-old boy who presented with a 1-month history of episodic tremulousness, diaphoresis, increased hunger, confusion and fainting. Initial laboratory investigations showed low blood glucose (64 mg/dL) and high blood insulin (6 μU/mL) levels. Patient was admitted in view of frequent hypoglycemic symptoms and possible pancreatic insulinoma. A 48-hour mentored fasting test was done and ceased within 3 hours due to occurrence of hypoglycemic symptoms. During the episode, blood was drawn and results showed low blood glucose level and high insulin, pro-insulin and C-peptide levels. The hypoglycemic symptoms were relieved greatly by glucose administration and Whipple's triad for insulinoma was met. An abdominal contrast-enhanced computed tomography scan showed a 10 x 12 x 17 mm, small, well-demarcated, heterogeneously enhancing lesion within the body of pancreas without dilatation of pancreatic duct. No evidence of lymphadenopathy or distant metastasis was identified. Patient underwent enucleation of pancreatic tumor. Histopathological and immunohistochemical examination of the pancreatic mass confirmed neuroendocrine tumor (insulinoma). Patient had an uneventful recovery. A post-operative 6-month follow-up showed resolution of hypoglycemic symptoms, normalized blood glucose, insulin, pro-insulin and C-peptide levels, and no evidence of recurrence. Although rare, sporadic insulinoma should be considered in the differential diagnosis of any young individual presenting with frequent hypoglycemic symptoms (neuroglycopenic and/or autonomic nervous system symptoms). Furthermore, a literature review on insulinoma is presented.


Mirror reading can reverse the flow of time.
How does culture shape our concepts? Across many cultures, people conceptualize time as if it flows along a horizontal timeline, but the direction of this implicit timeline is culture specific: Later times are on the right in some cultures but on the left in others. Here we investigated whether experience reading can determine the direction and orientation of the mental timeline, independent of other cultural and linguistic factors. Dutch speakers performed space-time congruity tasks with the instructions and stimuli written in either standard, mirror-reversed, or rotated orthography. When participants judged temporal phrases written in standard orthography, their reaction times were consistent with a rightward-directed mental timeline, but after brief exposure to mirror-reversed orthography, their mental timelines were reversed. When standard orthography was rotated 90° clockwise (downward) or counterclockwise (upward), participants' mental timelines were rotated, accordingly. Reading can play a causal role in shaping people's implicit time representations. Exposure to a new orthography can change the direction and orientation of the mental timeline within minutes, even when the new space-time mapping directly contradicts the reader's usual mapping. To account for this representational flexibility, we propose the hierarchical mental metaphors theory, according to which culturally conditioned mappings between space and time are specific instances of a more general mapping, which is conditioned by the relationship between space and time in the physical world. Conceptualizations of time are culture specific at one level of analysis but may be universal at another.


Awareness regarding clinical application of pharmacogenetics among Japanese pharmacists.
Advances in pharmacogenetic analysis technology have accelerated the movement to incorporate pharmacogenetic analysis data into medicine. Therefore, pharmacists will soon have to provide guidance and raise pharmaceutical questions regarding prescriptions based on patient pharmacogenomic information. The objective of this study was to clarify Japanese pharmacists' awareness of pharmacogenetics. We conducted a postal questionnaire survey among 372 pharmacists belonging to Tsuruha Holdings. Available data were collected from 268 pharmacists (male [n=133], <40 years old [n=170], drugstore pharmacists [n=182]). Of the pharmacists, 19.0% of the population were aware of the Ethical Guidelines for Human Genome/ Gene Analysis Research in Japan, 31.0% of the population had heard either or both the terms "pharmacogenomics" and "pharmacogenetics", and 16.8% of the population were aware that health insurance covered pharmacogenomic tests performed before prescription in Japan. Only 0.4% indicated that they could raise pharmaceutical questions regarding prescriptions based on patients' pharmacogenomic information, and 61.2% of the population indicated a preference to undertake pharmacogenomic tests to predict the efficacy or adverse reactions of a drug. We found a need for actions to improve the awareness of pharmacists about pharmacogenetics and create an environment in which pharmacists are able to provide appropriate medical service based on pharmacogenomic information.