Predictive value of circulating tumor cells (CTCs) in newly-diagnosed and recurrent ovarian cancer patients.
To determine whether circulating tumor cells (CTCs), as detected and enumerated by the Veridex CellSearch system, could predict for clinical outcomes in women with newly diagnosed or recurrent epithelial ovarian cancer. Serial measurements of CTC s and paired serum CA125 were collected in a series of 78 women with newly diagnosed or recurrent ovarian cancer seen at our institution over a period of 15 months. Clinical data were abstracted from patient medical records. CTCs were detected and enumerated by the CellSearch protocol, and patients were divided into CTC negative (<2 CTCs) or positive (≥2 CTCs) groups. CTC groups were correlated with clinical characteristics and outcomes. A longitudinal analysis of CTC change and CA125 trends was also performed. At least one CTC was isolated from the peripheral blood of over 80% of the women participating in this study, with a range from 0 to 8. No correlations were observed between CTC numbers and clinical characteristics or outcomes. Although both serum CA125 and CTC number exhibited an overall significant decreasing trend over time, there was no correlation observed between change in CTCs and CA125. Using the FDA-approved CellSearch system, CTCs can be isolated from women with newly diagnosed or recurrent ovarian cancer. However, CTC numbers do not significantly correlate with clinical characteristics or patient outcomes. Future studies should focus on phenotypic characterization of CTCs and whether different isolation protocols yield a higher number of CTCs or add prognostic value.


Does Perspective Taking Matter for Writing? Perspective Taking in Source-Based Analytical Writing of Secondary Students.
Perspective taking, one's knowledge of their own mental and emotional states and inferences about others' mental and emotional states, is an important skill for writing development. In the present study, we examined how perspective taking is expressed in writing and how it is related to overall writing quality. We analyzed seventh graders' source-based analytical essays (N = 195) to investigate (1) the extent to which students incorporated perspective taking in their essays, (2) how the extent of perspective taking in essays differ by students' sex and English learner status, and (3) the extent to which perspective taking in writing is associated with overall writing quality. Findings revealed that students wrote more from their own perspective than that of others. Moreover, the results of multi-level analyses suggested that female students exhibited more varied perspectives but there was no meaningful difference by English learner status. Lastly, greater extent of perspective taking, particularly that of higher level of perspectives (i.e., dual perspective), was associated with better writing quality, after accounting for students' demographic backgrounds (e.g., sex, poverty status, English learner status) and essay length. These results underscore the importance of writing from multiple perspectives on writing quality.


Functional loading of the dentition during mastication.
A method is described whereby the electrical activity in the masseter muscles is used as an index of chewing force. By using the kinesiograph, it was possible to determine the interrelationship of the phases of the chewing cycle and to measure the duration of each phase. On the basis of a pilot study of 10 dentate subjects and two complete denture wearers, it appears that, although the magnitude of the applied load is reduced in denture wearers, this is to some extent compensated for by an increase in the time it is applied. The results also suggest that a greater force is applied to the supporting mucoperiosteum when inverted cusp teeth are used in the construction of the dentures.


A Systematic Review of Patient Race, Ethnicity, Socioeconomic Status, and Educational Attainment in Prostate Cancer Treatment Randomised Trials-Is the Evidence Base Applicable to the General Patient Population?
Prostate cancer (PC) disproportionately affects men of Black race, and lower educational and socioeconomic status. Guidelines are based on randomised controlled trials (RCTs); however, the representation of different races, educations, and socioeconomic backgrounds in these trials is unclear. To assess reporting of equality, diversity, and inclusion characteristics (Equality, Diversity and Inclusion [EDI]) and differences in treatment effects between different races, and educational or socioeconomic status. We conducted a systematic review of CENTRAL, MEDLINE, and Embase in April 2020 examining RCTs investigating treatments for PC. Outcomes collected were race/ethnicity, educational attainment, and socioeconomic status. RCTs investigating PC treatment in any population or setting were included. Data extraction of characteristics was performed independently by pairs of reviewers and checked by a senior author. The Cochrane risk of bias tool assessed the quality of included papers. A total of 265 trials were included, and 138 of these were available as full-text articles. Fifty-four trials including 19 039 participants reported any EDI data. All 54 trials reported race, 11 reported ethnicity, three reported educational attainment, and one reported socioeconomic status. Patients of White race were the majority of the recruited population (82.6%), while the minority prevalence was as follows: Black 9.8% and Asian 5.7%. Three studies reported mortality outcomes depending on the participant's race. All three studies investigated different treatments, so a meta-analysis was not performed. No studies reported outcomes stratified by the educational or socioeconomic status of participants. There is poor reporting of patient race, ethnicity, socioeconomic background, and educational attainment in RCTs for PC treatments between 2010 and 2020. Addressing this for future studies will help explain differences in the incidence of and mortality from PC and improve the generalisability of results. In this study, we reviewed prostate cancer treatment trials to see whether these reported race, education, and socioeconomic backgrounds of their patient populations. We conclude that reporting of these characteristics is poor. This needs to be improved in future to improve outcomes for patients with prostate cancer of all ethnical, racial, and socioeconomic groups.


Oxidative stress measured by carbonyl groups level in postmenopausal women after oral and transdermal hormone therapy.
Menopause is associated with an increased risk of cardiovascular disorders, which are accompanied by oxidative stress. Our study was undertaken to determine whether oxidative stress in menopausal women could be reduced after six months of oral or transdermal hormonal therapy. Carbonyl groups of proteins in blood plasma were estimated by sensitive ELISA method with anti-DNP antibodies. In this method, protein samples diluted in phosphate-buffered saline were adsorbed to wells of an ELISA plate and then reacted with dinitrophenylhydrazine (DNPH). Plasma protein carbonyl levels of postmenopausal women treated with o-HT and t-HT for six months (o-HT: 1.785 ± 0.31 nmol/mg; t-HT: 1.838 ± 0.33 nmol/mg) were lower when compared with the control group (2.232 ± 0.28 nmol/mg). There was no statistically significant difference in carbonyl levels between women after oral and transdermal HT (P = 0.149). Hormonal therapy reduces the level of carbonyl protein, a marker of oxidative stress, suggesting potential protective effect.


Nucleolysis and diskography--an experimental study on interaction of chymopapain and contrast medium.
A test was carried out on 11 young, full sized mongrels to determine whether there is an interaction between chymopapain and the contrast agents iotrolan and iopamidol. A total of 75 intervertebral disks were punctured: nucleolysis alone was performed on 20, diskography with iotrolan and subsequent nucleolysis on 20, and diskography with iopamidol and subsequent nucleolysis on 10. Diskography alone was performed 10 times with iotrolan and 5 times with iopamidol. Aqua dest. was given intradiskally 5 times, and puncture was carried out 5 times without the administration of any substance. Following puncture, x-rays of the lumbar vertebral column were taken laterally: daily for the first 10 days, then weekly. Disk space narrowing typical of nucleolysis with chymopapain was found among the disks that were nucleolyzed only to the same extent as among those that had undergone diskography previously. There was no evidence of narrowing of the other disk spaces which had been punctured but not treated with chymopapain. On some of the dogs, CT and MRI examinations were carried out. The CTs showed a homogenous hypodensity in all of the disks, in which chymopapain had been injected. The MRI revealed a signal loss in all of the nucleolyzed disks. The results of short and long term follow up demonstrate that inhibition of chymopapain by iotrolan or iopamidol is not to be expected and therefore diskography prior to chemonucleolysis can be performed without danger of enzyme inactivation.


Enhancing the cellulose-degrading activity of cellulolytic bacteria CTL-6 (Clostridium thermocellum) by co-culture with non-cellulolytic bacteria W2-10 (Geobacillus sp.).
The effect of a non-cellulolytic bacterium W2-10 (Geobacillus sp.) on the cellulose-degrading activity of a cellulolytic bacterium CTL-6 (Clostridium thermocellum) was determined using cellulose materials (paper and straw) in peptone cellulose solution (PCS) medium under aerobic conditions. The results indicated that in the co-culture, addition of W2-10 resulted in a balanced medium pH, and may provide the required anaerobic environment for CTL-6. Overall, addition of W2-10 was beneficial to CTL-6 growth in the adverse environment of the PCS medium. In co-culture with W2-10, the CTL-6 cellulose degradation efficiency of filter paper and alkaline-treated wheat straw significantly increased up to 72.45 and 37.79 %, respectively. The CMCase activity and biomass of CTL-6 also increased from 0.23 U ml(-1) and 45.1 μg ml(-1) (DNA content) up to 0.47 U ml(-1) and 112.2 μg ml(-1), respectively. In addition, co-culture resulted in accumulation of acetate and propionate up to 4.26 and 2.76 mg ml(-1). This was a respective increase of 2.58 and 4.45 times, in comparison to the monoculture with CTL-6.


Prognostic value of DNA ploidy and S-phase fraction in relation to estrogen receptor content and clinicopathological variables in primary breast cancer.
Tumors from 472 women with primary breast cancer were analyzed by flow cytometry. Divided into four categories, DNA ploidy showed significant association with disease recurrence and mortality. When allowance was made for its correlation with nodal status and estrogen receptor (ER) content, DNA ploidy did not add prognostic information. S-phase fraction was estimated in 290 DNA histograms. In contrast, it was significantly related to recurrence and mortality when controlling for nodal status, tumor size and ER content. When the follow-up was divided into two periods DNA ploidy and S-phase fraction showed association with disease recurrence in the first period only (less than 2.5 years), while the association with mortality was valid for both periods. Light scatter was measured in 234 samples. A low light scatter variability for the stemline nuclei was related to a high recurrence rate during the early follow-up period. In conclusion, DNA flow cytometry adds prognostic information concerning breast cancer patients.


Late aortic obstruction due to ductal vasoconstriction on pulmonic end after transcatheter patent ductus arteriosus closure in an extremely low-birth-weight infant.
Device-induced aortic obstruction is a known rare complication following transcatheter closure of patent ductus arteriosus in extremely low-birth-weight infants. Various mechanisms have been proposed. We report the first description of late aortic obstruction due to ductal vasoconstriction on pulmonic end causing device to be gradually pushed out of aortic end in a 980-gram premature infant.


A Novel MicroRNA-124/PTPN1 Signal Pathway Mediates Synaptic and Memory Deficits in Alzheimer's Disease.
Synaptic loss is an early pathological event in Alzheimer's disease (AD), but its underlying molecular mechanisms remain largely unknown. Recently, microRNAs (miRNAs) have emerged as important modulators of synaptic function and memory. We used miRNA array and quantitative polymerase chain reaction to examine the alteration of miRNAs in AD mice and patients as well as the Morris water maze to evaluate learning and memory in the mice. We also used adeno-associated virus or lentivirus to introduce tyrosine-protein phosphatase non-receptor type 1 (PTPN1) expression of silencing RNAs. Long-term potentiation and Golgi staining were used to evaluate the synaptic function and structure. We designed a peptide to interrupt miR-124/PTPN1 interaction. Here we report that neuronal miR-124 is dramatically increased in the hippocampus of Tg2576 mice, a recognized AD mouse model. Similar changes were observed in specific brain regions of affected AD individuals. We further identified PTPN1 as a direct target of miR-124. Overexpression of miR-124 or knockdown of PTPN1 recapitulated AD-like phenotypes in mice, including deficits in synaptic transmission and plasticity as well as memory by impairing the glutamate receptor 2 membrane insertion. Most importantly, rebuilding the miR-124/PTPN1 pathway by suppression of miR-124, overexpression of PTPN1, or application of a peptide that disrupts the miR-124/PTPN1 interaction could restore synaptic failure and memory deficits. Taken together, these results identified the miR-124/PTPN1 pathway as a critical mediator of synaptic dysfunction and memory loss in AD, and the miR-124/PTPN1 pathway could be considered as a promising novel therapeutic target for AD patients.


[Not Available].
Intestinal infections in Germany due to enterohemorrhagic E. coli bacteria (EHEC) between 1998 and 2001 reveal a large scale of biological diversity of their pathogens. However, no dramatic increase of their clinical importance and public health implications has been observed. As strains of serovar O157:H7 have continuously declined as causative agents, other serovars such as O26:H11 and O103:H2 have replaced them. The great diversity of the EHEC pathogens might point to a great number of various infection routes and sources. Since recently new pathogenic factors of EHEC bacteria have been detected (especially by the sequencing of the genome of EHEC), it is currently not possible to define a clear-cut difference between human pathogens and nonhuman pathogens. The enhanced surveillance of EHEC pathogens with respect to their biological diversity and dynamics, their epidemic spread, and their infection routes and sources remain an essential task of the public health authorities.


The multifaceted roles of peptides in "always-on" near-infrared fluorescent probes for tumor imaging.
Tumor-targeted near-infrared (NIR) fluorescence imaging by using NIR fluorescent probes has attracted extensive attentions in the field of tumor imaging and is becoming an attractive strategy for early cancer diagnosis and surgical guidance for the past few decades. Especially, due to the high affinity and low toxicity, the peptide-based NIR fluorescent probes play an important role in the field of tumor-targeted imaging and therapy. Extensive attempts have been made to develop a set of nontoxic and efficacious "always-on" peptide-based NIR fluorescent probes. In this review, we give a comprehensive analysis of the "always-on" peptide-based NIR fluorescent probes for tumor-targeting for the past 5 years, highlighting the design strategy, chemical synthesis, therapeutical applications, spectroscopic and pharmacological characterization, as well as the multifaceted roles of peptides. A comprehensive understanding of the tumor-targeted, "always-on" peptide-based NIR fluorescent probes will increase our knowledge of cancer diagnosis and benefit clinical cancer therapeutics.


The trajectory of the caring role in Korea: A grounded theory study of mothers of children with blood cancer.
The purpose of this study was to investigate the trajectory of mothers caring for children with blood cancer. Fourteen mothers of children with blood cancer participated in in-depth interviews, from 30 min to 2 h in length, from July 1 through September 30, 2019. Grounded theory was used to investigate the trajectory for mothers of children with blood cancer. Purposive sampling and semi-structured questionnaires were employed to obtain in-depth interviews. 10 categories and 28 concepts were extracted from the raw data. The core category was 'living with anxiety: from life to independence of their sick child' which consisted of three phases: feeling chaos, immersing oneself in treatment, and returning to normal life. In the trajectory of mothers of caring for children with blood cancer, some participants felt like being on an island and hope to forget, whereas others tended to thank for the support of those near and find their own life according to the dimension of anxiety, support from others, and acceptance of illness. Healthcare providers must have a better understanding of how the mothers of children with blood cancer can accept and cope with their child's illness in spite of the ongoing anxiety as well as need to explore the ways in which families can accept their child's chronic illness and reconstruct their life.


Measurement of the plasma clearance of urographic contrast media for the determination of glomerular filtration rate.
Further experience with a new method to determine glomerular filtration rate is presented. The method depends on measurement by an x-ray fluorescence technique of the plasma disappearance of the injected iodine in standard nonionic radiographic contrast media used during excretory urography. The results of comparison of contrast clearance with 99m technetium-diethylenetriaminepentaacetic acid clearance in 33 cases showed excellent agreement with a correlation coefficient of 0.95. Reproducibility of the contrast clearance method was confirmed by repeated examination of 10 plasma samples at weekly intervals for 6 weeks, the results of which showed no significant differences. The contrast clearance technique for the measurement of glomerular filtration rate during excretory urography is simple, quick and accurate, and merits further development.


Urticarial vasculitis induced by OTC diet pills: a case report.
Urticarial Vasculitis (UV) is in most of the cases idiopathic; however it has been associated with several conditions and drugs. Over the counter (OTC) diet pills are widely available, even on-line, but they are rarely regulated by pharmaceutical control. We present the case of a 35-year-old female patient suffering of pruriginous and painful wheals more than 1 cm in diameter, with a burning sensation. The eruption lasted more than 24 hours and was accompanied by angioedema, headache and myalgia. No remarkable medical history was found, except for previous intake of OTC diet pills. UV diagnosis was confirmed by the skin biopsy of a lesion. OTC diet pills are widely available worldwide, and due to its widespread use, allergologists and dermatologist should be able to recognize symptoms and lesions of cutaneous vasculitis, which may be under reported.


Molecular Engineering on Bis(benzothiophene-S,S-dioxide)-Based Large-Band Gap Polymers for Interfacial Modifications in Polymer Solar Cells.
The development of effectively universal interfacial materials for both conventional and inverted polymer solar cells (PSCs) plays a very crucial role in achieving highly photovoltaic performance and feasible device engineering. In this study, two novel alcohol-soluble conjugated polymers (PBSON-P and PBSON-FEO) with bis(benzothiophene-S,S-dioxide)-fused aromatics (FBTO) as the core unit and amino as functional groups are synthesized. They are utilized as universal cathode interfacial layers for both conventional and inverted PSCs simultaneously. Ascribing to the enlarged conjugated planarity and higher electron affinity for an FBTO unit, both PBSON-P and PBSON-FEO exhibit versatile electron-transporting abilities. They show wide band gaps that are important for light absorption in inverted PSCs, at which point PBSON-P and PBSON-FEO are more progressive than some of the reported small band gap cathode interfacial materials. Importantly, PBSON-P and PBSON-FEO display deep highest occupied molecular orbital energy levels, which can block holes at the cathode and thus increase the fill factor. As a result, both conventional and inverted PSCs using PBSON-P and PBSON-FEO as cathode interlayers realize high photovoltaic performance. Therefore, this series of novel polymers are amphibious cathode interfacial materials for high-performance conventional and inverted PSCs.


The use of thioesterase II as a rat mammary epithelial cell-specific marker.
The avidin-biotin-peroxidase complex immunoperoxidase technique was employed to determine the intercellular distribution of thioesterase II in rat mammary glands. This enzyme is responsible for shifting the product specificity of the fatty-acid synthetase enzyme complex from long to medium chain fatty acids. Thioesterase II was found exclusively in the cells lining the lumen of the ductal and alveolar structures in glands from mature virgin (150 days old) and pregnant rats. The ductal cell staining intensity was considerably less than that of the alveolar cells in the mature virgin rat glands. No immunoreactive thioesterase II was found in the stromal, adipose, vascular, or myoepithelial components of the gland in the developmental stages examined. In the glands from immature virgin rats (40-45 days old) thioesterase II was again found only in the epithelial cells lining the lumen of the ductal and end-bud structures although this layer was usually more than one cell thick. Quantitative determination of thioesterase II activity in cytosol preparations revealed similar levels in mammary fragments from enzymatically-dissociated glands obtained from mature virgins and in end buds derived from immature virgins, but somewhat higher levels in mammary structures derived from late-pregnant animals. These immunohistological and biochemical results demonstrate thioesterase II's usefulness as a mammary epithelial cell-specific marker.


Luminescence complementation assay for measurement of binding to protein C-termini in live cells.
Protein-protein interactions (PPIs) involving the extreme C-terminus serve important scaffolding and regulatory functions. Here, we leveraged NanoBiT technology to build a luminescent complementation assay for use in studying this subcategory of PPI. As a model system, we fused one component of NanoBiT to the disordered C-terminus of heat shock protein (Hsp70) and the other to its binding partner, the tetratricopeptide repeat (TPR) domain of CHIP/STUB1. We found that HEK293 cells that stably express these chimeras under a doxycycline promoter produced a robust luminescence signal. This signal was sensitive to mutations and it was further tuned by the expression of competitive C-termini. Using this system, we identified a promising, membrane permeable inhibitor of the Hsp70-CHIP interaction. More broadly, we anticipate that NanoBiT is well-suited for studying PPIs that involve C-termini.


[Specific variability in the number of cells with X-chromatin in short-term buccal epithelium cultures from women following exposure to hormones at different phases in their individual diurnal biorhythm].
Changes in the number of cells with X- and K-chromatin were studied in the buccal epithelium of 4 women in vivo for 29 h, every 2--4 h, and similarly in cultures (3 h) with and without any hormone: ACTH, insulin, thyroxin. The biorhythm of the cells with X-chromatin (established by Kanyuka in 1973) both in vivo and ie vitro within the range of from 44 to 340 0/00 per 24 h was confirmed; individual variability of the mean heterochromatin index value (X-HClm) was revealed in vitro with and without any hormones. Cell incubation with hormones at the time of minimal X-HCl in vivo led to increase in the number of cells with X-chromatin within 3 h from 50 to 240 0/00, whereas incubation at the time of maximal X-HCl in vivo--to reduction from 190 to 70 0/00. It is suggested that the specific response to the hormones is preceded by the nonspecific tissue response, determined by its condition at the time of action (by the individual X-HCl biorhythm phase) and realized in the systemic reconstruction of the number of cells at various mitotic cycle phases. Stereotypic reaction was expressed in the changes in character of the nuclear chromatin sondensation; these processes were reversible.


Nursing in a posthuman era: Towards a technology-integrated ecosystem of care.
The healthcare sector has undergone significant transformation due to the rapid advancements in artificial intelligence and biotechnologies, presenting both opportunities and threats to the nursing profession. Posthumanism, as a critical perspective challenging anthropocentrism and emphasizing the increasingly blurred boundaries between humans and nonhumans, provides a novel lens to comprehend these technological advancements. In this commentary paper, I draw on the posthuman discourse to argue that in light of these technological forces, we need to contemplate the core values and fundamental patterns of knowing within the nursing discipline, reconfigure nursing scope, redefine its relations with other agents, and embrace a technology-integrated ecosystem of care.


Production of neutrophil extracellular traps (NETs) in response to Scedosporium apiospermum in a murine model of pulmonary infection.
Scedosporium apiospermum is an opportunistic emerging pathogen that can develop in both immunosuppressive and immunocompetent patients with pulmonary infections. Neutrophils are recognized as critical cells in the early response to a fungal infection through different mechanisms that eliminate or control the infection such as neutrophil extracellular traps (NETs). In this work, we investigate the presence of NETs in the lung tissue of immunocompetent mice infected with Scedosporium apiospermum. In the histopathological study the presence of filamentous basophilic material with hematoxylin-eosin and periodic acid Schiff stains suggestive of extracellular DNA was observed. We demonstrated the presence of NETs by immunofluorescence staining of extracellular DNA, myeloperoxidase, and elastase in lung tissue. Our results showed that on days 1 and 3 post-infection extracellular DNA, myeloperoxidase, and elastase correlate with areas of high concentration of cell infiltrates and fungal structures. The observation of fungal structures in the tissue decreased as did the presence of NETs by day 5 post-infection. We suggest that NETs release may play an important role in the early containment of Scedosporium apiospermum lung infection.


Hypoxia causes pancreatic β-cell dysfunction and impairs insulin secretion by activating the transcriptional repressor BHLHE40.
Hypoxia can occur in pancreatic β-cells in type 2 diabetes. Although hypoxia exerts deleterious effects on β-cell function, the associated mechanisms are largely unknown. Here, we show that the transcriptional repressor basic helix-loop-helix family member e40 (BHLHE40) is highly induced in hypoxic mouse and human β-cells and suppresses insulin secretion. Conversely, BHLHE40 deficiency in hypoxic MIN6 cells or β-cells of ob/ob mice reverses defects in insulin secretion. Mechanistically, BHLHE40 represses the expression of Mafa, encoding the transcription factor musculoaponeurotic fibrosarcoma oncogene family A (MAFA), by attenuating the binding of pancreas/duodenum homeobox protein 1 (PDX1) to its enhancer region. Impaired insulin secretion in hypoxic β-cells was recovered by MAFA re-expression. Collectively, our work identifies BHLHE40 as a key hypoxia-induced transcriptional repressor in β-cells that inhibit insulin secretion by suppressing MAFA expression.


Tremor signals during fluid injection are generated by fault slip.
Seismic tremor signals, also known as long-period, long-duration signals, have been reported in several locations where fluid injection for enhanced oil and gas exploration is taking place. However, the origin of these signals remains poorly constrained. We studied seismic tremor signals in Wellington Field, Kansas, using a seismic array during a carbon dioxide injection program. We show that these signals are generated below the surface during the time of carbon dioxide injection. They have a distinct spectral signature, similar to those observed in glacial and volcanic environments. The tremor sources are located near the injection site and aligned with preexisting faults. Modeling results imply that such tremors are generated by frictional slip on fault. These observations may reveal an important deformation mode, which is useful for studying associated stress, seismicity, and triggering, as well as for tracking fault activities during injection operations of all fluids, including supercritical carbon dioxide.


Exogenous application of urea and a urease inhibitor improves drought stress tolerance in maize (Zea mays L.).
Drought is believed to cause many metabolic changes which affect plant growth and development. However, it might be mitigated by various inorganic substances, such as nitrogen. Thus, the study was carried out to investigate the effect of foliar-applied urea with or without urease inhibitor N-(n-butyl) thiophosphoric triamide (NBPT) on a maize cultivar under drought stress simulated by 15% (w/v) polyethylene glycol 6000. Foliar-applied urea resulted in a significant increase in plant dry weight, relative water content, and photosynthetic pigments under water stress condition. Furthermore, the activities of superoxide dismutase (SOD), peroxidase (POD), and hydrogen peroxidase (CAT), were enhanced with all spraying treatments under drought stress, which led to decreases in accumulation of hydrogen peroxide (H2O2), superoxide anion ([Formula: see text]) and malondialdehyde (MDA). The contents of soluble protein and soluble sugar accumulated remarkably with urea-applied under drought stress condition. Moreover, a further enhancement in above metabolites was observed by spraying a mixture of urea and urease inhibitor as compared to urea sprayed only. Taken together, our findings show that foliar application of urea and a urease inhibitor could significantly enhance drought tolerance of maize through protecting photosynthetic apparatus, activating antioxidant defense system and improving osmoregulation.


Studies on the reduction of nitroblue tetrazolium chloride mediated through the action of NADH and phenazine methosulphate.
The general features of the reduction of nitroblue tetrazolium chloride (NBT) by NADH and phenazine methosulphate (PMS) have been studied under aerobic and anaerobic conditions. Under aerobic condition the reduction appears to be mediated through the intermediate formation of the superoxide anion radical O2-.; this reaction is strongly inhibited by superoxide dismutase and by a number of O2-. scavengers such as propyl gallate, (+)-catechin, manganous ions, reduced glutathione and benzoquinone. Cupric ions inhibited the overall reaction by reoxidising reduced PMS. Under anaerobic conditions, superoxide dismutase had only a small inhibitory action and, with the exception of cupric ions, the other substances mentioned above were ineffective as inhibitors. The data presented show that the use of NBT to detect the presence of O2-. is fraught with difficulties due to an equally rapid reduction of NBT by NADH and PMS under anaerobic conditions.


Systemic delivery of a DUX4-targeting antisense oligonucleotide to treat facioscapulohumeral muscular dystrophy.
Facioscapulohumeral muscular dystrophy (FSHD) is one of the most prevalent skeletal muscle dystrophies. Skeletal muscle pathology in individuals with FSHD is caused by inappropriate expression of the transcription factor DUX4, which activates different myotoxic pathways. At the moment there is no molecular therapy that can delay or prevent skeletal muscle wasting in FSHD. In this study, a systemically delivered antisense oligonucleotide (ASO) targeting the DUX4 transcript was tested in vivo in ACTA1-MCM;FLExDUX4 mice that express DUX4 in skeletal muscles. We show that the DUX4 ASO was well tolerated and repressed the DUX4 transcript, DUX4 protein, and mouse DUX4 target gene expression in skeletal muscles. In addition, the DUX4 ASO alleviated the severity of skeletal muscle pathology and partially prevented the dysregulation of inflammatory and extracellular matrix genes. DUX4 ASO-treated ACTA1-MCM;FLExDUX4 mice performed better on a treadmill; however, the hanging grid and four-limb grip strength tests were not improved compared to control ASO-treated ACTA1-MCM;FLExDUX4 mice. This study shows that systemic delivery of ASOs targeting DUX4 is a promising therapeutic strategy for FSHD and strategies that further improve the ASO efficacy in skeletal muscle are warranted.


Increasing recombinant protein production in Escherichia coli through metabolic and genetic engineering.
Different hosts have been used for recombinant protein production, ranging from simple bacteria, such as Escherichia coli and Bacillus subtilis, to more advanced eukaryotes as Saccharomyces cerevisiae and Pichia pastoris, to very complex insect and animal cells. All have their advantages and drawbacks and not one seems to be the perfect host for all purposes. In this review we compare the characteristics of all hosts used in commercial applications of recombinant protein production, both in the area of biopharmaceuticals and industrial enzymes. Although the bacterium E. coli remains a very often used organism, several drawbacks limit its possibility to be the first-choice host. Furthermore, we show what E. coli strains are typically used in high cell density cultivations and compare their genetic and physiological differences. In addition, we summarize the research efforts that have been done to improve yields of heterologous protein in E. coli, to reduce acetate formation, to secrete the recombinant protein into the periplasm or extracellular milieu, and to perform post-translational modifications. We conclude that great progress has been made in the incorporation of eukaryotic features into E. coli, which might allow the bacterium to regain its first-choice status, on the condition that these research efforts continue to gain momentum.


Regular use of acetaminophen or acetaminophen-codeine combinations and prescription of rescue therapy with non-steroidal anti-inflammatory drugs: a population-based study in primary care.
There are contrasting positions concerning the benefit-risk ratio of acetaminophen use for osteoarthritis (OA)-related pain. To clarify the effectiveness of acetaminophen or acetaminophen-codeine combinations according to their regimen of use, we evaluated whether being a regular user (adherent) of these medications decreased the occurrence of rescue therapy with non-steroidal anti-inflammatory drugs (NSAIDs). Using the Health Search IMS Health Longitudinal Patient Database, we formed a cohort of patients aged ≥18 years and newly treated with acetaminophen or acetaminophen-codeine combinations for OA between 1 January 2001 and 31 December 2013. These patients were followed up for one year in which they were categorized as regular or irregular users of these medications according to a variable medication possession ratio (VMPR) ≥ 50% or lower. We operationally defined the rescue therapy as the use of any NSAIDs prescribed for OA-related pain. Overall, 40,029 patients (69.5% females; mean age: 68 ± 13.57) treated with acetaminophen or acetaminophen-codeine combinations formed the cohort. After the first year of treatment, regular users showed a statistically significantly lower risk of being prescribed with rescue therapy with NSAIDs (OR = 0.89; 95% CI 0.84-0.96). These findings show that regular use of acetaminophen or acetaminophen-codeine combinations may reduce the need for NSAIDs to treat OA-related pain.


Similarity between the vaccinia virus 19K early protein and epidermal growth factor.
An analysis of the 1,217-amino acid residue sequence of the precursor of mouse epidermal growth factor (mEGF) revealed regions of considerable similarity with bovine factor X, a blood coagulation factor. Similarities of mEGF itself with factor X, pancreatic secretory trypsin inhibitor and, most strikingly, transforming growth factor I (TGF-I) have been observed. On the basis of the comparisons described here, it seems that the presumptive 140-residue 19K early protein (relative molecular mass (Mr) 19,000) of vaccinia virus from residues 40-91 shows an overall identity of 36% (19/53 residues) with both mEGF and urogastrone (human epidermal growth factor, hEGF); a single deletion is assumed for vaccinia virus 19K protein which allows the six Cys residues (positions 45-80) to be aligned with those of mEGF or hEGF. This protein is encoded in the 10.3-kilobase (kb) inverted terminal repeat. Because it is an early protein with an EGF-like central portion, the 19K vaccinia virus protein may have an autocrine function and may be required for DNA synthesis.


Lenalidomide in myelodysplastic syndrome and multiple myeloma.
The use of thalidomide is limited by adverse effects of sedation, constipation, neuropathy and thromboembolism. In order to discover more potent and less toxic immunomodulators than thalidomide, its chemical structure was modified and lenalidomide was formed. Lenalidomide is approved by the US FDA for the treatment of patients with low-risk myelodysplastic syndrome (MDS) with deletion 5q cytogenetic abnormality. Two studies and a case report have evaluated lenalidomide in these MDS patients and showed significantly higher cytogenetic responses and durable red blood cell transfusion independence. Lenalidomide should be the drug of choice for patients with low and intermediate-1 risk MDS (based on the International Prognostic Scoring System) with chromosome 5q31 deletion with or without other karyotype abnormalities. Lenalidomide, in combination with dexamethasone, has been compared with dexamethasone alone in patients with relapsed or refractory multiple myeloma (MM) in two studies (MM-009 in North America and MM-010 in Europe, Israel and Australia). In these two phase III trials, lenalidomide demonstrated impressive (58-59%) response rates with dexamethasone. Lenalidomide has also been shown to overcome thalidomide resistance in MM patients. Therefore, the lenalidomide plus dexamethasone regimen provides another treatment option, in addition to first line MM treatment regimens of bortezomib, thalidomide or high-dose dexamethasone, for the treatment of relapsed or refractory MM. Lenalidomide does not produce significant sedation, constipation or neuropathy, but does lead to significant myelosuppression, unlike thalidomide. The prescribing information has a black box warning for risk of myelosuppression, deep vein thrombosis/pulmonary embolism and teratogenicity. Administration of lenalidomide is recommended at a starting dose of 10 mg/day orally for deletion 5q in MDS patients. Significant risk of myelosuppression may lead to dose reduction in the majority of these patients. Clinical trials of relapsed and refractory MM have shown that lenalidomide is clinically efficacious at a dosage of 25 mg/day when administered in combination with dexamethasone. Lenalidomide should be continued until disease progression in both MDS and MM patients.


Replication-dependent and selection-induced mutations in respiration-competent and respiration-deficient strains of Saccharomyces cerevisiae.
Adaptive or selection-induced mutations are defined as mutations that occur in non-dividing cells as a response to prolonged non-lethal selective pressure such as starvation for an essential amino acid. In the absence of DNA replication, the processing of endogenous DNA lesions by repair enzymes probably acts as a source of mutations. We are studying selection-induced reversions of frameshift alleles in the eukaryote Saccharomyces cerevisiae. Here we show that respiration-deficient strains, totally devoid of mitochondrial DNA, yield selection-induced mutants at slightly elevated frequencies compared to isonucleic respiration-competent strains. Therefore factors of mitochondrial origin such as reactive oxygen species or hypothetical recombinogenic DNA fragments are unlikely to be mediators of selection-induced nuclear frameshift mutation in yeast. Furthermore we compared sequence spectra of reversions of the +1 hom3-10 frameshift allele and found a strong preference for -1 deletions in mononucleotide repeats in selection-induced and replication-dependent revertants, indicating slippage errors during DNA repair synthesis as well as during DNA replication. Remarkably, a higher degree of variation in the site of the reverting frameshift and accompanying base substitutions was found among selection-induced revertants.


Serum ferritin level as a prognostic biomarker for predicting dengue disease severity: A systematic review and meta-analysis.
Serum ferritin levels serves as biomarkers in many inflammatory and infectious diseases. This current systematic review and meta-analysis evaluated whether serum ferritin levels are associated with severe dengue and its utility as a biomarker of disease severity. Literature searches were conducted in PubMed, Scopus, ScienceDirect, the Cochrane library, and Google Scholar. A total of 18 studies examining the serum ferritin levels in dengue cases in the context of disease severity (nine studies having dengue classification as non-severe vs. severe dengue cases, and nine studies having dengue classification as dengue without warning signs (DwoWS), dengue with warning signs (DwWS), and severe dengue cases) were included and the quality of the studies was assessed using the Quality in Prognostic Factor Studies tool. The meta-analysis was performed using STATA software to calculate the effect size as a standardized mean difference (SMD) or Hedges 'g' for the continuous outcome. Higher serum ferritin levels were found in severe dengue cases compared to non-severe cases [SMD (Hedges 'g') 4.05 (95% C.I. 2.09-6.00), (I2 = 98.8%)]. In the second group, DwWS cases showed high serum ferritin levels compared to DwoWS [SMD 2.01 (95% C.I. 0.92-3.10), (I2 = 97.89%)], and severe dengue cases showed higher levels of serum ferritin compared to DwWS [SMD 2.66 (95% C.I. 1.72-4.48), (I2 = 98.78%)] and DwoWS cases [SMD 6.65 (95% C.I. 1.72-11.59), (I2 = 99.78%]. Subgroup analysis for the country of study (India vs. others), ferritin testing methods, and ferritin measurement day revealed testing method as a significant contributor to heterogeneity. To conclude, the present study suggests serum ferritin as a prognostic marker for dengue disease severity. Multi-centric studies involving a large number of dengue patients with a uniform case definition accounting for all the confounding variables might help in determining a universal cut-off value to discriminate between non-severe and severe dengue.


Susceptibility of anaerobic bacteria to PD 131628.
The in vitro activity of PD 131628 against anaerobic cocci, Propionibacterium acnes, Clostridium perfringens, Clostridium difficile, Bacteroides fragilis, Bacteroides spp. and fusobacteria was determined by the agar dilution method. This activity was compared with that of ciprofloxacin, piperacillin, cefoxitin, imipenem, clindamycin, metronidazole and chloramphenicol. PD 131628, imipenem, clindamycin, metronidazole and chloramphenicol were the most active agents tested.


Is continuous haemofiltration superior to intermittent dialysis and haemofiltration treatment?
1. Mortality in cases of acute renal failure has increased from roughly 30% to roughly 70% in recent decades. 2. The rise paralleled the creation of intensive care units. In such units, more seriously ill patients reach the stage of acute renal failure. Before the advent of intensive care units, these patients died before acute renal failure could occur. 3. From a theoretical viewpoint, continuous haemofiltration (CH) has substantial advantages as opposed to intermittent dialysis and haemofiltration treatment. 4. No clinical proof of the superiority of continuous haemofiltration to the intermittent techniques has yet been provided. 5. In our own patient group, total mortality for acute renal failure patients decreased following adoption of continuous haemofiltration. During a selected period of use of continuous haemofiltration for patients with an unfavourable prognosis, however, the mortality with continuous haemofiltration was higher than that with the intermittent methods.


Increased collagen metabolism in granulomata induced in rats deficient in endogenous prostaglandin precursors.
Collagen metabolism was measured (in terms of various hydroxyproline (HP), DNA and protein ratios) in granulomata obtained after s.c. implantation of carrageenan-impregnated and untreated polyether sponges into normal and essential fatty acid deficient (EFAD) rats for 8 and 15 days. Collagen synthesis (HP/protein) in day 8 and 15 untreated granulomata was the same for both normal and EFAD rats, though collagen breakdown (total HP) appeared to be greater in EFAD granulomata on day 15. With carrageenan-impregnated sponges, collagen synthesis in EFAD granulomata was much greater than in normal granulomata on both day 8 and day 15. Ratios of protein and/or HP to DNA (probably indicative of cellular infiltration) were increased in EFAD rats with both sponge types, though this increase was less pronounced with carrageenan-impregnated sponges. It is suggested that endogenous prostaglandin (PG) production (marledly reduced during EFA deficiency) may exert a negative feedback effect on collagen metabolism during proliferative inflammation.


The efficacy and safety of complement C5a inhibitors for patients with severe COVID-19: a systematic review and meta-analysis.
The clinical efficacy and safety of complement C5a inhibitors for patients with severe COVID-19 remains unclear. The PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched from their inception to 27 September 2022. Only studies that assessed the usefulness of C5a inhibitors for the treatment of patients with severe COVID-19 patients were included. The primary outcome was the risk of 28-day mortality. Six studies, including four randomized controlled trials (RCTs) and two non-RCTs, were included. The study group receiving C5a inhibitors had a significantly lower risk of mortality compared with the control group (23.6% [70/297] vs 39.2% [136/347]; odds ratio [OR], 0.53; 95% confidence interval [CI]: 0.37-0.76; P< 0.001), and no heterogeneity was detected (I2 = 0%; P= 0.58). Compared with control group, the study group was associated with a similar risk of serious adverse events (AEs) (OR, 0.84; 95% CI: 0.57-1.23; P0 = 0.37), infection (OR, 1.46; 95% CI: 0.77-2.79; P= 0.25) and acute kidney injury (OR, 0.89; 95% CI: 0.54-1.46; P= 0.64). C5a inhibitors could help reduce the risk of mortality in patients with severe COVID-19 infection while being as safe as placebos. These findings support the promising role of C5a inhibitors in the treatment of severe COVID-19.


Effect of surgical safety checklists on postoperative morbidity and mortality rates, Shiraz, Faghihy Hospital, a 1-year study.
The study intent was to (1) encourage the use of surgical safety checklists and (2) measure the effect checklists have in reducing surgical complications. An interventional study designed to improve postsurgical outcomes was performed. The study site was a 374-bed referral educational hospital in Shiraz, Iran, with 6 operating rooms. The study lasted 6 months. Patient selection involved a convenient sampling method with all eligible patients entering. Our checklist covered 3 surgical stages--before anesthesia, immediately before an incision, and before moving the patient to a recovery room. Persons included were operating room team members. Rates of postsurgical complication before and after application of the surgical safety checklist underwent comparison. Incidence of any complication before and after intervention was 22.9% and 10% (P = .03). Five checklist items were in total compliance. The most common complication was surgical site infection. Implementation of the checklist, responsibility in 2 stages, such as time out and sign out, were significant (P < .05). In most cases, these items reflected the performance of surgeons and anesthesia professionals as compared with the World Health Organization Surgical Safety Checklist. Complications decreased by 57% after intervention. Both high patient information detection and elevated levels of cooperation by surgical personnel were observed. Compliance likely helped prevent some adverse effects associated with surgery.


Alpinetin improves intestinal barrier homeostasis via regulating AhR/suv39h1/TSC2/mTORC1/autophagy pathway.
The injury of intestinal epithelial barrier is considered as the key pathophysiological process in response to gastrointestinal infection and inflammation, and plays an important role in the initiation and development of colitis. Alpinetin has been shown to improve intestinal barrier homeostasis under colitis condition, but the mechanism is still unclear. Here, we showed that alpinetin significantly improved transepithelial electrical resistance (TEER) in TNF-α-stimulated Caco-2 cells, which was mainly mediated by inhibiting the apoptosis. Mechanistic studies demonstrated that alpinetin markedly increased the production of autophagosomes, along with obvious regulation of LC3B-II, beclin-1, p62, Atg7 and Atg5 expressions. In addition, it also markedly repressed the activation of mTORC1 signaling pathway, which was ascribed to TSC2 rather than p-AKT, p-ERK, p-AMPKα or PTEN expressions in Caco-2 and NCM460 cells. Furthermore, the enrichment of H3K9me3 at TSC2 promoter region was decreased and ubiquitin proteasome degradation of suv39h1 was increased. Additionally, alpinetin activated aryl hydrocarbon receptor (AhR) and promoted co-localization of AhR with suv39h1 in the cytoplasm. The relationship between alpinetin-regulated AhR/suv39h1/TSC2/mTORC1 signals, autophagy and apoptosis of Caco-2 and NCM460 cells was confirmed by using CH223191, siAhR, siTSC2 and chloroquine. Finally, CH223191 and leucine abolished alpinetin-mediated inhibition of intestinal epithelial cells apoptosis, improvement of intestinal epithelial barrier and amelioration of colitis.


[Relationship between group G chromosomes, especially chromosome 21, and the sensitivity of human cells to Coxsackie B viruses].
The R-method of differential chromosome staining by length was applied to comparative karyological studies on the culture of J 96 human cells susceptible to enteroviruses, and on the J 41 cell line derived from this culture and possessing high specific resistance to Coxsackie B viruses. Karyotype of the J 41 cell line was shown to be deprived of chromosome G21 (P less than 0.0001). The number of other chromosomes varied from cell to cell, but they are constantly present in the majority of cells of both the J 96 and J 41 cell lines. A conclusion is drawn that chromosome G21 incorporates gene(s) which controls the human cells susceptibility to Coxsackie B viruses.


Changes in left ventricular performance after global ischemia: assessing LV pressure-volume relationship.
To determine the effect of ischemia and reperfusion on left ventricular systolic function, we studied the ischemia-induced rightward shift of the ventricular pressure-volume relationship. Eight mongrel dogs were intubated, and their hearts were exposed through a thoracotomy. A conductance catheter and micromanometer were used to obtain instantaneous left ventricular pressure-volume data. The dogs were subjected to 20 minutes of normothermic global myocardial ischemia, followed by 80 minutes of reperfusion under total cardiopulmonary bypass. Data were acquired during transient (10- to 12-second) periods of acute volume loading before ischemia and at 20-minute intervals during reperfusion as bypass was continued. The relationship between stroke work and end-diastolic volume (ie, preload recruitable stroke work [PRSW]) and the end-systolic pressure-volume relationship were highly linear throughout the study (mean r = 0.954 to 0.983 for PRSW; mean r = 0.954 to 0.984 for end-systolic pressure-volume relationship). Ischemia produced changes in the PRSW: (1) the slope decreased significantly at 20 minutes and 40 minutes of reperfusion then returned to preischemic levels at 60 minutes and 80 minutes, and (2) the x-intercept increased significantly up to 60 minutes. The preload recruitable work area (the area under the linear regression line of PRSW) reflected changes in both slope and x-intercept of PRSW and was significantly decreased throughout the 80 minutes of reperfusion despite gradual recovery. The slope and the x-intercept of the end-systolic pressure-volume relationship did not change after ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)


Theoretical Models of Generalized Quasispecies.
Theoretical modeling of quasispecies has progressed in several directions. In this chapter, we review the works of Emmanuel Tannenbaum, who, together with Eugene Shakhnovich at Harvard University and later with colleagues and students at Ben-Gurion University in Beersheva, implemented one of the more useful approaches, by progressively setting up various formulations for the quasispecies model and solving them analytically. Our review will focus on these papers that have explored new models, assumed the relevant mathematical approximations, and proceeded to analytically solve for the steady-state solutions and run stochastic simulations . When applicable, these models were related to real-life problems and situations, including changing environments, presence of chemical mutagens, evolution of cancer and tumor cells , mutations in Escherichia coli, stem cells , chromosomal instability (CIN), propagation of antibiotic drug resistance , dynamics of bacteria with plasmids , DNA proofreading mechanisms, and more.


Interstitial pulsed-dose-rate brachytherapy for the treatment of squamous cell anal carcinoma: A retrospective single institution analysis.
To examine the outcome of patients receiving interstitial pulsed-dose-rate brachytherapy (PDR-BT) after pelvic radiation therapy for treatment of an anal squamous cell carcinoma. Twenty-one patients were identified: 13, six, and two with stages I, II, and III tumors, respectively. After receiving received pelvic irradiation +/- concurrent chemotherapy, patients were delivered a PDR-BT boost to the residual tumor, with intention to deliver a minimal total dose of 60 Gy. The greatest dimension of residual tumor at the time of brachytherapy procedure was 12.5 mm (range: 0-20 mm). Brachytherapy implantation was performed according to the Paris system, only one plane implant being used. Median dose delivered through BT was 20 Gy (range: 10-30 Gy). Median number of pulses was 48 (range: 20-80 pulses). Median treated volume was 9 cm(3) (range: 5-16 cm(3)). Median dose per pulse was 40 cGy (range: 37.5-50 cGy). No Grade 3 or more acute toxicity was reported. No Grade 3 or more delayed toxicity was seen among 18 patients with more than 6 months follow-up. Median followup was 47 months (range: 6-73 months). Twenty patients (95%) were alive at last follow-up. Tumor relapses were experienced in four patients (19%), including local relapse in three patients (14%). With almost 4 years median followup, this study confirms previous data suggesting that PDR-BT is effective and safe in this indication. Local control rate and toxicity were in the range of what was seen with continuous low-dose-rate BT.


Comparison of portal and peripheral insulin delivery on carbohydrate metabolism in streptozotocin-diabetic rats.
Severely diabetic rats (150 mg streptozotocin/kg) were transplanted with fetal pancreatic islets: (a) under the kidney capsule to model peripheral insulin delivery, and (b) into the splenic pulp to model portal delivery. Long-term normoglycaemia, normal weight gain and normal peripheral insulin levels were achieved in both groups of transplanted animals. In both groups, 24-h fasted blood lactate, pyruvate and alanine were identical to those observed in sham-operated control animals. Blood glucose and plasma insulin responses to 300 mg oral glucose 8 weeks after transplantation were the same as in control animals. Hepatic glycogen concentration was, however, lower in fed rats with islets beneath the kidney capsule compared with control rats (p less than 0.01), suggesting inadequate hepatic insulinisation in the fed state with peripheral insulin delivery. Muscle glycogen was the same as in controls. Glucose turnover and glucose carbon recycling were not significantly different from results in normal control and splenic pulp islet-transplanted animals. The findings indicate that consistent normoglycaemia, normal glucose flux and normalisation of blood intermediary metabolites can be achieved in the rat with peripheral insulin delivery without associated hyperinsulinaemia.


GenBank.
The GenBank (Registered Trademark symbol) sequence database incorporates DNA sequences from all available public sources, primarily through the direct submission of sequence data from individual laboratories and from large-scale sequencing projects. Most submitters use the BankIt (Web) or Sequin programs to format and send sequence data. Data exchange with the EMBL Data Library and the DNA Data Bank of Japan helps ensure comprehensive worldwide coverage. GenBank data is accessible through NCBI's integrated retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome and protein structure information. MEDLINE (Registered Trademark symbol) s from published articles describing the sequences are included as an additional source of biological annotation through the PubMed search system. Sequence similarity searching is offered through the BLAST series of database search programs. In addition to FTP, Email, and server/client versions of Entrez and BLAST, NCBI offers a wide range of World Wide Web retrieval and analysis services based on GenBank data. The GenBank database and related resources are freely accessible via the URL: http://www.ncbi.nlm.nih.gov


Geographical trends in 137Cs fallout from the Chernobyl accident and leaching from natural surface soil in Norway.
In order to follow the turnover of (137)Cs in natural soils and estimate future trends in exposure of livestock, samples of natural surface soils were collected at 0-3 cm depth at 464 sites in 1995 and 463 sites in 2005 covering the country. In both cases the geographical pattern observed was similar to the original distribution from 1986, but the decline of (137)Cs activity in the surface soil was not the same everywhere. In 1995 the (137)Cs reduction since 1986 was found to be considerably greater in coastal areas than farther inland. The main reason for this appears to be the much greater deposition of marine cations such as Mg(2+) and Na(+) in the coastal areas, replacing Cs ions fixed on soil particle surfaces. This cation exchange appeared to be particularly strong near the southern coast where deposition of NH4(+) from transboundary air pollution is evident in addition to the marine cations. During 1995-2005 the (137)Cs decline in the surface soil was more uniform over the country than in the preceding 10-year period but still significantly higher in coastal areas than inland. Differences in precipitation chemistry may have influenced the uptake of (137)Cs in terrestrial food chains.


[Adjuvant treatment of keloid scars: electrons or brachytherapy?].
Evaluation of perioperative treatment of keloid scars with electron beam therapy or iridium 192 low dose rate brachytherapy. From 1994 to 2010, 95 patients with 142 keloid scars have been treated by immediate perioperative irradiation and retrospectively reviewed in our institute: 116 scars were treated by electrontherapy and 26 by brachytherapy. In the electrontherapy group treated locations were: earlobe (n=88, 76%), thorax (n=14, 12%), neck (n=9, 8%), limbs (n=5, 4%). The median size of lesions was 3cm (range [R]: 0.5-18cm). In 95.6% of cases, a dose of 15Gy was delivered in five fractions of 3Gy. The median follow-up was 70 months (R: 7-161 months). The 2-year and 5-year local control were respectively 69% (95% confidence interval [95% CI]: 59-76%) and 55% (95% CI: 45-64%). In the brachytherapy group treated locations were: neck (n=3, 11%), earlobe (n=8, 32%), abdomen (n=3, 11%), thorax (n=2, 8%), limbs (n=10, 38%). The median size of lesions was 6.6cm (R: 1.7-28cm). The median dose delivered at 5mm from the source was 20Gy (R: 15-20.69). The median follow-up was 113 months (R: 21-219 months). The 2-year and 5-year local control were respectively 84.6% (95% CI: 64-94%) and 73.5% (95% CI: 49-87%). So far, no radiation-induced cancer has occurred. A trend to a better local control with brachytherapy was noted (compared to electrontherapy, 2-year relapse is halved with brachytherapy) though this difference did not reach the significance (P=0.0991), probably due to the reduced number of patients in the brachytherapy group. Brachytherapy seems to provide better local control compared to electrontherapy, and should be proposed as first line treatment. However, electrontherapy is an interesting alternative in case of difficulty to realize brachytherapy. There is probably a dose effect: according to published data, 25 to 30Gy should at least be proposed.


The relation between ADHD symptoms, perceived stress and binge drinking in college students.
Binge drinking is a major public health problem associated with various negative short-term and long-term clinical and social outcomes. If there is evidence to suggest a relationship between ADHD and alcohol use in college students, no study has investigated the role of ADHD symptomatology in binge drinking. Thus, this research was designed to explore the relative contributions of inattention and hyperactivity/impulsivity symptoms to binge drinking in a sample of French college students while controlling for effects of perceived stress. Participants (N = 7011; mean age = 20.9; 74.9% of females) completed self-report surveys assessing ADHD symptoms, perceived stress, sociodemographic characteristics, and binge drinking frequency. Multinomial logistic regression revealed significant associations between higher levels of ADHD symptoms in general, but not perceived stress, and increasing frequency of binge drinking. Moreover, higher levels of inattention and hyperactivity/impulsivity symptoms were independently associated with greater frequency of binge drinking. The association was stronger between high rates of binge drinking and inattention than for hyperactivity/impulsivity. These findings, which remained statistically significant after adjusting for a range of potential confounders (including perceived stress), suggest that the presence of ADHD symptoms may be an important factor related to binge drinking.


Impact of Hedonics and Magnitude Upon Validated Psychophysical Olfactory Tests and Olfactory-Specific Quality of Life.
Patients often describe the olfactory loss as either the inability to detect unpleasant odors (eg, smoke or spoiled food) or noticeable impairment in enjoying pleasant odors (eg, food and fragrances). This complex relationship between the hedonics of various odors, their perceived magnitude in odor strength, and the impact on patient quality of life is not well understood. Sixty-five subjects underwent testing with the Henkin olfaction test which assesses hedonics and magnitude for odors traditionally deemed unpleasant (pyridine/dead fish and thiophene/gasoline) and pleasant (amyl acetate/banana and nitrobenzene/almond). Subjects also completed Smell Identification Test-40 (SIT-40), Sniffin' Sticks (Sniffin' Sticks), and Snap & Sniffin' Sticks (Snap) Olfactory Tests, as well as the 17-item Questionnaire for Olfactory Disorders Negative Statements (QODNS) and olfactory symptom visual analog scale (VAS). Spearman's rank correlations were conducted between various olfactory domains, QODNS and VAS. Mean age was 52.1 years (range: 28-86), with 63.1% females. Magnitude estimation was greatest for pyridine. Most people rated thiophene (75.4%) and pyridine (92.3%) as "unpleasant." Although most people rated amyl acetate (47.7%) and nitrobenzene (56.9%) as "pleasant," many rated amyl acetate (52.3%) and nitrobenzene (43.1%) as "neutral" or "unpleasant" scents. Hedonics for unpleasant odors correlated with each other (rs = 0.60), but not with hedonics for pleasant odors. Hedonics for unpleasant odors also correlated with magnitude estimation and other psychophysical tests. These findings were not seen for hedonics of pleasant odors. The use of unpleasant odors in Henkin testing showed unique relationship patterns with patient-reported outcome measures and validated olfactory tests, which may provide utility in characterizing olfactory dysfunction. The incorporation of more unpleasant odors in current psychophysical olfactory testing may provide enhanced information regarding the patient impact of olfactory dysfunction.


Myelolipoma in adenoma of accessory adrenal gland.
A tumor was incidentally found at autopsy in the vicinity of the right adrenal gland of a 69-year-old man who had died of liver cirrhosis with hepatoma. Microscopic examination disclosed a myelolipoma associated with a cortical adenoma occurring in an accessory adrenal gland. No evidence of hormonal abnormalities was found in the clinical record of the patient. The association of myelolipoma with cortical adenoma occurring in an accessory adrenal gland seems very unusual, and the present case is believed to be the first reported of this type of association.


Split-belt walking: An experience that is hard to forget.
The common paradigm to study the adaptability of human gait is split-belt walking. Short-term savings (minutes to days) of split-belt adaptation have been widely studied to gain knowledge in locomotor learning but reports on long-term savings are limited. Here, we studied whether after a prolonged inter-exposure interval (three weeks), the newly acquired locomotor pattern is subject to forgetting or that the pattern is saved in long-term locomotor memory. Can savings of adaptation to split-belt walking remain after a prolonged inter-exposure interval of three weeks? Fourteen healthy adults participated in a single ten-minute adaptation session to split-belt walking and five-minute washout to tied-belt walking. They received no training after the first exposure and returned to the laboratory exactly three weeks later for the second exposure. To identify the adaptation trends and quantify saving parameters we used Singular Spectrum Analysis, a non-parametric, data-driven approach. We identified trends in step length asymmetry and double support asymmetry, and calculated the adaptation volume (reduction in asymmetry over the course of adaptation), and the plateau time (time required for the trend to level off). At the second exposure after three weeks, we found substantial savings in adaptation for step length asymmetry volume (61.6-67.6% decrease) and plateau time (76.3 % decrease). No differences were found during washout or in double support asymmetry. This study shows that able-bodied individuals retain savings of split-belt adaptation over a three-week period, which indicates that only naïve split-belt walkers should be included in split-belt adaptation studies, as previous experience to split-belt walking will not be washed out, even after a prolonged period. In future research, these results can be compared with long-term savings in patient groups, to gain insight into factors underlying (un)successful gait training in rehabilitation.


Cardiopulmonary complications after major surgery: a role for epidural analgesia?
Improvement in postoperative pulmonary mechanics with epidural analgesia has been described. Data on the hemodynamic effects of this technique are absent from the surgical literature. To provide such data we have evaluated two groups of patients undergoing aortic reconstruction: group I (n = 25), general anesthesia and group II (n = 6), general anesthesia with adjunctive epidural analgesia. The groups were comparable preoperatively as judged by the incidence of cardiac history, preoperative ejection fraction, and measured hemodynamic parameters. Postoperatively there were no significant differences in the pressure-related parameters; however, rate-related factors including heart rate and double product were significantly decreased in group II with no reduction in cardiac index. Postoperative increases in total body oxygen consumption were also markedly attenuated by epidural analgesia. Epidural analgesia reduces the hemodynamic demands on the heart after major surgery and is a useful adjunct, especially in patients with coronary artery disease.


2,3,7,8-Tetrachlorodibenzo-p-dioxin alters embryonic palatal medial epithelial cell differentiation in vitro.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is teratogenic in mice, inducing cleft palate and hydronephrosis. After exposure in vivo, TCDD specifically alters differentiation of embryonic palatal medial epithelial cells. In this study, the palatal epithelial cell response to TCDD is determined in vitro. C57BL/6N palatal shelves were placed in organ culture on gestation day (GD) 12 in Richter's improved modified Eagle's medium:Ham's F12 medium (1:1) with 1% fetal bovine serum for 3 or 4 days. Medium contained 0.1% dimethylsulfoxide and TCDD at 0, 10(-13), 10(-12), 10(-11), 10(-10), and 10(-9) M, with some doses at 5 x 10(-11), 7.5 x 10(-11), and 5 x 10(-12) M. Epithelial cell responses to TCDD occurred over a narrow range of concentrations, with maximal response at 5 x 10(-11) M. Cytotoxicity was detected at 1 x 10(-10) M. At a stage when control medial cells ceased proliferation and EGF receptors were not detected immunohistochemically. TCDD-exposed medial cells incorporated [3H]thymidine and high levels of epidermal growth factor receptors were detected. TCDD prevented programmed cell death of medial peridermal cells, and induced a shift in the differentiation of medial cells toward an oral-like phenotype. The responses to TCDD observed after exposure in vitro were indistinguishable from previously reported effects observed after exposure in vivo. In the present study, the distribution of TCDD in the fetus after exposure in vivo was examined. The levels of exposure to TCDD are similar for in vitro and in vivo exposure routes. The levels of TCDD in 1 x 10(-11) to 1 x 10(-10) M solutions (3 to 32 pg/ml) were comparable to levels observed in fetal tissues after in vivo exposure on GD 11 to 30 microns/kg [3H]TCDD, where the palatal shelf contained 1.4 to 3.5. pg TCDD, representing 0.0003% of the total dose. In vivo, TCDD was detected in the GD 11 embryo 3 hr postexposure and the TCDD was equally distributed between the embryonic head and body. At 72 hr postexposure, 0.035% of the total dose was in fetal tissues, and 1% of the TCDD in the fetus was found in the palatal shelf. The present study shows that the palatal epithelium responds to TCDD in vitro in a manner comparable to that observed after in vivo exposure, and that the response occurs at a concentration comparable to in vivo levels in the fetus. The availability of an in vitro system will facilitate studies of TCDD toxicity that are difficult or impossible to perform in vivo, such as comparisons of TCDD effects between species, including human tissues.


An unusual feature of yolk sac placentation in Necromys lasiurus (Rodentia, Cricetidae, Sigmodontinae).
We studied the development of the inverted yolk sac in a New World rodent, Necromys lasiurus during early placentation. Ten implantation sites were investigated by means of histology, immunohistochemistry and electron microscopy. The yolk sac was villous near its attachment to the placenta. Elsewhere it was non-villous and closely attached to the uterus. The uterine glands were shallow and wide mouthed. They were associated with vessels and filled with secretion, suggesting the release of histotroph. This feature was absent at later stages. The intimate association of the yolk sac with specialized glandular regions of the uterus may represent a derived character condition of Necromys and/or sigmodont rodents.


New sesquicillins, insecticidal antibiotics produced by Albophoma sp. FKI-1778.
Four new antibiotics, sesquicillins B to E were isolated from the culture broth of Albophoma sp. FKI-1778 together with known sesquicillin (sesquicillin A in this paper). The structures of sesquicillins were elucidated by spectroscopic studies including various NMR experiments. All sesquicillins have a common pyrano-diterpene skeleton. Sesquicillins showed moderate inhibitory activity against the growth of Artemia salina (brine shrimps) and Jurkat cells.


Tumor free distance from serosa and survival rates of endometrial cancer patients: A meta-analysis.
Myometrial invasion and its extent have been directly associated with the risk of relapse as well as the overall survival of endometrial cancer patients. Tumor free distance from the serosal surface of the uterine wall has been investigated the last years by several studies, however, to date, its importance remains unknown. The present meta-analysis is based on a systematic search of the Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar databases and has been designed according to the PRISMA guidelines. Nine studies were included in the present systematic review that recruited pathology slides from 1,598 endometrial cancer patients and their meta-analysis indicated that TFD was significantly associated with the progression free survival of patients with endometrial cancer (OR 0.36, 95% CI 0.20, 0.65). The disease specific survival was not affected by the TFD (OR 0.30, 95% CI 0.09, 1.01). Sensitivity analyses revealed, however, that both the progression free and overall survival rates were associated with TFD. Significant discrepancies were observed in terms of histological subtypes and stage of the disease among included patients, hence, the actual importance of TFD in specific subgroups remains unknown. Future studies must evaluate the importance of this pathology marker particularly in patients with endometrioid subtypes and early-stage disease, as it is believed that in this group its importance will be more predictive as it will not be skewed by the presence of more important factors such as more aggressive histology and advanced stage disease.


Implications of peritoneal washing cytology in patients with potentially resectable pancreatic cancer.
The aim of this study was to assess the implications of positive peritoneal washing cytology for management of patients with potentially resectable pancreatic cancer. Cytological examination of peritoneal washings was performed in 134 patients who underwent surgical resection for pancreatic adenocarcinoma. The clinicopathological findings and the relationship between cytology results (including cytomorphology) and survival were investigated. One hundred and fourteen patients (85 per cent) had negative cytology results (group 1). Excluding one patient with atypical cells, positive cytology results were obtained in 19 patients (14 per cent): 16 patients without macroscopic peritoneal metastases (group 2) and three patients with minimal macroscopic peritoneal metastases (group 3). The patients in group 2 had significantly larger (P < 0.001) and more advanced (P = 0.022) tumours than those in group 1. However, there were no significant differences in postoperative cumulative survival rates between groups 1 and 2 (P = 0.347). Two patients in group 2 are long-term survivors (40 and 58 months). In cytomorphological analyses, the presence of clusters with ragged edges and isolated carcinoma cells can be considered to indicate a high risk of peritoneal recurrence. Positive cytology does not directly predict peritoneal carcinomatosis and, while associated with advanced disease, does not contraindicate radical surgery.


Enhanced expression of Ki-67, topoisomerase IIalpha, PCNA, p53 and p21WAF1/Cip1 reflecting proliferation and repair activity in UV-irradiated melanocytic nevi.
To investigate the effect of ultraviolet (UV) irradiation on the expression of cell cycle-associated proteins, melanocytic nevi from healthy volunteers were partially covered, irradiated with a defined UV dose, and excised 1 week thereafter. The irradiated and the protected parts were examined separately by conventional microscopy and immunohistochemistry using the antibodies Ki-S11 (Ki-67), Ki-S7 (topoisomerase IIalpha), PC10 (proliferating cell nuclear antigen [PCNA]), DO-7 (p53), 6B6 (p21WAF1/Cip1), and the melanocytic marker HMB-45. DNA nick-end labeling was used as a marker of apoptosis. Irradiation resulted in morphological changes and increased HMB-45 reactivity. Proliferation, as assessed by Ki-67 and topoisomerase IIalpha expression, was also clearly enhanced in the UV-exposed areas. This was confirmed by the appearance of occasional mitotic figures. PCNA expression levels markedly exceeded those of the proliferation markers and did not correlate with the latter in most cases. p21 immunolabeling indices were also consistently augmented after UV exposure; hence it is likely that growth-inhibitory mechanisms partly compensate for the proliferative impulse, and the disproportional rise in PCNA expression probably reflects DNA repair activity. Enhanced p53 immunostaining in four cases suggests that the induction of p21 after irradiation may be p53 mediated, whereas no concomitant apoptotic events were observed. We conclude that UV light can stimulate the proliferative activity of melanocytes in melanocytic nevi, but that simultaneously cell cycle inhibitors are activated to permit DNA repair.


Analytical solution and optimal design for the output performance of Galfenol cantilever energy harvester considering electromechanical coupling effect.
The theoretical model of a Galfenol cantilever energy harvester is investigated for vibration energy harvesting. Compared with the numerical solution, the analytical solution can better capture the intrinsic effects of the physical parameters on the performance of the harvester. In this work, an electromechanical coupled distributed-parameter model of the Galfenol cantilever energy harvester is established based on Hamilton's principle, linear constitutive equations of magnetostrictive material, and Faraday's law of electromagnetic induction. The definitions and expressions of the electric damping and modified frequency are proposed due to the electromechanical coupling. The explicit analytical expressions of the average harvested power across the load resistance and tip vibration displacement of the Galfenol energy harvesting model are derived using the methods of Galliakin decomposition and electromechanical decoupling. The accuracy of the derived analytical results is verified by the experimental data and numerical solutions. The vibration response and energy harvesting performance of the Galfenol energy harvesting model are investigated by varying the excitation frequency, external resistance, and excitation acceleration amplitude. The analytical results show that, with the increase of the external load resistance and excitation frequency, the harvested power increases first and then decreases, indicating the existence of the optimal resistance and excitation frequency. From the explicit analytical expressions of the average harvested power, the optimal external load resistance or excitation frequency could be easily found to achieve the maximum harvested power for any fixed excitation frequency or external load resistance. The concept of proposing the electric damping and modified frequency for the Galfenol cantilever energy harvester simplifies the solution process for the output performances benefiting from the exact relationship between the output performances and the electromechanical coupling parameter derived in this work.


Completely laparoscopic extraperigastric lymph node dissection for gastric malignancies located in the middle or lower third of the stomach.
Dissection of the extraperigastric lymph nodes is necessary in most submucosal gastric cancers. Laparoscopy-assisted gastrectomy with extraperigastric lymph node dissection via minilaparotomy has been performed, but, to our knowledge, completely laparoscopic extraperigastric lymph node dissection has never been reported. We successfully performed completely laparoscopic distal gastrectomy with extraperigastric lymph node dissection in 12 patients, of whom 11 had early gastric cancer and 1 had malignant lymphoma. This surgery is technically feasible, has an acceptable complication rate, and a curability similar to that with open surgery.


Donor gluconate rescues livers from uncontrolled donation after cardiac death.
Ischemia from organ preservation or donation causes cells and tissues to swell owing to loss of energy-dependent mechanisms of control of cell volume. These volume changes cause substantial preservation injury, because preventing these changes by adding cell impermeants to preservation solutions decreases preservation injury. The objective of this study was to assess if this effect could be realized early in uncontrolled donation after cardiac death (DCD) livers by systemically loading donors with gluconate immediately after death to prevent accelerated swelling injury during the warm ischemia period before liver retrieval. Uncontrolled DCD rat livers were cold-stored in University of Wisconsin solution for 24 hours and reperfused on an isolated perfused liver (IPL) device for 2 hours or transplanted into a rat as an allograft for 7 days. Donors were pretreated with a solution of the impermeant gluconate or a saline control immediately after cardiac death. Livers were retrieved after 30 minutes. In vivo, gluconate infusion in donors immediately before or after cardiac death prevented DCD-induced increases in total tissue water, decreased vascular resistance, increased oxygen consumption and synthesis of adenosine triphosphate, increased bile production, decreased lactate dehydrogenase release, and decreased histology injury scores after reperfusion on the IPL relative to saline-treated DCD controls. In the transplant model, donor gluconate pretreatment significantly decreased both alanine aminotransferase the first day after transplantation and total bilirubin the seventh day after transplantation. Cell and tissue swelling plays a key role in preservation injury of uncontrolled DCD livers, which can be mitigated by early administration of gluconate solutions to the donor immediately after death.


Antibody-mediated immunity against tuberculosis: implications for vaccine development.
There is an urgent need for new and better vaccines against tuberculosis (TB). Current vaccine design strategies are generally focused on the enhancement of cell-mediated immunity. Antibody-based approaches are not being considered, mostly due to the paradigm that humoral immunity plays little role in the protection against intracellular pathogens. Here, we reappraise and update the increasing evidence for antibody-mediated immunity against Mycobacterium tuberculosis, discuss the complexity of antibody responses to mycobacteria, and address mechanism of protection. Based on these findings and discussions, we challenge the common belief that immunity against M. tuberculosis relies solely on cellular defense mechanisms, and posit that induction of antibody-mediated immunity should be included in TB vaccine development strategies.


One step physically adsorbed coating of silica capillary with excellent stability for the separation of basic proteins by capillary zone electrophoresis.
The coating of capillary inner surface is considered to be an effective approach to suppress the adsorption of proteins on capillary inner surface in CE. However, most of coating materials reported are water-soluble, which may dissolve in BGE during the procedure of electrophoresis. In this study, a novel strategy for selection of physically coating materials has been illustrated to get coating layer with excellent stability using materials having poor solubility in commonly used solvents. Taking natural chitin as example (not hydrolyzed water soluble chitosan), a simple one step coating method using chitin solution in hexafluoroisopropanol was adopted within only 21 min with good coating reproducibility (RSDs of EOF for within-batch coated capillaries of 1.55% and between-batch coated capillaries of 2.31%), and a separation of four basic proteins on a chitin coated capillary was performed to evaluate the coating efficacy. Using chitin coating, the adsorption of proteins on capillary inner surface was successfully suppressed with reversed and stable EOF, and four basic proteins including lysozyme, cytochrome c, ribonuclease A and α-chymotrypsinogen A were baseline separated within 16 min with satisfied separation efficiency using 20 mM pH 2.0 H3PO4-Na2HPO4 as back ground electrolyte and 20 kV as separation voltage. What is more important, the chitin coating layer could be stable for more than two months during this study, which demonstrates that chitin is an ideal material for preparing semi-permanent coating on bare fused silica capillary inner wall and has hopeful potential in routine separation of proteins with CE.


Solution self-assembly and solid state properties of fluorinated amphiphilic calix[4]arenes.
A novel amphiphilic semifluorinated calix[4]arene has been shown to exhibit liquid crystalline character and to self-assemble in solvents of varying polarity.


The plane facts of PCP in the CNS.
Planar cell polarity (PCP) pathways have been defined by their ability to direct the development of obviously polarized cellular architectures. Recent studies indicate that PCP pathways also regulate aspects of cell morphology that are not restricted to the plane of the epithelium. In the developing nervous system, PCP-mediated changes in the cytoskeleton are fundamental to neuronal migration, neuronal polarity, axon guidance, and dendritic arborization, highlighting the importance of "planar polarity" genes for defining the shape of a neuron in all dimensions.


Aptahistochemistry in diagnostic pathology: technical scrutiny and feasibility.
Antibodies have been the workhorse for diagnostic immunohistochemistry to specifically interrogate the expression of certain protein to aid in histopathological diagnosis. This review introduces another dimension of histochemistry that employs aptamers as the core tool, the so-called aptahistochemistry. Aptamers are an emerging class of molecular recognition elements that could recapitulate the roles of antibodies. The many advantageous properties of aptamers suited for this diagnostic platform are scrutinized. An in-depth discussion on the technical aspects of aptahistochemistry is provided with close step-by-step comparison to the more familiarized immunohistochemical procedures, namely functionalization of the aptamer as a probe, antigen retrieval, optimization with emphasis on incubation parameters and visualization methods. This review offers rationales to overcome the anticipated challenges in transition from immunohistochemistry to aptahistochemistry, which is deemed feasible for an average diagnostic pathology laboratory.


Preparation of pepsin trypsin digested gliadin for stimulation experiments.
Celiac disease (CD) is a complex immune disorder of the intestine that developes in genetically susceptible individuals. CD develops as an intolerance to ingested gluten proteins (gliadins, secalins, hordeins and avenins), being gliadin one of the most immunogenic. Here we present a protocol for the preparation of digested gliadin for laboratory use, a fundamental axis for in vitro and in vivo stimulation studies related to celiac disease research. The importance of a scrupulous handling of materials, products and laboratory instruments to achieve a lipopolysaccharide free gliadin is explained and emphasized. Therefore, in the present chapter, a step-by-step set-up of the protocol for pepsin trypsin gliadin digestion is explained.


Dystrophin Dp116: A yet to Be Investigated Product of the Duchenne Muscular Dystrophy Gene.
The Duchenne muscular dystrophy (DMD) gene is one of the largest genes in the human genome. The gene exhibits a complex arrangement of seven alternative promoters, which drive the expression of three full length and four shorter isoforms. Dp116, the second smallest product of the DMD gene, is a Schwann cell-specific isoform encoded by a transcript corresponding to DMD exons 56-79, starting from a promoter/exon S1 within intron 55. The physiological roles of Dp116 are poorly understood, because of its extensive homology with other isoforms and its expression in specific tissues. This review summarizes studies on Dp116, focusing on clinical findings and alternative activation of the upstream translation initiation codon that is predicted to produce Dp118.


Verbal/Social Autopsy in Niger 2012-2013: A new tool for a better understanding of the neonatal and child mortality situation.
Niger, one of the poorest countries in the world, recently used for the first time the integrated verbal and social autopsy (VASA) tool to assess the biological causes and social and health system determinants of neonatal and child deaths. These notes summarize the Nigerien experience in the use of this new tool, the steps taken for high level engagement of the Niger government and stakeholders for the wide dissemination of the study results and their use to support policy development and maternal, neonatal and child health programming in the country. The experience in Niger reflects lessons learned by other developing countries in strengthening the use of data for evidence-based decision making, and highlights the need for the global health community to provide continued support to country data initiatives, including the collection, analysis, interpretation and utilization of high quality data for the development of targeted, highly effective interventions. In Niger, this is supporting the country's progress toward achieving Millennium Development Goal 4. A follow-up VASA study is being planned and the tool is being integrated into the National Health Management Information System. VASA studies have now been completed or are under way in additional sub-Saharan African countries, in each through the same collaborative process used in Niger to bring together health policy makers, program planners and development partners.


Tissue distribution of mirtazapine and desmethylmirtazapine in a case of mirtazapine poisoning.
An ingestion of an unknown quantity of mirtazapine in a suicide attempt leading to death is described. Sertraline and amitriptyline have been co-ingested. Because mirtazapine is reported to be relatively safe in overdose, body fluids and tissues were investigated for both mirtazapine and desmethylmirtazapine by high-pressure liquid chromatography/tandem mass spectrometry following liquid-liquid extraction. The limit of detection was sufficiently low to also apply the assay in pharmacokinetic studies. The levels of amitriptyline and nortriptyline were very low (38 and 19 ng/mL femoral venous blood) and the amount of sertraline in blood taken from the femoral vein (880 ng/mL) was considerably lower than those seen in overdosage. Accumulation of mirtazapine and N-desmethylmirtazapine was evident in fluids and tissues involved in enterohepatic circulation and excretion. The concentration determined in a brain sample suggests a contribution of the metabolite to the drug's pharmacodynamic activity. Based on literature data, significant adverse or synergistic effects among the drugs detected as well as adverse reactions such as a serotonin reaction appeared less probable. Mirtazapine exhibits alpha(1)-antagonistic properties on the cardiac-vascular system and may cause hyponatraemia. In the face of the cardiac findings at autopsy and the lack of an apparent cause of death, these effects of mirtazapine may have initiated a process leading to death.


Changes in microbial ecology in an anaerobic reactor.
This study examined the behaviour of the microbial population in an anaerobic reactor, in terms of changes in numbers of total bacterial community, autofluorescent methanogens, non-methanogens and morphology of the autofluorescent methanogens, using epifluorescence microscopy and microbiological enumeration techniques. A laboratory-scale, continuous flow-completely mixed anaerobic reactor, coupled with a conventional gravity settling tank and a continuous recycling system, was operated at an HRT range between 24 and 12 h, using dairy wastewater as the substrate. The numbers of the total bacterial community and autofluorescent methanogens both decreased during start-up. Also, the proportion of the number of autofluorescent methanogens in the total bacterial community varied from 5% to 16% during operation. In particular, the activity of the methane-forming bacteria decreased significantly at HRTs of 16 and 12 h. A membrane module, instead of a conventional settling tank, would obviously have been a more effective method if recycling were required in the anaerobic treatment system.


Reduced MTR in the corticospinal tract and normal T2 in amyotrophic lateral sclerosis.
The objective of this study was to test the hypothesis that magnetization transfer ratios (MTR) are decreased in the corticospinal tract of patients with amyotrophic lateral sclerosis (ALS); to determine if T2 is increased in corticospinal tract or reduced in motor cortex in ALS; to determine if corticospinal tract MTR correlates with a clinical measure of motor neuron function in ALS. Ten ALS patients and 17 age-matched controls were studied. Double spin echo MRI and 3D gradient echo MRI with and without off-resonance saturation were acquired on each subject. 3D data sets were coregistered and resliced to match the spin echo data set. MTR was calculated for corticospinal and non-corticospinal tract white matter. T2 was calculated for corticospinal and non-corticospinal tract white matter, motor cortex and non-motor cortex. MTR was reduced by 2.6% (p < .02) in corticospinal, but not in non-corticospinal, tract white matter in ALS. There was no difference in T2 in any brain region. The correlation between a clinical measure of motor neuron function and corticospinal tract MTR was statistically significant. These findings are consistent with the known pathology in ALS and suggest that MTR is more sensitive than T2 for detecting involvement of the corticospinal tract. Quantitative MTR of the corticospinal tract may be a useful, objective marker of upper motor neuron pathology in ALS.


Modified Unilateral Biportal Endoscopic Lumbar Discectomy Results in Improved Clinical Outcomes.
To evaluate and describe the clinical efficacy and safety of a modified unilateral biportal endoscopic lumbar discectomy. From February 2019 to February 2020, patients who met the inclusion criteria were treated using a modified unilateral biportal endoscopic lumbar discectomy. During the operation, the herniated disc was removed and the ligamentum flavum was preserved. Clinical efficacy was assessed via postoperative imaging and follow-up. A total of 70 patients were followed up for more than 2 years, including 51 males and 19 females, aged 49.4 ± 16.0 years. All operations were completed and no complications were noted. Postoperative lumbar magnetic resonance imaging showed that the decompression of the nerve root was sufficient and the ligamentum flavum was preserved in all patients. Postoperative lumbar CT showed that the caudal lamina and inferior articular process of the cephalad vertebral were partially removed. Lower back and leg pain were significantly relieved after surgery, and the Oswestry Disability Index was significantly improved compared to presurgery measurements (P < 0.01). After 2 years of follow-up, the sensory and muscle strength of nerve roots were significantly recovered (P < 0.01). According to the MacNab score of the patients, 40 cases were defined as "excellent," 26 cases were "good," 2 cases were "fair," and 2 cases were "poor." Modified unilateral biportal endoscopic lumbar discectomy can completely remove a lumbar herniated disc; relieve lower back and leg pain; improve lumbar function; reduce the risk of dural tearing, cerebrospinal fluid leakage, and epidural hematoma; and reduce the epidural adhesion and arachnoiditis caused by ligamentum flavum resection.


The soluble transferrin receptor reflects tumor load in chronic lymphocytic leukemia.
The soluble transferrin receptor (sTfR) is a parameter of erythropoietic activity and iron deficiency. Increased levels have also been described in hematological malignancies, especially in chronic lymphocytic leukemia (CLL). We investigated the value of sTfR in the assessment of tumor mass in 61 previously untreated CLL patients. Both hemolysis and iron deficiency were excluded. sTfR was measured nephelometrically (normal 0.81-1.75 mg/L). All Binet A patients had normal sTfR values (1.36+/-0.22 mg/L). In Binet B patients, the sTfR was increased (3.08+/-1.70 mg/L, p<0.0001) compared to Binet A patients. Binet B patients with normal sTfR had a small tumor load and no abdominal involvement. A further increase of sTfR in Binet C (3.75+/- 2.32 mg/L) was not significant compared to Binet B patients. sTfR values decreased or even normalized after successful treatment, whereas relapse or disease progression was associated with another increase of sTfR. The sTfR concentration directly reflects the tumor burden in CLL. Therefore, sTfR may be of clinical value in monitoring disease activity, response to treatment and disease progression.