The effects of rearing temperature on developmental stability and learning and memory in the honey bee, Apis mellifera.
Honey bee workers maintain the brood nest of their colony within a narrow temperature range of 34.5+/-1.5 degrees C, implying that there are significant fitness costs if brood is reared outside the normal range. However, the effects of abnormal incubation temperatures are subtle and not well documented. Here we show that short-term learning and memory abilities of adult workers are affected by the temperature they experienced during pupal development. In contrast, long-term learning and memory is not significantly affected by rearing temperature. Furthermore, we could detect no effects of incubation temperature on fluctuating asymmetry, as a measure of developmental stability, in workers, queens or drones. We conclude that the most important consequence of abnormal rearing temperatures are subtle neural deficiencies affecting short-term memory rather than physical abnormalities.


Design, synthesis and structure-activity relationship of novel quinoxalin-2-carboxamides as 5-HT3 receptor antagonists for the management of depression.
A novel series of quinoxalin-2-carboxamides were designed based on the ligand-based approach, employing a three-point pharmacophore model; it consists of an aromatic residue and a linking carbonyl group and a basic nitrogen. The target new chemical entities were synthesized from the key intermediate, quinoxalin-2-carboxylic acid, by coupling it with various amines in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl) and 1-hydroxybenzotriazole (HOBt). The obtained compounds' structures were confirmed by spectral data. The target new chemical entities were evaluated for their 5-HT(3) receptor antagonisms in longitudinal muscle myenteric plexus preparation from guinea pig ileum against 5-HT(3) agonist, 2-methyl-5-HT, which was expressed in the form of pA(2) value. All the synthesized compounds showed antagonism towards 5-HT(3) receptor; based on this result, a structure-activity relationship was derived, which reveals that the aromatic residue in 5-HT(3) receptor antagonists may have hydrophobic interaction with 5-HT(3) receptor. Regardless of their antagonistic potentials, all the synthesized molecules were screened for their anti-depressant potentials by using forced swim test in mice model; interestingly none of the tested compounds affect the locomotion of mice in the tested dose levels. Compounds with significant pA(2) values exhibited good anti-depressant-like activity as compared to the vehicle-treated group.


[Effects of overdosed fluoride on rat's incisor expression of matrixmetalloproteinase-20 and tissue inhibitors of metalloproteinase-2].
To investigate the effects of overdosed fluoride on the expression of MMP-20 and TIMP-2 in rat incisor. 20 Wistar rats were randomly divided into experiment group and control group. The distilled water was given in control group. 100 mg/L fluoride- was given in experiment group. After 8 weeks treatment, the rats were killed. Immunohistochemical staining was used to observe the expression of MMP-20 and TIMP-2 in rat incisors. Immunohistochemical results demonstrated the presence of MMP-20 and TIMP-2 protein in ameloblasts, odontoblasts, stratum intermedium and the stellate reticulum of rat incisor. The imagination analysis results showed that the expression of MMP-20 was reduesed in experiment group (P<0.01), and the expression of TIMP-2 had no significant difference (P>0.05). The overdosed fluoride inhibits the secretion of MMP-20 and leads to the disturbed balance between MMP-20, TIMP-2 in rat incisor, which leads to the delay of the amelogenin removal and the enamel demineralization.


Assessing fluoroquinolone-associated aortic aneurysm and dissection: Data mining of the public version of the FDA adverse event reporting system.
A recent large epidemiological study found fluoroquinolone use is associated with an increased risk of aortic aneurysm or dissection. We aimed to examine fluoroquinolone (ciprofloxacin, levofloxacin and moxifloxacin) associated aortic aneurysm or dissection through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS). Reports to the FAERS from 1 January 2004 to 31 December 2016 were analysed. Pharmacovigilance tools were used for quantitative detection of signals that is, drug-associated adverse events, including reporting odds ratio, proportional reporting ratio, information component given by a Bayesian confidence propagation neural network and empirical Bayes geometric mean. Sensitivity analyses that limited the data by gender and adverse event date also showed similar trends. Based on 3721 adverse event reports, all three fluoroquinolones are associated with aortic aneurysm, and levofloxacin is associated with aortic dissection. The risk of aortic aneurysm is higher than the aortic dissection. Oral administration of fluoroquinolones is more likely to produce these adverse events. The results obtained herein are consistent with clinical observations, suggesting the necessity for further clinical research on aortic aneurysm and dissection associated with fluoroquinolones.


Risk of beta-cell autoimmunity presence for progression to type 1 diabetes: A systematic review and meta-analysis.
Islet autoantibodies have been applied for diagnosis of type 1 diabetes mellitus (T1DM) at an asymptomatic stage in individuals with high-risk genotypes. Evidence is insufficient to support a broad application of islet autoantibody screening for T1DM in clinical practice. The aim of this study was to assess the evidence of an association between islet autoantibodies and the development of T1DM in a pooled population of both genetically at-risk individuals and general people without definite genetic background. A comprehensive literature search was performed of Pubmed, Web of knowledge and Cochrane library. Prospective cohort studies evaluating the role of islet autoantibodies in prediction of T1DM progression were included. Risk ratios (RRs) were calculated and pooled to arrive at summary estimate. χ2 and I2-values were calculated as measures of heterogeneity and subgroup analyses were performed to explore sources of heterogeneity. Twenty-one studies matched the inclusion criteria. A total of 71,482 nondiabetic participants who were genetically at-risk individuals or from the general population were included, and 926 cases of T1DM were reported during a median follow-up of 7 years. Compared with people free of islet autoantibody, those positive for any type or number of islet autoantibody showed a significantly increased risk of developing T1DM (RR 150.42 [95% CI 87.34, 259.04]). Moreover, the risk for people with multiple islet autoantibodies was 8.59-fold higher than the risk for those with single islet autoantibody, although a moderate heterogeneity existed between studies. The subgroup analysis further revealed that RRs of multiple islet autoantibodies in at-risk population and general population were 7.17 and 13.72, respectively. This study established the association between the seroconversion of islet autoantibodies and T1DM progression in nondiabetic people with or without definite genetic susceptibility, providing further evidence for an extensive application in routine clinical practice to identify individuals at risk of T1DM.


Rodent medial and lateral orbitofrontal cortices represent unique components of cognitive maps of task space.
The orbitofrontal cortex (OFC) has been proposed to function as a cognitive map of task space: a mental model of the steps involved in a task. This idea has proven popular because it provides a cohesive explanation for a number of disparate findings regarding the OFC's role in a broad array of tasks. Concurrently, evidence has begun to reveal the functional heterogeneity of OFC subregions, particularly the medial and lateral OFC. How these subregions uniquely contribute to the OFC's role as a cognitive map of task space, however, has not been explored. Here we propose that, in rodents, the lateral OFC represents the agent's initial position within that task map (i.e. initial state), determining which actions are available as a consequence of that position, whereas the medial OFC represents the agent's future position within the task map (i.e. terminal state), influencing which actions are selected to achieve that position. We argue that these processes are achieved somewhat independently and somewhat interdependently, and are achieved through similar but non-identical circuitry.


Gold nanoparticle-modified black phosphorus nanosheets with improved stability for detection of circulating tumor cells.
Gold nanoparticle (AuNP)-anchored BP nanosheets were synthesized through in situ growth of AuNPs onto BP. Due to the strong chelating ability of P or phosphorus oxides with AuNPs, the stability of BP is improved. As proof-of-concept demonstration of the functionalized BP, electrochemical detection of circulating tumor cells (CTCs) based on BP@AuNPs@aptamer as a probe combined with immunomagnetic separation is reported. The aptamer can specifically bind with CTCs, while the phosphorus oxides including phosphite ion and phosphate ion (PxOy species) on BP and aptamer can react with molybdate to generate an electrochemical current, leading to dual signal amplification. The biosensor is applied to MCF-7 cell detection and displays good analytical performance with a detection limit of 2 cell mL-1. Furthermore, the practicality of this biosensor was validated through sensitive determination of MCF-7 cells in human blood. Therefore, the reported biosensor could be applied to detect other biomarkers, offering an ultrasensitive strategy for clinical diagnostics. Graphical abstract Electrochemical detection of circulating tumor cells based on gold nanoparticle-modified black phosphorus nanosheets is reported.


Contractile activity of rabbit uterus at the end of pregnancy and a method for its registration.
We developed a method for synchronous registration of electrical activity of the myometrium in pregnant rabbit females and electrocardiograms of the female and fetus on a paper tape and on PC in the online mode using an original pickup for registration of intrauterine pressure in awaken animals in a natural (sitting) posture. The method causes no pregnancy complications and is adequate for evaluation of uterine contractility, female and fetal status in different variants of the experiment.


Correction to: Native Hawaiian Views on Biobanking.
The original version of this article unfortunately contained a mistake. The name of "Maile Taualii" is now corrected in the author group of this article.


Use of low-dose rocuronium for intubation of children during volunteer surgery abroad.
Low-dose rocuronium (ROC) might improve safety during volunteer surgery abroad (VSA) by facilitating intubation with a lower halothane concentration than is typically used. We hypothesized that 0.25 mg.kg(-1) of ROC would improve intubation conditions during 3% halothane induction and still allow for rapid return to spontaneous ventilation (SV). During Operation Smile's 2002 mission to Honduras, patients aged 3 months-11 years were randomized to receive ROC 0.25 mg.kg(-1) (n = 19), or placebo (n = 23). Induction was with 3% halothane in 100% O(2), with ventilation assisted and controlled when possible, and normocarbia maintained. An i.v. was placed after induction, and ROC or placebo given. Direct laryngoscopy (DL) was performed 3 min later by a blinded laryngoscopist who assessed conditions according to predetermined criteria. Adequate intubation conditions occurred in 89 and 87% of patients (P = 0.59), and mean times from DL until the return to SV were 9.8 and 4.3 min (P = 0.003), in the ROC and placebo groups, respectively. For the placebo group, the presence of SV at DL was predictive of inadequate intubation conditions (P = 0.006). When administering 3% halothane for induction of VSA patients, a high frequency of adequate intubation conditions can be achieved without a relaxant, rendering the known benefits of 0.25 mg.kg(-1) of ROC unapparent. ROC 0.25 mg.kg(-1) does allow rapid return to SV.


Analysis of complex drugs by comprehensive two-dimensional gas chromatography and high-resolution mass spectrometry: detailed chemical description of the active pharmaceutical ingredient sodium bituminosulfonate and its process intermediates.
The European pharmacopeia provides analytical methods for the chemical characterization of active pharmaceutical ingredients (APIs). However, the complexity of some APIs exceeds the limitations of the currently prevailing physicochemical methods. Sodium bituminosulfonate (SBS) is described by the collection of key parameters of generalizing criteria such as dry matter, sulfur and sodium content, and neutrality, but techniques to unravel the complexity on a molecular level are lacking. We present a study based on online derivatization with tetramethylammonium hydroxide in combination with comprehensive two-dimensional gas chromatography coupled to an electron ionization high-resolution time-of-flight mass spectrometer (GC × GC-HR-ToF-MS) for the chemical description of SBS as well as its process intermediates. The application of GC × GC allowed the comprehensive description of the chemical components in the API and the process intermediates for the first time. Furthermore, it was possible to classify peaks regarding their elemental and structural composition based on accurate mass information, elution behavior, and mass fragmentation pattern. This work demonstrates not only the general applicability, advantages but also limitations of GC × GC for the characterization of APIs for complex drugs.


[Aneurysm of the interatrial septum associated with Lutembacher's syndrome. Echocardiographic and Doppler study].
The case of a patient with suspected atrial septal defect is presented. Echocardiographic-Doppler study confirms the defect associated with mitral stenosis (Lutembacher syndrome) and shows an atrial septal aneurysm through which the shunt is revealed.


Role of inflammation, oxidative stress, and autonomic nervous system activation during the development of right and left cardiac remodeling in experimental pulmonary arterial hypertension.
This study investigated the impact of experimental pulmonary arterial hypertension (PAH) progression by evaluating morphometric and functional parameters, oxidative stress, autonomic nervous system (ANS) activation, and inflammation in the right (RV) and left (LV) ventricles. Male rats were first divided into two groups: monocrotaline (MCT) and control. The MCT group received a single MCT injection (60 mg/kg, intraperitoneal), while control received saline. The MCT and control groups were further divided into four cohorts based on how long they were observed: 1, 2, 3, and 4 weeks. Animals were submitted to echocardiographic and hemodynamic analysis. RV and LV were used for morphometric, biochemical, and histological measurements. Autonomic modulation was evaluated by cardiac spectral analysis, considering two components: low frequency (LF) and high frequency (HF). Lung and liver weight was used for morphometric analysis. MCT induced 100% mortality at 4 weeks. In the RV, disease progression led to mild inflammation and enhanced reactive oxygen species (ROS) in week 1, followed by moderate inflammation, ROS production, and hypertrophy in week 2. By week 3, there was moderate inflammation, oxidative stress, and ANS imbalance, with development of right heart dysfunction. LV biochemical changes and inflammation were observed at week 3. The initial changes appeared to be related to inflammation and ROS, and the later ones to inflammation, oxidative stress, and ANS imbalance in MCT animals. This study reinforces the severity of the disease in the RV, the late effects in the LV, and the role of ANS imbalance in the development of heart dysfunction.


Donepezil in vascular dementia: combined analysis of two large-scale clinical trials.
There are currently no drugs approved to treat vascular dementia (VaD). The objective of this study was to determine if treatment with donepezil, an acetylcholinesterase inhibitor, may provide benefit for VaD patients. Combined analysis of 2 identical randomized, double-blind, placebo-controlled, 24-week studies involving 1,219 patients enrolled at 109 investigational sites in the USA, Europe, Canada and Australia. Patients were randomized to receive donepezil 5 mg/day (n = 406) or 10 mg/day (after brief titration; n = 421) or placebo (n = 392). Patients were assessed on cognition [Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Mini-Mental State Examination (MMSE)], global function [Clinician's Interview-Based Impression of Change plus (CIBIC-plus), Clinical Dementia Rating-Sum of the Boxes (CDR-SB)] and function [Alzheimer's Disease Functional Assessment and Change Scale (ADFACS); instrumental activities of daily living (ADFACS-IADL)]. Both donepezil groups showed significant improvements in cognition compared with placebo (ADAS-cog, MMSE, p < 0.01). Significant global function benefits were seen on the CIBIC-plus in the 5 mg/day group (placebo vs. 5 mg/day, p < 0.001; vs. 10 mg/day, p = 0.006) and on the CDR-SB in the 10 mg/day group (placebo vs. 5 mg/day, p = 0.09; vs. 10 mg/day, p < 0.01). Significant functional benefits were also seen (ADFACS, placebo vs. 5 mg/day, p = 0.08; vs. 10 mg/day, p = 0.02; ADFACS-IADL, p < 0.05 for both donepezil groups). Donepezil was well tolerated, with low withdrawal rates due to adverse events. This combined analysis of the largest trial on VaD to date showed that donepezil-treated patients had significant benefits in cognition, global function and ability to perform IADL. Based on these findings and reported tolerability, donepezil should be considered as an important therapeutic element in the overall management of patients with VaD.


[Construction of eukaryotic expression vector encoding ACRBP and its expression in hepatocarcinoma cells].
To construct the eukaryotic expression vector pEGFP-N1/ACRBP and stably express ACRBP in human hepatocarcinoma cells, providing functional clues for ACRBP. A recombinant plasmid pMAL-C2/ACRBP was used as a template to amplify ACRBP cDNA. The PCR product was ligated into an eukaryotic expression vector pEGFP-N1 to construct a recombinant plasmid pEGFP-N1/ACRBP. Then the pEGFP-N1/ACRBP was transfected by Fugene HD into ACRBP-negative HepG2 cells. The stably transfected clones were selected by G418. RT-PCR and immunohistochemistry were used to detect the expression of ACRBP in HepG2 cells. The eukaryotic expression vector pEGFP-N1/ACRBP was constructed and confirmed by sequencing. The stably transfected HepG2 cells expressed ACRBP. The eukaryotic expression vector pEGFP-N1/ACRBP has been successfully constructed and transfected into HepG2 cells, resulting in stable expression of ACRBP.


CHANGES OF FIXATION STABILITY AND LOCATION AFTER EPIRETINAL MEMBRANE SURGERY.
This study aimed to evaluate fixation stability and position changes after epiretinal membrane (ERM) surgery. This is a retrospective study that included 60 consecutive eyes with idiopathic ERM. All patients received comprehensive ophthalmic examinations preoperatively and 1, 4, and 10 months postoperatively. Main outcome measures included fixation stability and position, bivariate contour ellipse area, and preferred retinal locus. The number of patients with stable fixation and predominantly central fixation was increased significantly after ERM surgery (61.7 vs. 73.3%, P = 0.001; 41.7 vs. 71.7%, P = 0.037). The correlation analysis showed that the preoperative factors associated with improved postoperative fixation stability were a larger bivariate contour ellipse area value (P < 0.001), poorer visual acuity (P = 0.002), advanced stage (P = 0.002), thicker central fovea thickness (P = 0.015), and a longer preferred retinal locus-fovea distance (P = 0.025). As for the improved fixation location, the associated preoperative factors were age (P = 0.003), central fovea thickness (P = 0.044), and preferred retinal locus-fovea distance (P < 0.001). Our observations point to the changes of fixation parameters in patients after ERM surgery. We found that patients with preoperative unstable, eccentric fixation and poor BCVA can significantly benefit from the surgery. This result indicates that even in patients with severe macular damage, the ERM surgery still has great benefits in recovering visual function.


A Case of Migraine With Aura Resolving on Warfarin But Not on Apixaban.
Several case reports have associated anticoagulants such as heparin and vitamin K antagonists with reduced symptoms in migraine, but no data exist for direct acting oral factor Xa inhibitors. We report the case of a 55-year-old female who experienced complete remission of migraine with aura for 12 years while on warfarin, with return of symptoms within 3 weeks of switching to apixaban, and resolution of symptoms once again within days of warfarin resumption. Our case suggests that anticoagulation alone is not sufficient to improve migraine symptoms. Further study of vitamin K-dependent proteins not involved in anticoagulation, such as the relatively novel growth arrest-specific gene 6, may clarify the link between warfarin and migraine symptoms.


Positional stable isotope tracer analysis reveals carbon routes during ammonia metabolism of Aedes aegypti mosquitoes.
In Aedes aegypti females, the ammonia released during blood meal digestion is partially metabolized to facilitate the disposal of excess nitrogen. In this study, we used low- and high-resolution liquid chromatography-mass spectrometry (LC/MS) techniques to investigate the role of glucose during ammonia detoxification. Mosquitoes were fed a blood meal supplemented with [1,2-13C2]glucose, and downstream metabolites were measured for 24 h. Quantification of [13C] amino acids in the entire mosquito body was conducted without sample derivatization using selected reaction monitoring of mass transitions that are indicative of the structural position of [13C] atom incorporation. Identification of unlabeled and [13C] isotopologs of 43 compounds, including amino acids, amino acid derivatives, and organic acids, was performed by high-resolution LC/MS techniques. Blood-fed mosquitoes synthesized [13C] metabolites in mainly 2 carbon positions from [1,2-13C2]glucose. [13C2]Ala and [13C2]Pro were the most abundant and rapidly labeled amino acids synthesized. Additional [13C] amino acids, [13C] amino acid derivatives, and [13C] organic acids in 1 or 2 carbon positions were also identified. Two kinetic routes were proposed based on the incorporation of a [13C] atom at position 1 in specific amino acids. Our findings provide evidence that glucose is used for ammonia detoxification and [13C] uric acid synthesis through multiple metabolic pathways, uncovering a metabolic link at the carbon atomic level in ammonia metabolism of A. aegypti-Horvath, T. D., Dagan, S., Lorenzi, P. L., Hawke, D. H., Scaraffia, P. Y. Positional stable isotope tracer analysis reveals carbon routes during ammonia metabolism of Aedes aegypti mosquitoes.


An overview of time series analysis.
In this paper John Belcher provides an introduction to some basic ideas in the analysis of time series data.


Constructing and deconstructing the bacterial cell wall.
The history of modern medicine cannot be written apart from the history of the antibiotics. Antibiotics are cytotoxic secondary metabolites that are isolated from Nature. The antibacterial antibiotics disproportionately target bacterial protein structure that is distinct from eukaryotic protein structure, notably within the ribosome and within the pathways for bacterial cell-wall biosynthesis (for which there is not a eukaryotic counterpart). This review focuses on a pre-eminent class of antibiotics-the β-lactams, exemplified by the penicillins and cephalosporins-from the perspective of the evolving mechanisms for bacterial resistance. The mechanism of action of the β-lactams is bacterial cell-wall destruction. In the monoderm (single membrane, Gram-positive staining) pathogen Staphylococcus aureus the dominant resistance mechanism is expression of a β-lactam-unreactive transpeptidase enzyme that functions in cell-wall construction. In the diderm (dual membrane, Gram-negative staining) pathogen Pseudomonas aeruginosa a dominant resistance mechanism (among several) is expression of a hydrolytic enzyme that destroys the critical β-lactam ring of the antibiotic. The key sensing mechanism used by P. aeruginosa is monitoring the molecular difference between cell-wall construction and cell-wall deconstruction. In both bacteria, the resistance pathways are manifested only when the bacteria detect the presence of β-lactams. This review summarizes how the β-lactams are sensed and how the resistance mechanisms are manifested, with the expectation that preventing these processes will be critical to future chemotherapeutic control of multidrug resistant bacteria.


Association between rates of premature delivery and intra-uterine growth retardation.
It has been suggested that there is a positive epidemiological correlation between the rates of premature delivery and intra-uterine growth retardation. This was tested across three series of live births, cross-classified according to gravidity and mother's age in two states, North Carolina (caucasians and blacks), and Washington (caucasians only) in the years 1970-74 and 1968-77, respectively. Premature-delivery rate was defined as the percentage of all births of known gestational age born before 37 weeks, and a surrogate measure of the growth-retardation rate as the percentage of all births weighing less than 2500g at term (less than or equal to 40 weeks). The correlations between the two rates for caucasian live births in North Carolina and Washington were found to be +0.74 and +0.73 respectively (p less than 0.0005 in each instance). The correlation coefficient (+0.12 for black live births in North Carolina was not significant. The correlation observed among caucasian births suggest that for growth-retarded fetuses, the risk of subsequent premature delivery is abnormally high.


The effects of a music enrichment program on parent-infant interactions during mealtime: A randomized controlled trial.
Parent-child interactions are linked to childhood obesity. Music enrichment programs enhance parent-child interactions and may be a strategy for early childhood obesity prevention. We implemented a 2-year randomized, controlled trial to assess the effects of a music enrichment program (music, n = 45) vs. active play date control (control, n = 45) on parent-child interactional quality and infant weight status. Typically developing infants aged 9-to 15-months were enrolled with a primary caregiver in the Music Together ® or a play date program. Participants attended once per week group meetings for 12 months and once per month group meetings for an additional 12 months. Parent-child interaction was measured using the Parent Child Early Relational Assessment (PCERA) at baseline, month 6, 12, and 24. We used a modified intent-to-treat mixed model regression to test group differences in parent-child interactions and Weight for length z-score (zWFL) growth trajectories were modeled. There were significant differential group changes across time for negative affect during feeding (group*month; p = 0.02) in that those parents in the music group significantly decreased their negative affect score compared with the control group from baseline to month 12 (music change = -0.279 ± 0.129; control change = +0.254 ± 0.131.; p = 0.00). Additionally, we also observed significant differential group changes across time for parent intrusiveness during feeding (group*month; p = 0.04) in that those parents in the music group significantly decreased their intrusiveness score compared with the control group from month 6 to month 12 (music change = -0.209 ± 0.121; control change = 0.326 ± 0.141; p = 0.01). We did not find a significant association between any of the changes in parental negative affect and intrusiveness with child zWFL trajectories. Participating in a music enrichment program from an early age may promote positive parent-child interactions during feeding, although this improvement in the quality of parent-child interactions during feeding was not associated with weight gain trajectories.


Meiotic recombination in yeast.
Over the past several years, the yeast Saccharomyces cerevisiae has proven to be an extremely useful model system for understanding how cells acquire high recombinational ability during meiosis. Due to recent advances in the physical monitoring of DNA intermediates during meiosis, new cytological methods for visualization of chromosomes during pairing and exchange, and progress in the identification and analysis of recombination-defective mutants, a general picture of the order and dependencies of specific recombination events is now emerging.


Microbacterium gilvum sp. nov., isolated from civet faeces.
A novel aerobic, non-motile, Gram-positive, rod-shaped actinobacterium, designated YIM 100951(T), was isolated from the faeces of civets (Viverra zibetha) living in the National Nature Protect Region in Selangor, Malaysia. Strain YIM 100951(T) shows high similarities with Microbacterium barkeri DSM 20145(T) (97.6 %), Microbacterium oryzae MB10(T) (97.3 %), Microbacterium lemovicicum ViU22(T) (97.1 %) and Microbacterium indicum BBH6(T) (97.0 %) based on their 16S rRNA genes. However, phylogenetic analysis showed that strain YIM 100951(T) formed a clade with Microbacterium halotolerans YIM 70130(T) (96.7 %), Microbacterium populi 10-107-8(T) (96.7 %) and Microbacterium sediminis YLB-01(T) (96.9 %). DNA-DNA hybridization was carried out between strains YIM 100951(T) and M. barkeri DSM 20145(T), the result showed a value of 23.2 ± 4.5 %. In addition, some of the physiological, biochemical and chemotaxonomic characteristics of strain YIM 100951(T) are different from the closely related strains. Thus, we suggest that strain YIM 100951(T) represents a novel species of the genus Microbacterium, for which the name Microbacterium gilvum sp. nov. is proposed. The type strain is YIM 100951(T) (=DSM 26235(T) = CCTCC AB 2012971(T)).


The possible role of physical activity in the modulation of gut microbiota in chronic kidney disease and its impact on cardiovascular risk: a narrative review.
Chronic degenerative non-communicable diseases (CDNCDs), in particular chronic kidney disease, induce gut microbiota (GM) dysbiosis, which, in turn, worsens the progression of CDNCDs and patients' quality of life. We analyzed literature studies to discuss the possible positive and beneficial impact of physical activity on GM composition and CV risk in CKD patients. Regular physical activity seems to be able to positively modulate the GM, reducing the systemic inflammation and consequently the production of uremic gut-derived toxins, which are directly correlated with the increase of cardiovascular risk. In particular, the accumulation of indoxyl sulphate (IS) seems to be able to induce vascular calcifications, vascular stiffness and cardiac calcifications, while p-Cresyl sulphate (p-CS) seems to be able to exert a cardiotoxic action through metabolic pathways, capable of inducing oxidative stress. In addition, trimethylamine N-oxide (TMAO) can alter lipid metabolism, inducing the production of foam cells and causing an accelerated atherosclerosis process. In this context, a regular physical activity program seems to represent an adjuvant non-pharmacological approach to the clinical management of CKD patients.


Nurse associate plan is seen by many as a cheap labour bid.
We do not think that we have ever read such a misleading press release as was issued by Health Education England (HEE) on its consultation over the new nursing associate role.


Exciton and bi-exciton mechanisms in amplified spontaneous emission from CsPbBr3 perovskite thin films.
We studied temperature-dependent amplified spontaneous emission (ASE) in CsPbBr3 perovskite thin films. For temperatures 180-360 K, a narrow-band lasing is observed. However, a new accompanying ASE band appears below 180 K, indicating a more complicated behavior. The two ASE bands are strongly correlated and in competition; they are assigned as exciton and bi-exciton recombination. We estimated the exciton binding energy (EB = 27.3 meV) and that of the bi-exciton, which is lower than the EB. The reduced effective mass of the exciton is estimated as μ = 0.11 me. This discovery identifies more details of the ASE phenomenon.


Sawing toward the fibular head during open-wedge high tibial osteotomy carries the risk of popliteal artery injury.
Popliteal artery injury is a rare but devastating complication of open-wedge high tibial osteotomy (OWHTO). The objectives of this study were: to document the location of the artery in the virtual osteotomy plane (VOP), to measure the minimal distance between the popliteal artery and three virtual saw-progression lines (VSLs), and to present a safe sawing technique for OWHTO. In total, 45 computed tomography angiographies were reconstructed and virtual osteotomy was simulated using 3D image-processing software. The VOP was defined as an inclined plane commencing 3.5 cm below the articular plane towards the fibular head. VSLs were defined as saw-progression guidelines that lie on the VOP: "VSL-mid" runs from the midpoint of the tibial medial cortex towards the fibular head; "VSL-ant" starts from the same point as VSL-mid, but runs 10° anterior to the fibular head; and "VSL-post" runs 10° posterior to the fibular head. The distances between the popliteal artery and the three VSLs were measured, and the risk of injury was assessed. The popliteal artery was located 20.7° posterior to VSL-mid and 51 mm from the starting point. The minimum distance between the popliteal artery and VSL-mid was 18 mm (99% confidence interval 9-27 mm). When the saw was moved along VSL-mid, 42% of the arteries were susceptible to injury. However, when it followed VSL-ant, there was no risk of injury. Sawing toward the fibular head carries a risk of popliteal artery injury and should not be performed. When sawing in OWHTO, the recommended target should be 10° anterior to the fibular head. This technique eliminates the risk of popliteal artery injury.


Family history of breast cancer in men with non-BRCA male breast cancer: implications for cancer risk counseling.
The role of genetic predisposition in male breast cancer (MBC) patients who test negative for a BRCA mutation is unclear. The aim of this study is to define the association between MBC and family history of breast cancer in patients without mutations in BRCA1 or BRCA2. We conducted an unmatched case-control study with men who received commercial testing for germline mutations in cancer susceptibility genes, including 3,647 MBC cases who tested negative for deleterious mutations in BRCA1/BRCA2, and 4,269 men with a personal history of colorectal cancer who tested negative for mutations in DNA mismatch repair genes to serve as controls. Associations between family history of breast cancer and MBC were estimated using unconditional multivariable logistic regression with adjustment for age, race/ethnicity and year of testing. Breast cancer in a first- or second-degree relative was associated with a four-fold increased odds of MBC (OR 4.7; 95% CI 4.1, 5.3). Associations with MBC were strongest for family history of breast cancer in 2 or more first-degree relatives (FDR) (OR 7.8; 95% CI 5.2, 11.6), for probands and FDR diagnosed at age < 45 years (OR 6.9; 95% CI 3.9, 12.4), and for family history of MBC (OR 17.9; 95% CI 7.6, 42.1). Findings were confirmed in a sensitivity analysis of MBC cases who tested negative on a 25-gene pan-cancer panel. MBC patients without mutations in BRCA1/2 have significantly higher odds of a family history of breast cancer, suggesting the existence of unidentified MBC susceptibility alleles.


Antibacterial properties of Magainin II peptide onto 304 stainless steel surfaces: A comparison study of two dopamine modification methods.
Marine biofouling is perplexing the development of marine industry, and the traditional antifouling methods are restricted by the requirements of marine environmental friendliness. Marine bacteria attachment is the initial stage of marine fouling and it can be effectively reduced by reducing bacterial attachment. In this study, two modification methods were reported to synthesize antibacterial surfaces based on the different order of Magainin Ⅱ (MAG Ⅱ) modification. The preparation of SS-DA-M was generated by modifying the 304 stainless steel (304 SS) surface with dopamine firstly and then grafting the MAG Ⅱ onto the dopamine modified surface; SS-M-DA was obtained by modifying 304 SS surface using MAG Ⅱ derivative which synthesized by MAG Ⅱ and dopamine under weak acid condition. XPS, contact angle, film thickness and surface topography analysis showed that both methods grafted MAG Ⅱ onto the 304 SS surface successfully, changing the morphology and wettability of the substrates. Antibacterial results demonstrated that the two modified surfaces possessed strong resistance against V. natriegens, and the antibacterial efficiency of SS-DA-M and SS-M-DA reached 98.07 % and 99.79 %, respectively. Robustness results illustrated that the modified surface could keep strong antibacterial capacity in seawater for a long time. The phy-chemical properties and antibacterial properties of SS-M-DA surface were superior to SS-DA-M surface because more MAG Ⅱ were grafted onto 304 SS surface and the distribution was more uniform than the SS-DA-M surface. The investigation may offer a new and promising strategy to tackle surface fouling of hull, aquaculture cage and other marine facilities.


Provision of Defect-Free Care: Implementation Science in Surgical Patient Safety.
Implementation science is the study of the translation of evidence-based practices to real-world clinical environments. Implementation is measured with specific outcomes including acceptability, adoption, appropriateness, feasibility, fidelity, penetration, sustainability, and implementation cost. There are defined frameworks and models that outline implementation strategies and assist researchers in identifying barriers and facilitators to achieve implementation and conduct implementation research using methods such as qualitative analysis, parallel group, pre-/postintervention, interrupted time series, and cluster or stepped-wedge randomized trials. Deimplementation is the study of how to remove ineffective or unnecessary practices from the clinical setting and is an equally important component of implementation science.


A convenient synthesis and molecular modeling study of novel purine and pyrimidine derivatives as CDK2/cyclin A3 inhibitors.
A series of novel purine and pyrimidine derivatives were prepared and biologically evaluated for their in vitro anti-CDK2/cyclin A3 and antitumor activities in Ehrlich ascites carcinoma (EAC) cell based assay. The novel purine derivatives 13a,b demonstrated potent inhibitor activities with IC(50) values of 14±9 and 13±9 μM, respectively. Additionally, compound 15a showed the highest potency (IC(50)=10±6 μM) in EAC cell based assay. Molecular modeling study, including fitting to a 3D-pharmacophore model and their docking into cyclin dependant kinase2 (CDK2) active site showed high fit values and docking scores.


Maximum urethral closure pressure and sphincter volume in women with urinary retention.
In 1988 a syndrome of isolated urinary retention in young women that is associated with electromyographic abnormality of the striated urethral sphincter was described. It was hypothesised that urinary retention resulted from a failure of sphincter relaxation. The electromyographic abnormality causes overactivity of the muscle and may induce changes of work hypertrophy. If the hypothesis that the electromyographic abnormality is the cause of urinary retention is correct, we would expect the urethral sphincter to be enlarged and the urethral pressure profile to be increased in these women. We evaluated the role of static urethral pressure profilometry and transvaginal ultrasound in women in urinary retention. A total of 66 women in complete or partial urinary retention underwent electromyography of the striated urethral sphincter using a concentric needle electrode, followed by urethral pressure profile and/or urethral sphincter volume measurement by transvaginal ultrasound. Maximum urethral closure pressure plus or minus standard deviation was significantly increased in patients with versus without the electromyographic abnormality (103 +/- 26.4 versus 76.7 +/- 18.4 cm. water, p <0.001). Maximum urethral sphincter volume was also increased in women with versus without the abnormality (2.29 +/- 0.64 versus 1.62 +/- 0.32 cm.3, p <0.001). The results of this study are consistent with the hypothesis that a local sphincter abnormality is the cause of urinary retention in a subgroup of women. Urethral pressure profilometry and sphincter volume measurement are useful for assessing these cases, especially when sphincter electromyography is not readily available.


Venous blood concentration of lidocaine after nasopharyngeal application of 2% lidocaine gel.
In 34 subjects undergoing topical anaesthesia with lidocaine gel (2% xylocaine gel), the concentrations of lidocaine base were measured in repeated venous blood samples. Twenty-three patients (Group I) were given 20 ml of 2% lidocaine gel (400 mg of lidocaine) and six subjects (Group II) 40 ml of 2% lidocaine gel (800 mg of lidocaine) nasopharyngeally, the gel reaching the pharynx being swallowed. Five minutes after administration of the gel, a gastric tube was introduced via the nasal cavity. In six patients (Group III), the bladder was catheterised in addition to insertion of a gastric tube. Before the catheter was introduced, these patients were given lidocaine gel nasopharyngeally (400 mg) and endourethrally (400 mg). After the introduction of the gastric tube, all subjects (except four volunteers in Group II) were given general anaesthesia. Before intubation, the patients in Group III also received lidocaine spray laryngotracheally (50 mg; 10% xylocaine spray). The initial absorption of lidocaine was rapid, although the blood concentrations were low. The mean peak concentrations (Cmax) of lidocaine in the three groups were 0.57, 1.39 and 0.73 micrograms/ml, respectively. The blood concentration in Group II was significantly higher than those in Groups I and III. The mean length of time between the nasopharyngeal application of lidocaine gel and the time when Cmax was reached (tpeak) was the same in all three groups (60-70 min).(ABSTRACT TRUNCATED AT 250 WORDS)


[Analysis and synthesis: retrospection and consideration of medical genetics].
The history of medical genetics was reviewed in this article, through formal genetics, cytogenetics and biochemical genetics to molecular genetics. The application of analysis and integration in medical genetics is summarized, and the blueprint of medical genetics is also discussed.


Transferring network analysis to the study of potential biogeochemical interactions of phosphorus-relevant elements in floodplain subsoils - A new use case for the Soilscape Network Approach (SNAp).
Subsurface phosphorus (P) loss from deep P stocks in floodplain subsoils can contribute to eutrophication of freshwaters. To date, knowledge on the complex biogeochemical interactions of P in floodplain subsoils is too scarce to enable targeted P management to mitigate subsurface P loss from deep P stocks. We propose using graph theory and the Soilscape Network Approach (SNAp) based on correlations between P-relevant elements to study these complex biogeochemical interactions in the soilscape. Complex interactions of several elements in soils are difficult to investigate from a holistic perspective with conventional data analysis. We translated soil element data from topsoils and subsoils of terrestrial sites, proximal and distal floodplain sites into relational data and analyzed network structure, centrality, and modularity. The results indicate that a higher frequency of groundwater level fluctuations in distal subsoils and proximal topsoils could result in 24-44 % less biogeochemical interaction compared to sites with stable conditions. Impeded microbial processes on the frequently disturbed sites may explain this finding. Our analyses suggest biogeochemical differences between floodplain topsoils and subsoils expressed in 24 % lower and 75 % higher network connectivity in distal and proximal subsoils (respectively). We also found 22 % lower network connectivity in distal than proximal floodplain subsoils, suggesting biogeochemical differences between both soil sections. These findings imply that floodplain P management should not take a whole-floodplain approach but a 3D-approach, which differentiates laterally between floodplain zones and vertically between soil sections. In addition, SNAp indicated that Fe(II) oxides are important in P biogeochemistry of floodplain subsoils but are not the key element. Instead, labile P forms are suggested to have different major associations in distal (Alox, Feox) versus proximal deep P stocks (Alox, Mn, Ca). Our study provides new insights into the biogeochemistry of deep P stocks in floodplain subsoils which require targeted validation by other methods.


Ideal atrial lead positioning to detect retrograde atrial depolarization by digitization and slope analysis of the atrial electrogram.
In 10 patients with intact retrograde (V-A) conduction (mean retrograde conduction time 296 +/- 45 msec), bipolar atrial electrograms were recorded simultaneously from three atrial sites (high right atrium [HRA], low right atrium [LRA], and right atrial appendage [RAA]) during sinus rhythm (anterograde electrogram) and paced ventricular rhythm (retrograde electrogram). Atrial electrograms were digitized and analyzed by a special feature detection program which uses sequential slew-rate changes to discriminate different analogue signals. In all patients, it was possible to distinguish anterograde and retrograde atrial depolarizations using the analogue or digital signal recorded from one and usually two [HRA and RAA] lead sites. Digital signal recognition was machine-based and fully automatic, and could be applied to the prevention of pacemaker-mediated tachycardia if incorporated into future microprocessor-based pulse generators.


Identification of ochratoxin A producing Aspergillus carbonarius and A. niger clade isolated from grapes using the loop-mediated isothermal amplification (LAMP) reaction.
To develop two assays based on the loop-mediated isothermal amplification (LAMP) of DNA for the quick and specific identification of Aspergillus carbonarius and ochratoxigenic strains of the Aspergillus niger clade isolated from grapes. Two sets of primers were designed based on the polyketide synthase genes involved or putatively involved in ochratoxin A (OTA) biosynthesis in A. carbonarius and A. niger clade. Hydroxynaphthol blue was used as indirect method to indicate DNA amplification. The limit of detection of both assays was comparable to that of a PCR reaction. Specificities of the reactions were tested using DNA from different black aspergilli isolated from grapes. The two LAMP assays were then used to identify A. carbonarius and ochratoxigenic A. niger and A. awamori grown in pure cultures without a prior DNA extraction. The two LAMP assays permitted to quickly and specifically identify DNA from OTA-producing black aspergilli, as well as isolates grown in pure culture. Monitoring vineyards for the presence of OTA-producing strains is part of the measures to minimize the occurrence of OTA in grape products. The two LAMP assays developed here could be potentially used to speed the screening process of vineyards for the presence of OTA-producing black aspergilli.


Common Variable Immunodeficiency Enteropathy and Its Unpredictable Biopsy Findings: Not Everything Is Black and White.
Common variable immunodeficiency syndrome (CVID) is a diverse entity characterized by hypogammaglobinemia and a propensity for recurrent infections. Involvement of the gastrointestinal tract has a variable manifestation ranging from asymptomatic involvement to florid signs and symptoms. Due to these incongruous findings, multiple concurrent biopsies are to be done for tissue diagnosis. Here, we present two cases diagnosed with CVID on the basis of clinical findings, lab investigations, and morphological features on biopsy.


Fumonisin intake of the German consumer.
In order to calculate the dietary fumonisin intake of the German consumer, a large survey was carried out on a variety of potentially contaminated products in the period between December 1998 and July 2001. A total of 1960 food samples comprising all known relevant groups of products were analysed for fumonisins. Furthermore, 272 of these samples were also analysed for hydrolysed fumonisins (HFB). For routine analysis enzyme immunoassay was used, confirmatory and control analyses were performed using HPLC-FLD after precolumn derivatisation, or by LC-MS/MS. Daily intake of fumonisins was calculated by combining fumonisin contamination data obtained in this study with available food consumption data for Germany. In a "mean case" scenario, median fumonisin levels in foods and mean food intake values were used. To generate a "bad case" scenario, the 90(th) percentile of fumonisin levels in foods and mean food intake values were combined. The overall daily fumonisin intake by the German consumer was 1.1 μg in the "mean case" scenario, and 21 μg in the "bad case" scenario. It was concluded that in general there is no increased risk for the German consumer in aspects of exceeding the recommended tolerable daily intake of fumonisins (2 μg/kg body weight). However, certain products (and certain brands of products) were repeatedly found to contain elevated fumonisin levels, which in a "worst case" scenario ("high" food intake of maize-based products) could pose a potential risk for the consumer, in particular concerning foods for infants and young children. High fumonisin levels were found in infant foods in 1999, but contamination levels decreased strongly in the following years. HFBs (mostly HFB1) were frequently found in processed cereals such as corn flakes, but in relatively low concentrations. According to our findings, the new European Union maximum levels for fumonisins are suitable to eliminate peak contamination levels of fumonisins in foods, but would lead to a regular excess of the TDI for infants and young children if these maximum levels would indeed be exhausted.


A study of PSORS1C1 gene polymorphisms in Chinese patients with psoriasis.
Although genetic analyses have identified the HLA-Cw*0602 allele as the major risk allele for chronic plaque psoriasis in various ethnic groups, it has been proposed that the association of Cw*0602 is due to linkage disequilibrium and that other nearby genes are involved in susceptibility to psoriasis. The psoriasis susceptibility 1 candidate 1 (PSORS1C1, formerly SEEK1) gene, located 127 kb telomeric to the HLA-C locus, is considered to be one of the potential candidate genes of psoriasis. Up to the present, no association study of the PSORS1C1 gene has been conducted on Chinese patients with psoriasis. We aimed to determine whether the genetic polymorphisms of the PSORS1C1 gene were associated with an increased risk of psoriasis in Chinese patients. We investigated the PSORS1C1 gene for disease association by direct sequencing of the PSORS1C1 gene in 143 Chinese patients with chronic plaque psoriasis and 188 control subjects. Genotyping for HLA-Cw*0602 and the alpha-helix coiled-coil rod homologue (C6orf18, formerly HCR) gene was also carried out using a sequence-based typing method. We identified 10 single nucleotide polymorphisms (SNPs) on the PSORS1C1 gene in our subjects; four of these SNPs cause amino acid change. We also detected poly(C) repeat variants from nucleotide positions 386-392 (poly(C)6-8). The poly(C) repeat polymorphisms cause a frame shift mutation. Another poly(C) repeat variant was also found at nucleotide positions 748-751. No significantly different allelic distributions of the PSORS1C1 SNPs or poly(C) repeat polymorphisms could be found between the patients with chronic plaque psoriasis and controls after correction for multiple testing. However, a significant increase of the Cw*0602 allele and tryptophan-tryptophan allele of the C6orf18 gene (HCR*WW) was found in patients with early onset psoriasis (21.9% vs. 4.8%, P < 10(-7)). Haplotype-based association analysis also showed a susceptibility haplotype carrying Cw*0602 and HCR*WW alleles in early onset Chinese patients. Our results indicate that the PSORS1C1 gene might not play an important role in the causation of chronic plaque psoriasis in Chinese people.


The effect of miniaturized manual versus mechanical instruments on calculus removal and root surface characteristics: An in vitro light microscopic study.
The aim of this study was to evaluate by light microscopy analysis the effect of the use of miniaturised piezoelectric tips versus mini-five area specific curets on calculus removal and postoperative root surface alterations. A total of 20 extracted teeth were used. Two square surfaces (5×5 mm) were marked on each root surface with a diamond bur mounted on a high-speed handpiece. Before and after instrumentation, a series of magnified images (4.2×) of each experimental surface were taken with a standardized approach. According to a randomization list, the two surfaces on each sample were instrumented in a standardised fashion either with a mine-five curet or a slim piezoelectric tip. The images were processed using an imaging software. Data were summarised as means and standard deviations for the two outcomes (calculus and alterations.) at each time (pre and post) for both of the groups (manual and mechanical). Both manual and mechanical instrumentation significantly reduced the calculus deposits (p < .001) without significant differences between the two groups. Both manual and mechanical treatments significantly increased alterations (p < .01). There was a statistically significant evidence of a greater increase in alterations from mechanical treatment. Slim mechanical piezoelectric tips and manual mini-five area-specific curets have similar effects on calculus removal. Manual instrumentation results in a more homogeneous postoperative root surface with less root alterations.


Efficacy of rhBMP-2 during distraction osteogenesis.
Osteoinductive ability of bone morphogenetic protein-2 (BMP-2) has been studied in recent reports. In this study, we evaluated the efficacy of BMP-2 during distraction osteogenesis. A group of 24 Japanese white rabbits were divided into four groups randomly and underwent lengthening of the right femur. Distraction was performed for 2 weeks (1.0 mm/day). Group A began distraction following a 7-day waiting period after surgery. For all other groups (B-D), distraction was started immediately after surgery. Groups A and B did not undergo any surgical intervention at the osteotomy site, as a control. The delivery system for rhBMP-2 used a polymer-coated gelatin sponge (PGS). Buffer/PGS was implanted into the osteotomy site in group C, and group D received rhBMP-2/PGS. Callus was evaluated radiographically at 1, 2, 4, and 6 weeks after the surgery, and all rabbits were killed at 6 weeks. One rabbit from each group was examined histologically; the remaining five rabbits underwent biomechanical testing. A significant increase in callus formation was evident in group D compared with that in other groups. In group D, regenerative changes were evident during the earlier phase. Formation of bone cortex and bone marrow cavity was almost complete in group D, and the cortex was thicker than that in the other groups. Torsional strength values (10(-2) Nm) of each group were as follows: A, 118.7 +/- 52.4; B, 160.0 +/- 40.7; C, 106.8 +/- 8.1; D, 266.1 +/- 93.1. Stiffness values (10(-3) Nm/degree) were as follows: A, 390.2 +/- 137.2; B, 391.8 +/- 158.4; C, 183.1 +/- 78.5; D, 624.4 +/- 214.2. Group D exhibited the highest values for both torsional strength and stiffness. Acceleration of the regenerative changes during the early phase occurred in the BMP-2-treated group. The efficacy of BMP-2 in distraction osteogenesis was recognized radiographically, histologically, and by biomechanical testing (torsional strength and stiffness).


Effect of tris-(2-chloroethyl)-phosphate (TCEP) at environmental concentration on the levels of cell cycle regulatory protein expression in primary cultured rabbit renal proximal tubule cells.
Tris-(2-chloroethyl)-phosphate (TCEP) is a typical organophosphate flame retardant and has been designated as a micropollutant in aquatic environment. However, the potential effect of TCEP at environmental concentration is mostly unknown. Thus, the purpose of this study was to investigate the renal effect of TCEP at environmental concentration using primary cultured rabbit renal proximal tubule cells (PTCs). The results showed that TCEP at 10 mg L(-1) decreased cell viability, 84.2% of the control, but increased lactate dehydrogenase, 150% fold of the control. TCEP at 10 mg L(-1) also inhibited expression of CDK4, cyclin D1, CDK2, and cyclin E (79.3%, 77.7%, 73.3%, and 67.8% of the control, respectively), but increased expression of p21(WAF/Cip1) and p27(Kip1) (167.7% and 141.3% of the control, respectively). TCEP decreased DNA synthesis and cell number, 77% and 70% of the control, respectively. Through study of cell viability, cell damage, cell cycle regulator expression, DNA synthesis and cell number, TCEP at 10 microg L(-1) only affected the cells that TCEP increased expression of p21(WAF/Cip1) and p27(Kip1), 118.6% and 121.5% of the control, respectively, but decreased DNA synthesis, 91.5% of the control. In conclusion, TCEP at 10 microg L(-1) significantly increased cell cycle regulatory protein expression (p21(WAF/Cip1) and p27(Kip1)), but slightly decreased DNA synthesis in primary cultured rabbit renal PTCs.


An in-house HIV genotyping assay for the detection of drug resistance mutations in Southeast Asian patients infected with HIV-1.
Genotyping for HIV drug resistance is costly and beyond the means for many Southeast Asian patients, who are self-funded. This prompted the development of a more cost-effective, in-house assay for an ethnically diverse, Southeast Asian population at the National University Hospital in Singapore, using Sanger-based sequencing. Plasma samples from 20 treatment-failure patients with a broad spectrum of HIV drug resistance mutations were used to validate this assay clinically. Blinded testing gave concordant results for 7/7 (100%) protease drug resistance-related mutations, including one major and six minor mutations, and 111/116 (95.7%) reverse-transcriptase (RT) drug resistance-related mutations, including 65 nucleoside RT inhibitors (NRTI) and 46 non-nucleoside RT inhibitors (NNRTI) mutations. There were five discordant results, involving three NRTI- and two NNRTI-resistance-associated mutations. Highly conserved primers designed to have a wide coverage of the HIV pol gene (covering the entire protease and 395 codons of the RT region) enabled efficient multi-ethnic population-based genotyping. Reagents for this in-house test cost around 60% less than those for commercially available assays (SGD150 vs. SGD350 per sample). In addition, this assay also identified mutations located within the C-terminal domain (codons 312-560) of RT that are beyond the reach of most published and commercial GRTs. Currently, most research on C-terminal drug-resistance-related mutations has been conducted on HIV subtype B infections. Therefore this assay enables further study of these C-terminal mutations in Southeast Asian populations, where there is a high prevalence of CRF01_AE and other non-subtype B HIV infections.


Primary bilateral adrenal non-Hodgkin's Burkitt-like lymphoma: a rare cause of primary adrenal insufficiency. Case report and literature review.
Primary bilateral adrenal non-Hodgkin's lymphoma is an extremely rare entity. Only 44 cases have been reported in the literature. The most common presenting symptoms are abdominal pain, fever, asthenia, constipation, weight loss or typical symptoms of adrenal insufficiency, hypertension, darkening of skin, orthostatic hypotension or an addisonian crisis. The case is presented of a 57-year-old man suffering from primary bilateral adrenal lymphoma with symptoms of adrenal insufficiency syndrome associated with bilateral, stabbing lumbar pain and a palpable mass on the left side. Laboratory tests revealed a considerable increase in lactate dehydrogenase levels, adrenal insufficiency, and high corticotropin levels. Abdominal CT scan showed two large adrenal masses. A CT-guided fine needle aspiration biopsy revealed a large B-cell non-Hodgkin's lymphoma. Combination chemotherapy according to the CHOP protocol with cyclophosphamide, doxorubicin, vincristine and prednisolone was initiated, which caused a slight reduction in size of the two adrenal masses. The patient underwent a bilateral adrenalectomy with almost complete excision of the tumors. Replacement therapy with cortisone acetate was initiated postoperatively. Adjuvant combination chemotherapy according to the CHOP protocol was started but renal failure gradually emerged and the treatment could not be completed. The patient died seven months after surgery due to acute bronchial pneumonia and progression of disease. Primary bilateral adrenal non-Hodgkin's lymphoma mainly affects adult men. Diagnosis is based on histological examination. Whether associated or not with radiotherapy, chemotherapy is the most recommended treatment. Surgery, where possible, seems to lead to an increase in survival rates, but it is not possible to draw any definite conclusions on its effectiveness as yet.


Pharmacokinetics and Safety of Bedaquiline in Human Immunodeficiency Virus (HIV)-Positive and Negative Older Children and Adolescents With Rifampicin-Resistant Tuberculosis.
Pharmacokinetic data for bedaquiline in children are limited. We described the pharmacokinetics and safety of bedaquiline in South African children and adolescents receiving treatment for multidrug/rifampicin-resistant tuberculosis (MDR/RR-TB) in routine care. In this observational cohort study, children aged 6-17 years receiving bedaquiline at recommended doses as part of MDR/RR-TB treatment underwent semi-intensive pharmacokinetic sampling. Bedaquiline and the M2 metabolite plasma concentrations were quantified, and nonlinear mixed-effects modeling performed. Pediatric data were described using a pre-established model of bedaquiline pharmacokinetics in adults. The exposure reference was 187 µg ⋅ h/mL, the median weekly area under the curve (AUC) of adults at week 24 of treatment with bedaquiline. Safety was assessed through monthly clinical, blood and electrocardiogram monitoring, and treatment outcomes described. Fifteen children (3 human immunodeficiency virus [HIV]-positive) with median age 13.3 years (range 6.5-16.3) were included. A bedaquiline pharmacokinetic model was adapted to be allometrically scaled in clearance and volume, centered in the median child population weight. Bedaquiline bioavailability was 57% of that in adults. Overall bedaquiline exposures were below target, and AUC reference attainment was achieved in only 3 (20%) children. Ten children experienced 27 adverse events at least possibly related to bedaquiline; no adverse events led to bedaquiline withdrawal. Two adverse events (arthritis and arthralgia) were considered severe, and 2 children had mild QT interval corrected for heart rate using Fridericia's formula (QT) prolongation. The evaluated doses of bedaquiline in children ≥ 6 years of age were safe but achieved slightly lower plasma concentrations compared to adults receiving the recommended dose, possibly due to delayed food intake relative to bedaquiline administration.


A web accessible resource for investigating cassava phenomics and genomics information: BIOGEN BASE.
The goal of our research is to establish a unique portal to bring out the potential outcome of the research in the Casssava crop. The Biogen base for cassava clearly brings out the variations of different traits of the germplasms, maintained at the Tapioca and Castor Research Station, Tamil Nadu Agricultural University. Phenotypic and genotypic variations of the accessions are clearly depicted, for the users to browse and interpret the variations using the microsatellite markers. Database (BIOGEN BASE - CASSAVA) is designed using PHP and MySQL and is equipped with extensive search options. It is more user-friendly and made publicly available, to improve the research and development of cassava by making a wealth of genetics and genomics data available through open, common, and worldwide forum for all individuals interested in the field. The database is available for free at http://www.tnaugenomics.com/biogenbase/casava.php.


Suppression of retinal neovascularization by erythropoietin siRNA in a mouse model of proliferative retinopathy.
Erythropoietin (EPO), an oxygen-regulated hormone stimulating erythrocyte production, was recently found to be critical for retinal angiogenesis. EPO mRNA expression levels in retina are highly elevated during the hypoxia-induced proliferation phase of retinopathy. The authors investigated the inhibition of retinal EPO mRNA expression with RNA interference as a potential strategy to suppress retinal neovascularization and to prevent proliferative retinopathy. The authors used a mouse model of oxygen-induced retinopathy. Retinal EPO and Epo receptor (EpoR) expression during retinopathy development were quantified with real-time RT-PCR in whole retina and on laser-captured retinal vessels and neuronal layers. Retinal hypoxia was assessed with an oxygen-sensitive hypoxyprobe. A small interference RNA (siRNA) targeting EPO or control negative siRNA was injected intravitreally at postnatal (P) day 12, P14, and P15 during the hypoxic phase, and the effect on neovascularization was evaluated in retinal flatmounts at P17. Retinal EPO mRNA expression in total retina was suppressed during the initial phase of vessel loss in retinopathy and was significantly elevated during the hypoxia-induced proliferative phase in all three neuronal layers in the retina, corresponding to an increased level of retinal hypoxia. EpoR mRNA expression levels also increased during the second neovascular phase, specifically in hypoxia-induced neovascular vessels. Intravitreous injection of EPO siRNA effectively inhibited approximately 60% of retinal EPO mRNA expression and significantly suppressed retinal neovascularization by approximately 40%. Inhibiting EPO mRNA expression with siRNA is effective in suppressing retinal neovascularization, suggesting EPO siRNA is a potentially useful pharmaceutical intervention for treating proliferative retinopathy.


Lipases of Endophytic Fungi Stemphylium lycopersici and Sordaria sp.: Application in the synthesis of solketal derived Monoacylglycerols.
Monoacylglycerols (MAGs) are amphiphilic compounds with wide range of applications such as emulsifiers, solubility agents, and chiral building blocks. These compounds are currently produced by chemical approaches involving alkaline glycerolysis or esterification under high temperatures and pressure, resulting in low yields and with by-products. Lipase-catalyzed processes have been alternative tools to provide more ecological approaches since MAGs can be obtained under milder reaction conditions and with higher selectivity. However, just a few papers have been explored the potential of endophytic fungi as lipase sources. In this work we summarized the screening of lipolytic activity of endophytic fungus S. lycopersici and Sordaria spp isolated from vegetal species collected in Jurubatiba Sandbank National Park, RJ, Brazil, as well as its applications as biocatalysts on the lipase-catalyzed synthesis of solketal 1-MAG derivatives. As a result, the crude enzymatic extract of S. lycopersici showed 98 U/mL and 110 U/mL of hydrolytic activity after 72 h and 96 h, respectively, against 74 U/mL (96 h) and, 86 U/mL (120 h) expressed by enzymatic extract of Sordaria spp.. Concerning the esterification activity, both crude enzymatic extracts and lyophilized fungi showed about 80 % conversion into ethyl oleate, in 100 min. On solketal derived 1-MAG synthesis, S. lycopersici both lyophilized and immobilized in polyurethane (PU) forms showed more than 75 % of conversion in the presence and absence of organic solvents. On MAG recycle assays, the PU biocatalyst could be reused after five reaction cycles while for the ethyl oleate synthesis, PU biocatalyst could be reused after six reaction cycles. Both microorganisms, immobilized in polyurethane, were successfully applied as biocatalysts in esterification reactions for solketal 1-MAG derivative production, in a solvent-free media.


Clinical significance of asymmetric hypointense signals in minimum intensity projections of brain magnetic resonance imaging in children with primary headache.
This study aimed to observe the changes of venous continuity using the susceptibility weighted imaging-minimum intensity projection (SWI-MinIP) images in children with primary headache. The headache types were classified following the International Headache Society's diagnostic criteria. Patients with secondary headaches were excluded. The presence of asymmetric vasculature in SWI-MinIP images was visually assessed. Moreover, the relationship between headache patterns and asymmetric hypointense signals was analyzed. In this single-center, retrospective study from 2016 to 2020, among 251 cases of primary headache (male/female, 108/143; mean age, 11.4 ± 4.0 years), 137 (54.6%), 75 (29.9%), and 39 (15.5%) patients had migraine, tension-type headache, and other primary headaches, respectively. On SWI-MinIP images, 14 (5.6%) patients showed an asymmetric venous pattern. All patients with SWI-MinIP asymmetry were included in the migraine group, accounting for 10.2% of patients with migraine. Five (35.7%) and nine (64.3%) patients were included in the aura and non-aura groups, respectively, without a significant difference in the frequency of asymmetric hypointense signals between the two groups (p = 0.325). All 14 patients with asymmetric hypervascularity had brain MRI within 12 h of headache onset. Ten (71.4%) of the 14 patients showed consistency between the laterality of headache and the hemisphere of predominant vascularity in SWI-MinIP. Patients with migraine had increased cerebral venous perfusion in the most involved region of the headache on the SWI-MinIP view on a 3.0 T scanner, which can be used as a qualitative indicator with low sensitivity and high specificity for the diagnosis of primary headache in the acute phase (< 12 h).


Outcomes and predictors of functioning, mental health, and health-related quality of life in adults born with very low birth weight: a prospective longitudinal cohort study.
Very low birth weight (VLBW: ≤1500 g) is associated with multiple short and long-term complications. This study aimed to examine outcomes and predictors of functioning, mental health, and health-related quality of life in adults born with VLBW. In this prospective longitudinal cohort study, 67 VLBW and 102 control participants were assessed using the Adult Self-Report of the Achenbach System of Empirically Based Assessment and Global Assessment of Functioning at 26 years, and the Hospital Anxiety and Depression Scale and Short Form-36 at 28 years of age. Associations between perinatal and childhood predictors and adult functioning were assessed using linear regression. Compared with controls, the VLBW group had lower mean raw scores on the Function and Symptom subscales of the Global Assessment of Functioning at 26 years, a higher sum score of symptoms of anxiety and depression due to more depressive symptoms, and poorer mental health-related quality of life at 28 years. The mean group differences ranged from 0.42 to 0.99 SD. Within the VLBW group, lower birth weight and gestational age, a higher number of days with respiratory support and poorer motor function at 14 years were associated with a higher sum score of symptoms of anxiety and depression at 28 years. Days with respiratory support and motor function at 14 years were also predictive of Global Assessment of Functioning scores at 26 years, and mental health-related quality of life at 28 years. Poorer motor and cognitive function at five years were associated with poorer physical health-related quality of life at 28 years. Parental socioeconomic status was related to mental and physical health-related quality of life. In this study, VLBW adults reported poorer functioning and mental health-related quality of life, and more depressive symptoms than their term born peers. Days with respiratory support and adolescent motor function predicted most of the adult outcomes. This study explicates perinatal and developmental markers during childhood and adolescence which can be target points for interventions.


Coinfection by Ixodes Tick-Borne Pathogens: Ecological, Epidemiological, and Clinical Consequences.
Ixodes ticks maintain a large and diverse array of human pathogens in the enzootic cycle, including Borrelia burgdorferi and Babesia microti. Despite the poor ecological fitness of B. microti, babesiosis has recently emerged in areas endemic for Lyme disease. Studies in ticks, reservoir hosts, and humans indicate that coinfection with B. burgdorferi and B. microti is common, promotes transmission and emergence of B. microti in the enzootic cycle, and causes greater disease severity and duration in humans. These interdisciplinary studies may serve as a paradigm for the study of other vector-borne coinfections. Identifying ecological drivers of pathogen emergence and host factors that fuel disease severity in coinfected individuals will help guide the design of effective preventative and therapeutic strategies.


Mobilizing phospholipids on tumor plasma membrane implicates phosphatidylserine externalization blockade for cancer immunotherapy.
In "healthy" tumor cells, phosphatidylserine (PS) is predominately localized in the inner plasma membrane leaflet. During apoptosis, PS relocates to the outer leaflet. Herein, we established PSout tumor models with tumor cells lacking PS flippase component CDC50A, constantly exposing PS but alive. PSout tumors developed bigger than wild-type (WT) tumors, featuring M2 polarized tumor-associated macrophages (TAMs) and fewer tumor-antigen-specific T cells. The PS receptor TIM-3 is responsible for PS recognition. Employing an opposite tumor model, PSin, with tumor cells lacking the PS scramblase Xkr8 and unable to expose PS during otherwise normal apoptosis, we find that the accumulated apoptotic tumor cells produce and release cyclic GAMP (cGAMP) to immune cells to activate the STING pathway, leading to TAM M1 polarization, suppressed interleukin (IL)-10 secretion, and natural killer (NK) cell cytotoxicity. Silencing Xkr8 in vivo by either short hairpin RNA (shRNA) or small interfering RNA (siRNA) to achieve a PS externalization blockade provides robust therapeutic anti-tumor efficiency.


Associative properties of butyryl-coenzyme A synthetase from ox liver mitochondria.
Butyryl-coenzyme A synthetase (butyrate:CoA ligase (AMP-forming), EC 22.214.171.124) from an acetone-dried powder of ox liver mitochondria was found to have a molecular weight of approx. 40 000. The sedimentation equilibrium analysis suggested the presence in solution of higher molecular weight forms of the enzyme and these could also be obtained by extracting the enzyme from the mitochondrial powder in non-reducing conditions. The enzyme was inhibited by sulphydryl reagents, and was found to have at least one available thiol group/molecule. The relationship between enzymic activity and concentration was non-linear, and suggested that an inactive monomer-active dimer equilibrium was present. The 5--6-fold activation by bovine serum albumin required the presence of free thiol groups in the albumin and involved association of albumin with the enzyme.


Isolation and characterization of Lactococcus piscium strains from vacuum-packaged refrigerated beef.
To characterize gram-positive, catalase-negative, psychrotrophic, lactic acid-homofermentative, non-motile cocci isolated from vacuum-packaged refrigerated beef using phenotypic and genotypic methods. A total of 89 strains was isolated at 2 and 6 weeks as one of the predominant microflora of five samples of vacuum-packaged beef stored at 2 degrees C. The strains were compared with reference strains of some gram-positive, catalase-negative cocci using SDS-PAGE whole-cell protein pattern analysis, biochemical characterization and 16S rDNA sequencing. The biochemical and physiological characteristics of the isolates resembled those of Lactococcus piscium GTC 552(T). Numerical analysis of the SDS-PAGE whole-cell protein patterns resulted in close clustering of the strains with L. piscium GTC 552(T) (r > 0.68). Other Lactococcus and Leuconostoc species could be distinguished from the isolates using SDS-PAGE whole-cell protein patterns (r < 0.58) and biochemical characteristics. The 16S rDNA sequencing of four randomly selected strains showed that the strains differed from L. piscium GTC 552(T) by two to three bases in the highly variable region of the sequence. This is the first report on the isolation of L. piscium from vacuum-packaged beef. The gram-positive catalase-negative cocci isolated from vacuum-packaged refrigerated beef have been identified as L. piscium. The findings of this work contribute to the knowledge of the microflora of vacuum-packaged refrigerated beef.


Sixteen-year trends in adolescent consumption of sugar-sweetened soda in six European countries with a soda tax and comparison countries: a repeated cross-sectional survey analysis.
To examine changes in the proportions of daily, weekly and occasional consumers of sugar-sweetened soda in six European countries that introduced/updated a tax between 2001-2002 and 2017-2018 and in neighbouring comparison countries (without a tax). Repeated cross-sectional surveys. Health Behaviour in School-aged Children study, spanning five survey years (school years 2001-2002 to 2017-2018). Nationally representative samples of 13-year- and 15-year-old adolescents (n 236 623, 51·0 % girls). Tax sizes (€0·02/l to €0·22/l) and pre-tax soda consumption were heterogeneous across countries. Prevalence of daily soda consumption reduced in the survey year following tax implementation in Latvia (from 17·9 to 11·9 %, P = 0·01), Finland (4·2 to 2·5 %, P = 0·001), Belgium (35·1 to 27·8 %, P < 0·001) and Portugal (17·4 to 14·9 %, P = 0·02), but not in Hungary (29·8 to 31·3 %, P = 0·47) or France (29·4 to 28·2 %, P = 0·27). However, reductions were similar (Finland) or smaller (Belgium, Portugal) than those in the comparison countries, except in Latvia where the reduction was larger (Pinteraction < 0·001). Prevalence of weekly soda consumption remained stable (Finland, Hungary and France) or increased (Latvia, Belgium); only Portugal experienced a decline (P < 0·001), which was larger than in the comparison country (Pinteraction < 0·001). Prevalence of occasional soda consumption (<1x/week) did not rise after implementation of the tax in Latvia, Finland, Hungary, France or Belgium, or the rise was similar to the comparison country in Portugal (Pinteraction = 0·15). Countries with a soda tax did not experience larger beneficial changes in post-tax adolescent consumption frequency of soda than comparison countries. Further studies, with different taxation types, are needed in the adolescent population.


Distribution of transganglionically labelled soybean agglutinin primary afferent fibres after nerve injury.
The distribution of the retrogradely-transganglionically transported lectin soybean agglutinin (SBA) and of SBA conjugated to horseradish peroxidase (SBA-HRP) has been examined in the L4-5 dorsal root ganglia, lumbar spinal cord and gracile nucleus at 2, 6 and 14 weeks after sciatic nerve transection and ligation. Cell size analysis showed there were no changes in the mean area of labelled DRG profiles after injury. In the spinal cord, terminal labelling was restricted to laminae I and II with no evidence of labelling in novel territories such as the deeper laminae after injury. At 2 weeks, the labelling on the injured side was similar in distribution and intensity to that of the contralateral, uninjured side. At 6-14 weeks the labelling on the injured side was significantly weaker as compared to the contralateral side, but not completely depleted. In the gracile nucleus, at all survival times, an increased distribution and amount of labelling was seen which may reflect sprouting of C and A-delta fibres. These results suggest that SBA is a useful tracer to study the effects of nerve injury on the central terminals of axotomised afferents terminating in laminae I-II and that C-fibres appear not to sprout outside their normal laminar distribution in the dorsal horn after injury.


GSH depletion enhances adenoviral bax-induced apoptosis in lung cancer cells.
The utility of dominant acting proapoptotic molecules to induce cell death in cancer cells is being evaluated in preclinical studies and clinical trials. We recently developed a binary adenoviral expression system to enable the efficient gene transfer of Bax and other proapoptotic molecules. Using this system, overexpression of Bax protein in four non-small-cell lung cancer (NSCLC) cell lines, H1299, A549, H226 and H322, was evaluated. The H322 line exhibited significant resistance to Bax-induced cell death compared to the other cell lines. H322 cells had the highest level of glutathione (GSH). GSH levels were significantly decreased following buthionine sulfoximine treatment and this coincided with enhanced apoptosis induction by Ad-Bax in H322 cells. GSH depletion enhanced Bax protein translocation to mitochondrial membranes. These findings suggest that the redox status may be a determinant of Bax-mediated cell death and that manipulation of intracellular thiols may sensitize cells to apoptosis by facilitating Bax insertion into mitochondrial membranes.


A subset of p53-deficient embryos exhibit exencephaly.
Defects in neural tube formation are among the most common malformations leading to infant mortality. Although numerous genetic loci appear to contribute to the defects observed in humans and in animal model systems, few of the genes involved have been characterized at the molecular level. Mice lacking the p53 tumour suppressor gene are predisposed to tumours, but the viability of these animals indicates that p53 function is not essential for embryonic development. Here, we demonstrate that a fraction of p53-deficient embryos in fact do not develop normally. These animals display defects in neural tube closure resulting in an overgrowth of neural tissue in the region of the mid-brain, a condition known as exencephaly.


Building Ultra-Stable and Low-Polarization Composite Zn Anode Interface via Hydrated Polyzwitterionic Electrolyte Construction.
Aqueous zinc metal batteries are noted for their cost-effectiveness, safety and environmental friendliness. However, the water-induced notorious issues such as continuous electrolyte decomposition and uneven Zn electrochemical deposition remarkably restrict the development of the long-life zinc metal batteries. In this study, zwitterionic sulfobetaine is introduced to copolymerize with acrylamide in zinc perchlorate (Zn(ClO4)2) solution. The designed gel framework with hydrophilic and charged groups can firmly anchor water molecules and construct ion migration channels to accelerate ion transport. The in situ generated hybrid interface, which is composed of the organic functionalized outer layer and inorganic Cl- containing inner layer, can synergically lower the mass transfer overpotential, reduce water-related side reactions and lead to uniform Zn deposition. Such a novel electrolyte configuration enables Zn//Zn cells with an ultra-long cycling life of over 3000 h and a low polarization potential (~ 0.03 V) and Zn//Cu cells with high Coulombic efficiency of 99.18% for 1000 cycles. Full cells matched with MnO2 cathodes delivered laudable cycling stability and impressive shelving ability. Besides, the flexible quasi-solid-state batteries which are equipped with the anti-vandalism ability (such as cutting, hammering and soaking) can successfully power the LED simultaneously. Such a safe, processable and durable hydrogel promises significant application potential for long-life flexible electronic devices.


Genome-wide linkage analysis of Scandinavian affected sib-pairs supports presence of susceptibility loci for celiac disease on chromosomes 5 and 11.
Celiac disease (CD) is a common chronic inflammatory disorder of the small intestine with a multifactorial aetiology. HLA is a well-known risk factor, but other genetic factors also influence disease susceptibility. To identify the genes involved in this disorder, we performed a genome-wide scan on 106 well-defined Swedish and Norwegian families with at least two affected siblings. We investigated familial segregation of 398 microsatellite markers, and utilised non-parametric linkage analysis. The strongest linkage with disease was found to the HLA locus (6p) (P<0.000006). There were eight regions besides HLA with a point wise P value below 0.05. Among these eight regions were 11q and 5q, both of which have been suggested in several linkage studies of independent celiac disease families. We also performed a stratification analysis of families according to their HLA genotypes. This resulted in significant differences on chromosome 2q. These results indicate that 11q, 5q and possibly also 2q are true susceptibility regions in CD.


Novel use of erbium:YAG (2,940-nm) laser for fractional ablative photothermolysis in the treatment of photodamaged facial skin: a pilot study.
The use of CO2 or conventional erbium laser ablation or more recent nonablative laser photothermolysis for skin rejuvenation is associated with significant disadvantages. The objective was to assess the efficacy of the erbium:YAG laser (2,940 nm) using the "ablative" fractional resurfacing mode to improve photodamaged skin. A total of 28 patients, 27 women and 1 man, aged 28 to 72 years (mean age, 54.2 years), with Fitzpatrick Skin Types II to IV, were treated for mild to moderate actinic damage using fractional erbium:YAG laser (2,940 nm) combined with Pixel technology. Sessions were scheduled at 4-week intervals. Response to treatment was evaluated by two physicians on a five-tiered scale. Patients underwent one to four treatment sessions (mean, 3.2). The initial reaction consisted of erythema and minimal swelling. On clinical assessment 2 months after the final treatment, the results were rated excellent by 21 patients (75%) and good by 7 (25%). Nineteen of the 21 were also evaluated 6 to 9 months after final treatment without any significant change in the results. Fractional ablative photothermolysis using erbium:YAG laser (2,940 nm) is a promising option for skin resurfacing with reduced risk and downtime compared to existing laser methods.


[Radiation dose in computed tomography. Risks and challenges].
The exponentially growing performance of newer scanner generations has increased diagnostic opportunities and utilization of computed tomography. The excellent clinical results with CT, however, have to be weighed against a high radiation exposure. While radiation exposure with modern scanners is well below the diagnostic reference values of the EU for most organ systems, radiation dose for retrospectively gated cardiac examinations can be substantially higher: organ doses can reach 100 mGy, a dose for which cancer induction been proven. For children, the situation may also be critical if scanning parameters are not adapted to their smaller size and increased radiation risk: the risk-benefit ratio may then no longer favor CT. The application of CT for young patients, patients with favorable prognosis and for frequent follow-up examinations will increase the radiation risk to the individual and the population. The growth rates for CT utilization in Germany are well below those in the United States but the increasing number of exams will lead to a substantial increase in population dose even if the dose per individual exam can be reduced. The combination of optimum scanning parameters, automated dose modulation and dose adaptation to the individual patient will help contain radiation dose. Further reduction is possible by reducing the number of scan phases, limiting the scan length and choosing a lower tube voltage. Most important, however, is the close collaboration with referring physicians: scanning technique and choice of imaging modality can only be adapted if the clinical question is clearly defined. In the light of radiation exposure the critical and knowledgeable use of CT becomes the more important the easier it is to request an exam and the better the clinical results.


Femoral tibial-peroneal bypass: the lateral approach and use of glutaraldehyde-tanned umbilical vein.
Access to the peroneal artery as well as to the anterior tibial artery can be accomplished by a lateral approach with fibular resection. The technic is described as well as the use of the glutaraldehyde-tanned human umbilical cord vein as a vascular prosthesis. The results using the latter have been extremely gratifying.


Handling the Cellular Complex Systems in Alzheimer's Disease Through a Graph Mining Approach.
In the last two decades, the medical sciences have changed their approach to pathogenesis as well as to the diagnosis and treatment of complex human diseases. The main reason for this change is the explosive development of biomedical technology and research, which produces a huge amount of information and data which are generated at an increasing rate. Toward this direction is the pathway analysis, a thriving research area of systems biology tools and methodologies which aim to unravel the inherent complexity of high-throughput biological data produced by the advent of omics technologies. Through this graph mining approach, we can deal with the complexity of the cellular systems of various diseases such as Alzheimer's disease. In this work, we developed a subpathway analysis method for single-cell RNA-seq experiments which isolates differentially expressed subpathways indicating potentially perturbed biological processes. The differential expression status of each gene is negotiated among well-established RNA-seq differential expression analysis tools in order to minimize false discoveries. Also, we demonstrate the efficacy of our method on a single-cell RNA-seq dataset for temporal tracking of microglia activation in neurodegeneration. Results suggest that our approach succeeds in isolating several perturbed biological processes known to be associated with neurodegeneration.


Electric response audiometry: clinical applications.
Electric response audiometry is an exciting new development in the field of otology. At the present time it is the best objective audiometric test for predicting the threshold in infants or uncooperative patients. Brain stem audiometry is a valuable addition to the audiologic test battery for acoustic tumor diagnosis. Electrocochleography offers a means for the study of the function of the inner ear and the differentiation of types of sensorineural hearing impairment.


Enhancing effect of iron on chromate reduction by Cellulomonas flavigena.
Cr(VI) is considerably toxic and the detoxification of Cr(VI) is of great importance. This study investigated the effect of iron on Cr(VI) reduction by Cellulomonas flavigena. The results demonstrated that addition of FeCl3 or lepidocrocite promoted Cr(VI) reduction, with the reduction ratio of above 90 and 80% achieved, respectively, but addition of hematite did not lead to the increase of reduction ratio, which suggests that the effect of iron on chromate reduction appears different with the diversity of iron-oxides. In this study, the effect of initial Cr(VI) and Fe(III) concentration on Cr(VI) reduction and the change of pH value were also investigated. The reduction ratio increased with the increase of the initial concentration ratio of Fe(III)/Cr(VI). The value of pH gradually increased from 7.0 to around 9.0.


Organizational and cultural changes for providing safe patient care.
To describe an approach and experience with fostering a culture of patient safety. (1) Organizational Change-The Department of Medicine established a patient safety committee (PSC) and charged it with reviewing adverse events. (2) Cultural Change-PSC sponsors and participants work to promote a culture of collaboration, study, learning, and prevention versus a culture of blame. (3) Collaboration-The PSC includes chief residents and members from medical informatics, nursing, pharmacy, quality assurance, risk management, and utilization management. (4) Evolution-The duties of the PSC progressed from merely learning from adverse event reports to implementing patient safety and quality improvement projects. (5) Standardization-The PSC uses standard definitions and procedures when reviewing cases of adverse events, and when conducting patient safety and quality improvement projects. (1) Developed an online adverse event reporting system, shortening the average report collection time by 2 days and increasing the number of adverse events reported. (2) Established a model for change using (a) safety rounds with residents, (b) e-mail safety alerts, and, in some cases, (c) decision alerts using electronic order entry. These changes in culture and capability led to improvements in care and improved financial results. Senior management support of a culture of learning and prevention and an organizational structure that promotes collaboration has provided an environment in which patient safety initiatives can flourish by providing not only safer and higher quality patient care but also a positive financial return on investment.


A novel protocol for the one-pot borylation/Suzuki reaction provides easy access to hinge-binding groups for kinase inhibitors.
The one-pot borylation/Suzuki reaction is a very efficient means of accessing cross-coupling products of two aryl-halide partners that generally requires the use of specific catalysts or ligands and/or relatively long reaction times. This new microwave-assisted method provides a quick one-pot borylation/Suzuki reaction protocol that we applied to the synthesis of various bi- or poly-aryl scaffolds, including a variety of aryl and heteroaryl ring systems and the core frameworks of kinase inhibitors vemurafenib and GDC-0879.


Relative bioavailability of carbocysteine from three dosage forms, investigated in healthy volunteers.
The aim of the present study was to evaluate the bioavailability of a new tablet formulation of carbocysteine relative against two other oral carbocysteine containing dosage forms, viz. a syrup and capsules. Plasma levels and urine concentrations of carbocysteine were monitored, following oral administration of all three dosage forms to healthy human volunteers, by direct derivatization of carbocysteine using dabsylchloride and subsequent high performance liquid chromatography. There was no difference in bioavailability of carbocysteine from these dosage forms as expressed by the respective areas under the plasma concentration-time curves and total amounts of unchanged carbocysteine excreted in urine.


Comparison of healing assessments of periapical endodontic surgery using conventional radiography and cone-beam computed tomography: A systematic review.
This systematic review aimed to compare assessments of the healing of periapical endodontic surgery using conventional radiography and cone-beam computed tomography (CBCT). This review of clinical studies was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. All articles published from 1990 to March 2020 pertaining to clinical and radiographic healing assessments after endodontic surgery using conventional radiography and CBCT were included. The question was "healing assessment of endodontic surgery using cone-beam computed tomography." The review was conducted by manual searching, as well as undertaking a review of electronic literature databases, including PubMed and Scopus. The studies included compared radiographic and CBCT assessments of periapical healing after periapical endodontic surgery. The initial search retrieved 372 articles. The titles and abstracts of these articles were read, leading to the selection of 73 articles for full-text analysis. After the eligibility criteria were applied, 11 articles were selected for data extraction and qualitative analysis. The majority of studies found that CBCT enabled better assessments of healing than conventional radiography, suggesting higher efficacy of CBCT for correct diagnosis and treatment planning. A risk of bias assessment was done for 10 studies, which fell into the low to moderate risk categories. Three-dimensional radiography provides an overall better assessment of healing, which is imperative for correct diagnosis and treatment planning.