Clinicopathological significance of LAT1 and ASCT2 in patients with surgically resected esophageal squamous cell carcinoma.
Amino acid transporters are highly expressed in various human cancers. L-type amino acid transporter 1 (LAT1) and system alanine-serine-cysteine amino acid transporter-2 (ASCT2) play a crucial role in tumor progression and survival. However, the clinicopathological significance of these transporters in patients with esophageal squamous cell carcinoma (ESCC) remains unclear. One hundred and fifty-seven patients with surgically resected ESCC were evaluated. Immunohistochemical analysis was performed for LAT1, ASCT2, CD98, Ki-67, and micro-vessel density (MVD), as determined by CD34 expression. LAT1 and ASCT2 were positively expressed in 59% (93/157) and 48% (76/157) of tumors respectively. LAT1 and ASCT2 expression significantly correlated with T factor, N factor, lymphatic permeation, vascular invasion, and CD98 expression. The 5-year survival rates of LAT1-high and -low and ASCT2-high and -low expressing patients were 62.0% and 69.6% (P < 0.05) and 59.6% and 70.1% (P = 0.068), respectively. The combined positive expression of LAT1 and ASCT2 was a significant prognostic factor in univariate analysis. High expression of LAT1 and ASCT2 correlates with metastasis and invasion. Accordingly, these proteins could serve as prognostic biomarkers and therapeutic targets for treating patients with surgically resectable ESCC. J. Surg. Oncol. 2016;113:381-389. © 2016 Wiley Periodicals, Inc.


Evaluation of ring-opening metathesis polymerization (ROMP)-derived monolithic capillary high performance liquid chromatography columns.
Novel monolithic capillary HPLC columns were prepared via ring opening metathesis polymerization (ROMP) within the confines of fused silica columns with 200 microm i.d. using norborn-2-ene (NBE), 1,4,4a,5,8,8a-hexahydro-1,4,5,8, exo, endo-dimethanonaphthalene (DMN-H6) as monomers, 2-propanol and toluene as porogens and RuCl2(PCy3)2(CHPh) as initiator. Using the monolithic capillary HPLC columns, different sets of analytes (i.e. standard systems) were used for the evaluation of the monolithic columns: (i) a protein standard consisting of six proteins in the range of 5000-66 000 g/mol, (ii) an insulin-albumin standard, and (iii) a peptide standard obtained from a tryptic digest of cytochrome C. With these three different standard systems the reproducibility of synthesis in terms of separation performance proved to be 1-2% relative standard deviation in tR. Variation of polymerization parameters had a significant influence on the monolithic morphology and therefore separation efficiency and back pressure. The maximum analytical loading capacity of ROMP-derived monolithic capillary columns for albumin was found to be 30-125 ng, depending on the monomer content. Long-term stability studies showed no alteration in separation performance.


Preliminary Study on the Efficient Electrohysterogram Segments for Recognizing Uterine Contractions with Convolutional Neural Networks.
Uterine contraction (UC) is the tightening and shortening of the uterine muscles which can indicate the progress of pregnancy towards delivery. Electrohysterogram (EHG), which reflects uterine electrical activities, has recently been studied for UC monitoring. In this paper, we aimed to evaluate different EHG segments for recognizing UCs using the convolutional neural network (CNN). In the open-access Icelandic 16-electrode EHG database (122 recordings from 45 pregnant women), 7136 UC and 7136 non-UC EHG segments with the duration of 60 s were manually extracted from 107 recordings of 40 pregnant women to develop a CNN model. A fivefold cross-validation was applied to evaluate the CNN based on sensitivity (SE), specificity (SP), and accuracy (ACC). Then, 1056 UC and 1056 non-UC EHG segments were extracted from the other 15 recordings of 5 pregnant women. Furthermore, the developed CNN model was applied to identify UCs using different EHG segments with the durations of 10 s, 20 s, and 30 s. The CNN achieved the average SE, SP, and ACC of 0.82, 0.93, and 0.88 for a 60 s EHG segment. The EHG segments of 10 s, 20 s, and 30 s around the TOCO peak achieved higher SE and ACC than the other segments with the same duration. The values of SE from 20 s EHG segments around the TOCO peak were higher than those from 10 s to 30 s EHG segments on the same side of the TOCO peak. The proposed method could be used to determine the efficient EHG segments for recognizing UC with the CNN.


Cloning and characterisation of the cytochrome c gene of Aspergillus nidulans.
The cytochrome c gene (cycA) of the filamentous fungus Aspergillus nidulans has been isolated and sequenced. The gene is present in a single copy per haploid genome and encodes a polypeptide of 112 amino acid residues. The nucleotide sequence of the A. nidulans cycA gene shows 87% identity to the DNA sequence of the Neurospora crassa cytochrome c gene, and approximately 72% identity to the sequence of the Saccharomyces cerevisiae iso-1-cytochrome c gene (CYC1). The S. cerevisiae CYC1 gene was used as a heterologous probe to isolate the homologous gene in A. nidulans. The A. nidulans cytochrome c sequence contains two small introns. One of these is highly conserved in terms of position, but the other has not been reported in any of the cytochrome c genes so far sequenced. Expression of the cycA gene is not affected by glucose repression, but has been shown to be induced approximately tenfold in the presence of oxygen and three- to fourfold under heat-shock conditions.


Coverage, universal access and equity in health: a characterization of scientific production in nursing.
to characterize the scientific contribution nursing has made regarding coverage, universal access and equity in health, and to understand this production in terms of subjects and objects of study. this was cross-sectional, documentary research; the units of analysis were 97 journals and 410 documents, retrieved from the Web of Science in the category, "nursing". Descriptors associated to coverage, access and equity in health, and the Mesh thesaurus, were applied. We used bibliometric laws and indicators, and analyzed the most important articles according to amount of citations and collaboration. the document retrieval allowed for 25 years of observation of production, an institutional and an international collaboration of 31% and 7%, respectively. The mean number of coauthors per article was 3.5, with a transience rate of 93%. The visibility index was 67.7%, and 24.6% of production was concentrated in four core journals. A review from the nursing category with 286 citations, and a Brazilian author who was the most productive, are issues worth highlighting. the nursing collective should strengthen future research on the subject, defining lines and sub-lines of research, increasing internationalization and building it with the joint participation of the academy and nursing community.


[Examples of screening investigations].
Primary prevention of cancer still only finds limited acceptance in the general population, therefore, secondary prevention plays an important role in order to avoid the high costs necessary for the treatment of advanced forms of cancer. Breast cancer, prostate cancer and colorectal carcinoma (CRC) are the most common forms of cancer with high mortality and a high socio-economic impact. Screening tests for these diseases are effective and simple to carry out. The measures for secondary prevention are well known but are only implemented to approximately 30-40%. For persons over 55 years old routine screening at 10-year intervals by ileocoloscopy is now established for CRC, or alternatively an annual examination for occult blood in faeces (FOBT) over 50 years of age. Screening mammography for women aged between 50 and 69 years old is firmly established in the guidelines of the Gemeinsamer Bundesausschuss since 2004 for early recognition of cancer. It is anticipated that the establishment of the screening programme in Germany will be completed in all Federal States by the end of March 2008. All men over 45 years of age who are compulsory insured are entitled to have an annual examination of the external genital organs and a digital rectal examination of the prostate under the compulsory cancer early recognition programme. PSA testing within the framework of preventive examinations is, however, not yet part of the catalogue of available tests.


Contribution of Posidonia oceanica meadows in the context of climate change mitigation in the Mediterranean Sea.
Coastal marine vegetation has been recently highlighted for its highly efficient carbon storage capacity. Among the sixty-four species of seagrass, Posidonia oceanica, a Mediterranean endemic species, appears to be the most effective in carbon fixation and storage. Based on new data from the study of one of the largest P. oceanica meadows in the Mediterranean Sea (100 km of coastline, 20 425 ha), and a synthesis of available data from the whole of the Mediterranean basin, the aim of this work is to evaluate the amount of carbon fixed each year by P. oceanica and sequestered in the matte, in relation with the mitigation of the impact of climate change (carbon sink). The mean total carbon fixation (blades, sheaths and rhizomes) per year varies between 33.5 and 426.6 g C.m-2 and the mean carbon sequestration (long-term sink in the matte), corresponding to the sheath and rhizome tissues, varies between 7.7 and 84.4 g C.m-2, with a clear decreasing trend according to depth because of the meadow density decrease. The synthesis of a hundred measurements made throughout the Mediterranean Sea and at depths between 0.5 and 32.0 m provides a basis for estimating the average annual carbon fixation and sequestration rate throughout the Mediterranean basin. The fixation of the blades is estimated at 1 024 t C.ha-1.yr-1, that of the sheaths at 220 t C ha-1.yr-1 and that of the rhizomes at 58 t C ha-1.yr-1; i.e. a total fixation rate of 1 302 t C ha-1.yr-1 and sequestration rate (dead sheaths and rhizomes) of 278 t C ha-1.yr-1. This annual carbon fixation represents only 0.61% on average of CO2 emissions/releases for all Mediterranean countries but in the large Mediterranean islands this fixation is on average 3.1% and can reach almost 14.4% for Corsica. Moreover, the major advantage of the P. oceanica meadow lies in its capacity to store carbon from annual carbon sequestration for centuries to millennia and can be compared to several terrestrial ecosystems considered to be efficient in carbon storage (peatlands).


The Draft Genome of the Small, Spineless Green Alga Desmodesmus costato-granulatus (Sphaeropleales, Chlorophyta).
Desmodesmus costato-granulatus (Skuja) Hegewald 2000 (Sphaeropleales, Chlorophyta) is a small, spineless green alga that is abundant in the freshwater phytoplankton of oligo- to eutrophic waters worldwide. It has a high lipid content and is considered for sustainable production of diverse compounds, including biofuels. Here, we report the draft whole-genome shotgun sequencing of D. costato-granulatus strain SAG 18.81. The final assembly comprises 48,879,637bp with over 4,141 scaffolds. This whole-genome project is publicly available in the CNSA (https://db.cngb.org/cnsa/) of CNGBdb under the accession number CNP0000701.


Spatially varying determinants of farmland conversion across Qiantang watershed, China.
This paper employed geographically weighted regression (GWR) to characterize the determinants of farmland conversion at administrative scale between 1994 and 2003 across Qiantang watershed, China. Six determinants were identified: total area of forest, distance to highway, distance to second road, distance to river, population, and gross domestic product. Relationships between these identified determinants and farmland conversion showed great spatial non-stationarity, since their character, nature, and strength varied significantly across space. Typically, for cities whose development was heavily relied on road infrastructure development, the impacts of "distance to second road" and "distance to river" was negative. However, in mountainous areas, the restriction of terrain factors led to positive impacts from these two variables. For areas undergoing rapid socio-economic development, farmland conversion was accelerated by population growth and economic development. However, for more urbanized regions, a slow-down rate of farmland conversion would be expected. Our study highlighted that the problem of spatial non-stationarity should be addressed when qualifying the determinants of farmland conversion. Linking our results within the context of farmland protection, we argue that implementing local-specific land management practices, instead of the current one-size-fits-all framework, is the key for the success of farmland protection in China.


Rapid and reliable HILIC-MS/MS method for monitoring allantoin as a biomarker of oxidative stress.
Allantoin is an excellent biomarker of oxidative stress in humans as the main product of uric acid oxidation by reactive oxygen species. Yet, allantoin determination is still not routinely performed in clinical laboratories. Therefore, we developed a fast, simple, selective, and sensitive UHPLC-MS/MS method for allantoin determination in human serum using an isotopically labeled internal standard. Our analytical protocol provided high sensitivity by mass spectrometry detection and high throughput by HILIC-MS/MS analysis within 4 min, with one-step serum sample preparation approximately within 7 min. Lastly, our protocol was fully validated to demonstrate its reliability in allantoin determination in human serum. The method showed an excellent linear range from 0.05 to 100 μM, with precision ranging from 1.8 to 11.3% (RSD), and with accuracy (relative error %) within ±6.0%. The method was then applied to analyze the concentration of allantoin in serum samples from 71 patients with chronic gout without treatment with xanthine oxidase inhibitors. The median serum allantoin concentration in the cohort was 2.8 μM (n = 71). Overall, our simple analytical protocol has the potential to be easily implemented in clinical routine practice for monitoring allantoin as a key oxidative stress biomarker.


Effects of continuous subcutaneous insulin infusion on renal morphology in experimental diabetes. I. Blood glucose levels, body size, kidney weight and glomerulotubular morphometry.
Observations have been made over a period of 16 weeks on three groups of rats: controls, untreated streptozotocin-diabetics and diabetics treated with continuous subcutaneous insulin infusion. Good control of circadian and diurnal blood glucose levels was achieved in the insulin-treated diabetics. Body weights and tibial lengths were reduced in untreated diabetics and improved, but not normalized, by insulin therapy. Kidney weights were similar in all groups. Glomerular size and number, tubule volume, glomerular basement membrane volume and surface area were essentially the same in all groups. However, the untreated diabetics possessed tubules of larger diameter and shorter length than those in controls. Both variables were preserved at normal values by insulin infusion therapy. These results illustrate the value of early blood glucose control for preventing at least some of the structural alterations associated with experimental diabetic nephropathy.


Blocking of Transient Receptor Potential Vanilloid 1 (TRPV1) promotes terminal mitophagy in multiple myeloma, disturbing calcium homeostasis and targeting ubiquitin pathway and bortezomib-induced unfolded protein response.
Chemoresistance remains a major treatment obstacle in multiple myeloma (MM). Novel new therapies are thus in need. Transient Receptor Potential Vanilloid type 1 (TRPV1) is a calcium-permeable ion channel that has been demonstrated to be expressed in solid tumors. Calcium channels have been shown to be involved in the regulation of cell proliferation, chemoresistance, migration and invasion. The aim of the current study was to evaluate its possible role in MM. Pharmacological inhibitor was used to evaluate the role of TRPV1 in MM cell lines and primary MM cells. Flow cytometry, molecular analysis, fluorescent microscopy, proteomic analysis and xenograft in vivo model of MM with BM involvement were employed to assess the effect of TRPV1 inhibition and decipher its unique mechanism of action in MM. TRPV1 was found to be expressed by MM cell lines and primary MM cells. TRPV1 inhibition using the antagonist AMG9810-induced MM cell apoptosis and synergized with bortezomib, overcoming both CXCR4-dependent stroma-mediated and acquired resistance. In accordance, AMG9810 suppressed the expression and activation of CXCR4 in MM cells. TRPV1 inhibition increased mitochondrial calcium levels with subsequent mitochondrial ROS accumulation and depolarization. These effects were reversed by calcium chelation, suggesting the role of calcium perturbations in oxidative stress and mitochondrial destabilization. Furthermore, AMG9810 abolished bortezomib-induced accumulation of mitochondrial HSP70 and suppressed protective mitochondrial unfolded protein response. Proteomics revealed unique molecular signature related to the modification of ubiquitin signaling pathway. Consequently, 38 proteins related to the ubiquitylation machinery were downregulated upon combined bortezomib/AMG9810 treatment. Concomitantly, AMG9810 abolished bortezomib-induced ubiquitination of cytosolic and mitochondrial proteins. Furthermore, bortezomib/AMG9810 treatment induced mitochondrial accumulation of PINK1, significantly reduced the mitochondrial mass and promoted mitochondrial-lysosomal fusion, indicating massive mitophagy. Finally, in a recently developed xenograft model of systemic MM with BM involvement, bortezomib/AMG9810 treatment effectively reduced tumor burden in the BM of MM-bearing mice. Altogether, our results unravel the mechanism mediating the strong synergistic anti-MM activity of bortezomib in combination with TRPV1 inhibition which may be translated into the clinic.


Effects of black carbon and mineral dust on glacial melting on the Muz Taw glacier, Central Asia.
Light-absorbing impurities (LAIs), including black carbon (BC) and mineral dust, in snow can trigger a positive feedback. In this study, we estimate the contribution of BC and dust to glacial melting in Central Asia. Average BC and dust concentrations in the surface snow of the Muz Taw glacier are 1788 ± 1754 ng g-1 and 172 ± 178 μg g-1, respectively. Simulation using the Snow Ice and Aerosol Radiation (SNICAR) model indicates that the combined effect of BC and dust reduces the snow albedo by approximately 6.24% to 50.4% relative to clean snow. Radiative forcing (RF) induced by BC and dust deposited in snow ranges from 1.61 to 32.69 W m-2, with an average of 16.74 W m-2 for the central scenario. Thus, glacier melting can be enhanced by 36.37 cm w.e. by BC and dust in snow, accounting for about 16.3% of the total glacier melt. LAIs deposited on the Muz Taw glacier mostly originate from Central Asia, West Siberia and local emissions during the study period. More than 80% of BC deposited is attributed to anthropogenic emissions. These results strengthen the important role of BC and dust in glacier melting in Central Asia, and further highlights the potential benefits of mitigation of BC emissions.


Childhood trauma history is linked to abnormal brain metabolism of non-medicated adult patients with major depressive disorder.
Childhood trauma is a risk factor that may lead to persistent brain metabolic abnormalities, predisposing individuals to major depressive disorder (MDD). To better elucidate the pathogenesis of MDD, we investigated the neurometabolic changes in unmedicated MDD patients who had experienced childhood trauma (CT). In this study, 37 unmedicated MDD patients with CT, 35 unmedicated MDD patients without CT, and 30 healthy control participants underwent high-resolution proton magnetic resonance spectroscopy (1H-MRS) examination. Bilateral metabolic ratios of N-acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr in the prefrontal white matter (PWM), anterior cingulate cortex (ACC), putamen, and cerebellum were obtained. MDD patients showed neurometabolic changes in the cortico-striato-cerebellar (CSC) circuit. Furthermore, MDD patients showed significantly lower NAA/Cr and higher Cho/Cr ratio in the bilateral ACC and putamen, and higher NAA/Cr and lower Cho/Cr ratio in the cerebellum. Childhood trauma reduced the Cho/Cr ratio in the left ACC, which played an important role in longer and more episodes of depression. Early childhood trauma has a long-lasting impact on the metabolism of adult MDD patients, leading to abnormal choline metabolism of the left ACC. Abnormal biochemical metabolism in the CSC circuit may be an underlying pathophysiology of MDD. As this is a small cross-sectional study, the impact of childhood trauma on the different stages of depression has not been observed.


DsRed as a highly sensitive, selective, and reversible fluorescence-based biosensor for both Cu(+) and Cu(2+) ions.
The wild type form of Red fluorescent protein (DsRed), an intrinsically fluorescent protein found in tropical corals, is found to be highly selective, reversible and sensitive for both Cu(+) and Cu(2+), with a nanomolar detection limit. The selectivity towards these ions is retained even in the presence of other heavy metal ions. The K(d) values for monovalent and divalent copper, based on single binding isotherms, are 450 and 540 nM, respectively. The wild type DsRed sensitivity to Cu(2+) (below 1 ppb) is seven orders of magnitude better than that of the related wild type Green Fluorescent protein (GFP), and it is even 40 times more sensitive than engineered mutants of GFP. Potential binding sites have been proposed, based on amino acid sequences for copper binding and the distance from the chromophore, with the aid of computer modeling.


Re-balancing cellular energy substrate metabolism to mend the failing heart.
Fatty acids and glucose are the main substrates for myocardial energy provision. Under physiologic conditions, there is a distinct and finely tuned balance between the utilization of these substrates. Using the non-ischemic heart as an example, we discuss that upon stress this substrate balance is upset resulting in an over-reliance on either fatty acids or glucose, and that chronic fuel shifts towards a single type of substrate appear to be linked with cardiac dysfunction. These observations suggest that interventions aimed at re-balancing a tilted substrate preference towards an appropriate mix of substrates may result in restoration of cardiac contractile performance. Examples of manipulating cellular substrate uptake as a means to re-balance fuel supply, being associated with mended cardiac function underscore this concept. We also address the molecular mechanisms underlying the apparent need for a fatty acid-glucose fuel balance. We propose that re-balancing cellular fuel supply, in particular with respect to fatty acids and glucose, may be an effective strategy to treat the failing heart.


Evidence for putative immediate early antigens in human herpesvirus 6-infected cells.
Human herpesvirus 6 (HHV-6) induced nuclear antigens in cells as early as 3 h after infection. These nuclear antigens were induced by all three strains of HHV-6 tested, and their de novo synthesis required the function(s) of the intact viral genome. Their appearance was not affected by 2,2'-anhydro(1-beta-D-arabinofuranosyl)cytosine, but was completely inhibited by cycloheximide. However, the nuclear antigens did appear if cycloheximide was replaced with actinomycin D. Thus, the nuclear antigens seem to be equivalent to the immediate early antigens of other herpesviruses.


Utility of the Etest GRD for detecting Staphylococcus aureus with reduced susceptibility to glycopeptides in cystic fibrosis patients.
Glycopeptide-intermediate S. aureus (GISA), particularly heterogeneous GISA (hGISA), remain difficult to detect in the routine practice of medical microbiology. Novel tools have been evaluated comparatively to the population analysis profile-area under the curve (PAP-AUC) reference method for detecting GISA/hGISA. Among them, the Etest GRD showed relatively high specificity (85.8-97%) and negative predictive value (97%) but lower sensibility (57-95%) and positive predictive value (30.8%). We investigated the utility of the Etest GRD for detecting GISA/hGISA among 180 strains isolated from 106 cystic fibrosis (CF) patients. Etest GRD was performed on all isolates, and those exhibiting a GISA/hGISA phenotype were further tested by PAP-AUC and other agar routine assays for GISA/hGISA detection. The Etest GRD allowed the detection of 15 GISA/hGISA strains, of which eight were confirmed by the reference method. Despite the 3.9% level of false positive results, the Etest GRD constitutes a useful routine tool for detecting GISA/hGISA overlooked by other routine assays, two strains being detected by the Etest GRD only. GISA/hGISA represented 7.7% of MRSA and 2.1% of MSSA, and were found in 4.7% of CF patients colonized/infected by S. aureus, which is the highest rate reported to date in this population.


Non-specific degradation of chloroacetanilide herbicides by glucose oxidase supported Bio-Fenton reaction.
Bio-Fenton reaction supported by glucose oxidase (GOx) for producing H2O2 was applied to degrade persistent chloroacetanilide herbicides in the presence of Fe (Ⅲ)-citrate at pH 5.5. There were pH decrease to 4.3, the production of 8 mM H2O2 and simultaneous consumption to produce •OH radicals which non-specifically degraded the herbicides. The degradation rates followed the order acetochlor ≈ alachlor ≈ metolachlor > propachlor ≈ butachlor with the degradation percent of 72.8%, 73.4%, 74.0%, 47.4%, and 43.8%, respectively. During the Bio-Fenton degradation, alachlor was dechlorinated and filtered into catechol via the production of intermediates formed through a series of hydrogen atom abstraction and hydrogen oxide radical addition reactions. The current Bio-Fenton reaction leading to the production of •OH radicals could be applied for non-specific oxidative degradation to various persistent organic pollutants under in-situ environmental conditions, considering diverse microbial metabolic systems able to continuously supply H2O2 with ubiquitous Fe(II) and Fe(III) and citrate.


Adequacy of percutaneous non-targeted liver biopsy under real-time ultrasound guidance when comparing the Biopince™ and Achieve™ biopsy needle.
The purpose of this study was to compare the adequacy rates of percutaneous liver biopsies, in parenchymal liver disease, using the BiopinceTM (Argon Medical, Texas, TX, ) 16G and AchieveTM (Carefusion, Illinois, IL, USA) 18G biopsy needles in relation to the Royal College of Pathologists guidelines and to assess risk of complications. Data for all percutaneous non-targeted "medical" liver biopsies using the Biopince 16G and Achieve 18G biopsy needles were collected retrospectively over a 2-year period. Total biopsy core length and number of portal tracts was recorded along with adequacy of biopsy as assessed according to Royal College of Pathologists criteria. In total, 194 percutaneous liver biopsies met the inclusion criteria; 53 using the Biopince needle and 141 using the Achieve needle. The mean total core length was 23 mm (SD 4.1) and 20 mm (SD 6.8) for the Biopince and Achieve needles, respectively (p = 0.0005). The mean number of portal tracts was 11 (SD 4.2) and 7 (SD 3.4) for the Biopince and Achieve needles, respectively (p < 0.0001). An adequate biopsy was obtained in 15 (31.3%) and 1 (1.3%) case using the Biopince and Achieve needles, respectively (p < 0.001). Compromised biopsies were obtained in 32 (66.7%) and 39 (50.6%) cases using the Biopince and Achieve needles, respectively. Inadequate biopsies were obtained in 1 (2%) and 37 (48.1%) cases using the Biopince and Achieve needles, respectively. The Biopince 16G needle, when compared with the Achieve 18G needle, acquires a significantly greater total core length and number of portal tracts with significantly improved adequacy rates. There were no major complications associated with its use. Advances in knowledge: The Biopince 16G needle achieves significantly better specimen adequacy, when compared with the Achieve 18G needle and with no added major complications associated with its use.


The provision of 125I-labelled tracers for radioimmunoassay of haptens: a general approach?
Use of 125iodinated progesterone 11 alpha-glucuronide-tyramine conjugate as radioligand with the majority of antisera raised against progesterone 11 alpha-hemisuccinate-bovine serum albumin is shown to produce steep and sensitive standard curves. Accurate precise and robust assays for progesterone which are clinically useful have been readily developed from such systems. Together with data from other heterologous-bridge systems, the results suggest a hypothesis concerning desirable structural features of the links in heterologous-bridge immunoassays for haptens. The hypothesis should facilitate the establishment of other adequately sensitive external-label assays, especially for gonadal steroids.


Investigations into pyrolytic behaviour of spent citronella waste: Slow and flash pyrolysis study.
Slow and flash pyrolysis of spent citronella biomass has been studied at varying temperatures. It is aimed to understand the pyrolytic behavior of spent citronella aromatic biomass with temperatures. Maximum bio-oil yield of 37.7 wt% was obtained with conversion of 71 wt% at 450 °C through slow pyrolysis. GC/MS, 1H NMR, and FTIR analysis of pyrolytic liquid (bio-oil) was done which indicated various functionalities with maximum area% for phenolics. However, flash pyrolysis at high heating rate of 20 °C/ms resulted into maximum area% for carbonyls at all temperatures. In addition, an increasing trend for phenolics with temperature was also observed. The properties of obtained biochar are analysed by CHNS, FTIR, TOC, XRD, and SEM, which confirmed the significant decomposition of biomass constituents. The characterisation results revealed the potential usage of pyrolytic liquid i.e., bio-oil and pyrolytic residue i.e., biochar for different applications.


Cognitive decline negatively impacts physical function.
Many older adults report difficulty performing one or more activities of daily living. These difficulties may be attributed to cognitive decline and as a result, measuring cognitive status among aging adults may help provide an understanding of current functional status. The purpose of the present investigation was to determine the association between cognitive status and measures of physical functioning. Seventy-six older adults participated in this study; 41 were categorized as normal memory function (NM) and 35 were poor memory function (PM). NM participants had significantly higher physical function as measured by Short Physical Performance Battery (SPPB; 9.4 ± 2.2 vs. 8.4 ± 2.0; p = .03) and peak velocity (0.67 ± 0.16 vs. 0.56 ± 0.19; p = .04) during a quick sit-to-stand task. Dual-task walking velocities were 22% and 126% slower between cognitive groups for the fast and habitual trials, respectively when compared to the single-task walking condition. Significant correlations existed between measures of memory and physical function. The largest correlations with memory were for peak (r = 0.42) and average (r = 0.38) velocity. The results suggest a positive relationship between physical function and cognitive status. However, further research is needed to determine the mechanism of the underlying relationships between physical and cognitive function.


[The evaluation of compressive strength of four filling materials for class I cavity].
Compressive strength of four filling materials which are usually used in clinic were evaluated, and the indication of Class I cavity was discussed. In vitro, the Class I cavities were prepared on eighty first molars. After filling the cavities with four filling materials, loading was applied with the same speed, and the compressive strength at the fracture point were recorded and analyzed. The compressive strength of silver amalgam was highest, GCFujiIXGP was lower, and 3M composite resin was lowest. For Class I cavity of posterior teeth, we should consider the compressive strength of filling materials first, and for anterior teeth, color is most important.


Speech perception with cochlear implants as measured using a roving-level adaptive test method.
This paper uses a new method of speech testing where the hearing aid or cochlear implant (CI) users are tested in a more realistic listening situation. Groups of 11 subjects matched for performance with 5 different CI systems, for a total of 55 subjects, were tested with an adaptive test regime where the presentation level of the speech signal roved by ±10 or ±15 dB. Speech reception thresholds varied widely between -4.8 and 17.3 dB with the ±15 dB roving condition being more difficult than the ±10 dB roving condition. We also found significant differences in speech reception threshold between groups using different devices. The test method used in our study, which attempts to test CI users in a more realistic listening situation, is sensitive to the effects of various subject-specific and technical parameters on everyday speech perception with CIs.


Refocusing neuroscience: moving away from mental categories and towards complex behaviours.
Mental terms-such as perception, cognition, action, emotion, as well as attention, memory, decision-making-are epistemically sterile. We support our thesis based on extensive comparative neuroanatomy knowledge of the organization of the vertebrate brain. Evolutionary pressures have moulded the central nervous system to promote survival. Careful characterization of the vertebrate brain shows that its architecture supports an enormous amount of communication and integration of signals, especially in birds and mammals. The general architecture supports a degree of 'computational flexibility' that enables animals to cope successfully with complex and ever-changing environments. Here, we suggest that the vertebrate neuroarchitecture does not respect the boundaries of standard mental terms, and propose that neuroscience should aim to unravel the dynamic coupling between large-scale brain circuits and complex, naturalistic behaviours. This article is part of the theme issue 'Systems neuroscience through the lens of evolutionary theory'.


Combination of microsurgical tissue reconstruction with osteointegrated dental implants. Presentation of a technique.
A technique is presented in which resected mandibles are restored with a combination of microsurgically revascularized jejunal grafts and bone grafts. The bone grafts served as a recipient for Branemark implants. The preliminary results showed that the jejunal mucosa tolerates the implants well and the masticatory function was adequately restored in the patients discussed.


Influence of load partial factors adjustment on reliability design of RC frame structures in China.
The partial factor method has been widely used in building design and the partial factors to ensure the safety of structures are specified in the adopted codes. The load partial factors in the design expressions have been increased in the lasted code in China, which leads to theoretically increment in reliability and a growth in the consumption of construction materials. However, the influence of load partial factors adjustment on design of building structures arises different points among scholars. Some believe that it has a great impact on the design, some think the influence is small. This makes designers have doubts in the safety of structures and investors are also confused about the cost. In order to illustrate the influence of load partial factor adjustment on safety level and material consumption of RC (Reinforced Concrete) frame structures, reliability analysis and material consumption analysis are performed using First Order Reliability Method (FORM). The approach is carried out according to the load partial factors in Chinese codes of (GB50153-2008) and (GB50068-2018), respectively. Then, the influence of load partial factors adjustment is demonstrated with a case design of RC frame structures with different load partial factors in codes. The results show that the partial factor has a noticeable influence on the reliability index. The adjustment of load partial factors in design leads to an increase of the reliability index, which is about 8-16%. The increase of material consumption used in RC structures is about 0.75-6.29%. And the case indicated that the adjustment of load partial factors mainly result in the increase of reinforcement consumption, while have little effect on the concrete consumption. This study provides an analytical and conclusive insight into the influence of load partial factor adjustment on safety level and material consumption, which is can be applied to a wide range of structures.


Patient-reported outcome measures (PROMs) comparing digital and conventional workflows for treatment with posterior single-unit implant restorations: A randomized controlled trial.
The aim of this randomized controlled trial (RCT) was to analyze patient-reported outcome measures (PROMs) of prosthetic therapy with monolithic implant crowns in completely digital workflows (test) with intraoral optical scanning (IOS) and conventional workflows (control) with conventional impressions. Secondary, an objective evaluation of the final implant restorations was performed using the Functional Implant Prosthodontic Score (FIPS). Forty patients who required an implant-supported single crown on posterior regions were randomly divided into test (n = 20) and control (n = 20) groups for impression taking. Each group was then equally separated into two subgroups according to the restorative material used: lithium disilicate (LS2, N!CE®, Straumann AG, Basel, Switzerland) or polymer-infiltrated ceramic networks (PICN, Enamic®, Vita, Bad Säckingen, Germany). Patient satisfaction was evaluated using PROM questionnaires with visual analog scales (VAS) after impression-taking and 1 week after prosthetic delivery. Patient satisfaction with the impression technique was assessed in six domains: length, comfort, anxiety, taste, nausea, and pain, whereas patient satisfaction with the final restoration was assessed in four domains: overall treatment outcome, functionality, esthetics, and cleanability. In addition, the final implant restorations were objectively assessed by an independent prosthodontist using the FIPS. Mann-Whitney U test was used to analyze the defined outcomes. Statistical analysis was completed with a level of significance set at α=0.05. PROMs focusing on the impression technique demonstrated higher levels of patient satisfaction for IOS compared to conventional impressions, especially in terms of "taste irritation" (p = 0.036); whereas no significant differences were found between both restorative CAD/CAM-materials. Mean FIPS values demonstrated similar results among subgroups. Within the limitation of this study, both completely digital and conventional protocols provided great levels of patient satisfaction in implant rehabilitation of single-tooth gaps in posterior sites with monolithic implant crowns. The restorative material, LS2 versus PICN, does not impact patient satisfaction with their treatment. However, a long-term follow up is needed to draw more specific conclusions on patient satisfaction with the restorations.


'Evaluation of adverse prognostic gene alterations & MRD positivity in BCR::ABL1-like B-lineage acute lymphoblastic leukaemia patients, in a resource-constrained setting.
Early detection of BCR::ABL1-like ALL could impact treatment management and improve the overall survival/outcome. BCR::ABL1-like ALL cases are characterised by diverse genetic alterations activating cytokine receptors and kinase signalling. Its detection is still an unmet need in low-middle-income countries due to the unavailability of a patented TLDA assay. This study's rationale is to identify BCR::ABL1-like ALLs using the PHi-RACE classifier, followed by the characterisation of underlying adverse genetic alterations in recurrent gene abnormalities negative (RGAneg) B-ALLs (n = 108). We identified 34.25% (37/108) BCR::ABL1-like ALLs using PHi-RACE classifier, characterised by TSLPR/CRLF2 expression (11.58%), IKZF1 (Δ4-7) deletion (18.9%) and chimeric gene fusions (34.61%). In overexpressed TSLPR/CRLF2 BCR::ABL1-like ALLs, we identified 33.33% (1/3) CRLF2::IGH and 33.33% (1/3) EPOR::IGH rearrangements with concomitant JAK2 mutation R683S (50%). We identified 18.91% CD13 (P = 0.02) and 27.02% CD33 (P = 0.05) aberrant myeloid markers positivity, which was significantly higher in BCR::ABL1-like ALLs compared to non-BCR::ABL1-like ALLs. MRD positivity was considerably higher (40% in BCR::ABL1-like vs. 19.29% in non-BCR::ABL1-like ALLs). With this practical approach, we reported a high incidence of BCR::ABL1-like ALLs, and a lower frequency of CRLF2 alteration & associated CGFs. Recognising this entity, early at diagnosis is crucial to optimise personalised treatment strategies.


The effect of sulfhydryl groups and disulphide linkage in the thermal aggregation of Z19 alpha-zein.
Zeins are the major storage proteins in corn seeds organized in protein bodies located in the endosperm. They are soluble in alcoholic solution and depict a high tendency to aggregation. The Z19 alpha-zein aggregates obtained by heating show a particular and interesting temperature-dependent behavior. This work was aimed at determining not only the effect of temperature on the aggregation behavior, but also the effect of the sulfhydryl groups and disulphide bonds on the thermal aggregation process under non-aqueous conditions. Z19 alpha-zein was chemically modified to obtain different sulfhydryl groups and disulphide-bonds content. Far-UV CD, ANS emission fluorescence, and dynamic light scattering, as well as differential scanning calorimetry, were performed to characterize this protein. Removal of these disulphide-bonds and alkylation of all the sulfhydryl groups in the protein promoted the lowest T(m) of 57.36 degrees C, eliminated aggregation, enhanced protein flexibility, and diminished thermal stability. These results suggest that the disulphide linkage could be the driving force for the Z19 alpha-zein aggregation.


Impact of suspected adverse drug reactions on mortality and length of hospital stay in the hospitalised patients: a meta-analysis.
To estimate the risk of mortality and length of stay in hospitalised patients who have experienced suspected adverse drug reactions (ADRs) as compared to patients who did not experience suspected ADRs. A systematic literature search was conducted on databases for observational and randomised controlled studies conducted in any inpatient setting that reported deaths and/or length of hospital stay in patients who had suspected ADRs and did not have suspected ADRs during hospitalisation. PRISMA guidelines were strictly followed during the review. The methodological quality of included studies was assessed using a tool designed by Smyth et al. for the studies of adverse drug reactions. The meta-analytic summary of all-cause mortality was estimated using odds ratio-OR (95% CI) and length of stay using mean difference-MD (95% CI). Both outcomes were pooled using a random effect model (DerSimonian and Laird method). Subgroup and meta-regression were performed based on study variables: study design, age group, study ward, study region, types of suspected ADRs (ADRAd-suspected ADRs that lead to hospitalisation and ADRIn-suspected ADRs that occur following hospitalisation), study duration, sample size and study period. The statistical analysis was conducted through the 'Review manager software version 5.4.1 and JASP (Version 0.14.1)'. After screening 475 relevant articles, 55 studies were included in this meta-analysis. Patients having suspected ADRs had reported significantly higher odds of all-cause mortality [OR: 1.50 (95% CI: 1.21-1.86; I2 = 100%) than those patients who did not have suspected ADRs during hospitalisation. Study wards, types of suspected ADRs and sample size were observed as significant predictors of all-cause mortality (p < 0.05). Patients having suspected ADRs had reported significantly higher mean difference in hospital stay [MD: 3.98 (95% CI: 2.91, 5.05; I2 = 99%) than those patients who did not have suspected ADRs during hospitalisation. Types of suspected ADRs and study periods were observed as significant predictors of length of stay (p < 0.05). Suspected ADRs significantly increase the risk of mortality and length of stay in hospitalised patients. CRD42020176320.


Brain ablation in the rat cerebral cortex using a tunable-free electron laser.
We used the MARK III free electron laser (FEL) tuned to molecular vibrational absorbance maxima in the infrared (IR) wavelength range of 3.0-6.45 microm to study the effect of these various wavelengths and a power level of 5 mJ/2 microseconds macropulse on photoablation of CNS tissue. Laser lesions were produced in the parietal cortex of anesthetized rats using thermal confined mid-IR (infrared) laser pulses tuned to the -OH, -CH, amide 1, and amide 2 absorbance bands. Histological assessments following recovery periods of 4 hours, 4 days, and 3 weeks were performed to determine the size, shape, and character of the photoablative lesions. Cell density studies were done in adjacent edematous tissue. Significant differences in lesion size and shape were observed as a function of wavelength. Although maximum ablation and collateral damage seemed to coincide with spectral peaks in the mid-IR, area and depth/width ratios did not. It was found in these experiments that wavelengths in the mid-IR could be selected for optimal ablative properties. Using tunable, high-peak-power pulsed lasers, it will be possible to produce well-defined photoablative lesions that conform to small, irregularly shaped neurosurgical targets.


NADH/NAD+ interaction with NADH: ubiquinone oxidoreductase (complex I).
The quantitative data on the binding affinity of NADH, NAD(+), and their analogues for complex I as emerged from the steady-state kinetics data and from more direct studies under equilibrium conditions are summarized and discussed. The redox-dependency of the nucleotide binding and the reductant-induced change of FMN affinity to its tight non-covalent binding site indicate that binding (dissociation) of the substrate (product) may energetically contribute to the proton-translocating activity of complex I.


Calcium signaling: septins organize the SOC channel.
Store-operated Ca(2+) entry is a widely encountered mechanism for generating cytoplasmic Ca(2+) signals. From a whole-genome screen in HeLa cells, a new study reveals that cytoskeletal septins play a critical role in this process, by organizing signaling structures in the plasma membrane.


Squamous cell carcinoma of the nasal septum with Wegener's granulomatosis treated with cyclophosphamide and corticosteroids.
Well differentiated squamous cell carcinoma of the nasal septum developed in a 55-year old man with Wegener's granulomatosis. It is suggested that the malignancy was induced by immunosuppressive state from an increased and prolonged use of cyclophosphamide and corticosteroids. Although the efficacy of the therapeutic concept using cyclophosphamide and corticosteroids is well established, there have been some few reports that cyclophosphamide could be implicated in the genesis of malignancies. The pathophysiology of Wegener's granulomatosis should be better understood, and effective and less toxic alternative protocol should be established.


Dissection of the Poly(Glu60Ala30Tyr10) (GAT)-specific T-cell repertoire in H-2Ik mice. II. The use of monoclonal antibodies to study the recognition of Ia antigens by GAT-reactive T-cell clones.
Twenty-five allospecific monoclonal antibodies (mAb), produced in the A. TH. A.BY, or B10.S (7R) anti-A.TL combinations, were shown to recognize determinants organized in four spatially distinct polymorphic regions on the same I-Ak-encoded molecule(s). These reagents were used to assess the recognition of the class II major histocompatibility complex (MHC) determinants in a series of GAT-reactive A.TL T-cell clones exhibiting various restriction specificity or alloreactivity patterns. Of the proliferative responses of 13 cloned T cells, 12 responses were found to be inhibited similarly by the same set of mAbs.A hierarchy in the blocking effects of these reagents that could be correlated with the spatial organization of their determinants was observed. (i) All the mAbs defining the epitope region I (i.e., recognizing public Ia.1- or Ia.17-like determinants, presumably expressed on the A beta subunit) and some of those identifying new public determinants in the epitope region II profoundly inhibited these T-cell responses. (ii) Intermediate blocking was observed when mAbs recognizing public determinants in the epitope region III were used. (iii) Finally, among the mAbs that identified the epitope group IV, the Ia.19-specific mAb 39.J was inhibitory, whereas mAbs directed against private Ia.2-like determinants were not. By contrast, the GAT-specific proliferative response of the T-cell clone AT-20.1, which recognized its nominal antigen in an extensively cross-reactive MHC-restricted fashion, could only be inhibited by a subset of the mAbs recognizing epitopes in groups I and II, but not by those recognizing epitopes in groups III and IV. It was also shown that the same subset of I-Ak-and I-Au-reactive mAbs displayed similar blocking effects on the proliferation of two T-cell clones exhibiting dual specificity for I-Ak- and I-Au-restricting and/or I-Ak- and I-Au-alloactivating determinants. Finally, all the cloned T-cell responses examined were found to be inhibited by rat mAbs against the LFA.1 molecule or the murine equivalent of the human OKT4 differentiation antigen. These studies suggest that class II specific mAbs can impair proliferation of cloned T-cells by a mechanism(s) other than the masking of the T-cells' restriction determinants per se.


Laparoscopic heminephrectomy in infants and children: first 54 cases.
Heminephrectomy in the pediatric population remains a popular open surgical procedure. We describe our experience with laparoscopic heminephrectomy using a retroperitoneoscopic approach. Data were collected retrospectively and prospectively on all patients undergoing laparoscopic heminephrectomy by a single surgeon using a prone retroperitoneoscopic approach. Information relating to the age, sex, laterality, duration of surgery, analgesic requirements, duration of hospital stay, postoperative complications and outcome was recorded. Between March 2001 and August 2005 54 laparoscopic heminephrectomies were performed in 48 children (34 girls and 14 boys). The median age at surgery was 14 months (range 2-112 months). Forty-four upper and 10 lower moieties were removed. The median operative time was 105 min (range 50-150 min). There were no intraoperative complications and no conversions. There were four minor complications, comprising haematuria (n=1) and postoperative pyrexia (n=3). The median length of follow up was 22 months (range 3-57 months). All patients remained asymptomatic at last follow up. Ultrasound findings included presence of a visible ureteric stump (n=7) and cysts at the resection margin of the remaining remnant (n=17); none of these patients manifested clinical symptoms (e.g. infection, pain). With advanced laparoscopic skills, laparoscopic heminephrectomy is a feasible operation for the treatment of non-functioning duplex renal units in children and infants.


The effect of secretin on bile production, splanchnohepatic hemodynamics and liver function in cats.
The effect of secretin on bile flow, biliary clearance of 14C-erythritol and bile composition was studied in fasting, chloralose anesthetized cats. Secretin (2 U.kg-1 . h-1) increased from values below the values above the erythritol clearance, which did not change significantly. It is therefore concluded that secretin altered ductular transfer of fluid from a net reabsorption to a net secretion of a bicarbonate rich fluid. Secretin did not affect the sphlanchno-hepatic hemodynamics or the overall function of the liver and Indomethacin did not significantly alter the response to secretin.


Is psychotic disorder associated with increased levels of craving for cannabis? An Experience Sampling study.
Although cannabis use among individuals with psychotic disorder is considerable, little is known about patterns of use and factors contributing to continuation of use. Therefore, we investigated craving in relation to cannabis use in patients with psychotic disorder and healthy controls. The study included 58 patients with non-affective psychotic disorder and 63 healthy controls; all were frequent cannabis users. Craving was assessed with the Obsessive Compulsive Drug Use Scale (OCDUS) for cannabis, as well as in daily life using the Experience Sampling Method (ESM). Patients scored higher on the OCDUS (B = 1.18, P = 0.022), but did not differ from controls in ESM indices of craving (all P > 0.05). In daily life, ESM craving predicted cannabis use and this was stronger in controls (χ(2) = 4.5, P = 0.033; Bcontrols = 0.08, P < 0.001; Bpatients = 0.06, P < 0.001). In both groups ESM craving was predicted by negative affect, paranoia, and hallucinations (Bnegativeaffect = 0.12, P = 0.009; Bparanoia = 0.13, P = 0.013; Bhallucinations = 0.13, P = 0.028), and followed by an increase in negative affect at non-cannabis-using moments (B = 0.03, P = 0.002). The temporal dynamics of craving as well as craving intensity in daily life appear to be similar in patients and controls. Further research is needed to elucidate the inconsistencies between cross-sectional and daily-life measures of craving in psychosis.


The gastric air-fluid sign: aid in CT assessment of gastric wall thickening.
The differentiation of apparent gastric wall thickening due to incomplete gastric distention from true pathologic wall thickening can be difficult on computed tomographic (CT) scanning. We have observed a transition in gastric wall thickening that is often present at or slightly above the gastric air-fluid or air-contrast level. The apparently thickened gastric wall in the dependent portion of the stomach undergoes an abrupt change to normal thickness at or above the air-fluid level. Review of CT scans in 259 patients without known or suspected gastric pathologic conditions revealed this finding, termed the "gastric air-fluid sign," in 57 patients (22%). While not considered diagnostic, the presence of this sign may allow for a greater degree of confidence in the CT assessment of gastric wall thickening in an appropriate clinical setting.


Chemical RNA Editing for Genetic Restoration: The Relationship between the Structure and Deamination Efficiency of Carboxyvinyldeoxyuridine Oligodeoxynucleotides.
Oligodeoxynucleotides containing 5-carboxyvinyl-2'-deoxyuridine ((CV) U-containing ODNs) for successful site-specific transition of cytosine to uridine by photo-cross-linking have three parts: the complementary sequence, hairpin loop and the 5'-terminal photoresponsive nucleobase (CV) U. Photo-cross-linking with (CV) U-containing ODNs was performed using UV (366 nm) irradiation, followed by heat treatment for deamination. The cross-linked nucleotide was cleaved by photosplitting (UV, 312 nm). The products were analyzed using restriction fragment length polymorphism and fluorescence measurements. In previous studies, we have successfully performed site-directed photochemical base substitution toward a synthetic single-stranded 100-mer ODN target (ss100-nt) and in vitro-synthesized full-length blue fluorescent protein mRNA as targets. Although the efficiency of C-to-U site-specific transition strongly depends on the sequence and structure of (CV) U-containing ODNs, the relationship between (CV) U-containing ODNs and the deamination efficiency of targeted editing remains unclear. Therefore, in this study, we attempted to identify the optimal sequence and primary structure of (CV) U-containing ODNs for site-directed specific transition. To evaluate the structure-deamination efficiency relationship, a series of eight (CV) U-containing ODNs were designed and studied. We showed that the optimal deamination efficiency was achieved with ODNs having a complementary sequence length slightly more than 14 nt and a hairpin length of 9 nt.


Elite Athletes and Pregnancy Outcomes: A Systematic Review and Meta-analysis.
The purpose of this systematic review was to evaluate fetal and maternal pregnancy outcomes of elite athletes who had participated in competitive sport immediately before conception. Online databases were searched up to March 24, 2020. Studies of any design and language were eligible if they contained information on the relevant population (pregnant women), exposure (engaged in elite sport immediately before pregnancy), and outcomes (birth weight, low birth weight, macrosomia, preterm birth, fetal heart rate and pulse index, cesarean sections, instrumental deliveries, episiotomies, duration of labor, perineal tears, pregnancy-induced low back pain, pelvic girdle pain, urinary incontinence, miscarriages, prenatal weight gain, inadequate/excess prenatal weight gain, maternal depression or anxiety). Eleven unique studies (n = 2256 women) were included. We identified "low" certainty evidence demonstrating lower rates of low back pain in elite athletes compared with active/sedentary controls (n = 248; odds ratio, 0.38; 95% confidence interval, 0.20-0.73; I2 = 0%) and "very low" certainty evidence indicating an increased odds of excessive prenatal weight gain in elite athletes versus active/sedentary controls (n = 1763; odds ratio, 2.47; 95% confidence interval, 1.26-4.85; I2 = 0%). Low certainty evidence from two studies (n = 7) indicated three episodes of fetal bradycardia after high-intensity exercise that resolved within 10 min of cessation of activity. No studies reported inadequate gestational weight gain or maternal depression or anxiety. There were no differences between elite athletes and controls for all other outcomes. There is "low" certainty of evidence that elite athletes have reduced odds of experiencing pregnancy-related low back pain and "very low"certainty of evidence that elite athletes have increased the odds of excessive weight gain compared with active/sedentary controls. More research is needed to provide strong evidence of how elite competitive sport before pregnancy affects maternal and fetal outcomes.PROSPERO Registration: CRD42020167382.


Tumor-associated trypsin inhibitor as a prognostic factor during follow-up of bladder cancer.
To evaluate the prognostic value of tumor-associated trypsin inhibitor (TATI) in the serum and urine of patients in follow-up for urinary bladder cancer. Serum and urine samples were taken during follow-up of 157 patients with transitional cell carcinoma of the bladder who were monitored by cystoscopy and cytology in 1986 to 1987. Initially, 117 (75%) of the 157 tumors were superficial. At the time of sampling, 93 patients (59%) had no detectable tumor and 48 (31%) had a superficial, and 16 (10%) an invasive, tumor. Cancer-specific survival was evaluated in 1998. During follow-up, 35 patients (22%) died of bladder cancer. An elevated TATI concentration in the serum (21 microg/L or more) was associated with a significantly shorter survival (P <0.001) compared with a normal value. Multivariate analysis showed that serum TATI and detectable cancer at sampling were independent prognostic factors (P <0.001 and P = 0.002, respectively), and age, grade, urine cytology findings, and urine TATI were not. Serum TATI is an independent prognostic factor in transitional cell carcinoma and is potentially useful for the identification of patients with an adverse prognosis.


Multidisciplinary approach to inherited causes of dual sensory impairment.
This article presents a review of the main causes of inherited dual sensory impairment (DSI) with an emphasis on the multidisciplinary approach. A narrative review of English literature published before January 2023 was conducted using PubMed, Medline, and Scopus databases. The different causes of inherited DSI are discussed from a multidisciplinary perspective. There are a wide range of dual sensory impairment (DSI), commonly referred to as blindness and deafness. While Usher syndrome is the most frequent genetic cause, other genetic syndromes such as Alport syndrome or Stickler syndrome can also lead to DSI. Various retinal phenotypes, including pigmentary retinopathy as seen in Usher syndrome, vitreoretinopathy as in Stickler syndrome, and macular dystrophy as in Alport syndrome, along with type of hearing loss (sensorineural or conductive) and additional systemic symptoms can aid in diagnostic suspicion. A thorough ophthalmologic and otorhinolaryngologic examination can help guide diagnosis, which can then be confirmed with genetic studies, crucial for determining prognosis. Effective hearing rehabilitation measures, such as hearing implants, and visual rehabilitation measures, such as low vision optical devices, are crucial for maintaining social interaction and proper development in these patients. While Usher syndrome is the primary cause of inherited dual sensory impairment (DSI), other genetic syndromes can also lead to this condition. A proper diagnostic approach based on retinal phenotypes and types of hearing loss can aid in ruling out alternative causes. Multidisciplinary approaches can assist in reaching a definitive diagnosis, which has significant prognostic implications.


Organochlorine pesticide levels in Ensis siliqua (Linnaeus, 1758) from Ría de Vigo, Galicia (N.W. Spain): influence of season, condition index and lipid content.
Levels of organochlorine pesticides (OCPs), including ΣDDTs, γ-HCH, HCB, aldrin, isodrin, trans-nonachlor, heptachlor and dieldrin, were determined in the razor clam, Ensis siliqua, collected monthly from February 2003 to April 2004 from the Islas Cíes in Ría de Vigo (Galicia, Spain). The sum of DDTs ranged from 2.17 to 26.9 ng g(-1) dry weight (dw). Principal component analysis showed seasonal trends in the levels of some OCPs (γ-HCH and dieldrin). Pearson correlations (p < 0.05) were observed between OCP levels and the biometric parameters of condition index and body lipids.


Usefulness of PKHs for studying cell proliferation.
Classical methods for proliferative assessment (such as tritiated thymidine or bromodeoxyuridine (BrdUrd) incorporation) need sample fixation. As an alternative, we have evaluated the use of a dye dilution method using PKH26 to determine the rate and extent of proliferation in cell lines. Flow cytometric analysis associated with modelling software makes it possible to estimate the number of cells having undergone different numbers of cell divisions by sampling the cell population at varying times post-labelling. Two major questions were addressed in these studies. (i) Does PKH26 give a stable and reproducible labelling? (ii) Does labelling with PKH26 alter cellular proliferation characteristics? We conclude that the methods developed here provide a simpler, more complete means for assessment of cell proliferation in patients with hematological malignancies.


A one-step purification method for monoclonal antibodies based on salt-promoted adsorption chromatography on a 'thiophilic' adsorbent.
A convenient and fast method for the purification of mouse monoclonal antibodies from the culture media of cloned cells or from ascites fluids by means of salt-promoted chromatography on a 'thiophilic' adsorbent is described. The adsorbent has a capacity to adsorb about 20 mg/ml of immunoglobulins and a broad specificity towards immunoglobulins derived from various animal species irrespective of the type or subclass to which they belong. The recovery of the purified IgG is better than 90% while that for IgM is considerably less, probably due to dissociation occurring during the adsorption-desorption process. This one-step procedure also leads to a considerable concentration of dilute solutions of immunoglobulins. Moreover, the purified Igs are eluted by an essentially salt-free buffer at near neutral pH thus obviating the need for post-treatment of the sample before storage or subsequent conjugation to enzymes for use in immunoassays. This purification method is also well suited for large-scale operations since sample preparation requires only the addition of 0.5 M K2SO4 to the ascited fluid or cell culture medium. The degree of purification obtained is, in certain instances, comparable to that obtained by biospecific affinity chromatography based on antigen-antibody interactions. In contrast to immunosorption and desorption methods, however, there is no risk of contamination of the immunoglobulins purified on the 'thiophilic' adsorbent by foreign proteins.


A balloon-assisted endoscopic submucosal dissection using long colonoscope and guidewire.
Balloon-assisted endoscopy enables stable endoscopic maneuverability. Balloon-assisted endoscopic submucosal dissection (BA-ESD) is useful in the treatment of proximal colorectal tumors where scope maneuverability is poor. Herein, we reported a case in which BA-ESD was successfully performed using a long colonoscope with a guidewire, although the lesion could not be reached using the balloon-assisted endoscopy technique with a therapeutic colonoscopy. A 50-year-old man underwent a colonoscopy that revealed a tumor in the ascending colon. BA-ESD was performed using a conventional therapeutic endoscope due to excessive intestinal elongation and poor endoscopic maneuverability. However, the transverse colon loop could not be reduced, and the total colonoscopy failed despite using balloon-assisted endoscopy. The scope was then changed from a conventional colonoscope to a long colonoscope, inserted into the terminal ileum, and the loop was reduced. After the guidewire was placed at the terminal ileum and the long colonoscope was removed, a therapeutic colonoscopy with an overtube was inserted into the ascending colon without reforming the colonic loop, allowing safe BA-ESD.


Benchmarking optimization methods for parameter estimation in large kinetic models.
Kinetic models contain unknown parameters that are estimated by optimizing the fit to experimental data. This task can be computationally challenging due to the presence of local optima and ill-conditioning. While a variety of optimization methods have been suggested to surmount these issues, it is difficult to choose the best one for a given problem a priori. A systematic comparison of parameter estimation methods for problems with tens to hundreds of optimization variables is currently missing, and smaller studies provided contradictory findings. We use a collection of benchmarks to evaluate the performance of two families of optimization methods: (i) multi-starts of deterministic local searches and (ii) stochastic global optimization metaheuristics; the latter may be combined with deterministic local searches, leading to hybrid methods. A fair comparison is ensured through a collaborative evaluation and a consideration of multiple performance metrics. We discuss possible evaluation criteria to assess the trade-off between computational efficiency and robustness. Our results show that, thanks to recent advances in the calculation of parametric sensitivities, a multi-start of gradient-based local methods is often a successful strategy, but a better performance can be obtained with a hybrid metaheuristic. The best performer combines a global scatter search metaheuristic with an interior point local method, provided with gradients estimated with adjoint-based sensitivities. We provide an implementation of this method to render it available to the scientific community. The code to reproduce the results is provided as Supplementary Material and is available at Zenodo https://doi.org/10.5281/zenodo.1304034. Supplementary data are available at Bioinformatics online.


Corrigendum: Long-term outcome of Bartter syndrome in 54 patients: a multicenter study in Korea.
[This corrects the article DOI: 10.3389/fmed.2023.1099840.].


E-Cadherin negatively modulates delta-catenin-induced morphological changes and RhoA activity reduction by competing with p190RhoGEF for delta-catenin.
delta-Catenin is a member of the p120-catenin subfamily of armadillo proteins. Here, we describe distinctive features of delta-catenin localization and its association with E-cadherin in HEK293 epithelial cells. In HEK293 cells maintained in low cell densities, approximately 15% of cells overexpressing delta-catenin showed dendrite-like process formation, but there was no detectable change in RhoA activity. In addition, delta-catenin was localized mainly in the cytoplasm and was associated with p190RhoGEF. However, at high cell densities, delta-catenin localization was shifted to the plasma membrane. The association of delta-catenin with E-cadherin was strengthened, whereas its interaction with p190RhoGEF was weakened. In mouse embryonic fibroblast cell, ectopic expression of E-cadherin decreased the effect of delta-catenin on the reduction of RhoA activity as well as on dendrite-like process formation. These results suggest that delta-catenin is more dominantly bound to E-cadherin than to p190RhoGEF, and that delta-catenin's function is dependent on its cellular binding partner.


A computer program for estimating the influence of the body bicarbonate pool during CO2 breath tests.
Mathematical representation of physiological systems is a useful means of monitoring various parameters and factors of such systems. The use of compartmental models for the study of physiological systems has led to the introduction of several new techniques for solving problems, concerning the kinetics between the individual sites of these systems. The computer program, presented here, allows the calculation of the influence of a mammillary model, representing the bicarbonate pool, on the expiration rate of the label, administered during a breath test. It consists of two modules, one for performing non-linear least squares regression fitting of discrete measurements from a breath test (model output) and a second one for estimating the corresponding label released into the bicarbonate pool (model input), based on the measurements of expired air. Data, derived from metabolic studies using oral administration of naturally labelled 13C-glucose in man, under various metabolic conditions, was used as an input to this program.


Radiotherapy of glioblastoma multiforme. Feasibility of increased fraction size and shortened overall treatment.
With regard to the poor prognosis of patients with glioblastoma multiforme, the aspect of life quality with a minimal treatment time becomes essential. The purpose of the present study is to evaluate whether the results of a radiotherapy schedule using increased single fractions applied over a shortened treatment time is feasible without compromising treatment efficiency or providing more side effects than a conventionally fractionated treatment. A total of 38 patients (f = 21, m = 17, mean age 58 years) with histologically proven glioblastoma multiforme were irradiated after (partial) resection (n = 29) or stereotactic surgery (n = 9) with single doses of 3.5 Gy (ICRU) 5 fractions a week up to a total dose of 42 Gy following individual treatment planning. Median survival was 45.7 weeks, survival rate after 6 months was 80.9% and decreased to 34.2% after 12 months. Radiotherapy was tolerated without any important acute toxicity or any late side effects during the follow-up period. The increase of the dose per fraction using a fraction size of 3.5 Gy enhanced neither acute nor late toxicity. The survival rate compared well to those described in the literature. Thus the shortened treatment schedule seems as efficient as conventional radiotherapy. Moreover, it seems preferable with regard to quality of life.


Parents' and Experts' Awareness of Learning Opportunities in Children's Museum Exhibits.
Informal learning outside of school are crucial for a child's development. Children's museums, in particular, are environments conducive to this sort of learning, especially when parents guide children's exploration. However, research suggests a gap between parents' and experts' perceptions of the value of informal learning. In Study 1, we asked groups of parents and experts (i.e., individuals in the community connected with the field of education or those with training in child growth and development) to rate the presence of learning opportunities available in two museum exhibits, finding that parents consistently provided lower ratings. In Study 2, we explored whether signage aimed at orienting parents toward the learning potential in these exhibits would have an impact on their ratings. Results suggested that signage made parents' ratings look more like those of experts. Taken together, these studies show that a simple intervention can help parents perceive the learning opportunities in children's museum exhibits as experts do.


Expression of the Drosophila melanogaster metallothionein genes in yeast.
The metallothionein system in Drosophila melanogaster is composed of two genes, Mto and Mtn, that code for distinctly different proteins. In order to compare the properties of Mto and Mtn, we transformed yeast with several fusion plasmids. The Mto and Mtn cDNAs, when placed under the control of CUP1 or PGK promoters, can confer a copper-resistance phenotype to copper-hypersensitive cells. Both Mto and Mtn proteins can be characterized in extracts from transformed yeast cells.


A high-throughput, low-cost method for the preparation of "sequencing-ready" phage DNA template.
We have developed a simple and efficient protocol for the isolation of good-quality recombinant phage DNA useful for all downstream processing, including automated sequencing. The overnight-grown phage particles were effectively precipitated (without any contaminating Escherichia coli DNA and other culture media components) by adjusting the pH of the culture medium to 5.2 with sodium acetate, followed by addition of ethanol to 25%. The phage DNA was selectively precipitated with ethanol in the presence of guanidinium thiocyanate under alkaline pH, resulting in uniform quality and quantity of phage DNA. The quality of the phage DNA preparation was demonstrated by DNA sequencing that provided an average read length of >700 bases (PHRED20 quality). This protocol for plating, picking, growing, and subsequent DNA purification of individual phage clones can be completely automated using any standard robotic platform. This protocol does not require any commercial kits and can be completed within 2h.


Epstein-Barr virus patterns in US Burkitt lymphoma tumors from the SEER residual tissue repository during 1979-2009.
Burkitt lymphoma (BL) occurs at all ages, but the patterns of Epstein-Barr virus (EBV) positivity in relation to human immunodeficiency virus (HIV), immunoprofiles and age have not been fully explored. BL tissues from residual tissue repositories, and two academic centers in the United States were examined by expert hematopathologists for morphology, immunohistochemistry, MYC rearrangement, EBV-encoded RNA (EBER), and diagnosed according to the 2008 WHO lymphoma classification. Analysis was done using frequency tables, Chi-squared statistics, and Student's t-test. Of 117 cases examined, 91 were confirmed as BL. The age distribution was 26%, 15%, 19%, and 29% for 0-19, 20-34, 35-59, 60+ years, and missing in 11%. MYC rearrangement was found in 89% and EBER positivity in 29% of 82 cases with results. EBER positivity varied with age (from 13% in age group 0-19 to 55% in age group 20-34, and fell to 25% in age group 60+ years, p = 0.08); with race (56% in Blacks/Hispanics vs 21% in Whites/Asians/Pacific Islanders, p = 0.006); and by HIV status (64% in HIV positive vs 22% in HIV negative cases, p = 0.03). EBER positivity was demonstrated in about one-third of tumors and it was strongly associated with race and HIV status, and marginally with age-group.


Determination of 17 macrolide antibiotics and avermectins residues in meat with accelerated solvent extraction by liquid chromatography-tandem mass spectrometry.
A method has been developed for simultaneous determination of 17 kinds of macrolide antibiotics and avermectins residues in animal origin foods. Samples were extracted with acetonitrile-methanol using accelerated solvent extraction (ASE) instrument. Parameters such as extraction temperature and pressure were investigated by a fractional factorial design (FFD) and the selected extraction (60 °C, 1500 psi for 10 min in two cycles) was most effective. High correlation coefficients (r > 0.999) of 17 macrolide antibiotics and avermectins were obtained within their respective linear ranges (2-400 μg/kg) using roxithromycin as internal standard. The recoveries of them were above 75% at different spiked levels in various samples. Using ASE the method was featured as short extraction times, reduction use of extraction solvent, high extraction yields, with high level of automation.


Experimental transmission of jaagsiekte (ovine pulmonary adenomatosis) to goats.
Jaagsiekte was successfully transmitted to at least 2 out of 6 goats inoculated intratracheally with partially purified jaagsiekte retrovirus. Multiple, small, well circumscribed nodules found in the lungs consisted of typical papilliform proliferations of neoplastic Type II epithelial cells. Histological evidence of a mild interstitial pneumonia in 4 of the experimental animals can probably be attributed to a contaminating lentivirus in the jaagsiekte retrovirus preparation, as suggested by the seroconversion of the animals.


A population founded by a single pair of individuals: establishment, expansion, and evolution.
Events occurring at the founding of a population, and in the next few generations, are potentially of great importance for the future evolution of the population. This study reports demographic, genetic, and morphological changes that took place during and after the colonization of the small Galápagos island of Daphne Major by three male and two female large ground finches, Geospiza magnirostris, at the end of 1982. Using assignment tests with microsatellite DNA data we demonstrate heterogeneity among the immigrants. Their sources included both a near island (Santa Cruz) and a far island (Marchena). However, almost all immigrants that stayed to breed were from an intermediate island (Santiago) and its satellites. Song may have been responsible for this selectivity. Mean heterozygosity stayed roughly constant over the next 15 years while allelic diversity almost doubled, after an initial decline, as the breeding population increased to a maximum of 30 pairs. Although close inbreeding occurred, with a reduction in heterozygosity, an expected net decline in heterozygosity did not occur, for two reasons: it was counteracted by continuing gene flow from immigrants at a low rate, and inbred birds (in one cohort) were at a selective disadvantage. An abrupt step-function shift in beak shape occurred after 9 years. Thus the study provides evidence of drift and selection causing morphological and genetic divergence in the establishment of a new population and in the first few generations.


Polymorphisms of estrogen receptor alpha in prostate cancer.
Estrogen receptor (ER) alpha polymorphisms have been shown to be involved in the oncogenesis of several organs. We hypothesize that polymorphisms of the ERalpha gene are risk factors for prostate cancer. The genotypic distributions of six different loci (codons: 10 T-->C, 87 G-->C, 243 C-->T, 325 C-->G, 594 G-->A, and intron 1 C-->T) of the ERalpha gene were analyzed in prostate cancer tissues. The DNA from 115 cases of prostate cancer (Japanese population) was analyzed by sequence-specific polymerase chain reaction (PCR) and direct sequencing to determine the genotypic and allelic frequencies of the six different polymorphic loci of ERalpha. The relative risk of variant genotype was calculated by comparison with 200 healthy controls. Results of this study showed that the frequency of the variant genotype (C/C) on codon 10 was significantly higher in prostate cancer patients. The odds ratio (OR) was calculated as 3.26 compared to wild-type (T/T) with a 95% confidence interval (CI) of 1.58-6.73. Allele frequency at codon 10 also differed between groups. No association was found between codon 10 polymorphism and the stage of cancer. Polymorphism was not observed in codon 87, and frequencies of genotypes and alleles at other loci (intron 1, codons 243, 325, and 594) were not statistically different between cancer and controls. The present study suggests that polymorphism in codon 10 of ERalpha may be a risk factor for prostate cancer. These results are important in understanding the role of ERalpha polymorphism in the pathogenesis of prostate cancer.


Volume-targeted ventilation and arterial carbon dioxide in neonates.
To review the arterial carbon dioxide tensions (PaCO(2)) in newborn infants ventilated using synchronized intermittent mandatory ventilation (SIMV) in volume guarantee mode (using the Dräger Babylog 8000+) with a unit policy targeting tidal volumes of approximately 4 mL/kg. Data on ventilator settings and arterial PaCO(2) levels were collected on all arterial blood gases (ABG; n = 288) from 50 neonates (<33 weeks gestational age) ventilated using the Dräger Babylog 8000+ ventilator (Dräger Medizintechnik GmbH, Lübeck, Germany) in SIMV plus volume guarantee mode. Data were analysed for all blood gases done on the entire cohort in the first 48 h of life and a subanalysis was done on the first gas for each infant (n = 38) ventilated using volume guarantee from admission to the nursery. The number of ABG showing severe hypocapnoea (PaCO(2) < 25 mmHg) and/or severe hypercapnoea (PaCO(2) > 65 mmHg) were determined. The mean (SD) PaCO(2) during the first 48 h was 46.6 (9.0) mmHg. The mean (SD) PaCO(2) on the first blood gas of those infants commenced on volume guarantee from admission was 45.1 (12.5) mmHg. Severe hypo- or hypercapnoea occurred in 8% of infants at the time of their first blood gas measurement, and in <4% of blood gas measurements in the first 48 h. Infants ventilated with volume guarantee ventilation targeting approximately 4 mL/kg (range: 2.9-5.1) have acceptable PaCO(2) levels at the first blood gas measurement and during the first 48 h of life; and avoid severe hypo- or hypercapnoea over 90% of the time.


Microelectrode investigations of the visual system at the Department Of Clinical Neurophysiology, Freiburg i.Br.: a historical account of the first 10 years, 1951-1960.
The history of the first ten years of neurophysiological science (1951-1960) at the Department of Clinical Neurophysiology in Freiburg i.Br. (Germany) is described by some of the participants. We describe the concepts of Richard Jung for the development of an experimental neurophysiology, the technical conditions which helped to realize these ideas, and the integration of the newly emerging German neurophysiological science into the international community, through the large number of foreign visitors. A short account is given of the young scientists working at the Freiburg laboratory during this period, their main lines of research, as well as the results of their studies.


Smell and taste dysfunction in patients infected with the Omicron variant of severe acute respiratory syndrome coronavirus-2.
Smell and taste dysfunctions (STD) are frequently observed in patients with coronavirus disease (COVID-19). To investigate the clinical characteristics of STD in COVID-19 patients. One-hundred six COVID-19 adult patients with the Omicron variant were enrolled. The clinical features of patients with and without STD were compared using questionnaires, laboratory tests, and imaging examinations. Of the 76 patients with smell and/or taste dysfunction, age (p = .002), vaccination time (p = .024), history of systemic diseases (p = .032), and smoking status (p = .044) were significantly different from those of the controls (n = 34). Fatigue (p = .001), headache (p = .004), myalgia (p = .047), and gastrointestinal discomfort (p = .001) were observed more frequently in these patients than in controls. The Hospital Anxiety and Depression Scale score of these patients was significantly higher than that of controls (p < .001). The taste visual assessment scale score of the STD group was significantly lower than that of the taste dysfunction group (p = .001), and perceptions of sour, sweet, and salty tastes were worse in the STD group than in the taste dysfunction group (p < .001). COVID-19 patients had similar changes in smell and/or taste dysfunctions and worse emotional states, possibly correlated with some factors, including age and vaccination time.


Umpolung AlaB Reagents for the Synthesis of Non-Proteogenic Amino Acids, Peptides and Proteins.
Non-proteogenic amino acids and functionalized peptides are important motifs in modern drug discovery. Here we report that AlaB can serve as universal building blocks in the synthesis of a diverse collection of modified amino acids, peptides, and proteins. First, we develop the synthesis of AlaB from redox-active esters of aspartic acid resulting in a series of β-boronoalanine derivatives. Next, we show that AlaB can be integrated into automated oligopeptide solid-phase synthesis. AlaB is compatible with common transformations used in preparative peptide chemistry such as native chemical ligation and radical desulfurization as showcased by total synthesis of AlaB -containing ubiquitin. Furthermore, AlaB reagents participate in Pd-catalyzed reactions, including C-C cross-couplings and macrocyclizations. Taken together, AlaB synthons are practical reagents to access modified peptides, proteins, and in the synthesis of cyclic/stapled peptides.


Pharmacokinetics of immunoglobulin administered via intravenous or subcutaneous routes.
This article reviews pharmacokinetic studies of IgG administration by intravenous and subcutaneous routes. Intravenous immunoglobulin pharmacokinetics have been studied during replacement therapy for primary and secondary immunodeficiencies and other special circumstances (eg, infection prophylaxis in neonates). Subcutaneous immunoglobulin pharmacokinetics have been studied only during replacement therapy for primary immunodeficiency. Published studies vary greatly with respect to the nature of the patients studied, dose regimens, sampling schedules, and pharmacokinetic models, making comparisons difficult. With either route of administration, there is large variation in individual IgG elimination rates. Periodic measurement of serum IgG concentration is critical to monitor the adequacy of replacement during therapy.


Development of a drinking water regulation for perchlorate in California.
Perchlorate is an environmental contaminant often associated with military installations and rocket propellant manufacture and testing facilities across the U.S. Highly water soluble, perchlorate has been found by federal and state agencies at almost 400 sites within the U.S. in groundwater, surface water, soil or public drinking water. There is no federal drinking water standard for perchlorate, but it is on the drinking water Contaminant Candidate List, and falls under the Unregulated Contaminant Monitoring Rule (UCMR) for which monitoring is required. The recent National Academy of Science (NAS) report on the potential health effects of perchlorate recommended a perchlorate reference dose of 0.0007 mg/kg of body weight which would be equivalent to a drinking water concentration of 24.5 microg/L. In California, approximately 395 wells in 96 water systems have been shown to contain perchlorate, and about 90% of these are located in Southern California. Water taken from the Colorado River, a major surface water supply to Southern California, has had reported detections of perchlorate ranging from non-detect to 9 microg/L. California has established a Public Health Goal (PHG) of 6 microg/L for perchlorate, and a proposed drinking water regulation is imminent. This review details the regulatory process involved with particular attention given to the occurrence of perchlorate in California drinking water sources and analytical methodology utilized.


Feasibility study of adjuvant chemotherapy with S-1 (TS-1; tegafur, gimeracil and oteracil potassium) for colorectal cancer.
The aim of this study is to evaluate feasibility and safety of 3-week method (3-week administration and 1-week withdrawal) for colorectal cancer as adjuvant chemotherapy with an oral anticancer drug, S-1. Forty-two patients with stage II or III colorectal cancer who underwent curative resection in our hospital during a one year period in 2005 were enrolled in the preliminary pilot study. Between 2006 and 2007, 104 patients with stage II or III colorectal cancer who underwent curative resection in our hospital were chosen and were randomly divided into two groups, 3-week method or 4-week method (4-week administration and 2-week withdrawal) for a prospective randomized trial. The one-year completion rate in the 3-week method group was 98% (50/51) which was significantly better than that in the 4-week method group, 68% (36/53) (p=0.035). There were no grade 3 or 4 adverse reactions in both laboratory and clinical findings in the pilot study and in the prospective randomized trial. Three-week method of S-1 administration had good feasibility, easily manageable toxicity, high accumulated dose in one year and good compliance. The 3-week method with S-1 may be a standard adjuvant chemotherapy schedule for colorectal cancer.


Beta-tricalcium phosphate, white mineral trioxide aggregate, white Portland cement, ferric sulfate, and formocresol used as pulpotomy agents in primary pig teeth.
The purpose of this study was to evaluate and compare the effects of formocresol (FC), ferric sulfate (FS), white mineral trioxide aggregate (WMTA), white Portland cement (WPC), and beta-tricalcium phosphate (beta-TCP) on pulpotomized primary teeth of pigs. Fifty teeth of three 3-month old pigs were pulpotomized with these materials. Three weeks later, the animals were euthanized and the specimens were prepared for histological examination. There was no significant difference between beta-TCP, WMTA, and WPC in terms of primary pulp response, hard tissue formation, and normal pulp tissue preservation. But, both FS and FC irritated the pulp tissue, provoking a more inflammatory pulp response than beta-TCP, WMTA, and WPC. Beta-TCP, WMTA, and WPC are histologically more effective pulpotomy agents than formocresol and ferric sulfate in primary pig teeth.


Double mutation of cell wall proteins CspB and PBP1a increases secretion of the antibody Fab fragment from Corynebacterium glutamicum.
Among other advantages, recombinant antibody-binding fragments (Fabs) hold great clinical and commercial potential, owing to their efficient tissue penetration compared to that of full-length IgGs. Although production of recombinant Fab using microbial expression systems has been reported, yields of active Fab have not been satisfactory. We recently developed the Corynebacterium glutamicum protein expression system (CORYNEX®) and demonstrated improved yield and purity for some applications, although the system has not been applied to Fab production. The Fab fragment of human anti-HER2 was successfully secreted by the CORYNEX® system using the conventional C. glutamicum strain YDK010, but the productivity was very low. To improve the secretion efficiency, we investigated the effects of deleting cell wall-related genes. Fab secretion was increased 5.2 times by deletion of pbp1a, encoding one of the penicillin-binding proteins (PBP1a), mediating cell wall peptidoglycan (PG) synthesis. However, this Δpbp1a mutation did not improve Fab secretion in the wild-type ATCC13869 strain. Because YDK010 carries a mutation in the cspB gene encoding a surface (S)-layer protein, we evaluated the effect of ΔcspB mutation on Fab secretion from ATCC13869. The Δpbp1a mutation showed a positive effect on Fab secretion only in combination with the ΔcspB mutation. The ΔcspBΔpbp1a double mutant showed much greater sensitivity to lysozyme than either single mutant or the wild-type strain, suggesting that these mutations reduced cell wall resistance to protein secretion. There are at least two crucial permeability barriers to Fab secretion in the cell surface structure of C. glutamicum, the PG layer, and the S-layer. The ΔcspBΔpbp1a double mutant allows efficient Fab production using the CORYNEX® system.


Phenotypic cross-species conservation and cross-generation directionality switching in epigenetic inheritance.
Evidence supporting non-DNA sequence-based inheritance in animals has increasingly been described in recent years, often under intergenerational inheritance or transgenerational epigenetic inheritance (TEI). Existence of the latter, a stronger indicator of germline transmission, has been demonstrated in invertebrates and mammals alike. The mechanisms and physiological implications of TEI, however, remain unclear. Here, in an unbiased approach, we compared existing transcriptomic data associated with so far available Drosophila models of inter- and trans-, and rodent models of inter-generational inheritance; observed phenotypic cross-species conservation and cross-generation directionality shift therein; and confirmed these observations experimentally in flies. Specifically, previous models of cold and diet-induced inheritance in both flies and mice were commonly associated with altered regulation of proteolysis genes. Besides, fly TEI models were in general characterized by opposite phenotypic regulation in transgenerational offsprings, compared to the ancestors. As insulin-producing cell (IPC) ablation was also associated with proteolysis gene dysregulation in one of the mouse models, we opted to use genetic ablation of IPCs in flies for the experimental validation. Remarkably, the ablation led to transcriptomic alterations across multiple generations, with dysregulated genes showing proteolysis enrichment. Similarly, phenotypic directionality changed in the opposite direction in transgenerational offsprings, in comparison of the ancestors. These results support evolutionary conservation, and both physiologically adaptive and maladaptive consequences of germline mediated epigenetic inheritance.


Clinical implications and mechanism of complement C1q in polymyositis.
Polymyositis (PM) is the most common autoimmune disease in neurology and among muscle disorders; it is of great significance to thoroughly understand the mechanism of PM to find new diagnosis and treatment methods. This research intends to elucidate the clinical implications and mechanisms of complement C1q in polymyositis (PM). One hundred fifteen PM patients (research group, RG) and 120 healthy subjects (control group, CG) who visited our hospital between March 2017 and March 2020 were selected. Peripheral blood C1q and creatine kinase (CK) levels of both groups were measured, and their correlations with clinical symptoms and prognostic recurrence of PM. Additionally, to further understand the mechanism of action of C1q in PM, we purchased BALB/c mice and grouped them as follows: control group with normal feeding, PM group with PM modeling, intervention group with PM modeling, and intraperitoneal injection of gC1qR monoclonal antibody 60.11, a C1q protein receptor. Inflammatory factors and muscle histopathology were detected in all groups of mice. Finally, rat macrophages (mø) were isolated, and changes in the biological behavior of mø were observed after silencing the expression of gC1qR. Serum C1q and CK were both higher in RG than in CG, with favorable diagnostic effects on PM (P < 0.05). C1q and CK increased in symptomatic anti-ribonuclear protein antibody (RNP)-positive patients but decreased in anti Jo-1 antibody (Jo-1)- and anti-neutrophil cytoplasmic antibody (ANCA)-positive patients (P < 0.05). PM mice were observed with elevated gC1qR, while model mice exhibited severe infiltration of inflammatory cells in muscle tissue, increased pro-IFs, and reduced anti-IFs, and the animals in the intervention group showed improved conditions (P < 0.05). Finally, it was found that CD68, CD86 protein, and invasion capacity of gC1qR-sh-transfected cells decreased, while CD206 and CD163 increased (P < 0.05). C1q is elevated in PM and is strongly linked to the pathological process of PM. Inhibition of gC1qR expression reduced inflammatory infiltration in PM mice.


Evaluation of preserved bovine tendon xenografts: a histological, biomechanical and clinical study.
Glutaraldehyde treated bovine tendon xenografts have been introduced into clinical trials as human knee ligament replacements recently, following animal experiments. This paper reports a further clinical study in which complications arose from implant debris. A laboratory study showed that the implants were not absorbed or integrated into the tissues of the host animals, as had been claimed by the originators. Mechanical tests of tendon reconstructions showed that the implants were not functional. It was concluded that this material is not suitable for clinical use within the knee joint as a cruciate ligament prosthesis.


[Hemorrhagic manifestation of moyamoya disease in a 19-year-old woman with mental retardation].
The paper presents a case of moyamoya disease, with first clinical sign subarachnoid haemorrhage in a 19-year old woman with mental impairment. The CT screen shows the presence of ischaemic areas of haemorrhagic type. MR, angio-MR and classical angiography confirmed the presence of ischaemic areas with contraction of the distal parts of the internal carotid arteries and left anterior cerebral artery. Authors call attention to the diagnostic problems of the case and accent the very important role of MR and MR angiography in the diagnosis of moyamoya disease.