Regioselective dioxygenation of ortho-trifluoromethylbenzoate by Pseudomonas aeruginosa 142: evidence for 1,2-dioxygenation as a mechanism in ortho-halobenzoate dehalogenation.
Pseudomonas aeruginosa strain 142 oxidizes 2-halobenzoates via a multicomponent oxygenase (V. Romanov and R.P. Hausinger, J. Bacteriol., 1994, 176(11), 3368-3374). The intermediacy of a highly unstable cis-diol in the reaction has been proposed. Direct evidence for this is currently lacking and the stereochemical course of the reaction cannot be inferred from previous studies. In this study, 2-trifluoromethylbenzoate was stoichiometrically oxidized by P. aeruginosa 142 to a chiral product identified as (-)2-trifluoromethyl-cis-1,2-dihydroxy-3,5-cyclohexadiene-1-carboxylic acid. These data rigorously establish a dioxygenative mechanism for 2-halobenzoate metabolism.


Model studies on protein glycation: influence of cysteine on the reactivity of arginine and lysine residues toward glyoxal.
Mixtures of N alpha-hippurylarginin, N alpha-hippuryllysine, and glyoxal were incubated in the absence and presence of N alpha-acetylcysteine in order to assess the individual reactivity of these nucleophilic amino acid residues. The incubations were performed under atmospheric and high hydrostatic pressure (400 MPa), and, at the same time, beta-casein was reacted with glyoxal. The results showed that arginine is the main partner for glyoxal in the absence of cysteine, whereas a lysine derivatization was not apparent. In the presence of cysteine, however, arginine was almost completely protected from the reaction, whereas a noticeable formation of lysine derivatives, mainly carboxymethyllysine, was observed. Based on these findings, a reaction mechanism is proposed to explain the influence of cysteine on the reaction.


Meeting the challenge of the Psychonomic Society's 2012 Guidelines on Statistical Issues: Some success and some room for improvement.
The Psychonomic Society (PS) adopted New Statistical Guidelines for Journals of the Psychonomic Society in November 2012. To evaluate changes in statistical reporting within and outside PS journals, we examined all empirical papers published in PS journals and in the Experimental Psychology Society journal, The Quarterly Journal of Experimental Psychology (QJEP), in 2013 and 2015, to describe these populations before and after effects of the Guidelines. Comparisons of the 2013 and 2015 PS papers reveal differences associated with the Guidelines, and QJEP provides a baseline of papers to reflect changes in reporting that are not directly influenced by the Guidelines. A priori power analyses increased from 5% to 11% in PS papers, but not in QJEP papers (2%). The reporting of effect sizes in PS papers increased from 61% to 70%, similar to the increase for QJEP from 58% to 71%. Only 18% of papers reported confidence intervals (CIs) for means; only two PS papers in 2015 reported CIs for effect sizes. Although variability statistics are important to understanding data, and to further analysis, they were only reported as numbers in just over half of the PS journal papers. Almost all PS and QJEP papers relied exclusively on null hypothesis significance testing to guide interpretation of the data. Changes associated with the Guidelines are in the desired direction with respect to reporting effect sizes and power analyses but are not yet reflected in researchers' practices in describing their data, addressing data assumptions, and thinking beyond the p value when interpreting their data.


Spontaneous hemothorax following thrombolytic and anticoagulant therapy for massive pulmonary embolism.
Massive spontaneous hemothorax following combined thrombolytic and anticoagulant therapy for pulmonary embolism(PE) is a rare event that is little documented in the literature. Here, we describe a rare case of spontaneous hemothorax in a 23-year-old woman with underlying systemic lupus erythematosus following combined administration of tissue plasminogen activator and low-molecular-weight heparin for massive PE. This report of our successful treatment of this case by video-assisted thoracoscopic thoracotomy demonstrates that although the occurrence is rare, massive hemothorax following anticoagulant and/or thrombolytic therapy for PE should be suspected if patients experience chest pain, dyspnea, or signs of anemia, and follow-up physical examination and hemogram should be performed to facilitate diagnosis of this life-threatening complication.


Detecting Task Functional MRI Activation Using the Multiband Multiecho (MBME) Echo-Planar Imaging (EPI) Sequence.
Blood oxygen level-dependent (BOLD) functional MRI (fMRI) has been widely applied to detect brain activations. Recent advances in multiband (MB) and multiecho (ME) techniques have greatly improved fMRI methods. MB imaging improves temporal and/or spatial resolution, while ME imaging has been shown to improve BOLD sensitivity. This study aimed to evaluate the novel MBME echo planar imaging (EPI) sequence utilizing MB and ME simultaneously to determine if the MBME outperform the MB single echo (MBSE) sequence for task fMRI. To compare the performance of MBME with MBSE in a task fMRI study. Prospective. A total of 29 healthy volunteers aged 20-46 years (9 male, 20 female). MBSE and MBME gradient-echo EPI sequences were applied at 3T. Additional T1 -weighted magnetization-prepared rapid acquisition with gradient echo (MPRAGE) was collected. A checkerboard visual task was presented during the functional MBSE and MBME scans. The MBME or MBSE signal was evaluated using the temporal signal-to-noise ratio (tSNR). Task activation was evaluated using the z-score, volume, sensitivity, and specificity. Test-retest metrics of task activation were examined with the Dice coefficient (DC) and intraclass correlation coefficient (ICC) on subjects with repeated scans. A linear mixed-effects model was used to compared MBME and MBSE activation at the voxel base. The paired t-test was used to compare tSNR, activation z-score, and volume, along with sensitivity, specificity, and DC between MBSE and MBME. While similar task activation was detected in the visual cortex, MBME showed higher activation volume and higher sensitivity compared with MBSE (P < 0.05). ICC was higher for MBME than MBSE, while there was a trend of differences in DC (P = 0.08). MBME resulted in higher task fMRI activation volume and sensitivity without losing specificity. Reliability was also higher for MBME scans compared with MBSE. 1 TECHNICAL EFFICACY STAGE: 1.


Aggressive surgical resection for the management of hepatic metastases from gastrointestinal stromal tumours: a single centre experience.
The outcome of surgical intervention for hepatic metastases from gastrointestinal stromal tumours (GIST) is still uncertain. This study evaluated the outcome of patients following aggressive surgical resection and Imatinib mesylate therapy (IM). This was a retrospective analysis of patients managed with hepatic metastases from GIST over a 13-year period (January 1993 to December 2005). Twelve patients were identified with a median age at diagnosis of 62 (32-78) years. The primary sites of GIST were stomach (n=5), jejunum (n=4), sigmoid (n=1), peritoneum (n=1) and pancreas (n=1). Eleven patients underwent surgical resection with curative intent and one patient had cytoreductive surgery. Following surgery with curative intent (n=11), the overall 2- and 5-year survival rates were both 91%, whereas the 2- and 5-year disease-free rates following primary hepatic resection were 30% and 10%, respectively. The median disease-free period was 17 (3-72) months. Eight patients had recurrent disease and were managed with further surgery (n=3), radiofrequency ablation (RFA) (n=2) and IM (n=8). Overall, there are four patients who are currently disease-free: two patients following initial hepatic resection and two patients following further treatment for recurrent disease. There was no significant association in clinicopathological characteristics between patients with recurrent disease within 2 years and patients who were disease-free for 2 years or more. Overall morbidity was 50% (n=6), with one postoperative death. The follow-up period was 43 (3-72) months. Surgical resection for hepatic GIST metastases may improve survival in selected patients. Recurrent disease can be managed with surgery, RFA and IM.


Safety/tolerability, efficacy and pharmacokinetics of 600-μg cotadutide in Japanese type 2 diabetes patients with a body mass index of 25 kg/m2 or higher: A phase I, randomized, double-blind, placebo-controlled study.
To assess the safety/tolerability, efficacy and pharmacokinetics of once-daily, 600-μg cotadutide in Japanese type 2 diabetes patients with a body mass index of 25 kg/m2 or higher. This phase I, randomized, double-blind, placebo-controlled study (NCT04208620) enrolled patients to receive subcutaneous cotadutide at an escalating dose to determine the highest tolerated clinical dose (Cohort 1), then applied in Cohort 2. The primary endpoint was safety, including treatment-emergent adverse events (TEAEs); secondary endpoints included glycaemic control and body weight. Sixteen patients were randomly allocated to receive cotadutide or placebo in a 3:1 ratio. All patients were Asian, 62.5% were male, and the median age and body mass index were 60 years and 27.2 kg/m2 , respectively. Through the follow-up period of the study, 11/12 (91.7%) patients in the cotadutide group experienced a TEAE versus 1/4 (25.0%) patients in the placebo group. All TEAEs were mild, except for one moderate event. There were no deaths, serious TEAEs or TEAEs leading to study discontinuation. Gastrointestinal-related events were the most common TEAEs. Cotadutide-treated patients achieved significantly improved 7-day mean glucose measured by continuous glucose monitoring; the 7-day mean (standard deviation) at the end of treatment (day 70) was 112.23 (20.79) versus 206.85 (3.62) mg/dL for placebo. Mean respective changes in HbA1c were -1.13% (0.64%) and -0.17% (0.65%); and mean percentage changes in body weight were -6.93% (3.44%) and -1.23% (1.20%). Cotadutide was well tolerated at doses up to 600 μg; efficacy versus placebo for weight loss and glycaemic control was shown.


X-linked hydrocephalus genes: Their proximity to telomeres and high A + T content compared to Parkinson's disease.
Proximity to telomeres (i) and high adenine and thymine (A + T) content (ii) are two factors associated with high mutation rates in human chromosomes. We have previously shown that >100 human genes when mutated to cause congenital hydrocephalus (CH) meet either factor (i) or (ii) at 91% matching, while two factors are poorly satisfied in human genes associated with familial Parkinson's disease (fPD) at 59%. Using the sets of mouse, rat, and human chromosomes, we found that 7 genes associated with CH were located on the X chromosome of mice, rats, and humans. However, genes associated with fPD were in different autosomes depending on species. While the contribution of proximity to telomeres in the autosome was comparable in CH and fPD, high A + T content played a pivotal contribution in X-linked CH (43% in all three species) than in fPD (6% in rodents or 13% in humans). Low A + T content found in fPD cases suggests that PARK family genes harbor roughly 3 times higher chances of methylations in CpG sites or epigenetic changes than X-linked genes.


Non-random distribution of homo-repeats: links with biological functions and human diseases.
The biological function of multiple repetitions of single amino acids, or homo-repeats, is largely unknown, but their occurrence in proteins has been associated with more than 20 hereditary diseases. Analysing 122 bacterial and eukaryotic genomes, we observed that the number of proteins containing homo-repeats is significantly larger than expected from theoretical estimates. Analysis of statistical significance indicates that the minimal size of homo-repeats varies with amino acid type and proteome. In an attempt to characterize proteins harbouring long homo-repeats, we found that those containing polar or small amino acids S, P, H, E, D, K, Q and N are enriched in structural disorder as well as protein- and RNA-interactions. We observed that E, S, Q, G, L, P, D, A and H homo-repeats are strongly linked with occurrence in human diseases. Moreover, S, E, P, A, Q, D and T homo-repeats are significantly enriched in neuronal proteins associated with autism and other disorders. We release a webserver for further exploration of homo-repeats occurrence in human pathology at http://bioinfo.protres.ru/hradis/.


Moral uncertainty and distress about voluntary assisted dying prior to legalisation and the implications for post-legalisation practice: a qualitative study of palliative and hospice care providers in Queensland, Australia.
There is little research on moral uncertainties and distress of palliative and hospice care providers (PHCPs) working in jurisdictions anticipating legalising voluntary assisted dying (VAD). This study examines the perception and anticipated concerns of PHCPs in providing VAD in the State of Queensland, Australia prior to legalisation of the practice in 2021. The findings help inform strategies to facilitate training and support the health and well-being of healthcare workers involved in VAD. The study used a qualitative approach to examine and analyse the perception and anticipated concerns of PHCPs regarding challenges of providing assisted dying in Queensland. Fourteen PHCPs were recruited using a purposive sampling strategy to obtain a broad representation of perspectives including work roles, geographical locations and workplace characteristics. Data were collected via one in-depth interview per participant. The transcripts were coded for patterns and themes using an inductive analysis approach following the tradition of Grounded Theory. The study was conducted in hospital, hospice, community and residential aged care settings in Queensland, Australia. These included public and private facilities, secular and faith-based facilities, and regional/rural and urban facilities. Interviews were conducted with fourteen PHCPs: 10 nurses and 4 physicians; 11 female and 3 male. The median number of years of palliative care practice was 17, ranging from 2 to 36 years. For inclusion, participants had to be practising palliative and hospice care providers. PHCPs are divided on whether VAD should be considered part of palliative care. Expectations of moral distress and uncertainty about practising VAD were identified in five areas: handling requests, assessing patient capacity, arranging patient transfers and logistical issues, managing unsuccessful attempts, and dealing with team conflicts and stigma. The possibility of having to practise VAD causes moral distress and uncertainty for some PHCPs. Procedural clarity can address some uncertainties; moral and psychological distress, however, remains a source of tension that needs support to ensure ongoing care of both patients and PHCPs. The introduction of VAD post-legalisation may present an occasion for further moral education and development of PHCPs.


Development of novel indole-linked pyrazoles as anticonvulsant agents: A molecular hybridization approach.
A series of 3-{2-[1-acetyl-5-(substitutedphenyl)-4,5-dihydropyrazol-3-yl]hydrazinylidene}-1,3-dihydro-2H-indol-2-ones 24-43 was synthesized using an appropriate synthetic route and evaluated experimentally by the maximal electroshock test. These compounds were evaluated for antidepressant and antianxiety activities. The most active compound, 3-{2-[1-acetyl-5-(4-chlorophenyl)-4,5-dihydropyrazol-3-yl]hydrazinylidene}-1,3-dihydro-2H-indol-2-one 25, exhibited an ED50 of 13.19 mmol/kg, a TD50 of 43.49 mmol/kg, and a high protective index of 3.29, compared with the standard drug diazepam. To get insights into the intermolecular interactions, molecular docking studies were performed at the active site of the GABAA receptor and the MAO-A enzyme. Molecular docking studies are also in agreement with the pharmacological evaluation with potent compounds, exhibiting docking scores of -1.5180 and 0.7458 for the GABAA receptor and MAO-A, respectively. The 3D-QSAR analysis was carried out by Vlife MDS engine 4.3.1, and a statistically reliable model with good predictive power (r2 = 0.7523, q2 = 0.3773) was achieved. The 3D-QSAR plots gave insights into the structure-activity relationship of these compounds, which may aid in the design of potent benzopyrrole derivatives as anticonvulsant agents. So, our research can make a great impact on those medicinal chemists who work on the development of anticonvulsant agents.


Comparison of Different Tyrosine Kinase Inhibitors for Treatment of Poor Performance Status Patients with EGFR-Mutated Lung Adenocarcinoma.
The aim of this retrospective study was to investigate the tolerability and survival outcomes of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment in patients with a performance status ≥ 2. The data for 517 patients treated with EGFR-TKIs between January 2011 and January 2018 at a regional hospital in northern Taiwan were analyzed. Clinical and pathological features were collected, and univariate as well as multivariable analyses were undertaken to identify potential prognostic factors. The overall objective response rate, median progression-free survival (PFS), and median overall survival (OS) were 56.3%, 11.4 months, and 15.3 months, respectively. The mutation status (exon 19 deletion), locally advanced disease, dose adjustment, and the lack of liver and pleural metastasis were independent and favorable prognostic factors for PFS. Age < 60 years, mutation status (exon 19 deletion), dose adjustment, and lack of lung, liver, and no pleural metastasis were independent and favorable prognostic factors for OS. GFR-TKIs demonstrated acceptable efficacy and safety in the current cohort. Dose adjustment was identified as an independent prognostic factor for both PFS and OS, regardless of which EGFR-TKIs were used. The current research provided novel evidence of the clinical prescription of frontline EGFR-TKIs for EGFR-mutated lung adenocarcinoma patients with a PS score ≥2.


Structural alterations of the language connectome in children with specific language impairment.
We evaluated brain white matter pathways associated with language processing in 37 children with specific language impairment aged 6-12 years and 34 controls, matched for age, sex and handedness. Arcuate fascicle (AF), inferior fronto-occipital fascicle (IFOF), inferior longitudinal fascicle (ILF) and uncinate fascicle (UF) were identified using magnetic resonance diffusion tensor imaging (DTI). Diffusivity parameters and volume of the tracts were compared between the SLI and control group. Children with SLI showed decreased fractional anisotropy in all investigated tracts, increased mean diffusivity and radial diffusivity component in arcuate fascicle bilaterally, left IFOF and left ILF. Further, bilaterally increased volume of the ILF in children with SLI was found. We confirmed previous findings indicating deficient connectivity of the arcuate fascicle and as a novel finding, demonstrate abnormal development of the ventral language stream in patients with SLI.


Linking Genome and Exposome: Computational Analysis of Human Variation in Chemical-Target Interactions.
The growing amount of available public data repositories containing a plethora of rich chemical and biomedical information is enabling new in silico research avenues. In this project we aim to link human genome variations and the exposome applying in silico biomedical informatics approaches to analyse the potential effects of those variants in the interactions with different chemicals.


Investigation of thrombomodulin and plasminogen activator inhibitor type-I in pregnancy induced hypertension and its clinical significance.
To measure the circulating levels of thrombomodulin (TM) and plasminogen activator inhibitor type-I (PAI-I) in women with pregnancy induced hypertension (PIH). Blood samples were drawn from 97 pregnant women in their third trimester, grouped as 25 mild PIH, 26 moderate PIH, 22 severe PIH and 24 normotensive healthy pregnant women for determining levels of TM by ELISA, PAI-I by colorimetric assay methods, and creatinine (Cr) in serum by biochemical method. Circulating levels of TM, PAI-I and TM/Cr ratio increased with increasing severity of PIH. There were no significant differences between mild and normotensive pregnant women. The parameters were significantly changed in the moderate and severe PIH groups. TM and PAI-I may serve as meaningful clinical markers for the assessment of the endothelial damage in PIH, which is very important in evaluating and following the development of PIH.


[Health assessment of managers 63 and 64 years old. (Results of the first step of a prospective study on the adaptation to retirement) (author's transl)].
A cross-sectional study has been carried out on a group of 180 male preretired managers and top executives in order to investigate their health status. This study is the first part of a longitudinal survey undertaken to analyze the adjustment to retirement among managers. These 180 subjects were 63 or 64 years old, still working at full time. The study included a standardized medical questionnaire, a medical examination as well as various biological, physiological and psychological measurements. For each main ICD categories of diseases, the prevalence rate was assessed; for each subject two indices of global morbidity were established. Furthermore, some risk factors of cardio-vascular diseases were assessed.


Multi-omics Profiling of Patients with Melanoma Treated with Nivolumab in Project HOPE.
Project HOPE (High-tech Omics-based Patient Evaluation) has been in progress since 2014 and uses whole-exome sequencing (WES) and gene expression profiling (GEP). Among a total of 1,685 patients with cancer, 13 with melanoma were registered and characterized using multi-omics analyses to investigate specific biomarkers in responders to programmed cell death-1 (PD-1) blockade. The patients with melanoma comprised of six males and seven females, and their mean age was 68 years. Five patients were treated with nivolumab, and two were responders. GEP analysis demonstrated that PD-L1 expression was positive in for cases, and melanoma-associated antigens and tumor signaling-associated genes were up-regulated in tumor compared with normal tissues. Additionally, WES analysis indicated more single nucleotide variants (SNVs) per melanoma tumor compared to other tumor types. Remarkably, a case of complete remission after nivolumab therapy showed high expression of PD-L1 protein and the highest number of SNVs. The novel approach used in Project HOPE might be an efficient tool that facilitates identifying specific biomarkers predictive of good responders to anti-PD-1 therapy.


Deinococcus radiodurans RecA nucleoprotein filaments characterized at the single-molecule level with optical tweezers.
Deinococcus radiodurans can survive extreme doses of ionizing radiation due to the very efficient DNA repair mechanisms that are able to cope even with hundreds of double-strand breaks. RecA, the critical protein of homologous recombination in bacteria, is one of the key components of the DNA-repair system. Repair of double-strand breaks requires RecA binding to DNA and assembly of the RecA nucleoprotein helical filaments. The Escherichia coli RecA protein (EcRecA) and its interactions with DNA have been extensively studied using various approaches including single-molecule techniques, while the D. radiodurans RecA (DrRecA) remains much less characterized. However, DrRecA shows some remarkable differences from E. coli homolog. Here we combine microfluidics and single-molecule DNA manipulation with optical tweezers to follow the binding of DrRecA to long double-stranded DNA molecules and probe the mechanical properties of DrRecA nucleoprotein filaments at physiological pH. Our data provide a direct comparison of DrRecA and EcRecA binding to double-stranded DNA under identical conditions. We report a significantly faster filaments assembly as well as lower values of persistence length and contour length for DrRecA nucleoprotein filaments compared to EcRecA. Our results support the existing model of DrRecA forming more frequent and less continuous filaments relative to those of EcRecA.


Dietary diversity and food variety scores and their association with nutrition and health status of Indian children and adolescents: A multicenter study.
The objectives of this study were to 1) evaluate the dietary diversity scores (DDS) and food variety scores (FVS) among Indian children and adolescents aged 9-18 y; 2) compare the DDS and FVS in association with demographic, socioeconomic, and health characteristics (growth and hemoglobin [Hb] concentrations); and 3) determine DDS and FVS cutoffs to identify dietary micronutrient adequacy. This study was performed in a subset (n = 1845) of children and adolescents enrolled in a multicenter study (2016-2017) from urban and rural areas of six Indian states. Height, weight, and Hb were measured, and anthropometric Z-scores were computed. Sociodemographic data were collected using a structured questionnaire. Dietary data collected by 24-h dietary recall were used to calculate the DDS and FVS. The mean adequacy ratio (MAR) for 10 micronutrients was computed. Receiver operating characteristic analysis was performed to define cutoffs of DDS and FVS. In comparison with children and adolescents from rural areas, urban children and adolescents consumed more diverse diets (urban, 4.1 ± 1.1; rural, 3.5 ± 1; P < 0.01) and had a higher mean FVS (urban, 19.9 ± 5.7; rural, 15.9 ± 4.5; P < 0.01). Both the DDS and FVS were significantly correlated with each other (r = 0.860; P < 0.01) and were positively correlated with MAR, growth, and Hb (P < 0.001) and mother's educational level (P < 0.01). The cutoffs of ≥6.5 (DDS) and ≥17 (FVS) were determined to predict micronutrient adequacy. Both the DDS and FVS can be used interchangeably for assessing growth, health status, and nutritional adequacy. Single cutoff values of the DDS and FVS may aid in prompt identification of children and adolescents with micronutrient inadequacy.


Regioselective hydroxylation of adamantane by Streptomyces griseoplanus cells.
Hydroxylation of adamantane using whole cells of bacteria, actinomyces, and molds was examined. The structure of the product was determined using gas chromatography (GC), nuclear magnetic resonance (NMR), and mass spectroscopy (MS). Among 470 strains tested, Streptomyces griseoplanus was highly regioselective to give 1-adamantanol (0.096 mmol) from adamantane (0.3 mmol) in a 32% molar conversion yield after 72-h cultivation in the presence of 3% (v/v) Tween 60. A P450 inhibitor such as 0.5 mM 1-aminobenzotriazole or menadione significantly inhibited the hydroxylation activity. These results suggested that a P450 oxidation system might be involved in this hydroxylation reaction.


Efficacy of artesunate-amodiaquine and artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria in Madagascar, 2018.
Since 2005, artemisinin-based combination therapy (ACT) has been recommended to treat uncomplicated falciparum malaria in Madagascar. Artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) are the first- and second-line treatments, respectively. A therapeutic efficacy study was conducted to assess ACT efficacy and molecular markers of anti-malarial resistance. Children aged six months to 14 years with uncomplicated falciparum malaria and a parasitaemia of 1000-100,000 parasites/µl determined by microscopy were enrolled from May-September 2018 in a 28-day in vivo trial using the 2009 World Health Organization protocol for monitoring anti-malarial efficacy. Participants from two communes, Ankazomborona (tropical, northwest) and Matanga (equatorial, southeast), were randomly assigned to ASAQ or AL arms at their respective sites. PCR correction was achieved by genotyping seven neutral microsatellites in paired pre- and post-treatment samples. Genotyping assays for molecular markers of resistance in the pfk13, pfcrt and pfmdr1 genes were conducted. Of 344 patients enrolled, 167/172 (97%) receiving ASAQ and 168/172 (98%) receiving AL completed the study. For ASAQ, the day-28 cumulative PCR-uncorrected efficacy was 100% (95% CI 100-100) and 95% (95% CI 91-100) for Ankazomborona and Matanga, respectively; for AL, it was 99% (95% CI 97-100) in Ankazomborona and 83% (95% CI 76-92) in Matanga. The day-28 cumulative PCR-corrected efficacy for ASAQ was 100% (95% CI 100-100) and 98% (95% CI 95-100) for Ankazomborona and Matanga, respectively; for AL, it was 100% (95% CI 99-100) in Ankazomborona and 95% (95% CI 91-100) in Matanga. Of 83 successfully sequenced samples for pfk13, no mutation associated with artemisinin resistance was observed. A majority of successfully sequenced samples for pfmdr1 carried either the NFD or NYD haplotypes corresponding to codons 86, 184 and 1246. Of 82 successfully sequenced samples for pfcrt, all were wild type at codons 72-76. PCR-corrected analysis indicated that ASAQ and AL have therapeutic efficacies above the 90% WHO acceptable cut-off. No genetic evidence of resistance to artemisinin was observed, which is consistent with the clinical outcome data. However, the most common pfmdr1 haplotypes were NYD and NFD, previously associated with tolerance to lumefantrine.


A proprietary extract from North American ginseng (Panax quinquefolium) enhances IL-2 and IFN-gamma productions in murine spleen cells induced by Con-A.
A patented aqueous extract from North American ginseng (Panax quinquefolium), containing mainly oligosaccharides and polysaccharides, is commercially available over the counter as COLD-FX (CVT-E002). This proprietary extract is used for the treatment of upper respiratory tract infections. Its in vitro stimulating effects on the immunoglobulin production by B lymphocytes and on natural immune responses by peritoneal exudates macrophages have been previously reported. Using C57 BL/6 mice, an ex vivo study was conducted to examine Con-A-induced splenocytic productions of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) as markers of acquired immune responses. CVT-E002 (10-500 microg/ml) significantly increased Con-A-induced IL-2 and IFN-gamma productions in spleen cells in a dose-dependent manner. Such response was seen by the ginseng extract originated from three different lots, suggesting consistency between the lots.


Development and Implementation of International Curricula for Joint Replacement and Preservation.
The number of patients undergoing joint replacement and preservation procedures continues to increase worldwide. Globally, there is no standardized educational pathway, training program, or recognized certification program for surgeons in these procedures. Development and implementation of new competency-based curricula to deliver specific educational events and resources may help trainees and practicing surgeons be able to perform these procedures more effectively and therefore improve patient outcomes in their respective countries. Ideally, a curriculum would be globally standardized and professionally designed to interactively meet the needs of surgeons. A competency-based approach with built-in assessment and evaluation processes is today's educational standard.


Scottish validation study of Cancer Registration data childhood leukaemia 1968-1981. Bone marrow review--II.
Following a review of central leukaemia registration data for Scottish children 1968-1981 a retrospective assessment of leukaemia type was made by inspection of bone marrow slides. Only 57% of slides were still available and in 72% of these the review panel confirmed the initial diagnosis of leukaemia and its type. In eight cases the panel disagreed with the diagnosis or the type of leukaemia designated. Central slide review at diagnosis in childhood leukaemia is essential if subsequent epidemiological studies are to be meaningful.


Selectivity for catecholamines of presynaptic alpha-receptors involved in feedback control of sympathetic neurotransmitter secretion in guinea-pig vas deferens.
The aim of the study was to quantitatively compare the relative affinities of noradrenaline, adrenaline, dopamine and isoprenaline for the, probably neural, receptors mediating feedback control of sympathetic neurotransmitter secretion. The experiments were carried out in isolated superfused field stimulated guinea-pig vas deferens, in which the noradrenaline stores had been labelled by preincubation with tritiated (-)-noradrenaline. Desipramine and normetanephrine were added to prevent rebinding of transmitter. Exogenous noradrenaline was found to cause a dose-dependent and reversible depression of the secretion of tracer noradrenaline evoked by field stimulation. Since the depressing effect was not affected by a ten-fold rise in the desipramine concentration, it seems likely that it was not due to uptake and preferential secretion of unlabelled exogenous noradrenaline, but was truly due to depression of the secretory mechanism. Adrenaline was significantly more potent than noradrenaline, as inhibitor of the secretion of tracer transmitter, while dopamine, at the same molar concentration, was without effect. The beta-agonist isoprenaline did not depress, but rather tended to enhance, the secretion of tracer noradrenaline. It is concluded that the receptors controlling the secretion of noradrenaline from the sympathetic nerves of guinea-pig vas deferens quantitatively-with regard to sensitivity-as well as qualitatively-with regard to order of preference for different catecholamines-resemble the "classical" alpha-receptors of e.g. smooth muscle in the same tissue.


Dolabrane-type diterpenes from the mangrove plant Ceriops tagal with antitumor activities.
Chemical examination of the barks of mangrove plant Ceriops tagal resulted in the isolation of six new dolabrane-type diterpenes with the trivial names of tagalenes A-F (1-6), together with 10 known analogues. The structures of new compounds were elucidated by extensive spectroscopic data analyses. Tagalenes A-C (1-3) are characterized by 18-nordolabrane scaffold, while tagalene F (6) featured by a 2,3-seco dolabrane derivative. Antitumor assay revealed that seven compounds exhibited potent inhibitory effects against a panel of tumor cell lines with IC50<10 μM, while tagalsin C (8) exerted the most potent activities in comparison with the IC50 values of the rest compounds. The primary structure-activity relationship is discussed. Tagalsin C also exerted the potent effects against a panel of drug-resistant human tumor cell lines, indicating it to be a promising molecule for further evaluation as an antitumor lead compound.


Methodological lessons and pilot data on the effect of proximity of homes and schools to highways on pediatric asthma and lung function.
Numerous studies have found that either living or attending school near highways or exposure to pollutants associated with heavy motor vehicle traffic are associated with a high prevalence of asthma and reduced lung function. Yet, few investigations have assessed school and home exposure in the same study. We recruited children aged 5-19 years from a pediatric clinic in an urban center (Boston Chinatown) for many of whom housing and school were located immediately adjacent to two major highways. A questionnaire was used to assess self-report of diagnosis of asthma and the proximity of schools and homes to highways, as well as basic demographic information. Spirometric lung function data were obtained and reviewed by a pediatric pulmonologist blinded to survey responses. During this review, we excluded lung function tests of low quality. The analyses did not demonstrate any associations or mean differences between near-highway exposure at school, at home, or both with diagnosed asthma (p>0.10, n=124). For the lung function data (n=87), neither direct measures (FEV1, FVC, and FEF(25-75)) nor ratio measures (FEV1/FVC and FEF(25-75)/FVC) had a significant association with near-highway exposure (p>0.10). Certain predisposing factors, such as diagnosed allergies and family history of asthma, were strongly associated with diagnosed asthma (p<0.05 and p=0.001, respectively), findings we have seen consistently in other work with children recruited from the same clinic. We also found that exposure to pests was significantly correlated with a smaller FEF(25-75)/FVC ratio (p=0.02). Our findings suggest that either limitations in our study design restricted our ability to see the associations reported by others or that such associations do not exist in this population. One possibility is that in this community, with heavy street traffic and many street canyons, the gradient of exposure next to the highway is not very well delineated by simple proximity.


No difference between tibia-first and femur-first techniques in TKA using computer-assisted surgery.
The measured resection technique and the gap-balancing technique are two philosophies used in total knee surgery. It is still unknown whether one or the other technique provides superior results when computer-assisted surgery is performed. We hypothesized that the gap-balancing technique improves joint stability because the technique relies primarily on the soft tissue. A prospective controlled study was performed in 116 patients using the tibia-first or femur-first technique. The Columbus(TM) total knee system and the Orthopilot(®) (Aesculap(®) AG, Tuttlingen, Germany) navigation system were used in all cases. Sixty-three patients were allocated to the femur-first technique (group F) and 53 patients to the tibial first technique (group T). The mean follow-up time was 11.4 ± 1.1 months. The KSS, KOOS and SF-36 were taken prior to surgery and at the time of follow-up for clinical assessment. Long-leg weight-bearing radiographs were performed to assess ligament alignment. Radiographs in varus and valgus stress were performed using the Telos(®)-Instrument (Telos(®) GmbH, Greisheim, Germany) under a force of 15 N at the time of follow-up for the assessment of medial-lateral stability. The nonparametric t test (Mann-Whitney U-test) was used in order to compare the ligament stability and the scores between group F and group T. The lateral joint space opening for groups F and T was 3.4° ± 1.4° and 3.9° ± 1.7°, respectively (n.s.), and the medial joint space opening for groups F and T was 4° ± 1.4° and 4.1° ± 1.7°, respectively (n.s.). The femorotibial mechanical axis for groups F and T revealed 1.4° ± 1.2° and 0.7° ± 2.0° of varus, respectively (p = 0.138). The clinical assessment showed significant improvement according to KSS, KOOS and SF-36 in all subscales. Neither of the sores showed significant differences between the two groups. The surgeon should use his/her preferred surgical technique providing the implantation is performed with computer assistance. It remains unclear whether the same findings will occur after conventional surgery. II.


Cardiac parasympathetic dysfunction related to depression in older adults with acute coronary syndromes.
To determine whether depression is associated with cardiac autonomic alterations in elderly patients with recent acute coronary syndromes (ACSs). Cross-sectional study on the association between a major depressive episode or isolated depressive symptoms (21-item Hamilton depression score) and heart rate variability abnormalities in 56 adults (31 women, 55%) 60 years of age and older with a recent (24-72 h) myocardial infarction (MI) or unstable angina (UA). Spectral and nonspectral parameters of respiratory sinus arrhythmia, indicative of parasympathetic activity on the heart, were decreased in patients with depression (high-frequency heart rate variability [log ms(2)] 2.12+/-0.4 vs. 2.52+/-0.5, P=.024; pNN50 [%] 1+/-2 vs. 9+/-15, P=.006; and rMSNN [ms] 16+/-6 vs. 28+/-22, P=.009). Also, high-frequency heart rate variability decreased with increasing depressive symptom severity. In a sample of older adults suffering from ACSs, depression was associated with impaired parasympathetic control of the heart.


Food preferences by Octodon degus (Rodentia caviomorpha): Their role in the chilean matorral composition.
The food preferences of Octodon degus are examined in laboratory test. Results indicate that degus prefer new rather than mature leaves of Chilean matorral shrubs, and that degus do not discriminate between new leaves (equivalents of shrub seedlings) of different shrub species. The significance of degus preferences in relation to matorral composition is discussed.


[Automated measurement of cardiac output during physical exercise using a rheographic method].
The authors propose the methods of measuring the hemodynamic indices on the basis of the impedance rheoplethysmography, electrocardiometer and programming microcalculator. The use of the disk electrodes instead of the circular electrodes makes it possible to take measurements during physical tests, e.g. veloergometric tests.


Photon and Proton irradiation in Patient-derived, Three-Dimensional Soft Tissue Sarcoma Models.
Despite their heterogeneity, the current standard preoperative radiotherapy regimen for localized high-grade soft tissue sarcoma (STS) follows a one fits all approach for all STS subtypes. Sarcoma patient-derived three-dimensional cell culture models represent an innovative tool to overcome challenges in clinical research enabling reproducible subtype-specific research on STS. In this pilot study, we present our methodology and preliminary results using STS patient-derived 3D cell cultures that were exposed to different doses of photon and proton radiation. Our aim was: (i) to establish a reproducible method for irradiation of STS patient-derived 3D cell cultures and (ii) to explore the differences in tumor cell viability of two different STS subtypes exposed to increasing doses of photon and proton radiation at different time points. Two patient-derived cell cultures of untreated localized high-grade STS (an undifferentiated pleomorphic sarcoma (UPS) and a pleomorphic liposarcoma (PLS)) were exposed to a single fraction of photon or proton irradiation using doses of 0 Gy (sham irradiation), 2 Gy, 4 Gy, 8 Gy and 16 Gy. Cell viability was measured and compared to sham irradiation at two different time points (four and eight days after irradiation). The proportion of viable tumor cells four days after photon irradiation for UPS vs. PLS were significantly different with 85% vs. 65% (4 Gy), 80% vs. 50% (8 Gy) and 70% vs. 35% (16 Gy). Proton irradiation led to similar diverging viability curves between UPS vs. PLS four days after irradiation with 90% vs. 75% (4 Gy), 85% vs. 45% (8 Gy) and 80% vs. 35% (16 Gy). Photon and proton radiation displayed only minor differences in cell-killing properties within each cell culture (UPS and PLS). The cell-killing effect of radiation sustained at eight days after irradiation in both cell cultures. Pronounced differences in radiosensitivity are evident among UPS and PLS 3D patient-derived sarcoma cell cultures which may reflect the clinical heterogeneity. Photon and proton radiation showed similar dose-dependent cell-killing effectiveness in both 3D cell cultures. Patient-derived 3D STS cell cultures may represent a valuable tool to enable translational studies towards individualized subtype-specific radiotherapy in patients with STS.


Aurora Kinase A as a Diagnostic and Prognostic Marker of Malignant Mesothelioma.
Malignant mesothelioma (MM) is a highly aggressive cancer with a poor prognosis. Despite the use of several well-known markers, the diagnosis of MM is still challenging in some cases. we applied bioinformatics to identify key genes and screen for diagnostic and prognostic markers of MM. The expression profiles of GSE2549 and GSE112154 microarray datasets from the Gene Expression Omnibus database contained 87 cases of MM tissue and 8 cases of normal mesothelial tissue in total. The GEO2R tool was used to detect differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs were performed using DAVID Bioinformatics Resources. The DEGs protein-protein interaction networks were constructed from the STRING database. Cytoscape was used to identify significant modules and hub genes. The GEPIA database was used to explore relationships between hub genes and prognosis of MM. Immunohistochemistry was used to analyze protein expression in tissue microarrays with 47 Chinese MM tissues. Statistical analyses diagnostic and prognostic values. 346 DEGs were identified: 111 genes upregulated, and 235 downregulated. GO analysis showed that the primary biological processes of these DEGs were cell adhesion, leukocyte migration, and angiogenesis. The main cellular components included the extracellular space, extracellular exosome, and extracellular region. The molecular functions were integrin binding, heparin binding, and calcium ion binding. KEGG pathway analysis showed that DEGs are primarily involved in PPAR signaling pathway, extracellular matrix-receptor interactions, and regulation of lipolysis in adipocytes. Survival analysis showed that seven genes-AURKA, GAPDH, TOP2A, PPARG, SCD, FABP4, and CEBPA-may be potential prognostic markers for MM. Immunohistochemical studies showed that Aurora kinase A (AURKA gene encode, Aurora-A) and GAPDH were highly expressed in MM tissue in comparison with normal mesothelial tissue. Kaplan-Meier analysis confirmed a correlation between Aurora-A protein expression and overall survival but did not confirm a correlation with GAPDH. The receiver operating characteristic curves of Aurora-A protein expression suggested acceptable accuracy (AUC = 0.827; 95% CI [0.6686 to 0.9535]; p = 0.04). The sensitivity and specificity of Aurora-A were 83.33% and 77.78%, respectively. Aurora-A could be an optimal diagnostic biomarker and a potential prognostic marker for MM.


Short-Term Outcomes of Secondary Liver Surgery for Initially Unresectable Colorectal Liver Metastases Following Modern Induction Systemic Therapy in the Dutch CAIRO5 Trial.
To present short-term outcomes of liver surgery in patients with initially unresectable colorectal liver metastases (CRLM) downsized by chemotherapy plus targeted agents. The increase of complex hepatic resections of CRLM, technical innovations pushing boundaries of respectability, and use of intensified induction systemic regimens warrant for safety data in a homogeneous multicenter prospective cohort. Patients with initially unresectable CRLM, who underwent complete resection after induction systemic regimens with doublet or triplet chemotherapy, both plus targeted therapy, were selected from the ongoing phase III CAIRO5 study (NCT02162563). Short-term outcomes and risk factors for severe postoperative morbidity (Clavien Dindo grade ≥ 3) were analyzed using logistic regression analysis. A total of 173 patients underwent resection of CRLM after induction systemic therapy. The median number of metastases was 9 and 161 (93%) patients had bilobar disease. Thirty-six (20.8%) 2-stage resections and 88 (51%) major resections (>3 liver segments) were performed. Severe postoperative morbidity and 90-day mortality was 15.6% and 2.9%, respectively. After multivariable analysis, blood transfusion (odds ratio [OR] 2.9 [95% confidence interval (CI) 1.1-6.4], P = 0.03), major resection (OR 2.9 [95% CI 1.1-7.5], P = 0.03), and triplet chemotherapy (OR 2.6 [95% CI 1.1-7.5], P = 0.03) were independently correlated with severe postoperative complications. No association was found between number of cycles of systemic therapy and severe complications (r = -0.038, P = 0.31). In patients with initially unresectable CRLM undergoing modern induction systemic therapy and extensive liver surgery, severe postoperative morbidity and 90-day mortality were 15.6% and 2.7%, respectively. Triplet chemotherapy, blood transfusion, and major resections were associated with severe postoperative morbidity.


Inactivated rotavirus vaccines: a priority for accelerated vaccine development.
Live oral rotavirus vaccines have proven to be generally safe and effective to prevent severe dehydrating diarrhea among children in high and some middle income countries. However, concerns linger about rare but severe adverse events, such as intussusception and their efficacy against the full range of rotavirus serotypes. More importantly, live oral vaccines have been less immunogenic and results of trials to assess their efficacy in poor children of both Africa and Asia will not be available for 2-3 years. This review describes the rationale for developing an inactivated rotavirus vaccine (IRV) as an alternative approach should live oral vaccines not work well in these challenging populations. Studies have demonstrated the protective role of serum antibody in animals and children and the robust serum antibody response and protection against rotavirus infection in animal models following parenteral immunization with IRV. Four years after licensing the first new generation of rotavirus vaccine, we still remain several years away from knowing how well they work in the target populations. Research to develop alternative approaches should be fostered as an insurance policy to protect against suboptimal efficacy or unanticipated adverse events that could hinder global immunization and protection of all children.


Customization of WHO Under-five Growth Standards for an Appropriate Quantification of Public Health Burden of Growth Faltering in India.
To examine the accuracy of World Health Organization (WHO) growth standard in under-5 year Indian children, and identify a method to contextualize the WHO standard for India. Data of Healthy children, defined by WHO selection criteria, extracted from nationally representative Indian surveys (National Family Health Surveys, NFHS-3, NFHS-4, NFHS-5 and Comprehensive National Nutrition Survey, CNNS). Height for age z score (HAZ) and weight for age z score (WAZ) and weight for height z score (WHZ) distributions in healthy sample were compared against the standard normal. If deviant, age-specific correction factors for z scores were estimated by hierarchical linear mixed effects mean and variance polynomial models. A new term, excess mean risk of growth faltering (EMRGF), was introduced to describe growth faltering. Measure of deviation of HAZ, WAZ and WHZ from standard normal distribution. Correction of WHO growth standards for India leading to accurate prevalence of stunting, underweight and wasting in Indian children using NFHS-5 data. Data on 10,384 healthy under-5 year children were extracted, of which 5377 were boys. Across surveys and metrics, the mean z scores were significantly lower than zero (-0.52 to -0.79). HAZ and WHZ variability (1.16, 1.07) were significantly higher than 1. Derived age-specific corrections reduced the NFHS-5 prevalence of growth faltering by 50%. The national EMRGF (after applying the age-specific correction) for height for age was 15.5% (95%CI:15.3-15.8), and weight for age was 15.0% (95%CI:14.8-15.3), respectively, in NFHS-5. The WHO growth standards need contextual customization for accurate estimation of the burden of growth faltering in under-5 year children in India. When corrected, the burden of growth faltering is lower, by half or more, in all the three indices.


Survival of Mycobacterium bovis in defined environmental conditions.
The survival of Mycobacterium bovis was investigated following artificial inoculation in dry and moist soils and bovine faeces held under various environmental conditions. M. bovis survived for 4 weeks in non-sterile dry and moist soils held under 80% shade, in darkness and in the laboratory. It was also isolated from sterile moist soil kept in the shade and in darkness. Re-isolation of M. bovis was not made at 4 weeks from any of the substrates exposed to sunlight nor from faeces held under any condition. M. bovis was not re-isolated from any substrate at 8 weeks or up to 32 weeks after inoculation.


Construction of the novel conformationally-restricted peptide library for screening of peptides that control the interaction between nucleobases.
A unique conformationally-restricted peptide library was constructed using a loop structure as a structural scaffold. This library was used for the screening of the amino acid sequences that control the interaction between nucleobase triplets. The peptides have PNAs at the C-terminus as the recognition site and the random amino acid sequence at the N-terminus as the effector for the interaction between PNA and its complementary DNA triplets. From the peptide libraries constructed by the positional scanning method, the sequences that affect the interaction between PNA and complementary DNA were selected. The difference in the characteristic results by using A-T and G-C pairs was presented. This study would also give us some useful information about interaction between peptides and nucleic acids, such as relevances between these biomolecules in a prebiotic era.


Multicellularity enriches the entrainment of Arabidopsis circadian clock.
The phase response curve (PRC) of the circadian clock provides one of the most significant indices for anticipating entrainment of outer cycles, despite the difficulty of making precise PRC determinations in experiments. We characterized the PRC of the Arabidopsisthaliana circadian clock on the basis of its phase-locking property to variable periodic pulse perturbations. Experiments revealed that the PRC changed remarkably from continuous to discontinuous fashion, depending on the oscillation amplitude. Our hypothesis of amplitude-dependent adaptability to outer cycles was successfully clarified by elucidation of this transition of PRC as a change in the collective response of the circadian oscillator network. These findings provide an essential criterion against which to evaluate the precision of PRC measurement and an advanced understanding of the adaptability of plant circadian systems to environmental conditions.


A topological model for chromatin transcription and a role for nucleosome linkers.
There is a good deal of evidence that transcribing RNA polymerase may translocate across nucleosomes without their displacement and (or) rearrangement. A topological model for RNA chain elongation on a nucleosome is considered here. A new mechanism of RNA polymerase translocation is suggested in order to avoid the steric hindrances inherent in the model. It is shown that a transcribed nucleoprotein fiber should be interrupted by protein-free DNA stretches (nucleosome linkers) to allow release of nascent RNA. Possible verifications and consequences of the model are discussed.


In vivo occupation of mouse brain opioid receptors by endogenous enkephalins: blockade of enkephalin degrading enzymes by RB 101 inhibits [3H]diprenorphine binding.
With the aim of possibly studying the local activity of brain enkephalinergic pathways by autoradiography and positron emission tomography, preliminary competition experiments of [3H]diprenorphine binding in mouse brain were carried out after i.v. administration of the first systemically-active mixed inhibitor of enkephalin degrading enzymes RB 101 (N(R,S)-2-benzyl-3[(S)-(2-amino-4-methylthiobutyldithio]-1-oxoprop yl]- L-phenylalanine benzyl ester). Although devoid of affinity for the opioid binding sites, RB 101 inhibited the [3H]diprenorphine binding to the opioid receptors in a dose-dependent manner. This effect, very likely due to an RB 101-induced increase in extracellular levels of enkephalins, reached a plateau at a dose of 10 mg/kg, where almost 30% displacement was observed. Intravenous administration of either 5 or 20 mg/kg of RB 101 in mice submitted to warm-swim stress led to an additional [3H]diprenorphine displacement, which reached 45% compared to unstressed controls. This ceiling effect could account for the reported minimal morphine-like side effects induced by mixed inhibitors. A large increase in endogenous enkephalin levels induced by RB 101, associated or not with stress, was also indirectly demonstrated by the analgesic responses elicited by i.v. injection of the mixed inhibitor. This effect was blocked by naloxone but not by the delta antagonist naltrindole (NTI), supporting a preferential implication of mu receptors in supraspinal analgesia. Taken together, these results suggest that RB 101 could be used to determine the precise in vivo localization of enkephalinergic pathways recruited by various stimuli.


[Frequency of altered male factor in an infertility clinic].
Infertility is the incapacity of a couple to conceive after a year of regular sexual life without using a method for family planning. The infertility state is dependent on the female factor as well as masculine factor; an altered masculine factor is designated when any cause or causes of infertility reside in the male. The masculine factor as a cause of infertility is present in 40 to 50% of cases hence the importance of an integral evaluation of male alterations and its fertility. The World Health Organization (WHO) has proposed to classify the masculine infertility based on semen features. To determine the frequency of the masculine factor altered in association to diagnosed abnormalities, according to the number of affected seminal indexes based on seminograms performed in infertile patients seen at the department of Human Reproductive Medicine, Hospital Juárez de México. An observational, descriptive, transverse, retrospective study was performed. the seminograms practiced were reviewed from 571 clinical files of couples that the consultation for infertility from January 1993 to February 2001. Collection and analysis of semen samples was based on standards settled by WHO. Of 571 seminogram informs, 371 (65%) showed alterations in the seminal indexes, the stocking of age of this group was of 31.89 years +/- SD 6.3 years. Our findings were: azoospermia in 89 (23.98%), astenonecrozoospermia in 44 (11.85%), hypospermia in 43 (11.59%), astenozoospermia in 33 (8.89%), oligoastenozoospermia in 31 (8.35%) hyponecrozoospermia in 30 (8.08%), oligozoospermia in 25 (6.73%), others in 21 (5.7%), necrozoospermia in 19 (5.12%), hypoastenozoospermia in 18 (4.85%), cryptozoospermia in 11 (2.97%), and hypooligoastenozoospermia in 7 (1.88%). In 62.6% of seminograms practiced there was an isolated alteration, in 34.4% two alterations and in the remaining 3% more than two alterations. We found masculine factor altered in 65% of couples who were requiring consultation for infertility. The three main alterations of seminal indexes were azoospermia, astenonecrozoospermia and hypospermia.


Giant compressive emphysema: a rare complication of COVID-19.
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a new ribonucleic acid (RNA) beta-coronavirus, responsible for a worldwide pandemic. Very few cases of SARS-COV-2-related emphysema have been described, except among patients with chronic obstructive pulmonary disease. The thoracic CT scan is the key examination for the diagnosis and allows to evaluate the severity of the pulmonary involvement. The prognosis of the patient with giant emphysema (GE) on coronavirus disease 2019 (COVID-19) in critical or severe form remains poor. We report an original case of COVID-19 pneumonia, critical form, complicated by a giant compressive left emphysema of 22.4 cm in a young subject without respiratory comorbidities. A 34-year-old man was hospitalized for left laterothoracic pain. He had no prior medical history. The physical examination revealed tympany on percussion of the left lung. The CT scan confirmed COVID-19 pneumonia with 95% lung involvement. Also, the presence of a voluminous left sub pleural emphysema of 22.4 cm with compression of the ipsilateral pulmonary parenchyma as well as the mediastinal structures towards the right side. The diagnosis COVID-19 pneumonia, critical form, complicated by a compressive left giant emphysema was made. He was put on oxygen, a dual antibiotic therapy, a corticotherapy, and curative doses of enoxaparin. A thoracic drainage surgery was performed at 24th day of hospitalization, which confirmed the giant emphysema. The patient remains on long-term oxygen therapy. The COVID-19 has polymorphic manifestations, pneumonia is the most important one. There are relatively few reports associating COVID-19 and emphysema; furthermore, reports associating COVID-19 and giant emphysema are extremely scarce. CT scans can confirm the diagnosis and differentiate it from a pneumothorax. The pulmonary prognosis of the association of COVID-19 in its severe or critical form with giant emphysema remains poor.


Nutrition project in a remote Australian aboriginal community.
Much of the ill health of Australian indigenous populations can be attributed to diet-related diseases. This community nutrition project is part of a wider renal screening and prevention program based in the Umoona aboriginal community in Coober Pedy in South Australia's far north. The nutrition project facilitates the capacity of the Umoona aboriginal community to identify and redress nutrition-related issues considered important in improving their overall health status. Project nutritionists developed and implemented a specialized nutrition training program with the Umoona aboriginal health workers. The nutritionists were responsive to requests from community groups to provide nutrition expertise and support in program development. Individual nutrition counseling for adults and children taking part in renal health screening was also provided. The aboriginal health workers reported increased nutritional knowledge and confidence in addressing nutrition-related issues within the community after nutrition training. Individual consultations and partnerships formed with community groups have increased awareness and prompted action to address the importance of nutrition in renal disease and overall health in the Umoona community.


Hypersensitivity to larvae of chironomids (non-biting midges). Cross-sensitization with crustaceans.
In 2,368 consecutive adult patients with asthma and/or rhinitis the incidence of positive skin prick test (SPT) with a chironomid extract (CHIR) (produced from "red feather mosquito larvae" used as fish food) was 14% (26% in atopics and 4% in non-atopics). RAST with chironomid was positive in 4% of 110 consecutive sera (8% in atopic sera). Significant correlations were found between RAST and SPT results with chironomid and between SPT results with CHIR and with various crustaceans. Correlations were also found reciprocally among SPT results with different crustaceans and between some crustaceans and moluscs (clam and oyster) as well as among RAST results with chironomid, shrimp and crab. Inhibition experiments showed that chironomid extracts inhibited RAST with shrimp, and vice versa. It is concluded that Chironomidae might be allergens of clinical importance in asthma and rhinitis in Sweden, that cross-allergy exists between chironomids and shrimp and that cross-allergy also might occur among chironomids, crustaceans and molluscs.


Tyrosinase-based biosensor for determination of bisphenol A in a flow-batch system.
A tyrosinase-based amperometric biosensor is proposed for determination of bisphenol A (BPA) in a flow-batch monosegmented sequential injection system. The enzyme was entrapped in a sol-gel TiO2 matrix modified with multi-walled carbon nanotubes (MWCNTs), polycationic polymer poly(diallyldimethylammonium chloride), (PDDA) and Nafion. Morphology of TYR/TiO2/MWCNTs/PDDA/Nafion matrix composite was studied via scanning electron microscopy (SEM). Electrochemical behavior of the developed biosensor towards bisphenol A was examined and analytical characteristics were assessed with respect to linear range, biosensor sensitivity, limit of detection, long term stability, repeatability and reproducibility. Linear range of biosensor response was found between 0.28 and 45.05 µM with high sensitivity of 3263 µA mM(-1) cm(-2) and detection limit 0.066 µM. The approach was successfully employed for determination of BPA in natural samples.


Fluorescence quenching-based assays for hydrolyzing enzymes. Application of time-resolved fluorometry in assays for caspase, helicase, and phosphatase.
We have developed assay technologies to measure hydrolyzing enzymes based on homogeneous time-resolved fluorescence quenching (TruPoint). High sensitivity was obtained using fluorescent europium chelates as labels, internally quenched by suitable quenchers and released upon enzymatic reaction. This approach allows robust and sensitive monitoring of low enzyme activities. The assay technology and the choice of donor-acceptor pairs were evaluated in three different enzymatic assays, a protease related to apoptosis, helicase involved in DNA unwinding, and phosphatase having an important role in cellular signaling cascades. All the assays produced an increasing signal, were sensitive, and had a good dynamic range. There were significant differences in optimized quenchers for each of the assays depending on the size, flexibility, and rigidity of the substrates. Also, clear differences in the energy-transfer reactions, their requirements for spectral overlapping, ionic interactions, and energy-transfer distances were found. Each of the enzymatic assays was briefly tested in a high-throughput screening environment by analyzing signal dynamics and statistical relevance as Z' factors.


Iontophoretic administration of S(+)-ketamine in patients with intractable central pain: a placebo-controlled trial.
The efficacy of 50 and 75 mg S(+)-ketamine administered daily by an iontophoresis-assisted transdermal drug delivery system was tested against placebo in a randomized, double-blind design in 33 patients with central neuropathic pain. At baseline and 1 week after the start of treatment subjects were evaluated with standard measures of efficacy: pain intensity measured by visual analog scale (VAS), health status (Pain Disability Index and EQ-5D) and quality of life (SF-36). Safety assessment included incidence and intensity of adverse events. No significant differences in pain scores (VAS) were observed between the ketamine groups and placebo during the course of the trial. Corrected for baseline levels, daily 50 mg S(+)-ketamine did not improve patient's health status or quality of life compared with placebo treatment. However, daily 75 mg S(+)-ketamine showed significant improvements on the Pain Disability Index, on the EQ-5D, and on the SF-36 except for the role-physical functioning and general health perception. Iontophoretic administration of S(+)-ketamine was well tolerated with a low incidence of adverse events (mild and transient in nature, resolving spontaneously). Iontophoretic administration of S(+)-ketamine was not more effective than placebo treatment in reducing pain scores in patients with severe central neuropathic pain. However, iontophoretic administration of 75 mg S(+)-ketamine improved the health status and the quality of life in these patients.


Effectiveness and safety of switching to adalimumab biosimilar ABP 501 in Crohn's disease.
We read with great interest the article "Effectiveness and safety of adalimumab biosimilar ABP 501 in Crohn's disease: an observational study" by Ribaldone et al., which was recently published in your journal. The authors report the first real-life study of the adalimumab biosimilar ABP 501 in Crohn's disease (CD). The study investigated the short-term effectiveness and safety of ABP 501 in 87 patients with CD, 25 patients naïve to adalimumab and 62 switched from the adalimumab originator. A meaningful proportion of CD patients treated with ABP 501 showed clinical benefit with a satisfactory safety profile until the end of follow-up.


Radiation dose effect of DNA repair-related gene expression in mouse white blood cells.
The aim of this study was to screen molecular biomarkers for biodosimetry from DNA repair-related gene expression profiles. Mice were subjected to whole-body exposure with 60Co gamma rays with a dose range of 0-8 Gy at a dose rate of 0.80 Gy/min. RNA was extracted from the peripheral blood of irradiated mice at 4, 8, 12, 24 and 48hrs post-irradiation. The mRNA transcriptional changes of 11 genes related to DNA damage and repair were detected using real-time quantitative polymerase chain reaction (RT-PCR). Of the 11 genes examined, CDKN1A (cyclin-dependent kinase inhibitor 1A or p21, Cip1) and ATM (ataxia telangiectasia mutated) expression levels were found to be heavily up- and down-regulated, respectively, with exposure dose increasing at different post-irradiation times. RAD50 (RAD50 homolog), PLK3 (polo-like kinase 3), GADD45A (growth arrest and DNA damage-inducible, alpha), DDB2 (damage-specific DNA-binding protein 2), BBC3 (BCL2-binding component 3) and IER5 (immediate early response 5) gene expression levels were found to undergo significant oscillating changes over a broad dose range of 2-8 Gy at post-exposure time points observed. Three of the genes were found not to change within the observed exposure dose and post-radiation time ranges. The results of this study add to the biodosimetry with biomarker data pool and will be helpful for constructing appropriate gene expression biomarker systems to evaluate radiation exposure doses.


Transdiagnostic versus disorder-specific and clinician-guided versus self-guided internet-delivered treatment for Social Anxiety Disorder and comorbid disorders: A randomized controlled trial.
Disorder-specific (DS-CBT) and transdiagnostic (TD-CBT) cognitive behaviour therapy have both been used to treat social anxiety disorder (SAD). This study compared internet-delivered DS-CBT and TD-CBT for SAD across clinician-guided (CG-CBT) and self-guided (SG-CBT) formats. Participants with SAD (n=233) were randomly allocated to receive internet-delivered TD-CBT or DS-CBT and CG-CBT or SG-CBT. Large reductions in symptoms of SAD (Cohen's d≥1.01; avg. reduction≥30%) and moderate-to-large reductions in symptoms of comorbid depression (Cohen's d≥1.25; avg. reduction≥39%), generalised anxiety disorder (Cohen's d≥0.86; avg. reduction≥36%) and panic disorder (Cohen's d≥0.53; avg. reduction≥25%) were found immediately post-treatment and were maintained or further improved to 24-month follow-up. No marked differences were observed between TD-CBT and DS-CBT or CG-CBT and SG-CBT highlighting the potential of each for the treatment of SAD and comorbid disorders.


The nuclear retention of transcription factor FOXO3a correlates with a DNA damage response and increased glutamine synthetase expression by astrocytes suggesting a neuroprotective role in the ageing brain.
The accumulation of reactive oxygen species leading to oxidative damage and cell death plays an important role in a number of neurodegenerative disorders. FOXO3a, the main isoform of FOXO transcription factors, mediates the cellular response to oxidative stress by regulating the expression of genes involved in DNA repair and glutamine metabolism, including glutamine synthetase (GS). Immunohistochemical investigation of the population-based neuropathology cohort of the Medical Research Council's Cognitive Function and Ageing Study (MRC CFAS) demonstrates that nuclear retention of FOXO3a significantly correlates with a DNA damage response and with GS expression by astrocytes. Furthermore, we show that GS expression correlates with increasing Alzheimer-type pathology in this ageing cohort. Our findings suggest that in response to oxidative stress, the nuclear retention of FOXO3a in astrocytes upregulates expression of GS as a neuroprotective mechanism. However, the activity of GS may be compromised by increasing levels of oxidative stress in the ageing brain resulting in dysfunctional enzyme activity, neuronal excitotoxic damage and cognitive impairment.


Population trends of nonmetropolitan cities and villages in subregions of the United States.
This is a comparison of the 1950-1970 trends in population size of U.S. nonmetropolitan cities and villages among 26 homogeneous subregions. There are wide variations in the proportion of the nonmetropolitan population in incorporated places, and, though this proportion generally increased over the 1950-1970 period, decentralizing tendencies also are evident. There was most often a decline in the differential between the growth rate of incorporated places and of open country over the two decades. The positive association between initial size of place and growth, present in half of the subregions in the 1950s and indicative of population centralization, was found only in the Corn Belt, Great Plains, and Rocky Mountain subregions in the 1960s. There were regionally distinctive differences in all variables considered; most notably, the percent of places growing ranged 50 percentage points over the 26 subregions. The extent of subregional variation revealed by this analysis indicates how differences in physiography, climate, history, and economy continue to be reflected in settlement trends which are obscured when larger regional groupings are used.


Inference to shape parameter of Nash model based on dynamic transport properties of channel networks.
This study investigates the relations between the shape of hydrologic responses and the dynamic transport properties of channel networks within the framework of random walks on fractal networks, focusing on the shape parameter of Nash model. To this end, we evaluate the static fractal structures and the dynamic transport properties of various channel networks and, then, validate Liu's conjecture (1992) for the shape of hydrologic responses. In the context of random walks on fractal networks, the fractal dimensions of channel networks can directly connect the static structure to the dynamic transport properties of channel networks through Horton's law of drainage composition. It is observed that the peak coordinates of hydrologic responses would have a more intimate relation to the connectivity of channel networks than the conductivity of those. The characteristic times of hydrologic responses also tend to be related to the connectivity of channel networks. Thereby, the shape of hydrologic responses would be expected directly affected by the fractal dimension of channel networks in terms of their static structure, while interpreted a combined result of the conductivity and the connectivity of channel networks in terms of their dynamic transport properties. So, the runoff hydrographs of a river basin could be considered shaped by the fractal dimensions of its channel networks following the linear hydrologic system theory.


Micro-CT versus synchrotron radiation phase contrast imaging of human cochlea.
High-resolution images of the cochlea are used to develop atlases to extract anatomical features from low-resolution clinical computed tomography (CT) images. We compare visualization and contrast of conventional absorption-based micro-CT to synchrotron radiation phase contrast imaging (SR-PCI) images of whole unstained, nondecalcified human cochleae. Three cadaveric cochleae were imaged using SR-PCI and micro-CT. Images were visually compared and contrast-to-noise ratios (CNRs) were computed from n = 27 regions-of-interest (enclosing soft tissue) for quantitative comparisons. Three-dimensional (3D) models of cochlear internal structures were constructed from SR-PCI images using a semiautomatic segmentation method. SR-PCI images provided superior visualization of soft tissue microstructures over conventional micro-CT images. CNR improved from 7.5 ± 2.5 in micro-CT images to 18.0 ± 4.3 in SR-PCI images (p < 0.0001). The semiautomatic segmentations yielded accurate reconstructions of 3D models of the intracochlear anatomy. The improved visualization, contrast and modelling achieved using SR-PCI images are very promising for developing atlas-based segmentation methods for postoperative evaluation of cochlear implant surgery.


A new chemical procedure for selective sequential separation of serum lipoproteins.
A new chemical procedure for selective sequential separation of serum lipoproteins is described. Low density lipoproteins (LDL) were precipitated by polyvinylsulfate and the precipitates were redissolved in NaCl 0.45 mol/l. Very low density lipoproteins (VLDL) were precipitated from LDL-free supernatants by PEG-6000 at 100 g/l final concentration, pH 10, and the precipitates were redissolved in NaCl 0.15 mol/l. For the precipitation of high density lipoproteins (HDL), apolipoprotein B-free supernatants were treated by PEG-6000 at 266 g/l final concentration and the precipitates were redissolved in NaCl 0.15 mol/l. The procedure was effective up to a serum triglyceride concentration of 4.0 mmol/l as well as in serum samples without chylomicrons or remnants. The determination of cholesterol and triglyceride contents in separated lipoproteins allows the study of their chemical composition in normo- and moderately hypertriglyceridemic serum samples.


Thermal decomposition studies of riot control agent ω-chloroacetophenone (CN) by pyrolysis-gas chromatography-mass spectrometry.
Pyrolysis-GC/MS system with on-line micro-furnace was used to make rapid evaluation of ω-chloroacetophenone (CN) decomposition under inert thermal atmospheres. The volatile products evolved during pyrolysis were analyzed by thermal gravimetric analysis (TGA) and Py-GC/MS to obtain specific thermogram and pyrogram. Thermal gravimetric analysis results showed that CN undergoes sublimation at 167°C prior to its decomposition at 229°C. Totally 45 degradation products were identified based on mass spectral library matching with the aid of correlation of the values of boiling point (bp) and retention time. A large number of mono-aromatics and polycyclic aromatic hydrocarbons were observed beyond 600°C. In addition to the aromatic hydrocarbons, oxygenated compounds were also observed during the pyrolysis process. The pyrolysis mechanism was proposed based on the determined pyrolysates and their relative abundance with temperature. The investigation results can provide significant information for understanding the thermal behavior of CN and evaluation of the potential influence of the pyrolysates to living being and the environment.


A Two-Phase Algorithm for Differentially Private Frequent Subgraph Mining.
Mining frequent subgraphs from a collection of input graphs is an important task for exploratory data analysis on graph data. However, if the input graphs contain sensitive information, releasing discovered frequent subgraphs may pose considerable threats to individual privacy. In this paper, we study the problem of frequent subgraph mining (FSM) under the rigorous differential privacy model. We present a two-phase differentially private FSM algorithm, which is referred to as DFG. In DFG, frequent subgraphs are privately identified in the first phase, and the noisy support of each identified frequent subgraph is calculated in the second phase. In particular, to privately identity frequent subgraphs, we propose a frequent subgraph identification approach, which can improve the accuracy of discovered frequent subgraphs through candidate pruning. Moreover, to compute the noisy support of each identified frequent subgraph, we devise a lattice-based noisy support computation approach, which leverages the inclusion relations between the discovered frequent subgraphs to improve the accuracy of the noisy supports. Through formal privacy analysis, we prove that DFG satisfies ϵ-differential privacy. Extensive experimental results on real datasets show that DFG can privately find frequent subgraphs while achieving high data utility.


Melanotic Neuroectodermal Tumor of Infancy: A Systematic Review.
Melanotic neuroectodermal tumor of infancy (MNTI) is a rare tumor, usually diagnosed within the first year of age, with a predilection for the maxilla. Although the tumor is usually benign, its rapidly growing nature and ability to cause major deformities in surrounding structures necessitate early diagnosis and intervention. It is important that medical and dental specialists are prepared to make the diagnosis and proceed with appropriate intervention. The authors performed a systematic review of the 472 reported cases from 1918 through 2013 and provided a comprehensive update on this rare entity that can have devastating effects on young patients. This investigation uncovered age at diagnosis as an important prognostic indicator, because younger age correlated with a higher recurrence rate. The authors also present a case report of a 5-month-old girl diagnosed with MNTI and review her clinical presentation and imaging and histopathologic findings.


Grit as a Predictor of Academic Success Among Associate Degree Nursing Students.
The purpose of this study was to explore whether grit is a predictor of success in associate degree nursing (ADN) programs. A question that challenges admission decision-making in nursing programs is "Who will succeed?" This question is particularly relevant in ADN programs, which often have higher attrition rates than baccalaureate programs. This longitudinal, mixed-methods study was conducted with 451 ADN students across nine programs, including interviews with seven unsuccessful students and nine successful students. Short Grit Scale scores were not found to be statistically significant as a predictor of academic success; however, themes that emerged from the interviews do align with the theory of grit. Further research is needed to explore whether recognizing the level of grit in students during admission processes would help identify students who are likely to succeed.


Inhibition of neovascularization by environmental agents.
The formation of new blood vessels, neovascularization, occurs by two unique processes: vasculogenesis, the de novo assembly of blood vessels from angioblast precursors, and angiogenesis, the formation of new capillary sprouts from preexisting vessels. There are many potential targets by which environmental pollutants may inhibit neovascularization and thus there are many possible phenotypic outcomes. Two examples of environmental pollutants that have been demonstrated to inhibit neovascularization include 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a prototypical halogenated aromatic hydrocarbon, and constituents found in environmental tobacco smoke. Studies have shown that TCDD disrupts neoangiogenesis by inhibiting the expression of angiogenic stimuli as well as by reducing the responsiveness of endothelial cells to those stimuli. Additionally, studies have shown that constituents of environmental tobacco smoke, including pyradine and pyrazine derivatives, can potently inhibit the angiogenic process of branching as well as the vasculogenic process involved in capillary plexus formation. Further, the inhibition of neovascularization by either TCDD or environmental tobacco smoke constituents is associated with reduced endothelial cell proliferation and altered expression of extracellular matrix proteins. Future research that identifies the specific angiogenic signaling pathways that are disrupted by these pollutants will improve our ability to assess their risk to human health. Finally, it is likely that many other environmental pollutants impact neovascularization; however, very few have been studied in sufficient detail. Thus, additional research also is needed to identify those environmental agents that mediate their toxicity by disrupting neovascularization.


Performance and structural comparison of hydrogels made from wheat bran arabinoxylan using enzymatic and coacervation methods as micro-and nano- encapsulation and delivery devices.
This study evaluated the structural and performance differences between arabinoglucuronoxylan micro-hydrogels that were enzymatically produced from alkaline-extracted wheat bran arabinoglucuronoxylans using recombinant α-L-arabinofuranosidase (AbfB) that selectively removes arabinose side chains, and chemically through coacervation process, as delivery devices for bioactive substances. The encapsulations of model bioactive substance, gallic acid (GA), in the hydrogels, were done either in-situ or ex-situ to identify the most effective encapsulation and delivery method. The hydrogels particle size distribution, polydispersity index, GA encapsulation efficiency, retention and release of functional GA (based on antioxidant activity) were assessed. The hydrogels formed in both coacervation and enzymatic processes had particle size ranges of 469-678 nm, which classify them as micro-hydrogels. However, the latter were monodispersed with polydispersity index (PdI) < 0.4 compared to the former with PdI > 0.7. In addition, enzymatically produced hydrogels attained higher zeta potential (-8.8 mV) and retained and released GA with higher anti-oxidant capacity (91%) than chemically formed micro-hydrogels (zeta potential = - 3.3 mV and antioxidant capacity = 80%). However, GA encapsulation efficiencies (72% in-situ and 68% ex-situ) were higher in chemically formed micro-hydrogels than enzymatically produced micro-hydrogels (59% in-situ and 52% ex-situ). The in-situ encapsulated GA experienced less initial burst during sustained release of 8 h compared to ex-situ encapsulation. Overall, enzymatic modification process and in-situ encapsulation were the most effective methods for production of arabinoglucuronoxylan micro-hydrogels delivery devices and for encapsulation of the GA, respectively, because of maintaining functional GA upon release and having the potential to customize the structural and functional properties of the micro-hydrogels.


Hidden Aspects of Valency in Immune System Regulation.
Valency can be defined as the number of discrete interactions a biomolecule can engage in. Valency can be critical for function, such as determining whether a molecule acts as a scaffold for assembling large supramolecular complexes or forms a functional dimer. Here, we highlight the importance of the role of valency in regulating immune responses, with a focus on innate immunity. We discuss some of the ways in which valency itself is regulated through transcriptional, post-transcriptional, and post-translational modifications. Finally, we propose that the valency model can be applied at the whole cell level to study differences in individual cell responses with relevance to putative therapeutic applications.


Review article: current antiviral therapy of chronic hepatitis B.
The long-term goals of therapy for chronic hepatitis B are to reduce serum HBV DNA to low or undetectable levels and ultimately reduce or prevent the development of cirrhosis and hepatocellular carcinoma. To review the current treatment of chronic hepatitis B, with a focus on diagnosis and management of resistance and active management of suboptimal responses. A systematic review of the literature, with a focus on recent guidelines, was undertaken. Among the six drugs licensed for the treatment of chronic hepatitis B in the US, the preferred agents in 2008 will include entecavir, peginterferon alfa-2a, possibly telbivudine, and tenofovir following licensure. When using an oral agent, a major focus of management is on the selection of a drug with high potency and low rate of resistance, and active on-treatment management to optimize therapy. Preventing the sequelae of antiviral drug resistance and appropriate management when resistance is initially detected are also the major focus of current management. The addition of an antiviral agent that is not cross-resistant is critical to restore suppression of viral replication. Newer agents and modified treatment strategies, especially using combination therapy, hold promise to optimize the management of patients with chronic hepatitis B by achieving the high potency and the lowest rate of resistance.


Cystic lymphoid hyperplasia: an orofacial lesion strongly associated with HIV and AIDS.
Cystic lymphoid hyperplasia (CLH) frequently affects the parotid gland in human immunodeficiency virus (HIV)-infected patients. This clinicopathological study, comprising 167 cases, aims to define the clinical-pathological parameters of CLH in order to elucidate the aetiopathogenesis. This retrospective study of 167 archival cases of CLH recorded patients' age, race and gender, and the nature, site and symptoms of CLH. A total of 109 cases were reviewed histologically and analyzed for HIV-1 p24 antigen immunopositivity using standard procedures. CLH of the parotid gland showed a male predominance, whereas submandibular gland (P = 0.27) and bilateral parotid involvement favoured females (2:1). CLH occurred at a younger mean age in females than males in the parotid gland (P = 0.0035) and in the submandibular gland (P = 0.0032). Intra-lymph nodal origin was favoured, with 76.1% of cases occurring within entrapped salivary gland remnants. P24 staining revealed ~90% sensitivity in HIV-associated CLH. CLH should be used preferentially to describe parotid enlargement in HIV-infected patients. This study strongly supports the hypothesis that CLH develops following ductal ectasia of entrapped salivary gland inclusions arising within lymph nodes. CLH should be classified as an orofacial lesion associated strongly with HIV and AIDS.


Transsexual surgery in the genetic female.
The increasing acceptance of the transsexual patient by society as well as a willingness of insurance companies to compensate for associated surgical procedures will result in an increase in patients presenting for sex reassignment. Data from gender identity centers suggest that the multidisciplinary approach leads to the best therapeutic results. Significant advances in phalloplasty techniques are yielding genitalia with more normal function and appearance.


The decision to feed by a scavenger in relation to the risks of predation and starvation.
Recent theoretical models have considered how nutritional status and predation risk affect the decision by an individual to forage. We consider the feeding behaviour of a scavenger under risk of predation. The intertidal gastropod Nassarius dorsatus Röding was used to test the following hypotheses: (1) a damaged conspecific should be a less preferred meal than a damaged predator or another species; (2) a scavenger should be able to discriminate between a damaged conspecific in the presence and one in the absence of its predator, preferring the latter; and (3) the decision by a scavenger to feed should reflect a trade-off between nutritional status and the above preferences. Results from the laboratory and field were consistent with predictions. Two hypotheses are suggested from the work: scavengers may generally be less willing to feed on carcases of conspecifics than on those of other species, and intertidal scavengers may commonly face a relative or absolute shortage of food.


Impact of the world hand hygiene and global handwashing days on public awareness between 2016 and 2020: Google trends analysis.
Scientific evidence suggest that hand hygiene as one of the most effective measures to control infection. To promote good hand hygiene practices, the World Health Organization introduced May 5 as World Hand Hygiene Day (WHHD), and international stakeholders established Global Handwashing Day (GHD) on October 15. However, its contributions to raising public awareness of hand hygiene is unclear. This study evaluates the impact of the WHHD and GHD on the public awareness of hand hygiene in Japan, the United Kingdom, the United States, and worldwide from 2016 to 2020, using the relative search volume of "Hand hygiene" in Google Trends as a surrogate. To identify a statistically significant timepoint of a trend change, we performed Joinpoint regression analysis. Upticks of the relative search volumes as well as joinpoints were noted worldwide around the WHHD and GHD from 2016 to 2019, but no joinpoints were identified around the WHHD and GHD in 2020. No such changes were observed in Japan, the United Kingdom, and the United States during these periods. While the WHHD was originally established to raise awareness of hand hygiene in healthcare facilities, our result suggests that the WHHD and GHD may not have effectively disseminated the importance of hand hygiene to the general public at a country level. Additional policy measures to advocate hand hygiene to the public are necessary to communicate its benefits.


Antiseptic quaternary ammonium compound tolerance by gram-negative bacteria can be rapidly detected using an impermeant fluorescent dye-based assay.
Biocides such as quaternary ammonium compounds (QACs) are potentially important contributors towards bacterial antimicrobial resistance development, however, their contributions are unclear due to a lack of internationally recognized biocide testing standards. Methods to detect QAC tolerance are limited to laborious traditional antimicrobial susceptibility testing (AST) methods. Here, we developed a rapid fluorescent dye-based membrane impermeant assay (RFDMIA) to discriminate QAC susceptibility among Gram-negative Enterobacterales and Pseudomonadales species. RFDMIA uses a membrane impermeant fluorescent dye, propidium iodide, in a 30-min 96-well fluorescent microplate-based assay where cell suspensions are exposed to increasing QAC concentrations. Our results demonstrate that RFDMIA can discriminate between QAC-susceptible and QAC-adapted Escherichia coli tolerant phenotypes and predict benzalkonium and cetrimide tolerance in all species tested except for intrinsically fluorescent Pseudomonas aeruginosa. RFDMIA identified a close association to minimum inhibitory concentration values determined by broth microdilution AST and increasing fluorescent dye emission values. RFDMIA emission values and scanning electron microscopy results also suggest that CET-adapted E. coli isolates have a CET dependence, where cells require sub-inhibitory CET concentrations to maintain bacilliform cell integrity. Overall, this study generates a new, rapid, sensitive fluorescent assay capable of detecting QAC-susceptible Gram-negative bacteria phenotypes and cell membrane perturbations.


Locking versus nonlocking T-plates for dorsal and volar fixation of dorsally comminuted distal radius fractures: a biomechanical study.
To see if locking volar plates approach the strength of dorsal plates on a dorsally comminuted distal radius fracture model. Volar plates have been associated with fewer tendon complications than dorsal plates but are thought to have mechanical disadvantages in dorsally comminuted distal radius fractures. Locking plates may increase construct strength and stiffness. This study compares dorsal and volar locking and nonlocking plates in a dorsally comminuted distal radius fracture model. Axial loading was used to test 14 pairs of embalmed radii after an osteotomy simulating dorsal comminution and plating in 1 of 4 configurations: a standard nonlocking 3.5-mm compression T-plate or a 3.5-mm locking compression T-plate applied either dorsally or volarly. Failure was defined as the point of initial load reduction caused by bone breakage or substantial plate bending. No significant differences in stiffness or failure strength were found between volar locked and nonlocked constructs. Although not significant, the stiffness of dorsal locked constructs was 51% greater than that of the nonlocked constructs. Locked or nonlocked dorsal constructs were more than 2 times stiffer than volar constructs. The failure strength of dorsal constructs was 53% higher than that of volar constructs. Failure for both volar locked and nonlocked constructs occurred by plate bending through the unfilled hole at the osteotomy site. Failure for both dorsal locked and nonlocked constructs occurred by bone breakage. Locking plates failed to increase the stiffness or strength of dorsally comminuted distal radius fractures compared with nonlocking plates. Failure strength and stiffness are greater for locked or nonlocked dorsal constructs than for either locked or nonlocked volar constructs. Whether the lower stiffness and failure strength are of clinical significance is unknown. The unfilled hole at the site of comminution or osteotomy is potentially a site of weakness in both volar locked and nonlocked plates.


Impaired median nerve mobility in patients with carpal tunnel syndrome: a systematic review and meta-analysis.
This systematic review and meta-analysis investigated the mobility of the median nerve (MN) in carpal tunnel syndrome (CTS) patients compared to healthy people. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline was followed and the electronic databases including PubMed, Scopus, EMBASE, and Cochrane Library were searched up to April 2022. All published observational studies comparing the excursion of MN between participants with and without CTS were included. The quality of research was assessed by the Newcastle-Ottawa Scale tool. The primary outcome was the excursion of the MN under dynamic examination, representing nerve mobility quantified by the standardized mean difference (SMD) for random effect meta-analysis. Fourteen studies were included in the qualitative review, and twelve entered the meta-analysis involving a total of 375 CTS patients and 296 healthy controls. The forest plot revealed that the mobility of the MN significantly decreased in the CTS group compared to the non-CTS control (SMD = -1.47, 95% CI: -1.91, -1.03, p < 0.001, heterogeneity 82%). In subgroup analysis, both transverse and longitudinal methods for nerve excursion showed less nerve mobility in CTS than in non-CTS. This meta-analysis showed that the patients with CTS exhibited less mobility of the MN than those without CTS, suggesting MN mobility as a potential CTS marker. • The patients with CTS revealed less mobility of the median nerve than those without CTS. • The mobility of the median nerve could be regarded as a potential CTS marker.