Structure and developmental expression of the D alpha 2 gene encoding a novel nicotinic acetylcholine receptor protein of Drosophila melanogaster.
Nicotinic acetylcholine receptors (nAChRs) represent a heterogeneous group of excitatory neurotransmitter receptors in the insect brain. We have characterized the D alpha 2 gene of Drosophila melanogaster, a new member of the nAChR gene family. The protein coding region is interrupted by six introns. The positions of three of these introns are shared with all other nAChR genes. The deduced D alpha 2 protein shows the structural features of ligand-binding nAChR alpha-subunits. Cytogenetically, the D alpha 2 gene maps at position 96A of the 3rd chromosome, close to the ALS gene which also encodes an alpha-like nAChR subunit. D alpha 2 transcripts are predominantly expressed in late embryos and in fly heads.


Activity, stability, and structure of metagenome-derived LC11-RNase H1, a homolog of Sulfolobus tokodaii RNase H1.
Metagenome-derived LC11-RNase H1 is a homolog of Sulfolobus tokodaii RNase H1 (Sto-RNase H1). It lacks a C-terminal tail, which is responsible for hyperstabilization of Sto-RNase H1. Sto-RNase H1 is characterized by its ability to cleave not only an RNA/DNA hybrid but also a double-stranded RNA (dsRNA). To examine whether LC11-RNase H1 also exhibits both RNase H and dsRNase activities, LC11-RNase H1 was overproduced in Escherichia coli, purified, and characterized. LC11-RNase H1 exhibited RNase H activity with similar metal ion preference, optimum pH, and cleavage mode of substrate with those of Sto-RNase H1. However, LC11-RNase H1 did not exhibit dsRNase activity at any condition examined. LC11-RNase H1 was less stable than Sto-RNases H1 and its derivative lacking the C-terminal tail (Sto-RNase H1ΔC6) by 37 and 13 °C in T(m) , respectively. To understand the structural bases for these differences, the crystal structure of LC11-RNase H1 was determined at 1.4 Å resolution. The LC11-RNase H1 structure is highly similar to the Sto-RNase H1 structure. However, LC11-RNase H1 has two grooves on protein surface, one containing the active site and the other containing DNA-phosphate binding pocket, while Sto-RNase H1 has one groove containing the active site. In addition, LC11-RNase H1 contains more cavities and buried charged residues than Sto-RNase H1. We propose that LC11-RNase H1 does not exhibit dsRNase activity because dsRNA cannot fit to the two grooves on protein surface and that LC11-RNase H1 is less stable than Sto-RNase H1ΔC6 because of the increase in cavity volume and number of buried charged residues.


Diabetes and cancer: A comprehensive review.
Diabetes mellitus (DM) is a common worldwide endocrine disorder characterized by hyperglycemia resulting from defects in insulin secretion and insulin action or both. A number of clinical studies have investigated diabetes and its causal relation with neoplasm. Several epidemiological studies have found that diabetic patients have an increased risk of different types of cancers, for example liver, pancreas, gastric (stomach), colorectum, kidney, and breast, and it is predicted that hyperglycemic state observed in diabetic milieu enhances the cancer risk in prediabetic and diabetic individuals. To explore the strength of evidence and biases in the claimed associations between type 2 DM (T2DM) and risk of developing cancer, an umbrella review of the evidence across published meta-analyses or systematic reviews is performed. The concurrence of T2DM with the growing burden of cancer globally has generated interest in defining the epidemiological and biological relationships between these medical conditions. Through this review, it was found that diabetes could be related to cancer. Yet, the results from most of the studies are obscure and conflicting and need a robust research so that the link between diabetes and cancer could be firmly and impeccably documented.


Massive subretinal exudate after retinal detachment surgery.
A 70-year-old woman developed massive subretinal exudation after surgical repair of a rhegmatogenous retinal detachment. Postoperative choroidal detachment suggested a choroidal source of the subretinal exudate. We believe the cause of the choroidal detachment and exudation was vortex ampulla obstruction resulting from the encircling band. The subretinal exudate underwent gradual resolution and did not influence the anatomic result of retinal reattachment.


Discovery and development of BMPs.
In the early 1970s, the isolation and identification of bone morphogenetic proteins (BMPs) was a major breakthrough for the understanding of the distinct biological events occurring during bone formation. Not surprising, since their discovery, BMPs have been perhaps one of the most intensively studied group of factors in various physiological processes. The prompt development of recombinant BMPs and various delivery methods made BMPs currently available for clinical use. Research and clinical studies on BMPs are ongoing, aiming to refine further our understanding of their activities in vivo and to optimise and expand their clinical use in humans.


Cardiac myosin filaments are directly regulated by calcium.
Classically, striated muscle contraction is initiated by calcium (Ca2+)-dependent structural changes in regulatory proteins on actin-containing thin filaments, which allow the binding of myosin motors to generate force. Additionally, dynamic switching between resting off and active on myosin states has been shown to regulate muscle contractility, a recently validated mechanism by novel myosin-targeted therapeutics. The molecular nature of this switching, however, is not understood. Here, using a combination of small-angle x-ray fiber diffraction and biochemical assays with reconstituted systems, we show that cardiac thick filaments are directly Ca2+-regulated. We find that Ca2+ induces a structural transition of myosin heads from ordered off states close to the thick filament to disordered on states closer to the thin filaments. Biochemical assays show a Ca2+-induced transition from an inactive super-relaxed (SRX) state(s) to an active disordered-relaxed (DRX) state(s) in synthetic thick filaments. We show that these transitions are an intrinsic property of cardiac myosin only when assembled into thick filaments and provide a fresh perspective on nature's two orthogonal mechanisms to regulate muscle contraction through the thin and the thick filaments.


Haplotype-based analysis resolves missing heritability in oculocutaneous albinism type 1B.
Oculocutaneous albinism (OCA) is a rare disorder of pigment production. Affected individuals have variably decreased global pigmentation and visual-developmental changes that lead to low vision. OCA is notable for significant missing heritability, particularly among individuals with residual pigmentation. Tyrosinase (TYR) is the rate-limiting enzyme in melanin pigment biosynthesis and mutations that decrease enzyme function are one of the most common causes of OCA. We present the analysis of high-depth short-read TYR sequencing data for a cohort of 352 OCA probands, ∼50% of whom were previously sequenced without yielding a definitive diagnostic result. Our analysis identified 66 TYR single-nucleotide variants (SNVs) and small insertion/deletions (indels), 3 structural variants, and a rare haplotype comprised of two common frequency variants (p.Ser192Tyr and p.Arg402Gln) in cis-orientation, present in 149/352 OCA probands. We further describe a detailed analysis of the disease-causing haplotype, p.[Ser192Tyr; Arg402Gln] ("cis-YQ"). Haplotype analysis suggests that the cis-YQ allele arose by recombination and that multiple cis-YQ haplotypes are segregating in OCA-affected individuals and control populations. The cis-YQ allele is the most common disease-causing allele in our cohort, representing 19.1% (57/298) of TYR pathogenic alleles in individuals with type 1 (TYR-associated) OCA. Finally, among the 66 TYR variants, we found several additional alleles defined by a cis-oriented combination of minor, potentially hypomorph-producing alleles at common variant sites plus a second, rare pathogenic variant. Together, these results suggest that identification of phased variants for the full TYR locus are required for an exhaustive assessment for potentially disease-causing alleles.


Unexpected presence of cytokeratins in human "glia-like" cells.
To demonstrate the unexpected features of the predominant cell population in adult human brain tissue cultures usually termed "glia-like" cells. Cytokeratins (CK) are intermediate filaments (IF) specific for normal and neoplastic epithelial cell differentiation. We examined adult human brain tissue cultures and cryosections prepared from ten biopsies. Immunofluorescence staining with monoclonal antibodies against IF proteins: anti-pan CK, glial fibrillary acidic protein (GFAP) and vimentin was performed on primary and secondary cultures up to passage 10. In primary cultures we detected only small numbers of immunocytochemically distinct astrocytes, oligodendrocytes and microglial cells. "Glia-like" cells were negatively stained with specific glial marker antibodies. They were positively stained with pan-CK antibodies in 8/10 cultures where 0.1 % to 70 % CK-positive cells were present in primary as well as in secondary cultures. Comparative immunofluorescence IF staining for CK, GFAP and vimentin showed differences in the cytoplasmatic distribution of IF fibres, numbers of positive cells and intensities of staining. Cryosections from brain biopsies stained negatively with pan-CK antibodies. These findings demonstrate the presence of CK in adult human brain cultures which is not caused by cross-reactivity of IF antibodies. Based on these results we propose that unexpected CK expression in human "glia-like" cells is due to cell dedifferentiation under culture conditions (Tab. 1, Fig. 2, Ref. 24).


Possible damage mechanism of the dielectric coatings for a KrF laser.
We discuss the fracture of dielectric coatings during the irradiation of a high-power (10(8-9) W/cm(2)) KrF laser by analyzing the thermal stress distribution within the coatings. It is shown that it is the compressive stresses perpendicular to the coating surface that make the optical coatings crack.


Non-paralleled increase of hepatocyte growth factor and vascular endothelial growth factor in the eyes with angiogenic and nonangiogenic fibroproliferation.
Vascular endothelial growth factor (VEGF) has been known as principal angiogenic factor in vasculogenesis, tumor angiogenesis and ocular angiogenesis. Currently, hepatocyte growth factor (HGF) has been reported to play a major role in ocular angiogenesis. We studied distribution of both growth factors in angiogenic and non-angiogenic fibroproliferation to determine the correlation of VEGF and HGF in retinal angiogenesis. Concentrations of VEGF and HGF molecules in vitreous samples from 27 eyes with angiogenic proliferative diabetic retinopathy (PDR) and 9 eyes with non-angiogenic proliferative vitreoretinopathy (PVR) were measured by enzyme-linked immunosorbent assay (ELISA). Vitreous samples with idiopathic macular role (IMH) served as a control. Concentrations of VEGF in the angiogenic PDR were 4.3 +/- 5.8 ng/ml (mean +/- SD), and were significantly higher than in non-angiogenic PVR (0.5 +/- 0.1 ng/ml). No significant differences were observed on VEGF concentrations between PVR to control. On the contrary, HGF concentrations were significantly higher in PVR (22.5 +/- 21.8 ng/ml) than in control (6.9 +/- 5.2 ng/ml), those of PDR (24.0 +/- 16.3 ng/ml) were also significantly higher than control. Among PDR samples, VEGF concentration was significantly higher than in the subgroup with higher angiogenic activity represented by iris neovascularization, although there were no significant differences on HGF concentration between the subgroups. Focal increases in HGF on fibroproliferation in the eye regardless of the involvement of angiogenesis were not in remarkable relation with angiogenic activity, unlike VEGF. These data suggested a more extensive role of HGF than VEGF strictly related to angiogenesis.


Difference in compliance with Standard Precautions by nursing staff in Brazil versus Hong Kong.
The Standard Precautions (SP) are measures to reduce the risk of transmission of bloodborne and other pathogens, and should be used by health professionals in the care of all patients regardless of their condition of infection. However, suboptimal compliance with SP has been consistently reported in the nursing literature. This study evaluated the differences of compliance with SP among nurses from Brazil and Hong Kong. This cross-sectional study was conducted in 2 countries-Hong Kong and Brazil-with nurses working in hospitals who responded to a self-administered questionnaire with demographic data and responses to a 20-item Compliance with Standard Precautions Scale. The compliance rate of 560 nurses was 69.4% for the Brazilian sample and 57.4% for the Hong Kong sample. The additional clinical experience of the Brazilian nurses versus those in Hong Kong may be related to differences in compliance with SP between nurses.


Efficient ultraviolet blocking film on the lignin-rich lignocellulosic nanofibril from bamboo.
The ultraviolet (UV) blocking performance of current bio-based devices is always limited by delignification and exploited chemical treatment. Lignocellulosic nanofibril (LCNF) is a promising green alternative that could efficiently impede UV radiation. Herein, we proposed a robust LCNF film that achieved 99.8 ± 0.19 % UVB blocking, 96.1 ± 0.23 % UVA blocking, and was highly transparent without complex chemical modification. Compared to conventional lignin composites, this LCNF method involves 29.5 ± 2.31 % lignin content directly extracted from bamboo as a broad-spectrum sun blocker. This bamboo-based LCNF film revealed an excellent tensile strength of 94.9 ± 3.6 MPa and outstanding stability, adapting to the natural environment's variability. The residual hemicellulose could also embed the link between lignin and cellulose, confirming high lignin content in the network. The connection between lignin and hemicelluloses in the cellulose network was explored and described for the fibrillation of lignocellulosic nanofibrils. This research highlights the promising development of LCNFs for UV protection and bio-based solar absorption materials.


The Role of the Three Rs in Improving the Planning and Reproducibility of Animal Experiments.
Training in the design of animal experiments focuses all too often on those aspects which can be approached mathematically, such as the number of animals needed to deliver a robust result, allocation of group size, and techniques such as randomization, blocking and statistical analysis. Important as they are, these are only a small part of the process of planning animal experiments. Additional key elements include refinements of housing, husbandry and procedures, health and safety, and attention at all stages to animal welfare. Advances in technology and laboratory animal science have led to improvements in care and husbandry, better provision of anesthetics and analgesics, refined methods of drug administration, greater competence in welfare assessment and application of humane endpoints. These improvements require continual dialogue between scientists, facility managers and technical staff, a practice that is a key feature of what has become known as the culture of care. This embodies a commitment to improving animal welfare, scientific quality, staff care and transparency for all stakeholders. Attention to both the physical and mental health of all those directly or indirectly involved in animal research is now an important part of the process of planning and conducting animal experiments. Efforts during the last 30 years to increase the internal and external validity of animal experiments have tended to concentrate on the production of guidelines to improve the quality of reporting animal experiments, rather than for planning them. Recently, comprehensive guidelines for planning animal studies have been published, to redress this imbalance. These will be described in this paper. Endorsement of this overarching influence of the Three R concept, by all the stakeholders, will not only reduce animal numbers and improve animal welfare, but also lead to more reliable and reproducible research which should improve translation of pre-clinical studies into tangible clinical benefit.


Innovative anthocyanins formulation protects neuronal-like cells against oxidative stress-induced damage: Pharmacotherapeutic application for Alzheimer's disease.
Oxidative stress is involved in the etiology of multiple chronic diseases including Parkinson's and Alzheimer's diseases (AD). Moreover, it is believed to be a primary cause in diseases pathogenesis. For instance, in AD lipid peroxidation by-products such as acrolein accumulated specifically in vulnerable regions of the brain from mild cognitive impairment and preclinical AD patients. Acrolein is a highly reactive aldehyde seen also as an initiator of oxidative stress. Although severalstudies have demonstrated that polyphenol-rich extracts could exert beneficial effect on cognitive impairment and oxidative stress, only a few of them could reach the brain. Among them, anthocyanins have been detected in hippocampus but in a very small amount. Thus, we hypothesised that polyphenols could have synergic effect at low concentrations leading to the neuroprotective effect. Our screening experiments lead to a formulation containing a mix of different anthocyanins (MAF) with antioxidant and neuroprotective effect at very low doses. Our results demonstrated that MAF showed a protective effect against acrolein- and b-amyloid-induced SK-N-SH cell toxicity. Our data demonstrated that MAF was able to lower protein carbonyl levels induced by acrolein or ß-amyloid. Moreover, MAF prevented glutathione depletion induced by acrolein. Our results also showed that MAF prevented the expression of ?-glutamylcystein synthetase, the nuclear translocation of Nrf2, the activation of both NF-?B and p66HSC by acrolein. In conclusion, we demonstrated that the innovative anthocyanin formulationMAF was not only a powerful antioxidant, but could also regulate cellular pathways involved in antioxidant defenses and cell survival. These effects of MAF were observed with low concentrations suggesting a synergistic effect of these polyphenolic compounds. These results indicate that MAF could be a promising agent for AD prevention.


Melanoma in 2011: a new paradigm tumor for drug development.
Melanoma has emerged as the paradigm tumor for drug development through mutation-targeted therapies (inhibitors targeting BRAF, MEK, and c-KIT) and immunotherapy. Exploring the combinations of both approaches is a challenge that will require scientific rationale and the cooperation of the pharmaceutical industry. But, with these challenges comes another opportunity to change the paradigms in drug development.


Inferior gluteal artery perforator (IGAP) flap in autologous breast reconstruction: A proportional meta-analysis of surgical outcomes.
The inferior gluteal artery perforator (IGAP) flap is an alternative technique for autologous breast reconstruction. In contrast to other commonly used techniques, there is a paucity of literature on the safety and efficacy of the IGAP flap. The aim of this study was to perform a systematic literature review and meta-analysis of postoperative outcomes and complications associated with the IGAP in autologous breast reconstructions to validate its safety. A systematic review of literature was performed following PRISMA guidelines. Articles reporting post-operative outcomes of IGAP flaps in autologous breast reconstruction were included. A proportional meta-analysis of post-operative complications was performed to obtain their proportions with 95% confidence intervals (CIs). Seven studies met the inclusion criteria, which represented a total of 239 IGAP flaps in 181 patients The total flap loss rate was 3% (95% CI 0-8%), partial flap loss rate was 2% (95% CI 0-4%), haematoma rate was 3% (95% CI 0-7%), overall donor-site complication rate was 15% (95% CI 5-28%), overall recipient-site complication rate was 24% (95% CI 15-34%), and the overall complication rate was 40% (95% CI 23-58%). This meta-analysis provides comprehensive knowledge on the safety and efficacy of the IGAP flap in autologous breast reconstruction. It evidences the IGAP flap in autologous breast reconstruction's overall safety and validates its role as an effective option in breast reconstruction.


[Stomach perforation and other complications after splenectomy].
The complications of 151 cases of splenectomy are analyzed, the methods of their prevention discussed. As a special complication two cases of gastric fistula following splenectomy are reported. As prevention we recommend several broad Lembert sutures to invert the entire danger zone.


Vertebral body reconstruction with a modified Harrington rod distraction system for stabilization of the spine affected with metastatic disease.
Anterior spinal decompression has become widely used for neoplasia arising from the vertebral bodies. Replacement for the resected vertebral body must achieve spinal stability, restitution of lost height, correction of kyphotic deformities, and allow for early ambulation. A spinal fixator based on the Harrington ratchet locking system was found to fulfill this requirement. The fixator, its technique of implementation, and surgical results in 10 patients are described.


Oncological Screening of Kidney Tumors After Renal Transplantation.
Among renal transplant recipients, renal cell carcinoma in the native kidneys represents the most common solid tumor. At the Department of Surgery, Transplantation and Gastroenterology of Semmelweis University annual control abdominal ultrasound examination is recommended for transplant patients. Our goal was to evaluate the effectiveness of the ultrasound screening program at our institute and to learn about the characteristics of shrunken kidney tumors. Retrospectively, we processed the results of abdominal and pelvic ultrasound examinations of 1687 kidney transplant patients, which were performed at our institute between January 1, 2012 and December 31, 2016. A total of 26 tumors were detected during the abovementioned period of time, of which 18 were renal cancers. Renal cancer was significantly (P = 0.029) more common in men. Seventeen renal cancers were classified as stage I and one as stage IV disease. The mean time of dialysis was 37.73 ± 24.37 months. The mean time between kidney transplantation and tumor recognition was 7.9 ± 6.29 years. The 5-year survival was 66%; however, it should be noted that only 1 patient lost his life due to his tumor disease. The mean time between the last 2 ultrasound examinations was 27.8 ± 23.89 months. Only 57% of tumors were detected by screening. No significant differences in tumor size, stage, and survival could be detected between screened and nonscreened renal cancer patients. Ultrasound examination at least every 2 years is an effective tool for the early detection of renal cell carcinoma of the shrunken kidneys.


Long story short: the serotonin transporter in emotion regulation and social cognition.
The gene encoding the serotonin transporter (5-HTT) contains a regulatory variation that has been associated with anxiety-related traits and susceptibility for depression. Here we highlight recent discoveries related to allelic variation of 5-HTT function with respect to emotion regulation and social behavior, drawing from an interdisciplinary perspective of behavioral genetics and cognitive neuroscience. Following a reductionistic path that leads from gene-behavior association studies to neuroimaging and epigenetic studies, we compare two models of 5-HTT-dependent modulation of brain activity and discuss the role of life stress experience in modifying 5-HTT function in the brain. Integration of these findings suggests that the impact of the 5-HTT gene on behavior is much broader than is commonly appreciated and may have a role in social cognition.


Five-year results of a modified left atrial maze IV procedure in the treatment of atrial fibrillation: a randomized study.
The left atrial maze IV (LAM-IV) alone has been used to eliminate atrial fibrillation (AF) without severe right heart diseases. However, we felt that it could be improved and developed a modified LAM-IV (MLAM-IV). In this prospective trial, we aimed to investigate 5-year clinical outcomes of AF in patients treated by the novel MLAM-IV technique. Between September 2012 and October 2013, 120 patients who underwent valve surgery and bipolar radiofrequency ablation for AF were randomized into the LAM-IV group (n = 60) or MLAM-IV group (n = 60). At postoperative follow-up examinations, data were recorded at 1, 3 and 6 months, and annually thereafter. The mean ablation time and postoperative ventilation time were shorter in the MLAM-IV group than in the LAM-IV group (P < 0.001 and P = 0.03, respectively). At 5 years, the rate of freedom from AF was 69.0% in the MLAM-IV group and 60.0% in the LAM-IV group (hazard ratio 0.71, 95% confidence interval 0.39 to 1.32, P = 0.42). There were no differences with respect to the early operative mortality and major complications, late mortality, and major adverse events. The MLAM-IV provides a technically simpler ablation process. The MLAM-IV was associated with less ventilation support in the early postoperative period. The long-term efficacy of the MLAM-IV in the treatment of AF is comparable to that of the LAM-IV.


Treatment-Free Remission: a New Therapeutic Goal in Chronic Myelogenous Leukemia.
Chronic myelogenous leukemia (CML) is a chronic myeloproliferative neoplasm characterized by the presence of Philadelphia chromosome [t(9:22)] leading to the presence of pathognomonic fusion gene product, BCR-ABL1. This leads to constitutive activation of ABL1 kinase. CML was a difficult-to-treat illness until the advent of small molecule tyrosine kinase inhibitor (TKI), imatinib which revolutionized therapy of CML. Since then, multiple second- and third-generation TKIs have been formulated which have proven effective and has led to marked improvement in survival. In this article, we review currently available data on possibility of holding TKI therapy in patients in deep remission [treatment-free remission (TFR)] and safety of this approach. As CML treatment has become more effective, new questions have emerged, most important being whether the treatment with TKIs can ever be stopped. This is especially relevant in patient experiencing side effects from therapy or who may be subject to increased health risks due to treatment. There is now evidence that some CML patients who have achieved stable deep molecular response can safely stop TKI. Furthermore, patients can safely re-establish remission after restarting their TKI therapy in the situation of relapse. CML is highly treatable disease, but the treatment has untoward physical and socioeconomic consequences. The idea of TFR is hence attractive. There is a growing body of evidence that some CML patients who have achieved stable deep molecular response can safely stop TKI.


Randomized Trial of Modified Chest Tube Placement vs Routine Placement After Lung Resection.
Chest tube placement after pulmonary resection is usually considered a mandatory procedure. However, peritubular leakage of pleural fluid and intrathoracic air is frequent after surgery. Therefore, we separated the chest tube from the intercostal space as a modified placement strategy. Patients undergoing robotic and video-assisted lung resection were enrolled in this study at our medical center between February 2021 and August 2021. All patients were randomly divided into either the modified group (n = 98) or the routine group (n = 101). The incidence of peritubular leakage of pleural fluid and peritubular air leaking or entering after surgery were the primary end points of the study. A total of 199 patients were randomized. Patients in the modified group had lower incidence of peritubular leakage of pleural fluid (after surgery, 39.6% vs 18.4% [P = .001]; after chest tube removal, 26.7% vs 11.2% [P = .005]), lower incidence of peritubular air leaking or entering (14.9% vs 5.1% [P = .022]), and fewer dressing changes (5.02 ± 2.30 vs 3.48 ± 0.94 [P < .001]). In patients undergoing lobectomy and segmentectomy, the type of chest tube placement was associated with the severity of peritubular pleural fluid leakage (P < .05). The modified chest tube placement was safe and had better clinical efficacy than the routine type. The reduction of postoperative peritubular leakage of pleural fluid resulted in better wound recovery. This modified strategy should be popularized, especially in patients undergoing pulmonary lobectomy or segmentectomy.


Hemodialysis prognostic nutrition index as a predictor for morbidity and mortality in hemodialysis patients and its correlation to adequacy of dialysis. Council on Renal Nutrition National Research Question Collaborative Study Group.
Prospectively examine the use of a hemodialysis prognostic nutrition index (HD-PNI) as a predictor for morbidity and mortality in hemodialysis patients and its correlation to adequacy of dialysis. Prospective randomized collaborative study group. There were 211 chronic hemodialysis centers; 202 from 43 United States, 9 from Canada. There were 1527 hemodialysis patients undergoing treatment a minimum of 3 months and at least 18 years of age. Sample mirrored United States Renal Data System data for age, sex, race, and etiology of renal failure. None; routinely collected demographic, biochemical, and clinical data for 8-month baseline and 3-month predictive phases. HD-PNI calculated from baseline data as linear mathematical equation using level of serum albumin, level of serum creatinine, and number of days and times hospitalized; HD-PNI risk defined as >/=0.8. Adequacy of dialysis calculated as urea reduction ratio (URR) from baseline data; adequacy risk defined as URR of </=65%. Number of times and days hospitalized, mortality. For this research, 1167 patients completed the study (76%) with 360 (24%) dropped due to death, incomplete data, transfer, or change in modality. Patients completing study with HD-PNI risk (n = 208, 18%) compared with patients who had no HD-PNI risk (n = 959, 82%) were hospitalized more often (57.2% v 28.5%, P <. 01), hospitalized with infection more often (14.6% v 4.6%, P <.01), and had greater mortality (7.7% v 2.5%, P <.01). Stratification of HD-PNI risk by URR of >/=65% did not significantly improve prediction. Use of HD-PNI is an effective screening tool to identify hemodialysis patients at risk for morbidity and mortality. No correlation was found between URR and HD-PNI.


Fluorescence tracing the degradation process of biodegradable PBAT: Visualization and high sensitivity.
Biodegradable plastics have emerged as a potential solution to the mounting plastic pollution crisis. However, current methods for evaluating the degradation of these plastics are limited in detecting structural changes rapidly and accurately, particularly for PBAT, which contains worrying benzene rings. Inspired by the fact that the aggregation of conjugated groups can endow polymers with intrinsic fluorescence, this work found that PBAT emits a bright blue-green fluoresces under UV irradiation. More importantly, we pioneered a degradation evaluation approach to track the degradation process of PBAT via fluorescence. A blue shift of fluorescence wavelength as the thickness and molecular weight of PBAT film decreased during degradation in an alkali solution was observed. Additionally, the fluorescence intensity of the degradation solution increased gradually as the degradation progressed, and was found to be exponentially correlated with the concentration of benzene ring-containing degradation products following filtration with the correlation coefficient is up to 0.999. This study proposes a promising new strategy for monitoring the degradation process with visualization and high sensitivity.


α-Selective Glycosylation with β-Glycosyl Sulfonium Ions Prepared via Intramolecular Alkylation.
Stereoselective glycosylation remains the main challenge in the chemical synthesis of oligosaccharides. Herein we report a simple method to convert thioglycosides into β-sulfonium ions via an intramolecular alkylation reaction, leading to highly α-selective glycosylations for a variety of glycosyl acceptors. The influence of the thioglycoside substituent and the protecting group pattern on the glycosyl donor was investigated and showed a clear correlation with the observed stereoselectivity.


Tritium nuclear magnetic resonance spectroscopy. Distribution patterns and nuclear Overhauser enhancements in some tritiated steroids.
The distribution of tritium atoms in some labeled steroids has been determined by tritium nuclear magnetic resonance spectroscopy. In addition, the distribution of molecular types (mono vs. polytritiated) and nuclear Overhauser enhancements have been determined. As near maximal NOE's were observed, quantitative distribution information was derived from NOE suppressed spectra.


Reconstruction of the middle-aged torn earlobe: a new method.
This paper describes a new method of reconstructing acquired complete and incomplete cleft earlobes which are elongated and have lost their normal bulk due to the wearing of heavy, dangling earrings. Results have been good and problems of breakdown of the repair have not been reported over a period of 2 years.


Molecular profiling of TOX-deficient neoplastic cells in cutaneous T cell lymphoma.
Cutaneous T cell lymphoma (CTCL) is a rare but potentially devastating primary cutaneous lymphoma. CTCL is characterized by localization of neoplastic T lymphocytes to the skin, with mycosis fungoides (MF) and its leukemic form, Sézary syndrome (SS) being the most common variants. Thymocyte selection-associated high-mobility group box (TOX) gene has been found to be highly expressed in MF and SS. It is reported that higher expression levels of TOX in patients will increase risks of disease progression and poor prognosis. However, the molecular events leading to these abnormalities have not been well understood. To better understand the molecular mechanism underlying TOX-mediated differentially expressed genes (DEGs) in CTCL, and to identify DEGs pathways triggered after knockdown of TOX gene in the CTCL cell line Hut78, we employed two shRNA-mediated lentiviruses to knock down TOX gene in the skin lymphoma cell line HuT78. RNA sequencing (RNAseq) analysis was applied to analyze DEGs, DEGs GO and their corresponding pathways. Knockdown of TOX can induce upregulation of 547 genes and downregulation of 649 genes, respectively. HOXC9 was the most significant downregulated gene. Most DEGs are enriched in malignancies and relate to the Wnt and mTOR signaling pathways, and therefore they can regulate cellular processes and induce different biological regulation. Transcriptome analysis of DEGs after knockdown of TOX in our study provides insights into the mechanism of TOX in CTCL and suggests candidate targets for therapy of CTCL.


New strategies in GVHD prophylaxis.
Despite immunosuppressive therapy using cyclosporine (CsA) and prednisolone and methotrexate (MTX), the incidence for aGVHD grade II to IV after transplantation from HLA matched unrelated donors (MUD) is 78%, the incidence for grade III and IV 36%. Since GVHD contributes to morbidity and mortality after MUD-BMT, a more effective prophylactic regimen is needed in order to prevent these transplant-associated complications. Recently, we described that mycophenolate mofetil (MMF, CellCept), an immunosuppressive agent successfully used for the prevention of acute rejection in renal allograft recipients, can safely and effectively be used for the treatment of aGVHD in hematopoietic stem cell transplantation. Information on the i.v. formulation of mycophenolic acid (MPA) is not yet available. Here we report on the i.v. formulation of MMF in hematopoietic stem cell recipients. MMF is effective in the prophylaxis of acute GVHD after stem cell transplantation; the optimal dosage needs further investigation. At the present time the relevance of measurement of plasma MPA concentrations on MMF dosage is not yet understood and further evaluation is required.


Experimental and numerical investigation of building effects on wind erosion of a granular material stockpile.
In the present work, wind tunnel experiments and numerical simulations were carried out to evaluate the physical behaviour of the fluid flow of a stockpile in the presence of an isolated cubic building. Comparing the obtained experimental results with those for the isolated stockpile configuration and observing the differences in the erosion patterns and emission estimates was possible to conclude that (i) the emissions considerably increase due to the presence of the building; (ii) the higher the free stream velocity, due to the presence of the obstacle, the more efficient the dynamics of the pavement process; and (iii) the increase of the gap between the building and the pile does not generate expressive changes in the emitted mass measurements. These findings play an important role since it is possible to obtain an optimal industrial open yard configuration where fewer particles are emitted to the atmosphere.


Brain coordination dynamics: true and false faces of phase synchrony and metastability.
Understanding the coordination of multiple parts in a complex system such as the brain is a fundamental challenge. We present a theoretical model of cortical coordination dynamics that shows how brain areas may cooperate (integration) and at the same time retain their functional specificity (segregation). This model expresses a range of desirable properties that the brain is known to exhibit, including self-organization, multi-functionality, metastability and switching. Empirically, the model motivates a thorough investigation of collective phase relationships among brain oscillations in neurophysiological data. The most serious obstacle to interpreting coupled oscillations as genuine evidence of inter-areal coordination in the brain stems from volume conduction of electrical fields. Spurious coupling due to volume conduction gives rise to zero-lag (inphase) and antiphase synchronization whose magnitude and persistence obscure the subtle expression of real synchrony. Through forward modeling and the help of a novel colorimetric method, we show how true synchronization can be deciphered from continuous EEG patterns. Developing empirical efforts along the lines of continuous EEG analysis constitutes a major response to the challenge of understanding how different brain areas work together. Key predictions of cortical coordination dynamics can now be tested thereby revealing the essential modus operandi of the intact living brain.


[Drug-induced hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency].
9 carriers of G6PD-defect with a drug induced haemolysis are reported. From a pathogenic point of view various medicaments and their degrading and detoxicating products will cause an accumulation of radically effective compounds. With the damaged red blood cell being unable to eliminate these compounds because of its limited provision of NADPH, cell destruction cannot be avoided. Therefore, the exposition prophylaxis, which also embraces medicaments having a depressive effect on the bone-marrow, can be considered as a necessary and efficient measure.


Native nephrectomy prior to pediatric kidney transplantation: biological and clinical aspects.
Pre-transplant nephrectomy is performed to reduce risks to graft and recipient. The aims of this study were to evaluate (1) indications, surgical approach, and morbidity of native nephrectomy and (2) the effects of kidney removal on clinical and biological parameters. This study was designed as a single-center retrospective cohort study in which 49 consecutive patients with uni- or bilateral native nephrectomies were identified from a total of 126 consecutive graft recipients in our pediatric kidney transplantation database between 1992 and 2011. Demographic, clinical, and laboratory details were extracted from charts and electronic records, including operation reports and pre- and post-operative clinic notes. Of the 49 nephrectomized patients, 47% had anomalies of the kidneys and urinary tract, 22% had cystinosis, 12% had focal segmental glomerulosclerosis, and 6% had congenital nephrotic syndrome. Nephrectomy decisions were based on clinical judgment, taking physiological and psychosocial aspects into consideration. Nephrectomy was performed in patients with polyuria (>2.5 ml/kg/h) and/or large proteinuria (>40 mg/m(2)/h), recurrent urinary tract infection or (rarely) hypertension. Urine output decreased from (median) 3.79 to 2.32 ml/kg/h (-34%), and proteinuria from 157 to 100 mg/m(2)/h (-40%) after unilateral nephrectomy (p=0.005). After bilateral nephrectomy, serum albumin, protein and fibrinogen concentrations normalized in 93, 73, and 55% of nephrectomized patients, respectively. Clinically relevant procedure-related complications (peritoneal laceration, hematoma) occurred in five patients. In summary, we demonstrate quantitatively that native nephrectomy prior to transplantation improved serum protein levels and anticipated post-transplant fluid intake needs in select children, reducing the risk of graft hypoperfusion and its postulated consequences for graft outcome.


Bronchoscopy in intensive care units.
Many situations exist imposing the use of bronchoscopy in intensive care units (ICU). There are many diagnostic and therapeutic indications. Interventional bronchoscopy represents a group of endoscopic techniques used in emergency or during the handling of different situations of airway obstruction. These situations seem quite frequent in paediatric ICU. This field has been developed with the availability of small endoscopes on the market and progress in instrumental and anaesthetic techniques.


Pre-clinical evidence of safety and protective effect of isatin and oxime derivatives against malathion-induced toxicity.
The inhibition of acetylcholinesterase (AChE) is a common outcome caused by organophosphorus (OPs) intoxication. Although inconsistent, the standard treatment consists of a muscarinic receptor antagonist (atropine) and AChE-reactivating molecules such as oximes. This study proposes to test unpublished compounds which contain the moieties of isatin and/or oxime have protective effects against the toxicity induced by malathion in two animal models: Artemia salina and Rattus norvegicus (Wistar rats). The lethality was assessed in A salina, and the calculated LD50 to (3Z)-5-chloro-3-(hydroxyimino) indolin-2-one oxime (Cℓ-HIN) and 2-(5-chloro-2-oxoindolin-3-ylidene)-hydrazinecarbothioamide (Cℓ-OXHS) was higher than 1000 µM while to 3-(phenylhydrazono) butan-2-one oxime (PHBO) was 38 µM. Our screening showed that Cℓ-HIN seems to be the most promising molecule, with low toxicity to A salina, protection against mortality (with or without atropine) and AChE inhibition induced by malathion. Similarly, the oral administration of 300 mg/kg of Cℓ-HIN induced low or no toxicity in rats. The plasma butyrylcholinesterase (BChE) and cortical AChE activities were reactivated by Cℓ-HIN (50 mg/kg, p.o.) in rats exposed to malathion (250 mg/kg, i.p). No difference was observed in paraoxonase-1 (PON-1) activity among groups treated. In conclusion, Cℓ-HIN restored the cholinesterase activities inhibited by malathion in A salina and rats with low toxicity in both. Thus, the data provide evidence that Cℓ-HIN, a compound that combines isatin and oxime functional groups, is safe and has important properties to reactivate the cholinesterases inhibited by malathion. In addition, we demonstrate the importance of a preliminary assessment in an alternative model in order to reduce the use of mammalians in drug discovery.


Allergic rhinitis and associated risk of migraine among children: a nationwide population-based cohort study.
Increased frequency of migraine was reported in adults with allergic rhinitis (AR). Although migraine is less common in children than in adults, it can begin in early childhood and persist into adulthood. We conducted this population-based cohort study to investigate the incidence and subsequent risk of migraine in children with AR. From 2000 to 2007, 461,850 children with recently diagnosed AR and 460,718 non-AR controls were included in the study. By the end of 2008, incidences of migraine in both cohorts, the AR to non-AR cohort hazard ratios (HRs), and confidence intervals (CIs) were measured. The incidence of migraine during the study period was 3.2-fold higher in the AR cohort (95% CI, 2.97 to 3.46) than in the non-AR cohort (11.4 vs 3.49 per 10000 person-years). The risk was greater for boys than for girls, and for children aged <6 years. The HR for migraine in children with AR was 1.44 (95% CI, 1.31 to 1.58) for those with ≤2 annual AR-related medical visits, whereas, 14.8 (95% CI, 13.6 to 16.2) for those with >4 visits (p < 0.0001, the trend test). The risk of migraine development in the AR cohort was highest within the first year after AR diagnosis (HR 4.89; 95% CI, 3.98 to 6.00). Children with AR were more likely to have migraine without aura than migraine with aura. Children with AR had a higher incidence and subsequent risk of migraine. Physicians should be more aware of migraine in children with AR who complain of headache.


Protective effect of Berberis aristata against peritonitis induced by carbapenem-resistant Escherichia coli in a mammalian model.
Berberis aristata is known to contain a variety of phenolic compounds contributing to its holistic capability of mitigating bacterial multidrug resistance. B. aristata stem bark extract was prepared and was characterised using liquid chromatography-mass spectrometry (LC-MS). The antimicrobial efficacy of the extract against carbapenem-resistant Escherichia coli was assessed in vivo in an animal model using Sprague Dawley rats. Microbial counts in blood and urine, physical health status, haematological and biochemical analysis of blood, and histopathology of the kidney were assessed as the study endpoints. An aquo-alcoholic extract of B. aristata (PTRC-2111-A) was found to effectively manage peritonitis induced by carbapenem-resistant E. coli in a rat model at a single post-exposure prophylactic dose of 0.5mg/kg body weight (BW). The extract was also found to show a no observed adverse effect level (NOAEL) up to a dose of 2000mg/kg BW. Physical, immunological, haematological, biochemical and histopathological aberrations were found to be restored to normal in the herbal-treated group at a dose of 0.5mg/kg BW. The antimicrobial and hepatorenal protective ability of PTRC-2111-A could be attributed to the presence of isoquinoline alkaloids.


Evaluation of diagnostic methods for Candida albicans translocation in a mouse model: seminested polymerase chain reaction, blood culture, and serological assays.
For the rapid diagnosis of systemic Candida infection, we compared the performance of an established seminested polymerase chain reaction (snPCR), serological tests for (1 --> 3)-beta-D-glucan assay and Candida mannan antigen assay, and blood culture in our murine model for Candida albicans translocation. In this mouse model, C. albicans disseminated to the liver from the intestine after day 6.5; the snPCR and blood culture results became positive from days 8 to 8.5 in about 60% of infected mice with culture-proven translocation, and in 100% on day 9. Both (1 --> 3)-beta-D-glucan and Candida mannan antigen were elevated in the serum as early as day 6.5 of infection, though they did not identify Candida species. Because the established snPCR can differentiate four clinically important Candida species and conventional microbiological methods require at least 48 h to identify Candida species in blood samples, the snPCR assay is advantageous for rapidly identifying Candida species in the blood. Therefore, the combination of the serological assays and the snPCR seems to be valuable for the early diagnosis of systemic C. albicans infection.


Reducing the risk of gestational diabetes mellitus in chronic hepatitis B virus carriers via more strict control of gestational weight gain.
To explore the association between gestational weight gain (GWG) and gestational diabetes mellitus (GDM) in hepatitis B surface antigen (HBsAg) -positive women using a retrospective cohort study to provide advice on the management of GWG. Our study included 39 539 pregnant women who gave birth at the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. Patients were divided into two groups: the HBsAg-negative and HBsAg-positive groups, comprising 36 500 and 3039 participants, respectively. We used univariate and multivariable logistic regression analyses to explore the association between GWG and GDM in maternal hepatitis B virus (HBV) carrier women. Being HBsAg positive and excessive GWG were independent risk factors for GDM. Excessive GWG was associated with a higher risk of GDM in HBsAg-positive women. Among pre-pregnancy women of normal weight, HBsAg-positive women with adequate GWG had a higher risk of GDM than HBsAg-negative women, whereas HBsAg-positive women with inadequate GWG had a lower risk of GDM. The optimal GWG ranges for pre-pregnancy normal-weight HBsAg-positive pregnancies might be lower than the US Institute of Medicine recommendations. HBsAg-positive women should strictly control GWG to reduce the risk of GDM.


Bleomycin clinical pharmacology by radioimmunoassay.
Bleomycin pharmacokinetics were studied by radioimmunoassay in 11 patients who received 7-30 U intravenously (IV) and eight patients who received 4-30 U subcutaneously (SC). For patients who received IV bleomycin plasma disappearance was biphasic, with a mean initial half-life of 0.26 h and a terminal half-life of 2.3 h. Mean plasma drug clearance was 67.8 ml/min/m2 and the volume of distribution was 13.2 l/m2. Urinary excretion accounted for 63.9% of the drug in 24 h. After SC administration peak plasma levels occurred in 1.1 h, with a mean elimination half-life of 4.3 h. Mean plasma drug clearance was 60.5 ml/min/m2 and the volume of distribution was 19.2 l/m2. Bleomycin plasma clearance correlated well with serum creatinine (r2 = 0.72). Bleomycin has a rapid plasma elimination and urinary excretion. Bleomycin bioavailability after SC administration appears comparable to that seen after IV administration as determined by the areas under the plasma disappearance curves. Prolonged plasma levels are seen after SC injection, suggesting this route of administration can produce plasma concentrations comparable to those attained with continuous IV infusions.


Carcinogenesis in Down syndrome: what can be learned from trisomy 21?
According to the currently prevailing perception, sporadic cancer arises as a result of somatic mutations in a cell that lead to its uncontrolled proliferation. It is generally accepted that somatic mutations occur randomly and that they are generally either "spontaneous" or due to various external agents (physical or chemical carcinogens). Constitutional genetic conditions, which modify cancer risk, may become instrumental in opening new concepts in carcinogenesis. For instance, evidence gathered from Down syndrome (DS) individuals has challenged the above perceived explanation since somatic mutations in these patients markedly differ from those arisen in the general population, and do not seem to occur at random. There is no global increase or decrease of somatic mutations in all genes in DS. Instead, specific mutations have been detected on particular loci, depending on the tissue type and the age of the DS person. In the context of constitutional trisomy 21, where cancer have a very particular and striking distribution, biochemical, physiological and architectural imbalances in specific tissues may be responsible for a vulnerable state leading to carcinogenesis. Conversely, in tissues of DS patients which seem resistant to cancer, the proliferative and maturation state of the cells would lead to a refractory state of neoplastic transformation. Experimentally, we observed that the proliferation of tumor cells in extracellular matrix produced by trisomic 21 fibroblasts appears to be inhibited when compared to that of those placed on an extracellular matrix produced by euploid fibroblasts. These observations challenge the current somatic mutation theory of carcinogenesis, and strongly suggest instead a critical role of cells and tissues in the microenvironment where carcinogenesis occurs.


Unexpected bleeding following eyelid tumor resection leading to the rare diagnosis of acquired haemophilia.
Our goal is to report for the first time in the literature a case of uncontrolled bleeding after an oculoplastic surgical procedure leading to the diagnosis of acquired haemophilia. An 82-year-old patient underwent tumor excision and reconstruction of his right lower eyelid. On the same day, uncontrolled bleeding occurred that resisted optimal blood pressure control, external compression, surgical haemostasis and wound revision. Usual coagulation screening tests were normal, except for a slightly prolonged activated partial thromboplastin time. Extensive coagulation check was performed, which showed a severely reduced factor VIII due to the presence of an inhibitor. The bleeding was immediately stopped after administration of recombinant factor VIIa. After healing of the wound, factor VIIa treatment was replaced by immunosuppressive therapy. The factor VIII inhibitor became unmeasurable and remained so for three months after stopping the immunosuppressive therapy. Ophthalmologists confronted with unexpected uncontrolled bleeding should think about the possibility of blood dyscrasia, in particular acquired haemophilia.


Evaluation of the genotoxic, cytotoxic, and antitumor properties of Commiphora molmol using normal and Ehrlich ascites carcinoma cell-bearing Swiss albino mice.
The genotoxic, cytotoxic and antitumor properties of Commiphora molmol (oleo gum resin) were studied in normal and Ehrlich ascites carcinoma cell-bearing mice. In normal mice, the genotoxic and cytotoxic activity was evaluated on the bases of the frequency of micronuclei and the ratio of polychromatic to normochromatic cells in bone marrow, which was substantiated by the biochemical changes in hepatic cells. The antitumor activity of C. molmol was evaluated from the total count and viability of Ehrlich ascites carcinoma cells and their nucleic acid, protein, malondialdehyde, and elemental concentrations in addition to observations on survival and the trend of changes in body weight. The tumors at the site of injection were evaluated for histopathological changes. Treatment with C. molmol (125-500 mg/kg) showed no clastogenicity but was found to be highly cytotoxic in normal mice. The results obtained in the Ehrlich ascites carcinoma cell-bearing mice revealed the cytotoxic and antitumor activity of C. molmol which was found to be equivalent to those of the standard cytotoxic drug cyclophosphamide. On the basis of the nonmutagenic, antioxidative, and cytotoxic potential of C. molmol as observed in the present study, its use in cancer therapy seems to be appropriate and further investigations are suggested.


Editorial: Considerations and Implications of a Nuanced Understanding of Neonatal Intensive Care Unit Distress for the Long-term Mental Health of Diverse Mothers and Children.
The perinatal period (pregnancy up to 1 year postpartum) is one of immense psychological and physical changes, many of which increase the risk for psychopathology for parent-child dyads. Families with infants requiring neonatal intensive care unit (NICU) interventions face additional challenges and distress in both the short and long term. Approximately 7% to 12% of infants require NICU admission for many factors including prematurity and neonatal complications1; 2% to 30% experience postpartum depression.2 Although something is known about NICU distress, a nuanced understanding of the experiences of NICU families is lacking, including their effects on longer-term mental health for parents and children. This is particularly true for families of minoritized groups, who often experience additional stressors, including interpersonal and systemic racism as well as differential Social Determinants of Health (SDoH)-the conditions in which people are born, grow, live, work, and age.


"Xylella is the Enemy that Must be Fought": Representations of the X. Fastidiosa Bacterium in the Media Discourse.
The paper explores media representations of Xylella fastidiosa, the bacterium that causes severe plant diseases, using data from online sources in English which reported on the developments in the bacterium spreading and treatment from 2015 to 2020. Two directions of analysis are pursued, the quantitative and qualitative one. Quantitative analysis reveals that the bacterium and its effects are described via the terms belonging to the lexical fields of fear, diseases, change, the supernatural, hostility, destruction, killing and war, with the latter three being the most dominant statistically speaking. Further, qualitative analysis attests that some of these terms are used metaphorically as instantiations of the war metaphor, which is generally effective in communicating the severity of the X. fastidiosa induced diseases and mobilising the necessary support. Based on the results, it may be argued that the language used in the media for describing X. fastidiosa fits into the prevalent "catastrophe discourse", with the purpose of raising awareness of the gravity of the threat the bacterium poses, as well as justifying the severe measures undertaken to contain it. The online version contains supplementary material available at 10.1007/s41701-022-00129-4.


Metabolism of injected flavins studied by using double-labeled [14C]flavin adenine dinucleotide and [14C, 32P]flavin mononucleotide.
The metabolism of flavins in mouse was studied with [F-(2)-14C, A-(2,8)-14C]FAD and [F-(2)-14C, 32P]FMN. Ninety minutes after injection, radioactive isoalloxazine nucleus of double-labeled FAD was markedly incorporated into FAD, FMN and riboflavin in the liver, whereas a small amount of radioactive adenine nucleus of double-labeled FAD was found in FAD in the liver. In the case of FMN, radioactive isoalloxazine nucleus of double-labeled FMN was markedly incorporated into FAD, FMN and riboflavin in the liver, whereas only a minute amount of radioactive phosphorus was incorporated into FMN and FAD in the same organ. These results indicate that FMN and FAD injected are rapidly hydrolyzed and resynthesized in animal body.


Rituximab induces a transient fluctuation of peripheral and follicular helper T cells in neuromyelitis optica spectrum disorder.
Autoreactive CD4+ helper T cells are implicated in the pathogenesis of neuromyelitis optica spectrum disorder (NMOSD). Both PD-1+CXCR5+CD4+ T follicular helper (Tfh) cells and PD-1+CXCR5-CD4+ T peripheral helper (Tph) cells can contribute to B-cell immune responses and the production of antibodies. Here we show the effect of B-cell depletion with rituximab on the homeostasis of Tfh cells, Tph cells and their subsets in patients with NMOSD. After rituximab treatment, total Tph cells, total Tfh cells, Tph17 cells, Tph17.1 cells, Tph1 cells, and Tfh1 cells tended to decrease at month 1, but gradually increased at month 6 and restored at month 12. Besides, Tph17.1 cells and Tfh17.1 cells were correlated with the proportion of CD19- antibody-secreting cells. Our data suggest that rituximab induced a fluctuation of proinflammatory Tph and Tfh subsets within one year after initiation of the treatment.


Recurrence of Hodgkin's disease 29 years later.
This article documents a case of recurrence in Hodgkin's disease, lymphocyte depletion type, 29 years after remission. This is the longest remission reported in the literature.


Diatoms as indicators in running waters: trends of studies on biological assessment and monitoring.
Despite the biodiversity and ecosystem services provided by lotic ecosystems, they are strongly affected by anthropogenic activities. Therefore, biological monitoring and assessment strategies are crucial in helping maintain these ecosystems and developing mitigation policies. We provide a global overview of the use of benthic diatoms as bioindicators in lotic environments, by analyzing 764 articles published in the past 20 years. We analyzed the influence of substrate type on samplings, which species have been highlighted as indicators and for which type of impacts, which anthropogenic impacts have been most commonly evaluated, and which metrics have been commonly used in studies using diatoms to assess and monitor the quality of lotic environments. We found that the most studied anthropogenic impact is artificial eutrophication and that some species, especially Nitzschia palea, have been thoroughly mentioned as indicators of this impact. Indicator species related to other types of impact are less common, demonstrating the need for studies on this issue. Moreover, we verified that traditional taxonomic metrics, such as diversity and diatom indices, have been widely used. Some alternative metrics have been used recently, such as those based on teratological valves, lipid bodies, valve size, and DNA metabarcoding. The number of biomonitoring and assessment studies based on diatoms has increased considerably in the past 20 years. Nonetheless, the demand for natural resources and consequently the degradation of lotic ecosystems have accelerated significantly. Thus, the development of low-cost and time-efficient biological assessment and monitoring strategies is essential for evaluating the health of lotic environments.


Mineral status and superoxide dismutase enzyme activity in Alzheimer's disease.
The study evaluated the dietary intake of zinc and copper, as measured by plasma and erythrocyte concentrations, the Cu/Zn ratio and measure the erythrocyte superoxide dismutase enzyme (eSOD) activity and the relationship between these markers and the degree of dementia in elderly individuals with and without Alzheimer's Disease (AD). A total of 93 elderly people aged 60-94 years were divided into two groups: with AD (n=44) and without AD (n=49). The NINCDS-ADRDA criteria were used for diagnosing AD, and dementia staging was determined using the Clinical Dementia Rating (CDR) scale. The dietary intake of Zn and Cu was obtained from a standard 3-day food record. Plasma and erythrocyte concentrations of the minerals were determined by flame atomic absorption spectrophotometry and by measuring eSOD activity in an automatic biochemical analyzer. The results showed dietary intake of Zn and Cu above the reference values with no differences observed between the two groups (p>0.05). Plasma and erythrocyte normocupremia as well as alteration in the Zn pool, with its reduced plasma concentrations and high in the erythrocytes, were observed in both groups (p>0.05). The plasma Cu/Zn ratio were not significantly different in patients with and without AD (p>0.05). The eSOD activity was high in both patient groups (p>0.05). However, among elderly patients with AD there was a positive correlation between this marker and dementia severity. According to our study results, we conclude that plasma and erythrocyte concentrations of Cu and Zn, as well as Cu/Zn ratio among elderly individuals is not related to Alzheimer's Disease. However, antioxidant activity of eSOD is associated with dementia severity.


A simple and rapid technique for preparing histological sections of brain.
A rapid technique for preparing histological sections of rodent brain is described. Sectioning and staining may be completed within two hours of sacrifice.


[Action of LSD and 5-methoxy-N,N-dimethyltryptamine on the high affinity uptake of [3H]-serotonin by isolated rat brain synaptosomes].
LSD (10(-7)M--10(-11)M) and 5-methoxy-N,N-dimethyltyptamine (10(-7)--10(-9)M) inhibited the high affinity uptake of [3H]-5HT into synaptosomes. These results suggest that the inhibition of the high affinity uptake is involved in the psychotomimetic action of LSD and 5MeODMT.


Growth, biofilm formation, antifungal susceptibility and oxidative stress resistance of Candida glabrata are affected by different glucose concentrations.
Glucose is an important fuel source to support many living organisms. Its importance in the physiological fitness and pathogenicity of Candida glabrata, an emerging human fungal pathogen has not been extensively studied. The present study aimed to investigate the effects of glucose on the growth, biofilm formation, antifungal susceptibility and oxidative stress resistance of C. glabrata. In addition, its effect on the expression of a putative high affinity glucose sensor gene, SNF3 was also investigated. Glucose concentrations were found to exert effects on the physiological responses of C. glabrata. The growth rate of the species correlated positively to the amount of glucose. In addition, low glucose environments were found to induce C. glabrata to form biofilm and resist amphotericin B. Conversely, high glucose environments promoted oxidative stress resistance of C. glabrata. The expression of CgSNF3 was found to be significantly up-regulated in low glucose environments. The expression of SNF3 gene in clinical isolates was found to be higher compared to ATCC laboratory strains in low glucose concentrations, which may explain the better survivability of clinical isolates in the low glucose environment. These observations demonstrated the impact of glucose in directing the physiology and virulence fitness of C. glabrata through the possible modulation by SNF3 as a glucose sensor, which in turn aids the species to adapt, survive and thrive in hostile host environment.


Synergy between erythropoietin and stem cell factor during erythropoiesis can be quantitatively described without co-signaling effects.
Synergistic interactions between cytokines underlie developmental processes fundamental to tissue and cellular engineering. However, a mechanistic understanding of the cell-specific and population-mediated effects is often lacking. In this study, we have investigated the synergistic generation of erythroid cells in response to erythropoietin (EPO) and stem cell factor (SCF). We have used a quantitative approach to determine if the effects of EPO and SCF superpose in a supra-additive fashion on the cell proliferation rate or on the death rate, suggesting a contribution from a joint cytokine effect (co-signaling). Primary mouse bone marrow hematopoietic cells and the stem cell-like FDCP-mix cell line were used to investigate the effects of EPO and SCF (individually or in combination) on erythroid output. Carboxyfluorescein diacetate succinimidyl ester (CFSE)-based cell-division tracking and mathematical modeling were used to measure cell type-specific proliferation and death rates. We observed a significant synergistic effect of EPO and SCF on the net generation of benzidine positive (erythroid) colony-forming cells, CD71++ (early erythroblasts) cells and TER-119+ (late erythroblasts and reticulocytes) cells in culture. When the observed increases in cell number were decomposed into proliferation and death rates, the cytokines were shown to act independently at different stages of erythroid development; SCF promoted the early proliferation of primitive cells, while EPO primarily promoted the survival of differentiating erythroid progenitor cells. Our analysis demonstrates that EPO and SCF have distinct and predominantly sequential effects on erythroid differentiation. This study emphasizes the necessity to separate proliferation rates from death rates to understand apparent cytokine synergies.


The effects of protein phosphatase inhibitors on the duration of central sensitization of rat dorsal horn neurons following injection of capsaicin.
Protein kinases and phosphatases catalyze opposing reactions of phosphorylation and dephosphorylation, which may modulate the function of crucial signaling proteins in central nervous system. This is an important mechanism in the regulation of intracellular signal transduction pathways in nociceptive neurons. To explore the role of protein phosphatase in central sensitization of spinal nociceptive neurons following peripheral noxious stimulation, using electrophysiological recording techniques, we investigated the role of two inhibitors of protein phosphatase type 2A (PP2A), fostriecin and okadaic acid (OA), on the responses of dorsal horn neurons to mechanical stimuli in anesthetized rats following intradermal injection of capsaicin. Central sensitization was initiated by injection of capsaicin into the plantar surface of the left paw. A microdialysis fiber was implanted in the spinal cord dorsal horn for perfusion of ACSF and inhibitors of PP2A, fostriecin and okadaic acid. We found that in ACSF pretreated animals, the responses to innocuous and noxious stimuli following capsaicin injection increased over a period of 15 min after injection and had mostly recovered by 60 min later. However, pre- or post-treatment with the phosphatase inhibitors, fostriecin or OA, significantly enhanced the effects of capsaicin injection by prolonging the responses to more than 3 hours. These results confirm that blockade of protein phosphatase activity may potentiate central sensitization of nociceptive transmission in the spinal cord following capsaicin injection and indicate that protein phosphatase type 2A may be involved in determining the duration of capsaicin-induced central sensitization.


Altered expression of neuroplasticity-related genes in the brain of depressed suicides.
Expression of the neuronal membrane glycoprotein M6a (GPM6A), the proteolipid protein (PLP/DM20) family member, is downregulated in the hippocampus of chronically stressed animals. Its neuroplastic function involves a role in neurite formation, filopodium outgrowth and synaptogenesis through an unknown mechanism. Disruptions in neuroplasticity mechanisms have been shown to play a significant part in the etiology of depression. Thus, the current investigation examined whether GPM6A expression is also altered in human depressed brain. Expression levels and coexpression patterns of GPM6A, GPM6B, and PLP1 (two other members of PLP/DM20 family) as well as of the neuroplasticity-related genes identified to associate with GPM6A were determined using quantitative polymerase chain reaction (qPCR) in postmortem samples from the hippocampus (n = 18) and the prefrontal cortex (PFC) (n = 25) of depressed suicide victims and compared with control subjects (hippocampus n = 18; PFC n = 25). Neuroplasticity-related proteins that form complexes with GPM6A were identified by coimmunoprecipitation technique followed by mass spectrometry. Results indicated transcriptional downregulation of GPM6A and GPM6B in the hippocampus of depressed suicides. The expression level of calcium/calmodulin-dependent protein kinase II alpha (CAMK2A) and coronin1A (CORO1A) was also significantly decreased. Subsequent analysis of coexpression patterns demonstrated coordinated gene expression in the hippocampus and in the PFC indicating that the function of these genes might be coregulated in the human brain. However, in the brain of depressed suicides this coordinated response was disrupted. Disruption of coordinated gene expression as well as abnormalities in GPM6A and GPM6B expression and expression of the components of GPM6A complexes were detected in the brain of depressed suicides.


Phospholipase A2, a nonnegligible enzyme superfamily in gastrointestinal diseases.
Gastrointestinal tract is important for digestion, absorption, detoxification and immunity. Gastrointestinal diseases are mainly caused by the imbalance of protective and attacking factors in gastrointestinal mucosa, which can seriously harm human health. Phospholipase A2 (PLA2) is a large family closely involved in lipid metabolism and is found in almost all human cells. A growing number of studies have revealed that its metabolites are deeply implicated in various inflammatory pathways and also regulates the maintenance of numerous biological events such as dietary digestion, membrane remodeling, barrier action, and host immunity. In addition to their phospholipase activity, some members of the superfamily also have other catalytic activities. Based on the in-depth effects of phospholipase A2 on bioactive lipid metabolism and inflammatory cytokines, PLA2 and its metabolites are likely to be involved in the pathogenesis, development or prevention of gastrointestinal diseases. Therefore, this review will focus on the physiological and pathogenic roles of several important PLA2 enzymes in the gastrointestinal tract, and reveals the potential of PLA2 as a therapeutic target for gastrointestinal diseases.


Conjugated linoleic acid inhibits DNA synthesis and induces apoptosis in TSU-Pr1 human bladder cancer cells.
Conjugated linoleic acid (CLA) has strong chemoprotective properties in experimental animal models. The insulin-like growth factor (IGF) system has been implicated as a risk factor for the development of bladder cancer. The present study examined CLA regulation of TSU-Pr1 bladder cancer cell proliferation and apoptosis and the influence of CLA on IGF-I receptor (IGF-IR) signaling. TSU-Pr1 cells were cultured in serum-free medium with 0, 2, 5, or 10 microM CLA and/or 10 nM IGF-I. [3H]Thymidne incorporation, DNA laddering, FACS analysis, immunoprecipitation and Western blotting were performed. CLA decreased DNA synthesis and induced apoptosis in TSU-Pr1 cells dose-dependently. Exogenous IGF-I alone increased viable cell numbers but did not counteract growth inhibition induced by CLA. CLA decreased IGF-IR and insulin receptor substrate (IRS)-1 protein levels. In addition, CLA decreased IGF-I-induced phosphorylation of IGF-IR and IRS-1, recruitment of the p85 subunit of phosphoinositide 3-kinase to IRS-1 and phosphorylation of Akt and extracellular signal-regulated kinase-1/2. These results suggest that CLA inhibits cell proliferation and stimulates apoptosis of TSU-Pr1 cells via its inhibition of the IGF-IR signaling pathway.


When and Why Threats Go Undetected: Impacts of Event Rate and Shift Length on Threat Detection Accuracy During Airport Baggage Screening.
We aimed to assess the impact of task demands and individual characteristics on threat detection in baggage screeners. Airport security staff work under time constraints to ensure optimal threat detection. Understanding the impact of individual characteristics and task demands on performance is vital to ensure accurate threat detection. We examined threat detection in baggage screeners as a function of event rate (i.e., number of bags per minute) and time on task across 4 months. We measured performance in terms of the accuracy of detection of Fictitious Threat Items (FTIs) randomly superimposed on X-ray images of real passenger bags. Analyses of the percentage of correct FTI identifications (hits) show that longer shifts with high baggage throughput result in worse threat detection. Importantly, these significant performance decrements emerge within the first 10 min of these busy screening shifts only. Longer shift lengths, especially when combined with high baggage throughput, increase the likelihood that threats go undetected. Shorter shift rotations, although perhaps difficult to implement during busy screening periods, would ensure more consistently high vigilance in baggage screeners and, therefore, optimal threat detection and passenger safety.


Disparity in association of obesity measures with ankle and brachial systolic blood pressures in Europeans and South Asians.
Obesity causes increases in brachial systolic-blood-pressures (SBP), risks of type 2 diabetes (T2DM) and cardiovascular diseases (CVD). Brachial and ankle SBPs have differential relationship with T2DM and CVD. Our objective was to study the relationship of obesity measures with brachial and ankle SBPs. A population of 1098 adults (South Asians n = 699; 41.70% male and 58.3% female) were recruited over 5 years from primary care practices in England. Their four limbs SBPs were measured using Doppler machine and body-mass-index (BMI) and waist-to-height-ratio (WHtR) calculated. Linear regressions were performed between SBPs and obesity measures, after adjustments for sex, age, ethnicity, T2DM and CVD. The mean age of all participants was 51.3 (SD = 17.2), European was 57.7 (SD 17.2) and South Asian was 47.8 (SD = 16.1). The left posterior tibial [Beta = 1.179, P = 4.559 × 10-15] and the right posterior tibial SBP [Beta = 1.178, P = 1.114 × 10-13] most significantly associated with the BMI. In South Asians, although the left brachial [Beta = 25.775, P = 0.032] and right brachial SBP [Beta = 22.792, P = 0.045] were associated to the WHtR, the left posterior tibial SBP [Beta = 39.894, P = 0.023], association was the strongest. For the first time, we have demonstrated that ankle SBPs had significant association with generalised obesity than brachial systolic blood pressures (SBP), irrespective of ethnicity. However, with respect to visceral obesity, the association with ankle SBP was more significant in South Asians compared to Europeans.


Improving fast and frugal modeling in relation to regression analysis: test of 3 models for medical decision making.
Data from 2 previous studies were reanalyzed, one on judgments regarding drug treatment of hyperlipidemia and the other on diagnosing heart failure. The original MH model and the extended MH model were compared with logistic regression (LR) in terms of fit to actual judgments, number of cues, and the extent to which the cues were consistent with clinical guidelines. There was a slightly better fit with LR compared with MH. The extended MH model gave a significantly better fit than the original MH model in the drug treatment task. In the diagnostic task, the number of cues was significantly lower in the MH models compared to LR, whereas in the therapeutic task, LR could be less or more frugal than the matching heuristic models depending on the significance level chosen for inclusion of cues. For the original MH model, but not for the extended MH model or LR, the most important cues in the drug treatment task were often used in a direction contrary to treatment guidelines. The extended MH model represents an improvement in that prevalence of cue values is adequately taken into account, which in turn may result in better fit and in better agreement with medical guidelines in the evaluation of cues.


A simple and sensitive determination of histamine and N tau-methylhistamine in biological fluids by high-performance liquid chromatography with electrochemical detection.
The determination of picomolar levels of histamine and its major metabolite, N tau-methylhistamine, in biological fluids was achieved using reversed-phase liquid chromatography coupled with electrochemical detection. A simple sample purification procedure for blood and urine samples was carried out prior to analysis using an Amberlite CG-50 cation-exchange resin, which afforded an excellent recovery of both compounds.


The diffusion-driven microfluidic process to manufacture lipid-based nanotherapeutics with stealth properties for siRNA delivery.
Our study investigated the manufacturing of lipid-based nanotherapeutics with stealth properties for siRNA delivery by employing a diffusion-driven microfluidic process in one or two-steps strategies to produce siRNA-loaded lipid nanocarriers and lipoplexes, respectively. In the one-step synthesis, siRNA in the aqueous phase is introduced from one inlet, while phospholipids dispersed in anhydrous ethanol are introduced from other inlets, generating the lipid nanocarriers. In the two-steps strategies, the pre-formed liposomes are complexed with siRNA. The process configuration with an aqueous diffusion barrier exerts a significant effect on the nanoaggregates synthesis. Dynamic light scattering data showed that lipid nanocarriers had a bigger particle diameter (298 ± 24 nm) and surface charge (43 ± 6 mV) compared to lipoplexes (194 ± 7 nm and 37.0 ± 0.4 mV). Moreover, DSPE-PEG(2000) was included in the formulation to synthesize lipid-based nanotherapeutics containing siRNA with stealth characteristics. The inclusion of PEG-lipid resulted in an increase in the surface charge of lipoplexes (from 33.7 ± 4.4-54.3 ± 1.6 mV), while a significant decrease was observed in the surface charge of lipid nanocarriers (30.3 ± 8.7 mV). The different structural assemblies were identified for lipoplex and lipid nanocarriers using Synchrotron SAXS. Lipid nanocarriers present a lower amount of multilayers than lipoplexes. Lipid-PEG insertion significantly influenced lipid nanocarriers' characteristics, drastically decreasing the number of multilayers. This effect was not observed in lipoplexes. The association between process configuration, lipid composition, and its effect on the characteristics of lipid-based vector systems can generate fundamental insights, contributing to gene-based nanotherapeutics development.


Sudden increase of plasma fibrinopeptide A levels after induced abortion.
Plasma fibrinopeptide A levels were studied before and after abortion induced during the first trimester of pregnancy. Fibrinopeptide A levels were significantly increased 15 min after the induced abortion, and returned to preoperative values 2h later. This finding suggests that thrombotic activity is transiently increased immediately after the induced abortion. Activation of the clotting factors during the induced abortion appears to be important in controlling uterine hemorrhage.


Monte Carlo modelling of pixel clusters in Timepix detectors using the MCNP code.
The track structure of the signal measured by the semiconductor pixel detector Timepix3 was modelled in the Monte Carlo MCNP® code. A detailed model at the pixel-level (256 × 256 pixels, 55 × 55 µm2 pixel size) was developed and used to generate and store clusters of adjacent hit pixels observed in the measured data because of particle energy deposition path, charge sharing, and drift processes. An analytical model of charge sharing effect and the detector energy resolution was applied to the simulated data. The method will help the user sort the measured clusters and distinguish radiation components of mixed fields by determining the response of Timepix3 detector to particular particle types, energies, and incidence angles that cannot be measured separately.


Investigation of the Inter- and Intrascanner Reproducibility and Repeatability of Radiomics Features in T1-Weighted Brain MRI.
Radiomics is the high throughput analysis of medical images using computer algorithms, which specifically assess textural features. It has increasingly been proposed as a tool for the development of imaging biomarkers. However, an important acknowledged limitation of radiomics is the lack of reproducibility of features produced. To assess reproducibility and repeatability of radiomics variables in brain MRI through a multivisit, multicenter study. Retrospective. Fourteen individuals visiting three institutions twice, 10 males with the mean age of 36.3 years and age range 25-51. 3D T1W inversion recovery on three 1.5-T General Electric scanners. Radiomics analysis by a consultant radiologist performed on the T1W images of the whole brain on all visits. All possible radiomics features were generated. Concordance correlation coefficient (CCC) and dynamic range (DR) for all variables were calculated to assess the test-retest repeatability. Intraclass correlation coefficients (ICCs) were calculated to investigate the reproducibility of features across centers. Of 1596 features generated, 57 from center 1, 15 from center 2, and 22 from center 3 had a CCC > 0.9 and DR > 0.9. Eight variables had CCC > 0.9 and DR > 0.9 in all centers. Forty-one variables had an ICC of >0.9. No variables had CCC > 0.9, DR > 0.9, and ICC > 0.9. Repeatability and reproducibility of variables is a significant limitation of radiomics analysis in 3DT1W brain MRI. Careful selection of radiomic features is required. 4 TECHNICAL EFFICACY STAGE: 2.


Tumor size does not predict risk of metastatic disease or prognosis of small renal cell carcinomas.
We characterized the clinicopathological features and the prognosis of small solid renal tumors defined as tumors 4 cm or smaller. We identified 1,208 patients who were treated with nephrectomy at 5 international academic centers for small solid renal tumors. Clinicopathological parameters and outcome data were collected for each patient and analyzed. Of the tumors 88% were renal cell carcinoma and 12% were benign. Of those with renal cell carcinoma 995 (93%) were localized (N0M0) and 72 (7%) presented with metastatic disease. Tumor size did not predict synchronous metastatic disease. The incidence of metastatic disease in the tumor size ranges 0.1 to 1.0, 1.1 to 2.0, 2.1 to 3.0 and 3.1 to 4.0 cm was 7%, 6%, 5% and 8%, respectively (p = 0.322). Survival rates were excellent. The majority of patients who died of renal cell carcinoma (54%) presented with synchronous metastatic disease, but 3% of patients with localized disease also died of renal cell carcinoma. In patients with localized disease there was a 7% chance of recurrence post nephrectomy at 5 years. Progression-free survival (28 months) was better than for patients with metastatic disease having a primary tumor greater than 4 cm (8 months). Tumor size was not retained as an independent prognostic factor of survival in multivariate analyses. The University of California Integrated Staging System and the Karakiewicz nomogram were the best predictors of cancer specific survival for all renal cell carcinoma stages (c-index 0.87). More than 85% of small solid renal tumors are renal cell carcinoma. The majority of localized small renal tumors can be cured with existing surgical approaches. However, there is a small but not insignificant risk of synchronous and metachronous metastatic disease and cancer associated death. Patients considering experimental therapies such as ablation and surveillance should be aware of this. Tumor size alone is not sufficient to distinguish renal cell carcinoma with benign behavior from aggressive small renal cell carcinoma. Survival of patients with small metastatic renal cell carcinoma is better then expected. The biology of these unique tumors should be further studied.


Analysis of ciliogenesis process in the bovine oviduct based on immunohistochemical classification.
The oviductal epithelium is composed of ciliated and non-ciliated cells. The proportions of these cells change during the estrous cycle. However, the mechanism underlying this cyclic change in the cell proportions remains unclear. Our previous study indicated that ciliated cells are derived from non-ciliated cells. Here, we aimed to investigate the mechanism regulating the changes in the populations of ciliated and non-ciliated cells during the estrous cycle. To this end, we examined the numbers of cells that were positive for acetylated-α-tubulin (cilia marker), Ki67 (proliferation marker), PAX8 (non-ciliated cell marker), and FOXJ1 and MYB (ciliogenesis markers) in the epithelial cells at four different estrous stages (Stage I: days 1-4 after ovulation, Stage II: days 5-10, Stage III: days 11-17, and Stage IV: days 18-20) by immunohistochemistry. The oviductal epithelial cells expressed either FOXJ1 or PAX8. All the acetylated-α-tubulin+ cells were positive for FOXJ1, although there were a few acetylated-α-tubulin-/FOXJ1+ cells. MYB was expressed in both the FOXJ1+ and PAX8+ cells, but it was not expressed in the Ki67+ cells. The numbers of Ki67+ and MYB+ cells were the highest in Stage IV, while the numbers of FOXJ1+ and acetylated-α-tubulin+ cells were the highest in the following Stage I, suggesting that ciliogenesis is associated with the estrous cycle. Thus, based on immunological classification, the oviductal epithelium contains at least seven types of cells at different translational/transcriptional states, and their number is regulated by the estrous cycle. This cyclic event might provide an optimal environment for gamete transport, fertilization, and embryonic development.


Digital subtraction bronchography with stable xenon.
An experimental animal study using digital subtraction fluoroscopy to image the bronchial tree with stable xenon shows that major bronchi can be imaged. A fast frame rate is necessary to minimize the effects of subject motion. Optimum contrast between air in lung and xenon in bronchi is obtained when the first two-thirds of a vital capacity breathhold consists of air or oxygen and the last one-third consists of 100% xenon.


On signaling pathways: hematopoietic stem cell specification from hemogenic endothelium.
Hematopoietic stem cells (HSCs) are specified and generated during the embryonic development and have remarkable potential to replenish the full set of blood cell lineages. Researchers have long been interested in clarifying the molecular events involved in HSC specification. Many studies have reported the development of methods for generating functional hematopoietic cells from pluripotent stem cells (PSCs-embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs)) for decades. However, the generation of HSCs with robust long-term repopulation potential remains a swingeing challenge, of which a major factor contributing to this failure is the difficulty to define the intraembryonic signals related to the specification of HSCs. Since HSCs directly derive from hemogenic endothelium, in this review, we summarize both in vivo and in vitro studies on conserved signaling pathways that control the specification of HSCs from hemogenic endothelial cells.


Immunization to Schistosoma mansoni in mice inoculated with radiated cercariae.
Preliminary experiments indicate that mice inoculated with cercariae of Schistosoma mansoni that have been exposed to cobalt-60 radiation in the range of 2500 to 3000 rep develop immunity to reinfection with nonradiated cercariae.


Compressive fatigue behavior of human vertebral trabecular bone.
Damage accumulation under compressive fatigue loading is believed to contribute significantly to non-traumatic, age-related vertebral fractures in the human spine. Only few studies have explored trabecular bone fatigue behavior under compressive loading and none examined the influence of trabecular architecture on fatigue life. In this study, trabecular bone samples of human lumbar and thoracic vertebrae (4 donors from age 29 to 86, n=29) were scanned with a microCT system prior to compressive fatigue testing to determine morphology-mechanical relationships for this relevant loading mode. Inspired from previous fabric-based relationships for elastic properties and quasi-static strength of trabecular bone, a simple power relationship between volume fraction, fabric eigenvalue, applied stress and the number of cycles to failure is proposed. The experimental results demonstrate a high correlation for this relationship (R2=0.95) and detect a significant contribution of the degree of anisotropy towards prediction of fatigue life. Step-wise regression for total and residual strains at failure suggested a weak, but significant correlation with volume fraction. From the obtained results, we conclude that the applied stress normalized by volume fraction and axial fabric eigenvalue can estimate fatigue life of human vertebral trabecular bone in axial compressive loading.


Open and closed cavity mastoid operations: comparing early hearing results.
The aim of the study is to compare audiological results in patients treated surgically with either an open or closed cavity mastoidectomy. A prospective review of a single surgeon's case series based at two district general hospitals. All patients with 1-year post-operative hearing results following an open or closed cavity mastoid surgery were included. Outcome measured included the preoperative and postoperative air-bone gap (ABG). Belfast rule of thumb was used to assess the benefit from middle ear surgery. A total of 128 patients were identified from the database with 1 year post-operative hearing results. Sixty-three patients had undergone an open cavity mastoidectomy and 65 had a closed cavity mastoidectomy. The mean post-operative ABG in patients with open cavity mastoidectomy was 24 dB and for closed cavity 21 dB (p = 0.12). There was no statistical difference between open and closed cavity mastoidectomy with or without ossiculoplasty and if the underlying pathology was squamous or mucosal disease. However, patient with post-operative ABG below or equal to 20 dB was 41% for closed cavity compared to 21% for open cavity. Using the Belfast rule of thumb, 79% of the patients in both groups had successful hearing results post surgery. The 1-year post-operative audiological results between open and closed cavity masoidectomy showed no statistical difference. The pathology affecting the middle ear also had no influence on the hearing results between the two groups. However, there was a higher percentage of patients with closed cavity procedures who had a post-operative ABG that was below or equal to 20 dB.


Granulomatous Polyangiitis With Renal Involvement: A Case Report and Review of Literature.
Granulomatosis with polyangiitis (GPA), formerly named Wegner's granulomatosis is an antineutrophilic cytoplasmic antibody (ANCA) associated vasculitis of the small vessels. GPA can affect several organ systems even though predominantly affects respiratory and renal systems. Pathogenesis is initiated by activation of the immune system to produce ANCA, Cytoplasmic (C-ANCA) antibody, which thereby leads to widespread necrosis and granulomatous inflammation. Multisystem involvement with varied symptomatology makes GPA diagnosis more challenging. Early diagnosis and management are vital and can alter the prognosis of the disease. We present a literature review and a clinical scenario of a 26-year-old male with a history of chronic sinusitis, testicular carcinoma in remission, recent onset of worsening cough, epistaxis, hoarseness of voice, weight loss, and dark-colored urine. Workup revealed high titers of C-ANCA, C-reactive protein, procalcitonin, CT chest evidence of mass-like consolidation, and bronchoscopy findings of friable tissue that was not amenable for biopsy. Methylprednisolone and rituximab (RTX) were administered, which resulted in marked clinical improvement. Therefore, a keen eye for details is necessary to diagnose GPA early, which can improve disease outcomes dramatically.


High expression of RASAL1, a hub gene in the progression of liver cancer, suggests a poor prognostis.
Liver cancer (LC) is a frequently occurring lethal malignancy worldwide, yet the molecular mechanisms of carcinogenesis and their development remain uncharacterized. In this study, bioinformatics methods were used to find candidate hub genes for prognosis assessment and clinical treatment of LC. Differential analysis was carried out based on the evidence of gene expression profiling in LC on The Cancer Genome Atlas (TCGA). The differentially expressed genes (DEGs) were constructed into co-expression networks and divided into modules by virtue of weighted gene co-expression network analysis (WGCNA). Based on the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), the module genes were subjected to functional enrichment analysis. The LC microarray (GSE105130) in the Gene Expression Omnibus was selected to verify the hub genes' expression profiles. The validity of the hub genes was verified via survival analysis, as well as expression correlation with the clinicopathological features. Thereafter, gene set variation analysis (GSVA) and single-sample gene set enrichment analysis (GSEA) were applied to investigate the possible biological functions of the hub genes. In total, 3780 DEGs and 17 co-expression modules were obtained. The blue module had the strongest correlation with the tumour stage and the module genes were principally enriched in tumour-associated GO terms, as well as pathways such as Ras protein signal transduction, ERK1/2 cascade, Ras signal pathway, and ECM-receptor interaction. RASAL1, which is highly expressed in LC, was identified as a hub gene for LC progression. Its high expression suggested unfavorable patient prognosis and was correlated with T stage, gender and tumour stage. Further analysis identified that the overexpression of RASAL1 was substantially enriched in cancer-associated gene sets. RASAL1 is a hub gene that influences LC progression, constituting a novel biomarker and molecular target in the future diagnosis and therapy of LC.


Time-resolved fluoroimmunoassay.
A method is reported to set up a standard competitive TR-FIA. A simple and inexpensive way to prepare reagents and carry out operations is presented as well, with the aim to make it possible to perform a very sensitive analytical procedure in a personalized way within a nondedicated biochemistry laboratory. This protocol is general and can be easily modified with consideration to the analytical target. Once the antibody is available, both its labeling with diethylenetriaminepentaacetic acid dianhydride and Eu3+, and the setting-up of the assay with measurement of europium ion time-resolved fluorescence in a home-made enhancement solution become feasible.


The Influence of Portion Size and Timing of Meals on Weight Balance and Obesity.
This review focuses on the influence of portion size and temporal distribution of food intake on weight balance and obesity in adults. The inconsistency of definitions in the area of meal patterns is also discussed. The conclusion is that regular eating habits might facilitate weight balance, while unplanned snacking as well as consuming the major part of the energy intake at the end of the day seem to be unfavourable. Altogether, the research suggests that large portions promote over-consumption and, therefore, limiting portion size of energy dense foods and drinks with added sugar could be recommended. Even if more research is needed, these factors should be taken into consideration in recommendations for obesity prevention.


Anaphylactic reaction to tranexamic acid in an adolescent undergoing posterior spinal fusion.
Tranexamic acid is an anti-fibrinolytic agent frequently used in pediatric surgery. Common side effects include nausea, flushing, and headache, but in rare instances, it may produce anaphylaxis; with only one previously reported case in a 72-year-old man. We report a case of a delayed anaphylactic reaction in a pediatric patient undergoing posterior spine fusion; and discuss the intraoperative management of the acute event, immunologic confirmation, and subsequent anesthetic approach.