Hemorrhagic dot score as a follow up marker in psoriasis on treatment: A prospective observational study.
Psoriasis assessment tools in use presently lack reproducibility and are cumbersome to use. An easily reproducible, objective tool with ability to maintain visual records for follow up is hence desirable. We conducted a study with the aim to assess dermoscopic changes in psoriasis while on treatment by recording the number of hemorrhagic dots (Hemorrhagic Dot Score-HDS) in a representative plaque and comparing it to the PASI score. A longitudinal prospective study was conducted between October 2018 to March 2020 in a dermatology centre of a tertiary hospital on cases of chronic plaque psoriasis on treatment over 6 months, assessed at baseline and thereafter monthly for 6 months. Hundred consenting patients of chronic plaque psoriasis were assessed, clinically, PASI and dermoscopically. HDS and other dermoscopic features were noted at every visit. ANOVA and F test of testing of equality of Variance; effect size in terms of Cohen were used to report the strength of an apparent relationship. Percentage improvement in the mean PASI scores and HDS and percentage improvement of mean was found significant in each month on follow up. Systemic therapy as compared to topical therapy showed higher effect size of 6.1 and 1.7, respectively. Hemorrhagic dot score can be used as an objective, definite assessment tool correlating with clinical severity of psoriasis with more accuracy which shows changes early following institution of therapy.


In situ studies on the effect of acid extraction on the DNA template activity of mature avian erythrocytes.
Exogenous E. coli RNA polymerase was used to determine the in situ DNA template activity of ethanol/acetone fixed avian erythrocytes. No RNA polymerase-catalyzed incorporation of 3H-UTP was detected in mature avian erythrocytes while simultaneously fixed avian lymphocytes did exhibit incorporation of 3H-UTP. Nuclei of mature erythrocytes which were subjected to treatments known to remove histones showed dramatic increases in RNA polymerase-catalyzed incorporation of 3H-UTP. The chromatin of treated cells was presumed to be more accessible to RNA polymerase as determined by the increase in RNA polymerase-catalyzed incorporation of 3H-UTP. Incubation of acid-treated nuclei in poly-L-lysine prior to incubation with RNA polymerase failed to inhibit the incorporation of 3H-UTP. Possible mechanisms for the inactivation of avian erythrocyte nuclei are discussed.


Epileptogenic activity of cephalosporins in rats and their structure-activity relationship.
The epileptogenic properties of 10 cephalosporins and penicillin G were compared by intraventricular application to rats. At doses greater than 32 micrograms per head, cefazolin provoked tremendous seizure signs, a spike-and-wave complex appeared in close succession for more than 30 min, and severe convulsions were observed repeatedly. Reactions to cefotiam, ceftezole, and cephaloridine were almost equal to reactions to penicillin. No epileptogenic signs were observed on EEGs, and no behavioral symptoms were observed after administration of 1,000 micrograms of cephalexin and cephradine per head. Reactions to cephapirin, cefmetazole, cephalothin, and ceftizoxime exhibited less marked epileptogenic features; activity was diminished in that order on EEGs and in behavioral signs. Compounds substituted with two different heterocyclic rings at position 7 (R1) and position 3 (R2) of 7-aminocephalosporanic acid were potent in producing epileptogenic signs both on EEGs and in behaviors. Compounds substituted with a heterocyclic ring at either position of 7-aminocephalosporanic acid were less potent. Compounds such as ceftizoxime, cephalexin, and cephradine, substituted at R2 with small groups, were almost incapable of producing epileptogenic activity. This may indicate that the substitution of a heterocyclic ring at position 3 will provoke the convulsive actions.


5-alpha reductase inhibitors (5-ARi) with or without alpha-blockers (α-B) for Benign Prostatic Hyperplasia do NOT lower the risk of incident Bladder Cancer: United States insurance claims data.
Chemoprotective effect of 5-alpha reductase inhibitors (5-ARi) on bladder cancer (BCa) risk in men with Benign Prostatic Hyperplasia (BPH) has been explored with conflicting results. We sought to examine the effect of 5-ARi on new BCa diagnoses in a large US database. Men ≥ 50 y/o with a prescription for 5-ARi after BPH diagnosis were identified in the IBM® Marketscan® Research de-identified Databases between 2007 and 2016 and matched with paired controls. Incident BCa diagnoses were identified after BPH diagnosis and/or pharmacologic treatment. Multivariable regression modeling adjusting for relevant factors was implemented. Sub-group analyses by exposure risk were performed to explore the association between 5-ARi and BCa over time. Administration of alpha-blockers (α-B) w/o 5-ARi was also examined. In total, n = 24,036 men on 5-ARi, n = 107,086 on 5-ARi plus alpha-blockers, and n = 894,275 without medical therapy for BPH were identified. The percentage of men diagnosed with BCa was 0.8% for the 5-ARi, 1.4% for the 5-ARi + α-B, and 0.6% for the untreated BPH group of incident BCa (adjusted hazard ratio [aHR], 0.90, 95% confidence interval [CI] 0.56 - 1.47), and 1.08, 95%CI 0.89 - 1.30, respectively). This was also true at both shorter (≤ 2 yr) and longer-term (> 2 yr) follow up. In addition, α-B alone had no change in BCa risk (HR 1.06, 0.86-1.30). We did not find any diminished risk of new BCa in men treated with 5-ARi (i.e., chemoprotective effect). The current report suggests that 5-ARi do not change a man's bladder cancer risk.


The impact of hyaluronan on monocyte Toll-like receptor expression in term infant cord blood.
To explore the possible effects of hyaluronan, an endogenous mediator of inflammation, on monocyte surface expression of Toll-like receptors 2 and 4 in human umbilical cord blood ex vivo, and in a model mimicking Gram-negative neonatal sepsis. Term infant cord blood was obtained after elective caesarean sections, n = 15. Both unstimulated and lipopolysaccharide-stimulated (10 ng/mL) blood was incubated with 500 μg/mL high- or low-molecular-weight hyaluronan for 6 h. Expression of Toll-like receptors 2 and 4 on monocytes was measured using flow cytometry, and plasma concentrations of proinflammatory cytokines and matrix metalloproteinase 9 were analysed. RESULTS (MEAN ± SEM): We found a significant decrease in Toll-like receptor 4 expression in the presence of high-molecular-weight hyaluronan (HMW HA) in unstimulated blood (median fluorescence intensity 141 ± 7.3 vs. 163 ± 9.8, p = 0.019). There were no significant changes in Toll-like receptor 2 expression. Levels of cytokines and matrix metalloproteinase 9 increased in the presence of both forms of hyaluronan. Our results confirm that hyaluronan affects the neonatal immune response. The biological significance of these findings requires further clarification. More studies are needed to validate the possible down-modulation of Toll-like receptor 4 exerted by HMW HA.


An analysis of the quality of research reports in the Journal of General Internal Medicine.
Forty-four "original articles" published in the Journal of General Internal Medicine were reviewed using a rating instrument with 13 items developed from previously published standards for the design, analysis, and presentation of medical research. Each item was rated on a four-point (poor-to-excellent) scale. Inter-rater agreement was good (86% agreement; kappa = 0.65). Seven items received excellent or good ratings in 80% or more of the articles, but six problem areas were identified: description of study scope (generalizability), informed consent procedures, reliability assessments, references for statistical procedures or computer programs, and the use of descriptive and comparative statistics. Guidelines for these and other criteria are offered to help researchers prepare clear and informative reports.


The morphology of cat spinal neurons projecting to both the lateral cervical nucleus and the dorsal column nuclei.
Morphological features of physiologically characterized doubly projecting spinocervical tract-dorsal column postsynaptic (SCT-DCPS) neurons were examined following intracellular injections of horseradish peroxidase. Their cell bodies and majority of dendrites were located in laminae III-IV. The SCT-DCPS neurons have rostrocaudally elongated dendritic trees with spiny fine caliber dendrites, and issue local axon collaterals that are studded with varicosities. The results show that the doubly projecting SCT-DCPS neurons do not represent a morphologically distinct subset of the spinocervical tract (SCT) or dorsal column postsynaptic (DCPS) cells.


Hard science, soft science: A political history of a disciplinary array.
A distinction between the "hard" and "soft" scientific disciplines is a modern commonplace, widely invoked to contrast the natural and the social sciences and to distribute value accordingly, where it was generally agreed that it was good to be "hard," bad to be "soft." I trace the emergence of the distinction to institutional and political circumstances in the United States in the second part of the twentieth century; I describe varying academic efforts to give the contrast coherent meaning; I note the distinction's uses in disciplines' reflections on their own present and possible future status; and I document the consequential circulation of the antonym in settings where resources for science were distributed. To follow the history of the "hard-soft" distinction is to open a window on changing sensibilities about what science is, what values are attached to it, and what it is for. I conclude with speculations about more recent changes in the value-schemes implicated in the "hard" and the "soft" and about pertinent changes in the place of the "soft" human sciences in governance and production. I envisage a possible future in which the commonplace distinction might wither away.


Extraintestinal manifestations of Edwardsiella tarda infection.
Summary Edwardsiella tarda, a member of the family Enterobacteriaceae, is a rare human pathogen. Gastroenteritis is the most frequently reported manifestation of E. tarda infection. In contrast, extraintestinal infection with E. tarda has rarely been reported. This study made a retrospective case and microbiological data review of patients with extraintestinal E. tarda infections to further understand this disease. This study retrospectively reviewed the charts of all isolates of E. tarda cultures from clinical specimens other than faeces at Chang Gung Memorial Hospital, Taoyuan, Taiwan from October 1998 through December 2001. Edwardsiella tarda was isolated from 22 clinical specimens from 22 hospitalised patients (13 females and nine males). The extraintestinal manifestations of E. tarda infection included biliary tract infection, bacteraemia, skin and soft tissue infection, liver abscess, peritonitis, intra-abdominal abscess, and tubo-ovarian abscess. The major underlying diseases predisposing to E. tarda extraintestinal infection were hepatobiliary diseases, malignancy and diabetes mellitus. The overall mortality rate of E. tarda extraintestinal infection in the present series was 22.7% (5/22), and four (40%) of 10 patients with bacteraemia expired. Although rare, human E. tarda extraintestinal infections can have diverse clinical manifestations and moreover may cause severe and life-threatening infections. Consequently, E. tarda should be considered a potentially important pathogen.


Expression of Fas and Fas ligand in primary cutaneous squamous cell carcinoma in association with grade of tumor differentiation.
The aim of this study was to evaluate whether Fas (CD95) and Fas ligand (FasL) immunoreactivity in cutaneous squamous cell carcinoma (SCC) are correlated with grade of tumor differentiation. A total of 31 cutaneous SCC specimens excised during 1997-2004 were collected from the four branch hospitals of the Catholic University of Korea. A tissue microarray technique was used for immunohistochemical staining. Expression of Fas and FasL was evaluated in correlation with the grade of tumor differentiation. Statistical analysis was performed using Fisher's exact test and exact trend test. Six of 31 SCCs exhibited strong (+++) intensity for Fas immunostaining, and all of these were well differentiated. Five of 31 SCCs exhibited strong (+++) intensity for FasL staining; all of these were moderately or poorly differentiated. Fas was expressed more strongly in well-differentiated SCCs than in poorly differentiated tumors. FasL was expressed more strongly in moderately and poorly differentiated tumors. These findings indicate that Fas and FasL play important roles in immune surveillance and grade of differentiation in SCC.


Mobile Phone Applications to Support Breastfeeding Among African-American Women: a Scoping Review.
Racial disparities persist with respect to breastfeeding. The use of health e-technology is increasing, with promise for a role in improving breastfeeding outcomes. We undertook a scoping review of both individual breastfeeding apps and the literature on breastfeeding apps to map the available evidence on app-based breastfeeding support for African-American mothers. A systematic search of online databases identified 241 English language papers published on or before June 2020 that included e-technology in support of breastfeeding. We included those that (1) described individual human subjects research studies utilizing any research design, (2) described app-based breastfeeding support, and (3) could be pertinent for African-American mothers, and assessed for inclusion and relevance for this population. We also searched app stores for breastfeeding apps, and evaluated features with a rubric. Our aim was to identify if gaps exist relative to breastfeeding support for African-Americans. Of the 15 publications meeting inclusion criteria, 9 focused on app development, 4 examined user experience, and 3 examined breastfeeding outcomes with use of an app (one study overlapped categories). The percentage of African-American participants ranged from 100% (2 studies) to none (7 studies); 3 studies (20%) focused on African-American mothers' breastfeeding experience. Of 77 apps that met inclusion criteria, just one was both breastfeeding-focused by content and targeted for African-Americans by picture predominance. The quality of studies was generally high and many included African-American participants, but research focused on breastfeeding apps specifically for African-American mothers/parents is limited, creating a meaningful gap in the literature.


Diazepam terminates brief but not prolonged seizures in young, naïve rats.
Ample evidence exists from both clinical and animal studies that the success of benzodiazepine intervention during status epilepticus (SE) in the mature nervous system is inversely related to seizure duration. This relationship has not been well studied in the developing nervous system. The objective of this study was to investigate the relation of age and success of diazepam (DZP) treatment in the lithium-pilocarpine model of secondarily generalized seizure in the rat by using naïve rats of three age groups, roughly corresponding to the human ages of infancy (P15), adolescence (P20), and adult (P60). In all age groups, the dosage of DZP that stopped the seizures at 5 min was not effective in terminating seizures at 60 min. This decline in efficacy was present as early as 15 min after seizure onset. These findings demonstrate that the inverse relation between the success of benzodiazepine intervention and seizure duration is observed in young as well as in adult rats and provide further evidence that intervention for SE should commence early.


Recent trends for the management of diabetes for older adults in the context of universal coverage and COVID-19: evidence from Mexico.
To identify trends in the epidemiological and economic burden of diabetes in the elderly. Using the Box-Jenkins method to estimate expected cases for the period 2020-2022, costs were determined with the instrumentation technique. The population base was 4 032 189 older adults diagnosed with diabetes in 2019. Regarding the epidemiological burden, there is an increase of 11-15% (p<0.001). Comparing the economic burden for 2020 vs 2022, the increase is estimated as 29% (p<0.05). In the framework of the coronavirus disease 2019 pandemic, the increase in diabetes cases and costs in older adults substantially complicates the scope of universal coverage for patients with diabetes.


Effect of antimuscarinic agents on the contractile responses to cholinomimetics in the rat anococcygeus muscle.
1 The effects of antimuscarinic agents alone and in the presence of neostigmine on the contractile responses to exogenously applied cholinomimetics or (-)-noradrenaline were studied in the rat anococcygeus muscle.2 Atropine (1 x 10(-9) -1 x 10(-6)M) alone, in the presence of hexamethonium (1 x 10(-4)M), or phentolamine (1 x 10(-6)M), inhibited responses to acetylcholine but not to (-)-noradrenaline. The inhibitory effect with the higher concentrations of atropine (1 x 10(-8) - x 10(-6)M), was seen as an increase in the slopes of the concentration-response curves. Atropine (1 x 10(-8)M) alone inhibited the responses to methacholine and carbachol without altering the slopes of the concentration-response curves.3 Homatropine (1 x 10(-6)M) alone had no effect on responses to (-)-noradrenaline and inhibited responses to acetylcholine and methacholine. The inhibitory effect on responses to acetylcholine but not to methacholine, included an increase in the slopes of the concentration-response curves.4 Neostigmine (1 x 10(-6)M) alone had no effect on responses to (-)-noradrenaline and potentiated responses to acetylcholine and methacholine. The potentiating effect included an increase in the slopes of the concentration-response curves.5 In the presence of neostigmine (1 x 10(-6)M), atropine (1 x 10(-9)M - 1 x 10(-6)M) caused a parallel concentration-dependent shift of the concentration-response curves to acetylcholine. The pA(2) values, in the presence of neostigmine, were independent of the concentration of atropine and of the agonist (acetylcholine, methacholine, or carbachol) used. In the presence of neostigmine (1 x 10(-6)M), homatropine (1 x 10(-6)M) also failed to alter the slopes of the concentration-response curves to acetylcholine and was approximately 100 times less potent than atropine as an antimuscarinic agent.6 These results illustrate that, in the rat anococcygeus muscle, it is necessary to inhibit acetylcholinesterase before determining the relative potencies of antagonists at muscarinic receptors.


Inhibitory effects of astaxanthin on postovulatory porcine oocyte aging in vitro.
Mammalian oocytes represent impaired quality after undergoing a process of postovulatory aging, which can be alleviated through various effective ways such as reagent treatment. Accumulating evidences have revealed the beneficial effects of astaxanthin (Ax) as a potential antioxidant on reproductive biology. Here, porcine matured oocytes were used as a model to explore whether Ax supplement can protect against oocyte aging in vitro and the underlying mechanism, and therefore they were cultured with or without 2.5 μM Ax for an additional 24 h. Aged oocytes treated with Ax showed improved yield and quality of blastocysts as well as recovered expression of maternal genes. Importantly, oxidative stress in aged oocytes was relieved through Ax treatment, based on reduced reactive oxygen species and enhanced glutathione and antioxidant gene expression. Moreover, inhibition in apoptosis and autophagy of aged oocyte by Ax was confirmed through decreased caspase-3, cathepsin B and autophagic activities. Ax could also maintain spindle organization and actin expression, and rescue functional status of organelles including mitochondria, endoplasmic reticulum, Golgi apparatus and lysosomes according to restored fluorescence intensity. In conclusion, Ax might provide an alternative for ameliorating the oocyte quality following aging in vitro, through the mechanisms mediated by its antioxidant properties.


Molecular characterization and functional analysis of glutathione S-transferase genes of pine wood nematode (Bursaphelenchus xylophilus) for avermectin.
Pine wilt disease (PWD), caused by Bursaphelenchus xylophilus (pine wood nematodes, PWNs), is a forest disease that seriously threatens the health of Pinus forestry. Glutathione S-transferases (GSTs) play important roles in xenobiotic metabolism, lipophilic compound transport, antioxidative stress reactions, anti-mutagenesis, and antitumor activity. The analysis and investigation of the specific functions of GSTs in the metabolism of toxic substances in nematodes are important for identifying potential target genes to control the spread and transmission of B. xylophilus. In this study, 51 Bx-GSTs were found in the genome of B. xylophilus. Two key Bx-gsts (Bx-gst12 and Bx-gst40) were analyzed when B. xylophilus was exposed to avermectin. The expression of Bx-gst12 and Bx-gst40 was significantly increased when B. xylophilus was exposed to 1.6 and 3.0 mg/mL avermectin solutions. Notably, combined silencing of both Bx-gst12 and Bx-gst40 did not further increase the mortality rates under avermectin exposure. Mortality rates were significantly increased in nematodes treated with dsRNA compared to control nematodes (p < 0.05) after RNAi. The feeding ability of nematodes was also significantly reduced after treatment with dsRNA. These results suggested that Bx-gsts are associated with the detoxification process and feeding behavior of B. xylophilus. Silencing Bx-gsts leads to increased susceptibility to nematicides and reduces the feeding ability of B. xylophilus. Therefore, Bx-gsts will be a new control target of PWNs in the future.


Inactivated PCV2 one shot vaccine applied in 3-week-old piglets: improvement of production parameters and interaction with maternally derived immunity.
The present study describes the effects of a commercially available vaccine against Porcine circovirus type 2 (PCV2) on clinical, pathological and virological outcomes of 3-week-old piglets from two farms with a clinical history of postweaning multisystemic wasting syndrome (PMWS). The study was a controlled, double-blinded, parallel group (1:1) and randomized trial (with a negative control) involving a total of 1239 animals. The study period comprised from weaning age (time of vaccination or PBS inoculation) until the first shipment of pigs to the slaughterhouse. The vaccine product was able to reduce clinical signs, PCV2 viral load in sera and faeces, and overall mortality in nurseries and fattening units. Moreover, average daily gain was significantly higher in vaccinated versus non-vaccinated piglets during the trial period. On the other hand, it was shown that maternally derived antibodies interfered with the development of an active humoral immune response after PCV2 vaccination.


HISET: Hybrid interpretable strategies with ensemble techniques for respiratory sound classification.
The human respiratory systems can be affected by several diseases and it is associated with distinctive sounds. For advanced biomedical signal processing, one of the most complex issues is automated respiratory sound classification. In this research, five Hybrid Interpretable Strategies with Ensemble Techniques (HISET) which are quite interesting and robust are proposed for the purpose of respiratory sounds classification. The first approach is termed as an Ensemble GSSR technique which utilizes L2 Granger Analysis and the proposed Supportive Ensemble Empirical Mode Decomposition (SEEMD) technique and then Support Vector Machine based Recursive Feature Elimination (SVM-RFE) is used for feature selection and followed by classification with Machine Learning (ML) classifiers. The second approach proposed is the implementation of a novel Realm Revamping Sparse Representation Classification (RR-SRC) technique and third approach proposed is a Distance Metric dependent Variational Mode Decomposition (DM-VMD) with Extreme Learning Machine (ELM) classification process. The fourth approach proposed is with the usage of Harris Hawks Optimization (HHO) with a Scaling Factor based Pliable Differential Evolution (SFPDE) algorithm termed as HHO-SFPDE and it is classified with ML classifiers. The fifth or the final approach proposed analyzes the application of dimensionality reduction techniques with the proposed Gray Wolf Optimization based Support Vector Classification (GWO-SVC) and another parallel approach utilizes a similar kind of analysis with the Grasshopper Optimization Algorithm (GOA) based Sparse Autoencoder. The results are examined for ICBHI dataset and the best results are shown for the 2-class classification when the analysis is carried out with Manhattan distance-based VMD-ELM reporting an accuracy of 95.39%, and for 3-class classification Euclidean distance-based VMD-ELM reported an accuracy of 90.61% and for 4-class classification, Manhattan distance-based VMD-ELM reported an accuracy of 89.27%.


Cell Biology: An Open Solution for Closed Mitosis.
At the end of mitosis, cells must remodel their nuclear envelope to produce two identical daughter nuclei. Two new studies using Schizosaccharomyces pombe provide insight into how compartmentalized nuclear pore complex disassembly allows cells that undergo closed mitosis to achieve nuclear division.


Association of HLA-G 3'UTR polymorphisms with response to malaria infection: a first insight.
Malaria represents one of the most important causes of mortality and morbidity in Africa. Variability in clinical presentation is partly due to host genetic polymorphisms. Among them, human leukocyte antigen (HLA) class I and class II alleles may be responsible for malaria susceptibility; however less is known about the possible role of non classical HLA molecules. Among them, HLA-G is a tolerogenic molecule with immunomodulatory properties, which differs from classical HLA class I molecules by its lower genetic diversity, tissue expression and function. Although primarily associated with maternal-fetal tolerance, HLA-G is now known to be involved in a wide range of physiopathological conditions, such as tumor, autoimmunity, transplantation, inflammation and viral infection by suppressing the function of various immune cells. In this work, we present the first evidence of an association between HLA-G 3'UTR polymorphisms and malaria infection. More precisely, we showed that HLA-G polymorphisms are associated with asymptomatic infection through two parasitological phenotypes, the intensity of Plasmodium falciparum infection and the mean level of parasite density. The allele+3187G and its haplotype (UTR-1, 14bp-Del/3001C/3003T/3010G/3035C/3052C/3142C/3187G/3196C) was associated with lower level of infection under a dominant model, and the haplotype UTR-3 (Del/3001C/3003T/3010C/3035C/3152C/3142G/3187A/3196C) was associated with high levels of infection under a recessive model. In conclusion, although further investigations are on the way to better address the possible involvement of the HLA-G molecule in the control of P. falciparum infection, this work presents the first evidence of an association between HLA-G polymorphisms and malaria infection. Further investigations are on the way to take into account the particularities of African populations.


Venous thromboembolism: Exploring incidence and utility of screening in spinal cord injury.
To assess the incidence and possible risk factors for venous thromboembolism (VTE) in patients admitted to a SCI rehabilitation center. Retrospective review. Acute neurorehabilitation hospital specializing in SCI. Records of 228 consecutive admissions were reviewed. All patients received screening four limb ultrasounds on admission. Charts were reviewed to determine whether VTE was diagnosed at the acute care hospital or in the rehabilitation center; either on admission screening or later in the rehabilitation stay. Charts were reviewed to identify potential risk factors for VTE as well as the incidence of bleeding complications in patients on full anticoagulation. In this cohort, 115 deep venous thromboses (DVTs) were identified in the following settings: 27% in acute care [n = 31], 70% on admission to rehabilitation [n = 80], and 24% during the rehabilitation stay [n = 28]. Of those on therapeutic anticoagulation due to admission diagnosis of VTE [n = 63], 12.7% developed recurrent DVT and 9.5% had bleeding complications. Of those who were initiated and continued on therapeutic anticoagulation, there was zero incidence of PE. Risk factors for the development of VTE included age, body mass index (BMI), rehabilitation length of stay, injury etiology, spinal cord-related surgery, and history of inferior vena cava filter. DVT was identified in 70% of this cohort with screening ultrasound on admission to rehabilitation and of those initiated and continued on therapeutic anticoagulation, none developed PE, while 9.5% had bleeding complications. Given the findings of this study, prospective research in noninvasive vascular ultrasound screening for VTE should be considered.


Trunk muscle electromyography and whole body vibration.
By measuring the electromyographic (EMG) activity of the paraspinal muscles, we have estimated the average and peak-to-peak torque imposed on the spine during whole body vibration. Six subjects had surface electrodes placed on their erector spinae muscles at the L3 level. The EMG-torque relationship was estimated by having each subject perform isometric horizontal pulls in an upright seated posture. The subject was then vibrated vertically and sinusoidally in a controlled, flexed, slightly lordotic seated posture, in 1 Hz increments from 3 to 10 Hz at a 0.1 g RMS seat acceleration level. Between vibration readings taken at each frequency, a static reading was also taken with the subject maintaining the same posture. The entire vibration-static 3-10 Hz test was repeated for reliability purposes. Specialized digital signal processing techniques were developed for the EMG signals to enhance the measured cyclic muscle activity and to allow automatic measurement of the time relationship between the mechanical displacement and the estimated torque. We found significantly more average and peak-to-peak estimated torque at almost all frequencies for vibration vs static sitting.


Enrichment post-library preparation enhances the sensitivity of high-throughput sequencing-based detection and characterization of viruses from complex samples.
Sequencing-based detection and characterization of viruses in complex samples can suffer from lack of sensitivity due to a variety of factors including, but not limited to, low titer, small genome size, and contribution of host or environmental nucleic acids. Hybridization-based target enrichment is one potential method for increasing the sensitivity of viral detection via high-throughput sequencing. This study expands upon two previously developed panels of virus enrichment probes (for filoviruses and for respiratory viruses) to include other viruses of biodefense and/or biosurveillance concern to the U.S. Department of Defense and various international public health agencies. The newly expanded and combined panel is tested using carefully constructed synthetic metagenomic samples that contain clinically relevant amounts of viral genetic material. Target enrichment results in a dramatic increase in sensitivity for virus detection as compared to shotgun sequencing, yielding full, deeply covered viral genomes from materials with Ct values suggesting that amplicon sequencing would be likely to fail. Increased pooling to improve cost- and time-effectiveness does not negatively affect the ability to obtain full-length viral genomes, even in the case of co-infections, although as expected, it does decrease depth of coverage. Hybridization-based target enrichment is an effective solution to obtain full-length viral genomes for samples from which virus detection would fail via unbiased, shotgun sequencing or even via amplicon sequencing. As the development and testing of probe sets for viral target enrichment expands and continues, the application of this technique, in conjunction with deeper pooling strategies, could make high-throughput sequencing more economical for routine use in biosurveillance, biodefense and outbreak investigations.


Identification of EC cells in the human intestine: a comparative study between immunohistochemical and silver impregnation techniques.
Selective immunohistochemical identification of enterochromaffin (EC) cells in the human duodenum and colon has been carried out, using a highly specific rabbit antiserotonin serum and the unlabeled peroxidase-antiperoxidase complex (PAP) technique. The sensitivity of the reaction, and morphology of the cells, were compared with those of the argentaffin or argyrophil reactions on the same sections at the light microscopic level. All argentaffin cells were argyrophil and PAP positive, but a small number of PAP-positive cells were neither argentaffin nor argyrophil. In addition, a few EC cells stained by the PAP method were shown to be argyrophil but not argentaffin. The PAP method permitted the clear morphological identification of the entire cell, particularly its cytoplasmic processes, whereas both the argentaffin and argyrophil reactions were basically seen in the basal regions of the cells and often failed to demonstrate the cytoplasmic processes. These findings indicate that the immunohistochemical method is more sensitive and advantageous than silver impregnations for the selective demonstration of EC cells.


Morphological and physiological responses of rice seedlings to complete submergence (flash flooding).
Reducing damage to rice seedlings caused by flash flooding will improve the productivity of rainfed lowland rice in West Africa. Accordingly, the morphological and physiological responses of different forms of rice to complete submergence were examined in field and pot experiments to identify primary causes of damage. To characterize the physiological responses, seedlings from a wide genetic base including Oryza sativa, O. glaberrima and interspecific hybrids were compared using principle component analysis. Important factors linked to flash-flood tolerance included minimal shoot elongation underwater, increase in dry matter weight during submergence and post-submergence resistance to lodging. In particular, fast shoot elongation during submergence negatively affected plant growth after de-submergence. Also shoot-elongating cultivars showed a strong negative correlation between dry matter weight of the leaves that developed before submergence and leaves developing during submergence. Enhancement of shoot elongation during submergence in water that is too deep to permit re-emergence by small seedlings represents a futile escape strategy that takes place at the expense of existing dry matter in circumstances where underwater photosynthetic carbon fixation is negligible. Consequently, it compromises survival or recovery growth once flood water levels recede and plants are re-exposed to the aerial environment. Tolerance is greater in cultivars where acceleration of elongation caused by submergence is minimal.


Coyotes, deer, and wildflowers: diverse evidence points to a trophic cascade.
Spatial gradients in human activity, coyote activity, deer activity, and deer herbivory provide an unusual type of evidence for a trophic cascade. Activity of coyotes, which eat young mule deer (fawns), decreased with proximity to a remote biological field station, indicating that these predators avoided an area of high human activity. In contrast, activity of adult female deer (does) and intensity of herbivory on palatable plant species both increased with proximity to the station and were positively correlated with each other. The gradient in deer activity was not explained by availabilities of preferred habitats or plant species because these did not vary with distance from the station. Does spent less time feeding when they encountered coyote urine next to a feed block, indicating that increased vigilance may contribute, along with avoidance of areas with coyotes, to lower herbivory away from the station. Judging from two palatable wildflower species whose seed crop and seedling recruitment were greatly reduced near the field station, the coyote-deer-wildflower trophic cascade has the potential to influence plant community composition. Our study illustrates the value of a case-history approach, in which different forms of ecological data about a single system are used to develop conceptual models of complex ecological phenomena. Such an iterative model-building process is a common, but underappreciated, way of understanding how ecological systems work.


Social subordination produces distinct stress-related phenotypes in female rhesus monkeys.
Social subordination in female macaques is imposed by harassment and the threat of aggression and produces reduced control over one's social and physical environment and a dysregulation of the limbic-hypothalamic-pituitary-adrenal axis resembling that observed in people suffering from psychopathologies. These effects support the contention that this particular animal model is an ethologically relevant paradigm in which to investigate the etiology of stress-induced psychological illness related to women. Here, we sought to expand this model by performing a discriminate analysis (DA) on 33 variables within three domains; behavioral, metabolic/anthropomorphic, and neuroendocrine, collected from socially housed female rhesus monkeys in order to assess whether exposure to social subordination produces a distinct phenotype. A receiver operating characteristic (ROC) curve was also calculated to determine each domain's classification accuracy. DA found significant markers within each domain that differentiated dominant and subordinate females. Subordinate females received more aggression, showed more submissive behavior, and received less of affiliation from others than did dominant females. Metabolic differences included increased leptin, and reduced adiponectin in dominant compared to subordinate females. Dominant females exhibited increased sensitivity to hormonal stimulation with higher serum LH in response to estradiol, cortisol in response to ACTH, and increased glucocorticoid negative feedback. Serum oxytocin, CSF DOPAC and serum PACAP were all significantly higher in dominant females. ROC curve analysis accurately predicted social status in all three domains. Results suggest that socially house rhesus monkeys represent a cogent animal model in which to study the physiology and behavioral consequences of chronic psychosocial stress in humans.


Preclinical safety studies with Temofel, a new choleretic compound.
Temofel (2,5-dimethyl-alpha-ethyl-benzhydrol) is a choleretic compound. Safety studies required for Phase I and II clinical trials were performed. No oestrogenic, antioestrogenic, androgenic or antiandrogenic effect was induced in infantile rats treated with 100 and 200 mg/kg. No CNS effects were induced by 50 mg/kg in mice. No haemodynamic or respiratory changes were induced in dogs by 300 mg/kg. In a 28-day oral toxicity study with 40, 80, 160, 320, 640 and 1280 mg/kg doses on Lati: CFY (SD) rats died at the 2 highest doses (640 and 1280 mg/kg). Large necrotic foci in the liver were found at the highest dose 1280 mg/kg. In rats treated with 320 mg/kg and higher doses, hepatic hyperplasia, renal tubular hyperplasia and protein retention in the renal cortex were observed. Testicular atrophy, damaged spermiogenesis, spermiohistogenesis and regulative Leydig-cell hyperplasia were induced by 640 and 1280 mg/kg. In a 28-day study on Velz: BEAGLE dogs with daily doses of 40, 120 and 360 mg/kg sporadically increased SAP activity occurred at the high dose. In a 6-month study rats were fed 400, 2000 and 10000 ppm Temofel. Growth was retarded in the medium and high dose group, no sperm could be seen in the urinary sediment of the high dose group. Testicular atrophy, complete lack of spermiogenesis, spermiohistogenesis occurred in this group. In contrast to the administration of 1280 mg/kg for 28 days by gavage, no hepatic or renal changes were induced by 10000 ppm consumed for 6 months. A 6-month canine study with 40, 120 and 360 mg/kg doses revealed sporadic SAP increase at the high dose.(ABSTRACT TRUNCATED AT 250 WORDS)


Epidemiology and Clinical Characteristics of Individuals with Hepatitis C Virus Infection in the United States, 2017-2019.
Hepatitis C virus (HCV) is the most common bloodborne chronic infection in the US. Following approval of highly effective, direct-acting antivirals in 2014, the diagnostic and treatment rates for HCV infection in the US have evolved. This study assessed the number of individuals with HCV screening or diagnostic testing and the clinical characteristics and treatment of HCV-infected individuals between 2017 and 2019. Individuals screened for HCV antibody and/or tested for HCV ribonucleic acid (RNA) from 2017 to 2019 by two large US laboratory companies were included in this analysis. Clinical characteristics, such as HCV genotype, fibrosis stage, HIV coinfection and demographics, were assessed in HCV RNA-positive individuals. HCV treatment and subsequent achievement of sustained virologic response were imputed using data-driven algorithms based on successive viral load decline and negativity. From 2017 to 2019, the number of individuals tested for HCV antibody increased by 5.7%, from 7,580,303 in 2017 to 8,009,081 in 2019. The percentage of individuals tested who were HCV antibody positive was stable, ranging from 5.0% in 2017 to 4.9% in 2018 and 2019. The number of HCV RNA-positive individuals decreased by 5.0% from 382,500 in 2017 to 363,532 in 2019. Of HCV RNA-positive individuals, the proportions with genotype (GT) 3 and minimal fibrosis increased over time; proportions of individuals aged < 40 years increased, while the proportion aged 50 to 59 years decreased. Treatment rates increased from 23.4% in 2017 to 26.8% in 2019. The percentage of HCV antibody-positive individuals remained stable from 2017 to 2019. The number of individuals tested HCV RNA positive decreased over the years. Demographics shifted toward a younger population with less fibrosis and higher rates of GT3. More than 70% of diagnosed individuals were not treated during this interval, highlighting a need for unfettered access to treatment.


The influence of desiccation and predation on vertical size gradients in populations of the gastropod Oxystele variegata (Anton) on an exposed rocky shore.
Oxystele variegata (Anton.) exhibits a vertical size gradient contrary to the model proposed by Vermeij (1972) for low/mid intertidal species, as shell size increases in an upshore direction. Settlement occurs in the lowest zones and juveniles are restricted to the lower shore by conditions of desiccation higher up the beach. Juveniles suffer rapid water loss due to a relatively large opercular surface area and circumference and have a much lower resistance to water loss than adults. This leads to high mortality under conditions of low humidities, and juveniles caged at the top of the balanoid zone, where adults normally occur, die within a few days. As animals increase in size their resistance to desiccation rises allowing them to migrate upshore. This is a response to high rates of predation by the whelk Burnupena delalandii in the lower balanoid zone. Predation is so intense as to override the advantages of higher food availability which lead to a greater body weight for adults protected by cages on the lower shore.


Clonogenic assays in the B16 melanoma: response to cyclophosphamide.
The survival of clonogenic cells in the B16 melanoma has been studied simultaneously by 3 methods: an in vitro assay in soft agar, a lung-colony assay, and the end-point dilution technique. Details of the first 2 methods have previously been reported, but those of the third are described here. The 3 methods have agreed well in investigations of the response of the B16 melanoma to cyclophosphamide.


A Natural Language Processing Algorithm for Classifying Suicidal Behaviors in Alzheimer's Disease and Related Dementia Patients: Development and Validation Using Electronic Health Records Data.
This study aimed to develop a natural language processing algorithm (NLP) using machine learning (ML) and Deep Learning (DL) techniques to identify and classify documentation of suicidal behaviors in patients with Alzheimer's disease and related dementia (ADRD). We utilized MIMIC-III and MIMIC-IV datasets and identified ADRD patients and subsequently those with suicide ideation using relevant International Classification of Diseases (ICD) codes. We used cosine similarity with ScAN (Suicide Attempt and Ideation Events Dataset) to calculate semantic similarity scores of ScAN with extracted notes from MIMIC for the clinical notes. The notes were sorted based on these scores, and manual review and categorization into eight suicidal behavior categories were performed. The data were further analyzed using conventional ML and DL models, with manual annotation as a reference. The tested classifiers achieved classification results close to human performance with up to 98% precision and 98% recall of suicidal ideation in the ADRD patient population. Our NLP model effectively reproduced human annotation of suicidal ideation within the MIMIC dataset. These results establish a foundation for identifying and categorizing documentation related to suicidal ideation within ADRD population, contributing to the advancement of NLP techniques in healthcare for extracting and classifying clinical concepts, particularly focusing on suicidal ideation among patients with ADRD. Our study showcased the capability of a robust NLP algorithm to accurately identify and classify documentation of suicidal behaviors in ADRD patients.


Reactive lymphoid hyperplasia of the liver and pancreas. A report of two cases and a comprehensive review of the literature.
Reactive lymphoid hyperplasia (RLH) is a rare non-neoplastic extranodal pathology with exceedingly rare occurrence in the liver and pancreas. We present two cases of hepatic RLH, one which had coinciding pancreatic involvement. To the best of our knowledge, concomitant hepatic and pancreatic RLH has not been previously reported. We also present a comprehensive review of the literature on hepatic and pancreatic RLH. An extensive literature search for all published reports on hepatic or pancreatic RLH was conducted. Data on clinical, radiographic and histopathological features were extracted in addition to therapeutic options and outcomes. Forty-two hepatic and three pancreatic cases of RLH were described in the literature. The mean age of hepatic cases was 58 years, with a male-to-female ratio of above 1:7. Almost 25% of cases were associated with internal malignancy. Four hepatic cases were managed through active observation. The remainder (84%) underwent surgical resection. Due to their small number, no meaningful analysis could be made on the pancreatic cases. No recurrences were identified in any of the reported cases. RLH should be considered in the diagnosis of hepatic nodules where biopsies fail to demonstrate malignant cells. Confirmed RLH lesions should be managed by active observation. Investigation and treatment of any potential source of lymphoid reactivity should be undertaken. More reports on pancreatic RLH need to be studied prior to drawing any useful recommendations on its management.


Enhanced α-ketoglutaric acid production and recovery in Yarrowia lipolytica yeast by effective pH controlling.
The replacement of chemical synthesis by environmentally friendly energy-efficient technologies for production of valuable metabolites is a principal strategy of developing biotechnological industry all over the world. In the present study, we develop a method for α-ketoglutaric acid (KGA) production from rapeseed oil with the use of Yarrowia lipolytica yeast. Sixty strains of Y. lipolytica yeasts were tested for their ability to produce KGA, and the strain Y. lipolytica 212 (Y. lipolytica VKM Y-2412) was selected as a promising KGA producer. Using a three-stage pH controlling, in which pH was 4.5 in the growth phase, then since 72 to 144 h, pH was maintained at 3.5 and in the later phase of acid production, the titration by KOH was switch off, selected strain produced 106.5 g l(-1) of KGA with mass yield of 0.95 g g(-1). KGA in the form of monopotassium salt was isolated from the culture broth and purified. The isolation procedure involved separation of biomass, extraction of residual triglycerides, filtrate bleaching, and acidification with mineral acid (to pH 2.8-3.4), concentration, precipitation of mineral salts, and crystallization of the product. The purity of KGA isolated from the culture filtrate reached 99.1 %.


Modification of intraaortic balloon catheter to permit introduction by cardiac catheterization techniques.
Intraaortic balloon counterpulsation has been widely applied for treatment of left ventricular pump failure and intractable angina. However, its use has been limited by the difficulty of balloon insertion in some patients and vascular complications in others. An AVCO intraaortic balloon was modified by the addition of a central lumen to allow pressure monitoring, injection of contrast medium and passage of a guide wire. The device was successfully used in 15 of 16 patients, including 4 of 5 in whom attempts to place a standard balloon catheter had failed. No significant vascular complications occurred in any patient. The modified balloon catheter appears to increase the efficacy and safety of insertion and allows immediate and continuous monitoring of arterial pressure.


A three-dimensional perspective of phosphorus retention across a field-buffer strip transition.
Vegetated filter strips (VFS) act as buffer zones between fields and water bodies that are supposed to retain incoming runoff, sediment, and nutrients. The factors that govern nutrient retention and cycling in VFS are complex and act in all three dimensions. A key element that determines VFS effectivity is flow type, e.g., sheet vs. concentrated flow. These aspects are, however, often insufficiently accounted for in VFS research and design recommendations. In this study, we attempt to tackle these shortcomings by examining the nutrient distribution in detail at two field-VFS transitions, applying a three-dimensional sampling array together with extensive laboratory analyses. Concentrated runoff was the dominant type we found and we argue that flow convergence is the norm rather than the exception. Further complicating this issue is that entry locations of runoff may vary, calling for more sophisticated sampling designs. Overall trends were similar across the analyzed nutrient fractions (different K- and P-pools) and there were distinct trends of decreasing nutrients along the longitudinal (from the field to the VFS) and vertical planes. The horizontal plane (from outside to inside the area of concentrated flow) showed mostly inconclusive or U-shaped gradients. Both sites were similar and close to each other, nevertheless, there were significant differences that affected nutrient retention in the VFS which were linked to site-specific factors. The spatial extent (i.e., width) is often considered the main variable in VFS designs. However, other VFS traits such as vegetation type and structure, as well as external factors such as field topography and the severity of erosive events are equally important and should be attributed more significance.


Temporary loss of renal function: an unusual complication of perinephric hemorrhage after percutaneous renal biopsy.
Two cases of temporary loss of function following percutaneous renal biopsy are reported. The mechanism was probably restriction of renal perfusion brought about by the compression of the perirenal hematoma.


Interaction between opioid agonists or naloxone and 5-HTP on feeding behavior in food-deprived rats.
Morphine and the enkephalin analogs DAME, DADLE and FK-33824, as well as the opioid antagonist naloxone, decrease feeding in food-deprived rats after intraventricular or subcutaneous administration, FK-33824 being by far the most potent drug tested. The administration of subeffective doses of either morphine or naloxone given by the subcutaneous route induces anorexia when given in combination with a subeffective dose of 5-HTP whereas the treatment with subeffective intraventricular doses of any of the opioids or naloxone fails to potentiate 5-HTP. Similarly, the anorexia induced by FK-33824 is blocked by either morphine or naloxone given subcutaneously but not by intraventricular administration of the same two drugs. The results appear to suggest that central or peripheral opioid receptors differentially affect feeding behavior in the rat and, on the other hand, that the interaction of opiates with the serotonergic system appears to occur preferentially in the periphery.


Preparation and characterization of biocompatible oil-loaded polyelectrolyte nanocapsules.
The aim of this work was to develop a novel preparation method for polyelectrolyte nanocapsules. The prepared capsules have a three-layer polyelectrolyte shell and a core consisting of medium-chain triglycerides. The preparation is based on a high-pressure homogenized emulsion that is stabilized by a modified starch, followed by the stepwise addition of the additional layer components chitosan and lambda-carrageenan. Producing polyelectrolyte nanocapsules with an average size of 130 nm without alternating with separation steps resulted in an efficient preparation technique. The characterization of the nanocapsules by zeta-potential, light-scattering techniques, nuclear magnetic resonance, and transmission electron microscopy played a major role. All ingredients are nontoxic and biocompatible. These properties could be extremely useful to the food or pharmaceutical industry for incorporating lipophilic substances. The encapsulation may be beneficial regarding improved stability and protection capability of labile substances.


Overcoming MET-mediated resistance in oncogene-driven NSCLC.
This study evaluates the efficacy of combining targeted therapies with MET or SHP2 inhibitors to overcome MET-mediated resistance in different NSCLC subtypes. A prevalence study was conducted for MET amplification and overexpression in samples from patients with NSCLC who relapsed on ALK, ROS1, or RET tyrosine kinase inhibitors. MET-mediated resistance was detected in 37.5% of tissue biopsies, which allow the detection of MET overexpression, compared to 7.4% of liquid biopsies. The development of drug resistance by MET overexpression was confirmed in EGFRex19del-, KRASG12C-, HER2ex20ins-, and TPM3-NTRK1-mutant cell lines. The combination of targeted therapy with MET or SHP2 inhibitors was found to overcome MET-mediated resistance in both in vitro and in vivo assays. This study highlights the importance of considering MET overexpression as a resistance driver to NSCLC targeted therapies to better identify patients who could potentially benefit from combination approaches with MET or SHP2 inhibitors.


Imaging VOC distribution in cities and tracing VOC emission sources with a novel mobile proton transfer reaction mass spectrometer.
Volatile organic compounds (VOCs) are important precursors of ozone (O3) and secondary organic aerosols (SOAs). Tracing VOC pollution sources is important for controlling VOC emissions and reducing O3 and SOAs. We built a novel mobile proton transfer reaction mass spectrometry (M-PTR-MS) instrument to image the distribution of VOCs and trace their emission sources in cities and industrial parks. The M-PTR-MS is composed of a vibration-resistant proton transfer reaction mass spectrometry (PTR-MS) with a global positioning system receiver, modified box vehicle, and geographic information system (GIS) software. The PTR-MS, mounted on a vehicle, sends VOC data and vehicle position information to the GIS software. These data are used to image the space distribution of VOCs in real time while the vehicle platform is in motion and the VOC sources are precisely traced using the GIS. The spatial data resolution of the M-PTR-MS is typically 0.8 m. The limits of detection, sensitivity, and repeatability of the M-PTR-MS are 43.5 ppt, 347 counts ppb-1, and 2.4% (RSD, n = 5), respectively. The intensity of reagent ions is stable over 8 h (RSD = 0.45%). Compared with commercial PTR-MS equipment, the M-PTR-MS demonstrated high consistency, with a correlation coefficient of 92.665%. Several field experiments were conducted in China using the M-PTR-MS. In one field experiment, the VOC distribution along three different routes was surveyed; the navigation monitoring lasted 1.8 h over a distance of 26.7 km at an average speed of 15 km h-1. The VOC sources in an industrial park were identified by analyzing the components near different factories. The main species from a VOC source in an underground garage was related to paint. The M-PTR-MS instrument can be used by environmental protection agencies to trace VOC pollution sources in real time, and by researchers to survey VOC emissions in regions of concern.


Gestational diabetes mellitus care re-imagined - A cost-minimisation analysis: Cost savings from a tertiary hospital, using a novel, digital-based gestational diabetes management model.
Diagnosis of gestational diabetes mellitus (GDM) in a pregnancy has a significant impact on health service resources and represents a substantial financial and time impost on women. To describe a cost-minimisation analysis conducted following the demonstration of clinically equivalent care of women using a novel, digital model for GDM management, compared with conventional care. A pre-implementation model of care was compared with the post-implementation model of care which included systematic development and delivery of education videos, use of the Commonwealth Scientific and Industrial Research Organisation 'M♡THer' smart phone app/portal and a dramatically reduced schedule of visits. The Mater Mothers' Hospital Brisbane cares for approximately 1200 women with GDM per annum, on which the cost estimates were based. Service costs were estimated using the resource method, where resource volumes and costs were gathered from experts within the health service. Patient costs were estimated using results from a short survey completed by a cohort of the study population. Health service costs showed a modest saving of AU$17 441.78 (US$12 158.92) in the intervention group over a 12-month period. Cost savings for the woman were estimated at $566.56 (US$394.96) per patient after accounting for lost wages, childcare expenses, and travel expenses avoided. This reduction led to an overall saving of $679 872 (US$473 948.82) for the cohort of 1200 women, primarily due to the reduction in face-to-face visits. Re-imagining GDM patient care by introducing a novel, digital-based GDM model of care has substantial positive cost implications for patients.


[Genetic polymorphism of 9 STR loci in Han nation population in Shandong Province].
To study genetic polymorphism of 9 STR loci in Han nation population in Shangdong Province. We investigated 100 unrelated individuals of Han nation population in Shandong Province and studied their genetic distribution of 9 STR loci and Amelogenin locus. Primers of 10 loci were labeled with the NHS-ester fluorescent dye 5-FAM (blue), Joe (green) or NED (yellow). The data of Han nation population were generated by multiple amplification and subjected to GeneScan, genotype and genetic distribution analysis. 83 alleles and 220 genotypes were observed, with the corresponding frequency of 0.0050-0.4050 and 0.0100-0.2100. The average of heterozygosity was 0.7778, the accumulated discrimination power was 0.9999. The accumulated probability of exclusion paternity was 0.9999. The polymorphism information content was 0.5823-0.8396. Chi-Square test indicated that the distribution of genotypes agreed with Hardy-Weinberg equilibrium.


Use of psychotropic medications in children with developmental disabilities.
Working with children who have developmental disorders is challenging. Besides having physical deficits, or intellectual deficits, or both, these children are at high risk for developing psychiatric disorders. This article describes three developmental disorders-autistic spectrum disorders, fragile X syndrome, and fetal alcohol syndrome-and their associated mental health issues, and provides recommendations for pharmacologic interventions.


Senna alexandrina Mill. induced ultrastructural changes on Hymenolepis diminuta.
Senna alexandrina Mill. has been used for antimicrobial activity. In the present study, the crude ethanolic extract of the plant and a synthetic compound Sennoside were tested in vitro on Hymenolepis diminuta to evaluate its potential anthelmintic efficacy through ultrastructural changes. Worms were maintained between rat model and beetle and the test parasites were exposed to different concentrations of crude ethanolic leaf extracts of S. alexandrina. Praziquantel was used as a reference drug. Dose dependent efficacy was observed in terms of motility and time of mortality in all treated parasites. Ultrastructural micrography revealed irrevocable destruction all over the body tegument accompanied with sloughing of microtriches and swellings of the basal lamina. Vacuolization of the syncytium along with sparsely cytoplasmic cytons and depletion of parenchymatous layer were observed accompanied by deformities in the cell organelles. Extensive deformities in the tegument indicates that the plant extract alter membrane permeability of the parasite leading to paralysis and subsequent death. Thus, S. alexandrina can be regarded as a potential anthelmintic agent.


Looking ahead and behind at supplemental oxygen: A qualitative study of patients with pulmonary fibrosis.
Supplemental oxygen is prescribed to patients with pulmonary fibrosis to normalize oxygen saturations, decrease symptoms and improve quality of life. Along with potential benefits, patients face challenges as they incorporate oxygen into their lives. Our aim was to better understand the perceptions and experiences of patients with pulmonary fibrosis as they confronted the possibility and realities of using supplemental oxygen. We performed a mixed-methods study in which we conducted a series of four structured telephone interviews with five patients with pulmonary fibrosis enrolled in a longitudinal observational study. Questionnaires were administered at the time of the interviews, which were conducted at enrollment in the longitudinal study, immediately prior to starting supplemental oxygen, one month and then 9-12 months after starting oxygen. We used conventional content analysis to analyze interview data for themes within and across the four time points. Prior to starting supplemental oxygen, participants uniformly expected it would improve their physical function and quality of life. They also expected practical and psychological limitations, which after starting oxygen, they found to be more pronounced than anticipated. Despite the challenges, participants attributed benefits in symptoms, confidence and mobility to oxygen and came to a reluctant acceptance of it. Their expectations for guidance and support were inadequately met. For patients with pulmonary fibrosis, starting and using supplemental oxygen on an everyday basis confers benefits while also presenting a significant number of challenges. The process could be improved by providing them with clearer expectations and trustworthy educational resources. Oxygen case managers could help patients incorporate supplemental oxygen more seamlessly into their lives.


Missed nursing care, nurse staffing levels and patient safety outcomes in low-income country acute care settings: An observational study.
The aim of this study was to measure the level of missed nursing care and determine its relationship with nurse staffing and patient safety outcomes in acute care settings in Ethiopia. Missed nursing care in hospitals increases the likelihood of patient adverse events, complications, disability and death. However, little is known about the level of missed nursing care and its impact on patient outcomes in low-income countries. An observational study was conducted comprising of a survey of nurses at two time points (n = 74 and 80, respectively) and a medical record review of 517 patients in four units across two hospitals between September 2018 and March 2019. The level of missed nursing care in the study units was very high. The hospital type and hours nurses worked during the last week were significantly associated with missed nursing care. A unit increase in missed nursing care score increased the incidence of adverse patient outcomes by 10%. There was a higher level of missed nursing care in the study units compared with similar studies from high-income countries. Higher level of missed nursing care was significantly associated with higher incidence of adverse patient safety outcomes.


Predicting the Functional Types of Singleplex and Multiplex Eukaryotic Membrane Proteins via Different Models of Chou's Pseudo Amino Acid Compositions.
Given a membrane protein sequence, how can we identify its type, particularly when a query protein may have the multiplex character, i.e., simultaneously exist at two or more different types. However, most of the existing predictors or methods can only be used to deal with the single-type or "singleplex" membrane proteins. Actually, multiple-type or "multiplex" membrane proteins should not be ignored because they usually posses some unique biological functions worthy of our special notice. In this study, three different models were developed, which have the ability to deal with the systems containing both singleplex and multiplex membrane proteins. The overall success rate thus obtained was 0.6440, indicating that the study may become a very useful high-throughput tool in identifying the functional types of membrane proteins.


Technology and uses of cell cultures from the tissues and organs of bony fish.
For a wide range of purposes, primary cell cultures and/or cell lines have been prepared from most tissues and organs of a small fraction of the estimated 20,000 species of bony fish. These cell cultures usually have been maintained with mammmalian sera. For many applications their usefulness would be enhanced by a more piscine and defined environment. However, the piscine equivalents of mammalian polypeptide growth and differentiation factors are largely unknown and are unlikely ever to be available commercially. In the future they might be obtained from the medium in which fish cells have been grown. Therefore, by being a potential source of fish polypeptide growth and differentiation factors, a cell line from a fish organ might be utilized as a Rossetta stone to decipher thein vitro proliferation and differentiation of other cells from this or other organs from the same or different species.


A prospective comparison of continuous wave versus high pulse repetition frequency Doppler echocardiography for quantifying transvalvular pressure gradients in adults with aortic stenosis.
To evaluate the relative accuracy of continuous wave (CW) and high pulse repetition frequency (HPRF) Doppler for estimating aortic transvalvular pressure gradients, Doppler examinations with both devices were obtained in 87 consecutive patients with aortic valve disease. Thirty-seven (43%) also underwent catheterization and direct determination of the pressure gradient. The correlation between CW Doppler and catheterization measurements was high (r = 0.91) and significantly superior to HPRF Doppler (r = 0.72; p less than 0.005). Disparities between the Doppler measurements predominantly occurred in patients with gradients exceeding 50 mm Hg in whom underestimation by the HPRF instrument was frequent. These data suggest that continuous wave Doppler is the preferred modality for the estimation of transvalvular pressure gradients in adult patients with moderate or severe aortic stenosis.


A new approach to estimate fugitive methane emissions from coal mining in China.
Developing a more accurate greenhouse gas (GHG) emissions inventory draws too much attention. Because of its resource endowment and technical status, China has made coal-related GHG emissions a big part of its inventory. Lacking a stoichiometric carbon conversion coefficient and influenced by geological conditions and mining technologies, previous efforts to estimate fugitive methane emissions from coal mining in China has led to disagreeing results. This paper proposes a new calculation methodology to determine fugitive methane emissions from coal mining based on the domestic analysis of gas geology, gas emission features, and the merits and demerits of existing estimation methods. This new approach involves four main parameters: in-situ original gas content, gas remaining post-desorption, raw coal production, and mining influence coefficient. The case studies in Huaibei-Huainan Coalfield and Jincheng Coalfield show that the new method obtains the smallest error, +9.59% and 7.01% respectively compared with other methods, Tier 1 and Tier 2 (with two samples) in this study, which resulted in +140.34%, +138.90%, and -18.67%, in Huaibei-Huainan Coalfield, while +64.36%, +47.07%, and -14.91% in Jincheng Coalfield. Compared with the predominantly used methods, this new one possesses the characteristics of not only being a comparably more simple process and lower uncertainty than the "emission factor method" (IPCC recommended Tier 1 and Tier 2), but also having easier data accessibility, similar uncertainty, and additional post-mining emissions compared to the "absolute gas emission method" (IPCC recommended Tier 3). Therefore, methane emissions dissipated from most of the producing coal mines worldwide could be more accurately and more easily estimated.


Functional expression of adenosine A2A and A3 receptors in the mouse dendritic cell line XS-106.
There is increasing evidence to suggest that adenosine receptors can modulate the function of cells involved in the immune system. For example, human dendritic cells derived from blood monocytes have recently been described to express functional adenosine A1, A2A and A3 receptors. Therefore, in the present study, we have investigated whether the recently established murine dendritic cell line XS-106 expresses functional adenosine receptors. The selective adenosine A3 receptor agonist 1-[2-chloro-6[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-1-deoxy-N-methyl-beta-D-ribofuranuronamide (2-Cl-IB-MECA) inhibited forskolin-mediated [3H]cyclic AMP accumulation and stimulated concentration-dependent increases in p42/p44 mitogen-activated protein kinase (MAPK) phosphorylation. The selective adenosine A2A receptor agonist 4-[2-[[-6-amino-9-(N-ethyl-beta-D-ribofuranuronamidosyl)-9H-purin-2-yl]amino]ethyl]benzene-propanoic acid (CGS 21680) stimulated a robust increase in [3H]cyclic AMP accumulation and p42/p44 MAPK phosphorylation. In contrast, the selective adenosine A1 receptor agonist CPA (N6-cyclopentyladenosine) did not inhibit forskolin-mediated [3H]cyclic AMP accumulation or stimulate increases in p42/p44 MAPK phosphorylation. These observations suggest that XS-106 cells express functional adenosine A2A and A3 receptors. The non-selective adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA) inhibited lipopolysaccharide-induced tumour necrosis factor-alpha (TNF-alpha) release from XS-106 cells in a concentration-dependent fashion. Furthermore, treatment with Cl-IB-MECA (1 microM) or CGS 21680 (1 microM) alone produced a partial inhibition of lipopolysaccharide-induced TNF-alpha release (when compared to NECA), whereas a combination of both agonists resulted in the inhibition of TNF-alpha release comparable to that observed with NECA alone. Treatment of cells with the adenosine A2A receptor selective antagonists 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5ylamino]ethyl)phenol (ZM 241385; 100 nM) and 5-amino-2-(2-furyl)-7-phenylethyl-pyrazolo[4,3-e]-1,2,4-triazolo[1,5c]pyrimidine (SCH 58261; 100 nM) and the adenosine A3 receptor selective antagonist N-[9-chloro-2-(2-furanyl)[1,2,4]-triazolo[1,5-c]quinazolin-5-benzeneacetamide (MRS 1220; 100 nM) partially blocked the inhibitory effects of NECA on lipopolysaccharide-induced TNF-alpha release. Combined addition of MRS 1220 and SCH 58261 completely blocked the inhibitory effects of NECA on lipopolysaccharide-induced TNF-alpha release. In conclusion, we have shown that the mouse dendritic cell line XS-106 expresses functional adenosine A2A and A3 receptors, which are capable of modulating TNF-alpha release.


Subunit composition of native myosin isoenzymes of some striated mammalian muscles.
Six "native" isomyosins of characteristic electrophoretic mobility are present in various proportions according to the muscle type (fast, slow or mixed). SM2 and SM1 contain MHC1; IM contains MHC2A; FM1, FM2 and FM3 contain MHC2A and MHC2B. SM2, SM1 and IM contain MLC1s; SM1, IM, FM2 and FM3 contain MLC1f; FM2 and FM1 contain MLC3f. The six isomyosins appear to separate on the base of their myosin light chain content.


Recent progress in nanomaterial-based electrochemical and optical sensors for hypoxanthine and xanthine. A review.
This review (with 160 ref.) summarizes the progress that has been made in the methods for chemical or biochemical sensing of hypoxanthine and xanthine, which are produced as part of purine metabolism and are precursors of uric acid. An introduction discusses the importance of hypoxanthine and xanthine as analytes due to their significance in the clinical and food science, together with the conventional methods of analysis. A large section covers methods for the electrochemical hypoxanthine and xanthine sensing. It is divided into subsections according to the nanomaterials used including carbon nanomaterials, meal oxide nanoparticles, metal organic frameworks, conductive polymers, and bio-nanocomposites. A further large section covers optical methods for hypoxanthine and xanthine sensing, with subsections on nanomaterials including carbon nanomaterials, nanosheets, nanoclusters, nanoparticles, and their bio-nanocomposites. A concluding section summarizes the current status, addresses current challenges, and discusses future perspectives. Graphical abstractSchematic representation of the hypoxanthine and xanthine electrochemical and optical sensors incorporating various nanomaterials like graphene, carbon nanotubes (CNT), quantum dots (QD), nanoparticles and polymers, which are implemented in clinical and food analysis.


Proximate Composition Analysis.
The proximate composition of foods includes moisture, ash, lipid, protein and carbohydrate contents. These food components may be of interest in the food industry for product development, quality control (QC) or regulatory purposes. Analyses used may be rapid methods for QC or more accurate but time-consuming official methods. Sample collection and preparation must be considered carefully to ensure analysis of a homogeneous and representative sample, and to obtain accurate results. Estimation methods of moisture content, ash value, crude lipid, total carbohydrates, starch, total free amino acids and total proteins are put together in a lucid manner.


Natural history of ankle function during gait in youth with Charcot-Marie-Tooth disease types 1 and 2.
Charcot-Marie-Tooth disease (CMT) can cause progressive muscle weakness and contracture, leading to gait abnormalities such as increased and delayed peak ankle dorsiflexion and reduced ankle power generation in terminal stance. Understanding strength loss on ankle function during gait is important for interpreting treatment outcomes and evaluating new therapies designed to improve gait. Do ankle kinematics and kinetics vary as a function of age, disease progression with associated loss of muscle strength and CMT type in youth with CMT types 1 and 2? A prospective convenience sample of 45 participants with CMT1 and 2, ages 7-22 years, underwent comprehensive gait analysis. Seventeen patients underwent repeat analyses totaling 67 tests. Generalized mixed effects linear modeling was used to compare CMT1 versus CMT2 and to examine the effects of age on ankle strength, range of motion, kinematics, and kinetics within each CMT type. Plantarflexor and dorsiflexor strength were less in CMT2 compared with CMT1 (p ≤ 0.05), while peak dorsiflexion in terminal stance (TST) was greater (p = 0.02). Peak plantarflexion moment and power generation were also less in CMT2 (p ≤ 0.02). In CMT1, peak dorsiflexion in TST increased with age through 13 years (p = 0.004); then plateaued in the normal range (p = 0.73). Peak ankle angle in mid-swing was closely related to the angle in TST (p < 0.001) following a similar pattern with age. In CMT2, no significant associations were observed between age, peak dorsiflexion in TST, and peak ankle angle in mid-swing (p ≥ 0.19). There were no consistent trends with age for individual patients with repeat tests. The heterogeneity of joint level impairments and gait kinematics and kinetics point to the importance of having an in-depth understanding of gait at the individual patient level using comprehensive gait analysis including valid and reliable strength measures.


Correlation between effects of the particle size and magnetic field strength on the magnetic hyperthermia efficiency of dextran-coated magnetite nanoparticles.
A precise control of the particle size of dextran-coated magnetite nanoparticles (Dex-M NPs) was successfully performed by combination of co-precipitation and hydrothermal synthesis methods. The Dex-M NPs, in the size range 3.1-18.9 nm, were used to fabricate biocompatible magnetic fluids for application in magnetic hyperthermia therapy (MHT). The effects of the carrier fluid viscosity, particle size, and applied magnetic field strength (Happl) on the specific loss power (SLP) of the Dex-M NPs were investigated at a fixed magnetic field frequency (f). The experimental results show that SLP of the larger Dex-M NPs significantly decreases for a highly viscous carrier fluid. Moreover, regardless of the carrier fluid viscosity, the particle size strongly affects the heating efficiency of the Dex-M NPs. SLP ranges from zero for the smallest Dex-M NPs (with particle size d = 3.1 nm) to 55.21 W/g for the largest ones (d = 18.9 nm) at Happl = 28 kA/m and f = 120 kHz. The most important finding in our research is that, at a fixed frequency, the optimal size of the Dex-M NPs (the size that maximizes SLP) shows a rising trend by enhancing Happl. In fact, the highest values of SLP at Happl = 11 kA/m, 13 - 17.5 kA/m, and 19 - 28 kA/m are obtained for the Dex-M NPs with d = 11.5 nm, 15 nm, and 18.9 nm, respectively. The shift of optimal size to the higher values by increasing Happl could shed light on the correlated effects of the particle size and Happl on the heating efficiency of magnetic nanoparticles (MNPs) and pave a new way toward the better tuning of them for an effective and biologically safe treatment.


Ghrelin gene products in acute and chronic inflammation.
Ghrelin gene products--the peptides ghrelin, unacylated ghrelin, and obestatin--have several actions on the immune system, opening new perspectives within neuroendocrinology, metabolism and inflammation. The aim of this review is to summarize the available evidence regarding the less known role of these peptides in the machinery of inflammation and autoimmunity, outlining some of their most promising therapeutic applications.


Study and QTL mapping of reproductive and morphological traits implicated in the autofertility of faba bean.
Autofertility describes the ability of faba bean flowers to self-fertilize thereby ensuring the productivity of this crop in the absence of pollinators or mechanical disturbance. In the legume crop faba bean (Vicia faba L.), lack of autofertility in a context of insufficient pollination can lead to a severe decrease in grain yield. Here we performed the first QTL analysis aimed at identifying the genomic regions controlling autofertility in this crop. We combined pod and seed setting scores from a recombinant inbred population (RIL) segregating for autofertility in different environments and years with measurements of morphological floral traits and pollen production and viability. This approach revealed 19 QTLs co-localizing in six genomic regions. Extensive co-localization was evident for various floral features whose QTLs clustered in chrs. I, II and V, while other QTLs in chrs. III, IV and VI revealed co-localization of flower characteristics and pod and seed set data. The percentage of phenotypic variation explained by the QTLs ranged from 8.9 for style length to 25.7 for stigma angle. In the three QTLs explaining the highest phenotypic variation (R 2 > 20), the marker alleles derived from the autofertile line Vf27. We further inspected positional candidates identified by these QTLs which represent a valuable resource for further validation. Our results advance the understanding of autofertility in faba bean and will aid the identification of responsible genes for genomic-assisted breeding in this crop.


Triamcinolone acetonide injections for the treatment of recalcitrant post-radical prostatectomy vesicourethral anastomotic stenosis: A retrospective look at efficacy and safety.
We aimed to evaluate the success of bladder neck injections of triamcinolone at the time of transurethral bladder neck incision (BNI) for prevention of recurrent vesicourethral anastomotic stenosis (VUAS) following prostate cancer treatment. This is a retrospective cohort study examining patients with recurrent VUAS post-radical prostatectomy (RP) ± radiation treated with triamcinolone injections at the time of BNI. VUAS was diagnosed by symptoms followed by cystoscopy or urethrography. The outpatient procedures were done under general anesthesia. Cold knife incisions were made at the three, nine, and 12 o'clock BN positions, followed by triamcinolone injections (4 mg/mL) into the three and nine o'clock incision sites. Treatment outcomes were determined with cystoscopy. Eighteen men underwent 25 procedures over a four-year period. Median age at diagnosis of VUAS was 65 (interquartile range [IQR] 61-68); median time to VUAS from RP was eight months (IQR 5-12). Fourteen patients (78%) had radiation treatment. The cohort had 128 unsuccessful VUAS treatments, with a median of five failed treatments per patient (IQR 3-10). Failed treatments included BN dilation, BNI, BN injection of mitomycin C, and urethral stent placement. Success rate after a mean of 16.3 months (standard deviation [SD] 8.1) from the time of triamcinolone injection was 83% (15/18). Six patients went on to have successful incontinence surgery. Five patients (28%) had treatment complications (bleeding, urinary tract infection, pain, and urinary extravasation). The three non-responders are stable and awaiting re-treatment with triamcinolone injection. Triamcinolone bladder neck injections for post-RP VUAS are a useful and safe treatment for recurrent stenosis.


Chlamydia trachomatis and mycoplasma infections in tubal pregnancy.
Chlamydia trachomatis (CT) infection is an important factor for tubal pregnancy. However, whether Ureaplasma urealyticum (UU) and Mycoplasma hominis (MH) infections are also involved in tubal pregnancy remains unknown. This study is aimed to detect CT, UU, and MH in cervical secretions from patients with tubal pregnancy and control women in early pregnancy, to explore their prevalence rates and drug susceptibilities. Analysis was performed on patients with tubal pregnancy and those requiring termination of early pregnancy at <12 weeks from July 2013 to March 2014. Cervical secretions were tested for UU/MH with a UU/MH isolation and culture kit and for CT antigen by an immunochromatographic assay. Mycoplasma samples were tested for resistance to 12 antibiotics. There were no cases of CT infection detected. Mycoplasma infection rates (single or mixed) were similar in the tubal pregnancy and control groups, but the total rate of infection was higher for tubal pregnancy. All MH samples were sensitive to tetracyclines as well as josamycin and azithromycin. Josamycin and clarithromycin were effective against all UU cultures. Over 50% of the samples tested were resistant to ciprofloxacin.


Individual prepacemaker neurons can modulate the pacemaker cycle of the gymnotiform electric fish, Eigenmannia.
The prepacemaker nucleus (PPN) in the midbrain of the gymnotiform electric fish Eigenmannia provides the only known neuronal input to the medullary pacemaker nucleus, which triggers each electric organ discharge (EOD) cycle by a single command pulse. Electrical stimulation of the PPN elicited two distinct forms of modulations in the pacemaker activity, brief accelerations, hence referred to as 'chirps', and gradual frequency shifts with a time constant of approximately one second. The associated EOD modulations were indistinguishable from natural communication signals. Depending upon the site of stimulation, the two forms of modulation could be elicited alone or superimposed (Fig. 1). Stimulation sites eliciting only chirps could be separated from sites eliciting only gradual shifts by as little as 60 micron. The magnitude of the elicited chirps depended upon the timing of the pulse stimulus with reference to the phase of the pacemaker cycle (Figs. 2, 3). Extracellular and intracellular recordings of single PPN neurons revealed that an action potential from a single neuron generates a chirp, and that the magnitude of the chirp depends upon the timing of the action potential with reference to the phase of the pacemaker cycle (Figs. 4, 5). The spike activity of these neurons had no relation to the jamming avoidance response (JAR), suggesting independent neuronal mechanisms for chirps and the JAR. Depolarization of such neurons by current injection produced bursts of chirps (Fig. 6), and intracellular injection of Lucifer Yellow identified these cells as a large type of PPN neuron which could also be retrogradely labeled from the pacemaker with horseradish peroxidase (HRP) (Fig. 7).(ABSTRACT TRUNCATED AT 250 WORDS)


Access to augmentative and alternative communication: new technologies and clinical decision-making.
Children with severe physical impairments require a variety of access options to augmentative and alternative communication (AAC) and computer technology. Access technologies have continued to develop, allowing children with severe motor control impairments greater independence and access to communication. This article will highlight new advances in access technology, including eye and head tracking, scanning, and access to mainstream technology, as well as discuss future advances. Considerations for clinical decision-making and implementation of these technologies will be presented along with case illustrations.


Identifying clinical competencies that support rehabilitation and empowerment in individuals with severe mental illness.
Individuals with severe mental illness often do not receive appropriate treatment or rehabilitation. One approach to improving their care begins by identifying competencies that clinicians should possess. This project developed a set of core clinical competencies that pertain to community-based care and support the goals of empowerment and rehabilitation. Development of the competency set began with review of existing literature and competency statements, and focus groups and interviews with clients, family members, clinicians, managers, experts, and advocates. Representatives from each of these groups participated in a national panel and used a structured process to identify 37 final competencies. Panel members agreed that these competencies are very important in determining outcomes and often are not present in current clinicians. This project demonstrates that it is possible to develop a core competency set that can be strongly supported by diverse groups of stakeholders. These competencies may be useful in clinician training, recruitment, and credentialing efforts.


Religious experience. Catholic Health Association's Sister Keehan lands top spot on our annual 100 Most Powerful ranking, underscoring her devotion to achieving a long-elusive goal: access to healthcare for everyone.
The hunger for reform and transparency in healthcare is palpable in this year's listing of the 100 Most Powerful People in Healthcare. The first six are all people who have helped lead efforts to increase access or protect patient privacy, including No. 3, California. Gov. Arnold Schwarzenegger, left. Find out who leads the pack.


A nucleus-directed bombesin derivative for targeted delivery of metallodrugs to cancer cells.
We have synthesized a set of bombesin derivatives with the aim of exploring their tumor targeting properties to deliver metal-based chemotherapeutics into cancer cells. Peptide QRLGNQWAVGHLL-NH2 (BN3) was selected based on its high internalization in gastrin-releasing peptide receptor (GRPR)-overexpressing PC-3 cells. Three metallopeptides were prepared by incorporating the terpyridine Pt(II) complex [PtCl(cptpy)]Cl (1) (cptpy = 4'-(4-carboxyphenyl)-2,2':6,2″-terpyridine) at the N-terminus of BN3 or at the NƐ- or Nα-amino group of an additional Lys residue (1-BN3, Lys-1-BN3 and 1-Lys-BN3, respectively). 1-Lys-BN3 displayed the best cytotoxic activity (IC50: 19.2 ± 1.7 μM) and similar ability to intercalate into DNA than complex 1. Moreover, the polypyridine Ru(II) complex [Ru(bpy)2)(cmbpy)](PF6)2 (2) (bpy = 2,2'-bipyridine; cmbpy = 4-methyl-2,2'-bipyridine-4'-carboxylic acid), with proven activity as photosensitizer, was coupled to BN3 leading to metallopeptide 2-Lys-BN3. Upon photoactivation, 2-Lys-BN3 displayed 2.5-fold higher cytotoxicity against PC-3 cells (IC50: 7.6 ± 1.0 μM) than complex 2. To enhance the accumulation of the drugs into the cell nucleus, the nuclear localization signal (NLS) PKKKRKV was incorporated at the N-terminus of BN3. NLS-BN3 displayed higher cellular internalization along with nuclear biodistribution. Accordingly, metallopeptides 1-NLS-BN3 and 2-NLS-BN3 showed increased cytotoxicity (IC50: 12.0 ± 1.1 μM and 2.3 ± 1.1 μM). Interestingly, the phototoxic index of 2-NLS-BN3 was 8-fold higher than that of complex 2. Next, the selectivity towards cancer cells was explored using 1BR3.G fibroblasts. Higher selectivity indexes were obtained for 1-NLS-BN3 and 2-NLS-BN3 than for the unconjugated complexes. These results prove NLS-BN3 effective for targeted delivery of metallodrugs to GRPR-overexpressing cells and for enhancing the cytotoxic efficacy of metal-based photosensitizers.


Mitochondria: mitochondrial RNA metabolism and human disease.
Post-transcriptional control of RNA stability, processing, modification, and degradation is key to the regulation of gene expression in all living cells. In mitochondria, these post-transcriptional processes are also vital for proper expression of the thirteen proteins encoded by the mitochondrial genome, as well as mitochondrial tRNAs and rRNAs. Our knowledge on mitochondrial RNA (mt-RNA) metabolic pathways, however, is far from complete. All the proteins involved in mt-RNA metabolism are encoded by the nucleus, and must be imported into the organelle. Mutations in these nuclear genes can lead to perturbations in mitochondrial RNA processing, modification, stability and decay and thus are a cause of human mitochondrial disease. This review summarises the current knowledge on mt-RNA metabolism and its links with human mitochondrial pathologies.


Laboratory and field tests of temephos (AbateR) on mosquito larvae and non-target organisms in rice fields in Malaysia.
The toxic effects of Abate (temephos) on mosquito larvae and non-target organisms were studied in the rice-field and in the laboratory. In the laboratory tests, Culex tritaeniorhychus larvae and cladoceran zooplanktons (predominantly Diaphanosoma and Moinodaphnia species) were found to be highly susceptible to Abate with LC50 values of 0.27 and less than 0.10 parts per billion respectively. Other non-target species in decreasing degree of susceptibility to Abate were copepods (Tropodiaptomus spp.), Aplocheilus panchax and Tubifex worms. In field study, Abate at concentrations 60, 100 and 200 gm hectare-1 is effective in maintaining the rice-fields free of Anopheles and Culex mosquitoes for at least 2 days. No mortality was observed for Aplocheilus panchax and Tubifex worms at the above concentrations; nevertheless, populations of cladoceran zooplanktons and copepods were reduced up to seven days posttreatment.


Antidepressants and weight gain.
Weight gain is an often reported, but incompletely understood, side effect of many antidepressant medications. We will discuss the literature with respect to the following issues: weight gain as a pharmacological effect of antidepressants or as an effect of recovery from depression; the incidence of antidepressant-induced weight gain and possible reasons for individual variability in its occurrence; possible mechanisms of antidepressant-induced weight gain; and options for clinical management. Further elucidation of these issues may contribute to our understanding of the neurobiology of affective disorders and appetitive mechanisms.


Effect of dietary anthocyanins on biomarkers of glycemic control and glucose metabolism: A systematic review and meta-analysis of randomized clinical trials.
Anthocyanins, as natural food colorants, are bioactive substances with several health advantages. In this research, the effects of dietary anthocyanins on biomarkers of glycemic control and glucose metabolism was evaluated through a meta-analysis. The results revealed a significant reduction in levels of fasting blood sugar (FBS; -2.70 mg/dl, 95% CI: -4.70 to -1.31; P < 0.001), 2-h postprandial glucose (2-h PPG; -11.1 mg/dl, 95% CI: -18.7 to -3.48; P = 0.004), glycated hemoglobin (HbA1c; -11.1 mg/dl, 95% CI: -18.7 to -3.48; P = 0.004), homeostasis model assessment of insulin resistance (HOMA-IR; -0.54, 95% CI: -0.94 to -0.14; P = 0.008), resistin (-1.23 µg/l, 95% CI: -2.40 to -0.05; P = 0.041), and plasminogen activator inhibitor-1 (PAI-1; -5.09 µg/l, 95% CI: -9.45 to -0.73; P = 0.022) following administration of anthocyanins, whilst changes in the levels of fasting insulin (0.33 mU/l, 95% CI: -0.18 to 0.85; P = 0.207) and C-peptide (-0.02 µg/l, 95 %CI: -0.20 to 0.16; P = 0.816) was not statistically significant. Consumption of anthocyanins for >8 weeks and at doses >300 mg/day significantly reduced levels of FBS, 2-h PPG, HbA1c, and HOMA-IR. Moreover, anthocyanins administration reduced the levels of FBS, 2-h PPG, HbA1c, and HOMA-IR in type 2 diabetic subjects and HOMA-IR in overweight/obese individuals. Overall, dietary anthocyanins can be used as an adjuvant therapy to improve biomarkers of glycemic control and glucose metabolism specially in diabetic subjects.


Children's views on their involvement in clinical research.
To examine the level of children's understanding of informed consent in clinical trials and factors that may influence these processes. Twenty nine children who were included in clinical trials for treatment of cancer or HIV, were offered the possibility to complete a semidirective interview, with parental permission. Children's understanding was measured by a score of 0-9 including items required to obtain a valid consent according to French and European legislations. Children were 8.5-18 years old (13.6 +/- 2.8 years). The higher percentage of understanding was obtained for the study objectives (n = 18, 62%), the risks (n = 17, 58%), the potential self-benefits (n = 18, 62%) and the potential benefits to other children (n = 17, 58%). The lower percentage of understanding was obtained for the procedures (n = 5, 17%), the possibility of alternative treatments (n = 9, 31%), the duration of participation (n = 6, 21%), their right to withdraw (n = 6, 21%), and the voluntary participation (n = 6, 21%). Sixteen children (55%) thought that the given information was adequate. Understanding was significantly correlated with child's age (r = 0.65; P = 0.0001) and the mean score was higher in patients over 14 years old compared to patients under the age of 14 (4.4 +/- 2.4, n = 14 vs. 2.6 +/- 2.6, n = 15, P < 0.05). The mean score was also higher in children when informed consent was sought some time after the diagnosis (>7 days) rather than at the same time (<7 days) (score: 4.14 +/- 2.59 n = 21 vs. 1.87 +/- 2.03 n = 8; P = 0.03). The clarity of information perceived by children did not influence their understanding (score: 3.6 +/- 2.6 n = 14 vs. 3.5 +/- 2.7 n = 15; P = 0.91). Children have an incomplete understanding of the elements included in the informed consent forms. Understanding is related to age and timing of informed consent.


Helping the Help for CD8+ T Cell Responses.
Eickhoff et al. and Hor et al. use time-lapse intravital microscopy to show an unexpected choreography of CD4+ and CD8+ T cells "dancing" between different dendritic cell sub-populations during priming of cytotoxic immune responses to viruses.