Fluorescence properties of gold nanorods and their application for DNA biosensing.
This communication reveals new and unique optical properties with respect to enhanced fluorescence of gold nanorods as they elongate; a novel strategy for DNA hybridization studies based on monitoring the fluorescence intensity of gold nanorods has been demonstrated.


Characteristics of an ultrasonic phased array transmitter in medium range.
An ultrasonic phased array transmitter (PAT) consisting of 12×12 elements was designed and fabricated to evaluate its experimental characteristic performance in the medium range of 2m-10m for its directivity, pulse width affect and sound pressure level (SPL) measurements as a function of distance from its center in the open air. The SPL was measured at 2 m, 5m, and 10m distances as 135dB, 126dB and 68dB, respectively. The experimentally measured directivity patterns were found in good agreement with the theoretical results obtained by using MATLAB simulations. The SPL showed negligible change as a function of the ultrasonic pulse widths such as 0.5ms, 1ms and 2ms. The SPL and directivity of the PAT at 2m distance were measured for ultrasonic pulse width of 0.1ms only while as at 10m distance these were measured for the ultrasonic pulse widths of 0.5ms, 1ms and 2ms. The present investigations on the PAT characteristics are expected to be useful for its industrial, scientific and biomedical applications, e.g., robotics for 3D range imaging with improved and efficient object presence sensing as well as nondestructive health monitoring.


Investigation on the possibility of dynamic COVID-Zero strategy in China: a population-based transmission model analysis and economic evaluation.
To explore the feasible and cost-effective intervention strategies to achieve the goal of dynamic COVID-Zero in China. A Susceptible-Exposed-Infectious-Recovered model combined economic evaluation was used to generate the number of infections, the time for dynamic COVID-Zero and calculate cost-effectiveness under different intervention strategies. The model simulated the 1 year spread of COVID-19 in mainland China after 100 initial infections were imported. According to close contact tracing degree from 80% to 100%, close contact tracing time from 2 days to 1 day, isolation time from 14 days to 7 days, scope of nucleic acid testing (NAT) from 10% to 100% and NAT frequency from weekly to every day, 720 scenarios were simulated. Cumulative number of infections (CI), social COVID-Zero duration (SCD), total cost (TC) and incremental cost-effectiveness ratio. 205 of 720 scenarios could achieve the total COVID-Zero since the first case was reported. The fastest and most cost-effective strategy was Scenario 680, in which all close contacts were traced within 1 day, the isolation time was 14 days and 10% of the national population was randomly checked for NAT every day. In Scenario 680, the CI was 280 (100 initial infections) and the SCD was 13 days. The TC was ¥4126 hundred million and the cost of reducing one infection was ¥47 470. However, when the close contact tracing time was 2 days and the degree of close contact tracing was 80%-90%, the SCD would double to 24-101 days and the TCs increased by ¥16 505 to 37 134 hundred million compared with Scenario 680. If all close contact was controlled within 1 day, the rapid social COVID-Zero can be achieved effectively and cost-effectively. Therefore, the future prevention and control of emerging respiratory infectious diseases can focus on enhancing the ability of close contact tracing.


The experiences of the process of planning, starting and organizing a culturally specific nursing home for Finnish-speaking older persons: a qualitative study.
Globally there are growing multicultural and multilingual societies. As a result of extensive international migration, the number of elderly migrants has increased and will further increase in the future. This makes it necessary for elderly healthcare services to meet elderly migrants' healthcare needs concerning language and cultural barriers. To our knowledge, previous research in the area of culturally specific nursing homes for migrant seniors is still limited. Thus, the study aimed to investigate the experiences of planning, starting and organizing a culturally specific nursing home for Finnish-speaking older persons. An explorative qualitative study using both semi-structured individual interviews and focus group interviews as data collection. Thirteen informants were purposively recruited, two from Finnish-speaking association, seven healthcare professionals and two family members. Data were analysed by qualitative content analysis. Three categories, each with sub-categories, emerged from the data: 1) Motivation to develop this particular culture-specific nursing home; 2) Organizational issues and 3) Aspirations for the future. The study found that information from policy makers, the localization and activities of the nursing home, having healthcare staff who speak the minority language, organizing the nursing home as a mixture of older members of both the majority and the minority communities, all affected the planning, starting and organization of a culturally specific nursing home. This study found that information, localization, activities and language adapted to elderly migrants affected the planning, starting and organization of a culturally specific nursing home for Finnish-speaking older persons. These findings should support the healthcare organization in planning, managing and organizing sustainable nursing home care for older people belonging to a minority in order to attain the aim of person-centered and equal healthcare.


An ultrasonic measurement of superficial femoral artery wall thickness.
An ultrasonic measurement of the superficial femoral artery wall thickness was performed on 16 volunteers. The measurement included all echogenic tissue between the lumen of the superficial femoral artery and the lumen of the superficial femoral vein. The average arterial wall plus vein wall thickness in volunteers with peripheral arterial disease was 2.13 +/- 0.87 mm, significantly greater than the 1.27 +/- 0.50 mm found in those without detectable peripheral arterial disease.


Chronically increased oxidative stress in fibroblasts from Alzheimer's disease patients causes early senescence and renders resistance to apoptosis by oxidative stress.
It is well established that oxidative stress is involved in several neurodegenerative disorders, including Alzheimer's disease (AD). Study of the induction and consequences of oxidative stress in the peripheral tissues of the familial AD patients can help to elucidate the inherent abnormalities and the mechanism of pathogenesis of this disease. AD fibroblasts have been used as a model to investigate the underlying mechanisms of oxidative stress. In our study, we used AD fibroblasts from six different donors who are either at high risk of developing AD or have already been diagnosed with AD to study the effect of oxidative stress in comparison with the effect on non-AD normal human fibroblast. Oxidative stress was induced by a brief exposure of the cells to 250microM H(2)O(2) followed by incubation in normal conditions. Neuronal loss due to oxidative stress is a characteristic of Alzheimer's patients; however, our results showed that AD fibroblasts were more resistant to oxidative stress compared to non-AD fibroblasts. Measurement of reactive oxygen species (ROS) indicated that AD fibroblasts produced more ROS than did non-AD NHF cells either in basal conditions or after induction of oxidative stress. Furthermore, we found that expression of p21 was significantly higher in AD cells than in non-AD cells and expression of Bax, a pro-apoptotic protein was downregulated/absent in AD cells during normal or under conditions of external oxidative stress. Further experiments revealed that mitochondria in AD cells moved to the peri-nuclear region following induction of oxidative stress. Thus, these results suggest that AD fibroblasts are chronically exposed to oxidative stress that may trigger senescent phenotype, making AD cell resistant to apoptosis by external oxidative stress.


Alpha- and beta-adrenergic receptors of the rat salivary gland. Elevation after chemical sympathectomy.
Binding of [3H]dihydroergokryptine and [3H]dihydroalprenolol to membrane preparations from rat submaxillary gland was measured to characterize the alpha- and beta-adrenergic receptors, respectively. Kinetic analysis of the data revealed a high affinity binding site for each radioligand. Inhibition of binding at each site was stereospecific for the active isomer of the catecholamine used. The greater ability of a beta1 than beta2 specific beta-adrenergic antagonist to displace [3H]dihydroalprenolol binding indicated that this binding site was of the beta1 type. Chemical sympathectomy with reserpine or 6-hydroxydopamine resulted in a significant increase in both [3H]dihydroalprenolol and [3H]dihydroergokryptine binding in the rat submaxillary gland. 3scatchard analysis of the data indicated that these increases in binding were due to a change in total number of binding sites for [3H]dihydroergokryptine and [3H]dihydroalprenolol with little change in apparent affinities. This suggests that changes in alpha- and beta-adrenergic receptor density may be important in the development of supersensitivity in salivary glands after reserpine and 6-hydroxydopamine treatment.


Single-Shot Readout Performance of Two Heterojunction-Bipolar-Transistor Amplification Circuits at Millikelvin Temperatures.
High-fidelity single-shot readout of spin qubits requires distinguishing states much faster than the T1 time of the spin state. One approach to improving readout fidelity and bandwidth (BW) is cryogenic amplification, where the signal from the qubit is amplified before noise sources are introduced and room-temperature amplifiers can operate at lower gain and higher BW. We compare the performance of two cryogenic amplification circuits: a current-biased heterojunction bipolar transistor circuit (CB-HBT), and an AC-coupled HBT circuit (AC-HBT). Both circuits are mounted on the mixing-chamber stage of a dilution refrigerator and are connected to silicon metal oxide semiconductor (Si-MOS) quantum dot devices on a printed circuit board (PCB). The power dissipated by the CB-HBT ranges from 0.1 to 1 μW whereas the power of the AC-HBT ranges from 1 to 20 μW. Referred to the input, the noise spectral density is low for both circuits, in the 15 to 30 fA/[Formula: see text] range. The charge sensitivity for the CB-HBT and AC-HBT is 330 μe/[Formula: see text] and 400 μe/[Formula: see text], respectively. For the single-shot readout performed, less than 10 μs is required for both circuits to achieve bit error rates below 10-3, which is a putative threshold for quantum error correction.


Inhibition of lysosomal vacuolar proton pump down-regulates cellular acidification and enhances E. coli bactofection efficiency.
Endosomal escape is considered a crucial barrier that needs to be overcome by integrin-mediated E. coli for gene delivery into mammalian cells. Bafilomycin, a potent inhibitor of the H+ proton pump commonly employed to lower endosomal pH, was evaluated as part of the E. coli protocol during delivery. We found an increase in green fluorescent protein expression up 6.9, 3.2, 5.0, 2.8, and 4.5 fold in HeLa, HEK-293, A549, HT1080, and MCF-7 respectively, compared to untreated cells. Our result showed for the first time that Inhibition of lysosomal V-ATPase enhances E. coli efficiency.


Clinical technology assessment, cost-effective adoption, and quality management by hospitals in the 1990s.
Technology assessment in the 1990s must become an integral part of a hospital's strategic priority goals, with active participation of physicians and top management. Technology assessment should involve a wide range of criteria and health care consumer expectations, so that the appropriateness, effectiveness, cost-effectiveness, and quality improvement aspects of new technologies are all considered. Mount Carmel Health's Advanced Treatment and Bionics Institute (ATBI), established in 1986, monitors significant developments in new technologies and performs technology and outcomes assessments. ATBI activities, which have facilitated adoption of 35 treatment-based projects, are integrated into the existing QA structure of Mount Carmel hospitals. Through resolution of identified problems, quality care can be promoted, while providing patients innovative medical treatments.


Endoscopic Decompression Can Be Effective for Diagnosing and Treating Tubercular Spondylodiskitis with Early Epidural Spinal Compression: A Retrospective Study of 18 Cases.
Retrospective study. In this study, we describe an endoscopic method of effectively treating tubercular lumbar spondylodiskitis with early onset epidural spinal cord compression in the lumbar spine on magnetic resonance imaging (MRI). Percutaneous aspiration and biopsy of spondylodiskitis under ultrasonography and computer tomography scan invariably provides an inadequate diagnosis. From May 2015 to May 2017, 18 patients presented with intractable back pain and were diagnosed with tubercular spondylodiskitis on MRI; these patients were enrolled in this study. The goal was to confirm the pathogen on biopsy, drain the abscess, and perform debridement. Chemotherapy was started after histologic diagnosis, and data collected included blood cell counts, erythrocyte sedimentation rate, C-reactive protein, and repeat MRI after 3 months. Mean duration of surgery was 52 minutes. Mean follow-up was 17 months. The average preoperative Visual Analog Scale score of 8 (range, 6-10) decreased to 3 (range, 1-8) postoperatively. Tubercular spondylodiskitis was observed in 14 cases; two cases were pyogenic, and the biopsy was inconclusive in two cases. After adequate chemotherapy, no recurrences were noted. We hereby conclude that endoscopic biopsy and drainage can provide a better diagnosis and decrease pain in a predictable manner.


Functions of lysine 2-hydroxyisobutyrylation and future perspectives on plants.
Lysine 2-hydroxyisobutyrylation (Khib) is a novel protein post-translational modifications (PTMs) observed in both eukaryotes and prokaryotes. Recent studies suggested that this novel PTM has the potential to regulate different proteins in various pathways. Khib is regulated by lysine acyltransferases and deacylases. This novel PTM reveals interesting connections between modifications and protein physiological functions, including gene transcription, glycolysis and cell growth, enzymic activity, sperm motility, and aging. Here, we review the discovery and the current understanding of this PTM. Then, we outline the networks of complexity of interactions among PTMs in plants, and raise possible directions of this novel PTM for future investigations in plants.


Biosynthesis mechanism, genome mining and artificial construction of echinocandin O-sulfonation.
Micafungin, a semisynthetic derivative of the cyclic hexapeptide FR901379 produced by Coleophoma empetri fermentation, is the only O-sulfonated echinocandin-type antifungal drug. However, the detailed formation mechanism of O-sulfonate group, whether before or after the assembly of hexapeptide, remains elusive. Here, we confirmed that O-sulfonylation occurs after hexapeptide assembly as a kind of postmodification in the biosynthesis of FR901379. The released cyclic hexapeptide was hydroxylated by cytochrome P450 McfP and successively sulfonated by sulfotransferase McfS. And other three echinocandin sulfotransferases were identified through genome mining by using McfS as a sequence probe. Moreover, pneumocandin B0, the precursor of caspofungin, could be O-sulfonated by heterologously introducing the McfP-McfS into the pneumocandin B0-producing species Glarea lozoyensis. The water-solubility of sulfonated pneumocandin B0 is 4000 times higher than that of pneumocandin B0. The revealed O-sulfonation mechanism will provide new insights into the design and production of novel sulfonated echinocandins by metabolic engineering.


Chiropractic manipulation and acute neck pain: a review of the evidence.
The aim of this study was to review the chiropractic and medical literature in an effort to determine the extent of current evidence supporting the use of chiropractic manipulation for the treatment of acute neck pain. A literature search of the MEDLINE/PubMed and MANTIS (Manual Alternative and Natural Therapy Index System) databases, extending from 1966 to September 2003, was conducted. Search terms included "cervical," "neck," "chiropractic," "neck pain," "patient satisfaction," and "manipulation." The inclusion criteria for article selection were studies dealing with the treatment of neck pain by means of chiropractic manipulation, regardless of the number of subjects involved or whether randomization was implemented. Two hundred sixty-seven citations were identified. Most were eliminated because they either did not specifically deal with the treatment of acute neck pain with manipulation or were not written in English. Less than 10 articles marginally dealt with the treatment of acute neck pain with cervical manipulation. Moreover, there has only been one randomized clinical trial published in the English language that specifically dealt with the treatment of acute neck pain by manipulation. Other studies involved patients with neck pain of a subacute or chronic nature or treated test subjects with mobilization techniques rather than manipulation. There has been scant investigative research into the treatment of acute neck pain with chiropractic manipulation. Consequently, more data are needed and appropriate studies should be initiated.


Artifacts in sodium dodecyl sulfate-polyacrylamide gel electrophoresis due to 2-mercaptoethanol.
Mercaptoethanol, when present in the sample buffer during sodium dodecyl sulfate-polyacrylamide gel electrophoresis, is responsible for the appearance of two nonprotein bands (electrophoretic mobilities corresponding to 68 and 54 kdalton) stainable with silver and with Coomassie blue. After iodination in vitro of DNA preparations isolated by alkaline phenol extraction using chloramine-T procedure, part of the radioactive label is found in these bands, provided the reaction is terminated by mercaptoethanol, whereas only a diffuse background is present in this area if the reaction is stopped by sodium metabisulfite. Similar results are obtained with highly purified total cytoplasmic RNA. The results indicate that the appearance of the 68- and 54-kdalton bands is in artifact. The relevance of these results to the proteins tightly bound to DNA is discussed.


Rheological and Biological Impact of Printable PCL-Fibers as Reinforcing Fillers in Cell-Laden Spider-Silk Bio-Inks.
The development of bio-inks capable of being 3D-printed into cell-containing bio-fabricates with sufficient shape fidelity is highly demanding. Structural integrity and favorable mechanical properties can be achieved by applying high polymer concentrations in hydrogels. Unfortunately, this often comes at the expense of cell performance since cells may become entrapped in the dense matrix. This drawback can be addressed by incorporating fibers as reinforcing fillers that strengthen the overall bio-ink structure and provide a second hierarchical micro-structure to which cells can adhere and align, resulting in enhanced cell activity. In this work, the potential impact of collagen-coated short polycaprolactone-fibers on cells after being printed in a hydrogel is systematically studied. The matrix is composed of eADF4(C16), a recombinant spider silk protein that is cytocompatible but non-adhesive for cells. Consequently, the impact of fibers could be exclusively examined, excluding secondary effects induced by the matrix. Applying this model system, a significant impact of such fillers on rheology and cell behavior is observed. Strikingly, it could be shown that fibers reduce cell viability upon printing but subsequently promote cell performance in the printed construct, emphasizing the need to distinguish between in-print and post-print impact of fillers in bio-inks.


Prediction of peptide-MHC binding using profiles.
Prediction of peptide binding to major histocompatibility complex (MHC) molecules is a basis for anticipating T-cell epitopes. Peptides that bind to a given MHC molecule are related by sequence similarity. Therefore, a position-specific scoring matrix (PSSM)---also known as profile--derived from a set of aligned peptides known to bind to a given MHC molecule can be used as a predictor of both peptide-MHC binding and T-cell epitopes. In this approach, the binding potential of any peptide sequence (query) to the MHC molecule is determined by its similarity to a set of known peptide-MHC binders and can be obtained by comparing the query to the PSSM. Following structural considerations of the peptide-MHC interaction, we will describe here how to derive alignments and PSSMs that are suitable for the prediction of peptide-MHC binding.


Direct observation of bicarbonate and water reduction on gold: understanding the potential dependent proton source during hydrogen evolution.
The electrochemical conversion of CO2 represents a promising way to simultaneously reduce CO2 emissions and store chemical energy. However, the competition between CO2 reduction (CO2R) and the H2 evolution reaction (HER) hinders the efficient conversion of CO2 in aqueous solution. In water, CO2 is in dynamic equilibrium with H2CO3, HCO3 -, and CO3 2-. While CO2 and its associated carbonate species represent carbon sources for CO2R, recent studies by Koper and co-workers indicate that H2CO3 and HCO3 - also act as proton sources during HER (J. Am. Chem. Soc. 2020, 142, 4154-4161, ACS Catal. 2021, 11, 4936-4945, J. Catal. 2022, 405, 346-354), which can favorably compete with water at certain potentials. However, accurately distinguishing between competing reaction mechanisms as a function of potential requires direct observation of the non-equilibrium product distribution present at the electrode/electrolyte interface. In this study, we employ vibrational sum frequency generation (VSFG) spectroscopy to directly probe the interfacial species produced during competing HER/CO2R on Au electrodes. The vibrational spectra at the Ar-purged Na2SO4 solution/Au interface, where only HER occurs, show a strong peak around 3650 cm-1, which appears at the HER onset potential and is assigned to OH-. Notably, this species is absent for the CO2-purged Na2SO4 solution/gold interface; instead, a peak around 3400 cm-1 appears at catalytic potential, which is assigned to CO3 2- in the electrochemical double layer. These spectral reporters allow us to differentiate between HER mechanisms based on water reduction (OH- product) and HCO3 - reduction (CO3 2- product). Monitoring the relative intensities of these features as a function of potential in NaHCO3 electrolyte reveals that the proton donor switches from HCO3 - at low overpotential to H2O at higher overpotential. This work represents the first direct detection of OH- on a metal electrode produced during HER and provides important insights into the surface reactions that mediate selectivity between HER and CO2R in aqueous solution.


Aiming to IgE: Drug development in allergic diseases.
The incidence of allergic disease significantly increases in recent decades, causing it become a major public health problem all over the world. The common allergic diseases such as allergic dermatitis, allergy rhinitis, allergic asthma and food allergy are mediated, at least in part, by immunoglobulin E (IgE), and so IgE acts as a central role in allergic diseases. IgE can interact with its high-affinity receptor (FcεRⅠ) which is primarily expressed on tissue-resident mast cells and circulating basophils, initiating intracellular signal transduction and then causing the activation and degranulation of mast cells and basophils. On the other hand, IgE interaction with its low-affinity receptor (CD23), can regulate various IgE-mediated immune responses including IgE-allergen complex presentation, IgE synthesis, the growth and differentiation of both B and T cells, and the secretion of pro-inflammatory mediators. With the deeper mechanism research for allergic diseases, new therapeutic strategies for interfering IgE are developed and receive a great attention. In this review, we summarize a current profile of therapeutic strategies for interfering IgE in allergic diseases. Besides, we suggest that targeting memory B cells (including long-lived plasma cells and (or) IgE+ memory B cells) may help to completely control allergic diseases, and highlight that the development of drugs synergistically aiming to multiple targets can be a better choice for improving treatment efficacy which results from allergic diseases as the systemic disorders caused by an impaired immune system.


Synthetic biology by controller design.
Natural biological systems display complex regulation and synthetic biomolecular systems have been used to understand their natural counterparts and to parse sophisticated regulations into core design principles. At the same time, the engineering of biomolecular systems has unarguable potential to transform current and to enable new, yet-to-be-imagined, biotechnology applications. In this review, we discuss the progression of control systems design in synthetic biology, from the purpose of understanding the function of naturally occurring regulatory motifs to that of creating genetic circuits whose function is sufficiently robust for biotechnology applications.


The versatility of spandex photographic retractor for transoral surgical procedures.
The trend toward transoral access, be it for pathology or facial cosmetic surgery, has become increasingly popular over the last two decades with facial incisions being used more and more sporadically than otherwise. Transoral access because of its inherent limitations, retraction of the oral and perioral tissues without inducing physical or thermal injury makes it a daunting task for the operating surgeon. The use of conventional retractors in conjunction with surgical instruments can lead to inadvertent injury to the perioral tissues resulting in untoward postoperative sequelae leading to patient discomfort and delayed recovery. This article elucidates the versatility of a simple photographic retractor (spandex) as a useful adjunctive tool in the retraction and protection of the perioral tissues for almost all transoral surgical procedures.


Natural killer T cells are required for the development of a superantigen-driven T helper type 2 immune response in mice.
We show, here, that one single injection or weekly injections of staphylococcal enterotoxin B (SEB), starting in 1-day-old newborn mice, induced a powerful immune response with a T helper type 2 (Th2) pattern, as judged by the isotype and cytokine profile, with the production of large amounts of SEB-specific immunoglobulin G1 (IgG1), detectable levels of SEB-specific IgE and increased production of interleukin-4 by spleen cells. These protocols also induced an increase in the levels of total IgE in the serum. Memory of SEB was transferred to secondary recipients by using total spleen cells from primed animals. The secondary humoral response in transferred mice was diminished if spleen cells from SEB-treated mice were previously depleted of CD3+ or Vbeta8+ T cells or NK1.1+ cells. In vivo depletion of NK1.1+ cells in adult mice resulted in a marked reduction in the SEB-specific antibody response in both the primary and secondary immune responses. Additionally, purified NK1.1+ T cells were able to perform SEB-specific helper B-cell actions in vitro and in vivo. These results suggest that NK1.1+ T cells are required for the full development of humoral immunological memory, whilst making neonatal tolerance to SEB unachievable.


Physiological assessment of paroxysmal dystonia secondary to subacute sclerosing panencephalitis.
We report on a 26-year-old woman with subacute sclerosing panencephalitis (SSPE) who presented with frequent paroxysmal dystonic posturing. Electroencephalogram demonstrated generalized 5 to 10-second episodes of high-amplitude (150-300 microV) delta activity alternating with 10 to 20-second periods of theta activity (40-50 microV). The patient experienced episodes of dystonic posturing coinciding with the periods of delta activity. Ictal Tc-99m Ceretec SPECT demonstrated marked increased activity in the bilateral caudate (R>L). The frequency and amplitude of the episodes initially markedly improved after the addition of carbamazepine. We suggest that the movements seen in this case of SSPE may represent basal ganglia ictal activity.


Rhodamine-123 as a new photochemosensitizing agent with the argon laser: "nonthermal" and thermal effects on human squamous carcinoma cells in vitro.
A human squamous carcinoma cell line (P3) was first exposed to a nontoxic dose of Rhodamine-123 (1 microgram/ml for 1 hour), then subjected to treatment with a single mode argon laser at 514.5 nm. The temperature and energy levels delivered to the target cells were determined by a reproducible method of dosimetry. Cell viability was assessed by the trypan blue exclusion test. Cell duplication and DNA synthesis were measured by the incorporation of 3H-thymidine at 6 and 24 hours post-treatment. The results indicate that Rhodamine-123 at nontoxic doses of 1 microgram/ml enhanced the tumoricidal effects of the argon laser at reduced temperatures as low as 40 degrees C. Furthermore, at physiological temperature ranges as low as 28 to 39 degrees C, an immediate and/or delayed inhibition of cell duplication was demonstrated, while cell viability was not affected. These observations, suggest that Rhodamine-123 can be used effectively as a chemosensitizing agent in the treatment of human tumor cells with the argon laser at 514.5 nm. This new technique of tumor cell targeting by Rhodamine sensitization and specific laser treatment may offer real advantages without the extreme photosensitivity associated with hematoporphyrin derivatives.


Identification of PKD1 and PKD2 gene variants in a cohort of 125 Asian Indian patients of ADPKD.
Autosomal Dominant Polycystic Kidney Disease (ADPKD) accounts for 2.6% of the patients with chronic kidney disease in India. ADPKD is caused by pathogenic variants in either PKD1 or PKD2 gene. There is no comprehensive genetic data from Indian subcontinent. We aimed to identify the pathogenic variants in the heterogeneous Indian population. PKD1 and PKD2 variants were identified by direct gene sequencing and/or multiplex ligation-dependent probe amplification (MLPA) in 125 unrelated patients of ADPKD. The pathogenic potential of the variants was evaluated computationally and were classified according to ACMG guidelines. Overall 300 variants were observed in PKD1 and PKD2 genes, of which 141 (47%) have been reported previously as benign. The remaining 159 variants were categorized into different classes based on their pathogenicity. Pathogenic variants were observed in 105 (84%) of 125 patients, of which 99 (94.3%) were linked to PKD1 gene and 6 (6.1%) to PKD2 gene. Of 159 variants, 97 were novel variants, of which 43 (44.33%) were pathogenic, and 10 (10.31%) were of uncertain significance. Our data demonstrate the diverse genotypic makeup of single gene disorders in India as compared to the West. These data would be valuable in counseling and further identification of probable donors among the relatives of patients with ADPKD.


Metal-metal d-d interaction through the discrete stacking of mononuclear M(II) complexes (M = Pt, Pd, and Cu) within an organic-pillared coordination cage.
Two molecules of planar MII(acac)2 complexes (M = Pt, Pd, and, Cu; acac = acetylacetonato) are efficiently stacked within an organic-pillared coordination cage, exhibiting characteristic spectroscopies (for M = Pt and Pd) and electron spin-spin coupling (for M = Cu) attributable to metal-metal interaction.


Spanish National Registry of Major Osteoporotic Fractures (REFRA) seen at Fracture Liaison Services (FLS): objectives and quality standards.
REFRA-FLS is a new registry in Spain aimed at identifying individuals over 50 years of age with a fragility fracture. Using this registry, we found hip fracture is the most prevalent fracture. Treatment for osteoporosis was 87.7%, with 65.3% adherence. REFRA-FLS provides fundamental data in the study of fragility fractures. Fragility fractures are a growing public health concern in modern-aged societies. Fracture Liaison Services (FLS) have been shown to successfully lower rates of secondary fractures. A new registry (REFRA-FLS) has been created to monitor quality indicators of FLS units in Spain and to explore the occurrence and characteristic of fragility fractures identified by these centers. We conducted a prospective cohort study based on fragility fractures recorded in the REFRA-FLS registry. Participants were individuals 50 years or above who suffered a low energy fragility fracture identified by the 10 participating FLS units during the study period. The type of FLS unit, the characteristics of the individuals at baseline, along with patient outcomes as quality indicators among those who completed 1 year of follow-up were analyzed. A total of 2965 patients and 3067 fragility fractures were identified, and the most frequent locations were hip (n = 1709, 55.7%) and spine (n = 492, 16.0%). A total of 43 refractures (4.5%) and 46 deaths (4.9%) were observed among 948 individuals in the follow-up analyses. Time from fracture to evaluation was less than 3 months in 76.7% of individuals. Osteoporosis treatment was prescribed in 87.7%, and adherence was 65.3% in Morisky-Green test. Our results provide a comprehensive picture of fragility fractures identified in FLS units from Spain. Overall, quality indicators are satisfactory although a much higher use of DXA would be desirable. As the registry grows with the incorporation of new FLS units and longer follow-up, incoming analyses will provide valuable insight.


Mobilization of maternal mRNA in amphibian eggs with special reference to the possible role of membraneous supramolecular structures.
Current knowledge of the mechanism of mobilization of maternal mRNA is summarized herein and a working hypothesis has been constructed to explain the mechanism on the assumption that the mRNA enters the cytoplasm in association with the cytoplasmic membraneous structures and is then stored in the structures until liberation and relocation at the step of oocyte maturation. An extensive turnover of poly(A) sequences as well as the occurrence of repetitive sequences in the maternal mRNA may be relevant to mRNA activation.


Prognostic value of a proliferation index including MIB1 and argyrophilic nucleolar organizer regions proteins in node-negative breast cancer.
This study was designed to evaluate a cell proliferation marker, including the percentage of cycling cells (MIB1), and the duration of the cell cycle (assessed by argyrophilic nucleolar organizer regions proteins [AgNORs] measurement). We included 90 patients with invasive node-negative breast cancer. None received chemotherapy. With the help of a double-staining technique, a proliferation index (PI) was determined by multiplying the percentage of MIB1-positive cells by the mean area of the AgNORs present in those MIB1-positive cells. PI was evaluated for its impact on overall survival (OS) and disease-free survival (DFS). We demonstrated that PI was correlated to OS. For DFS, it conserved its high prognostic value only in univariate analysis. The global amount of AgNORs was more discriminative for DFS. PI and AgNOR quantification supplied additional prognosis information in node-negative patients, and we propose to integrate them in further studies.


Prenatal Exposure to Antibiotics and Development of Epilepsy in Children.
We aimed to confirm or reject previous reports on the association of prenatal antibiotic exposure and development of epilepsy in offspring by accounting for known and unidentified confounding factors. In a retrospective cohort investigation, we enrolled children aged 3-18 years born between 1998 and 2012 at a single regional hospital and their mothers. A computerized medication database was linked with hospital records. The exposed group included children whose mothers purchased 1 or more antibiotic medications for use during pregnancy. Epilepsy was defined by epilepsy diagnosis and/or by chronic dispensing of antiepileptic drugs. We analyzed maternal exposure to antibiotics 2 years after delivery (but not during pregnancy and/or the 2 years following delivery) as part of the specificity analysis. We enrolled 88 899 children and their 74 416 mothers. The group exposed prenatally to antibiotics comprised 36 622 children (41.2%). Of them, 326 (0.9%) developed epilepsy compared with 370 of 52 277 (0.7%) in the unexposed group (relative risk [RR], 1.24; 95% confidence interval [CI], 1.07-1.44: P = .004). Exposure during the first, second, and third trimesters was characterized by incidence of epilepsy in 0.8% (P = .943), 0.9% (P = .266), and 0.9% (P = .073) of children, respectively, compared with the unexposed group, with an RR of 1.01 (95%CI, 0.83-1.23), 1.12 (95%CI, 0.92-1.36), and 1.19 (95%CI, 0.98-1.45), respectively. Similarly, prenatal exposure by antibiotic class was associated with epilepsy. Nevertheless, the specificity analysis strongly suggested the possibility of confounding by indication. Our findings indicated that pregnant women should receive the indicated antibiotic treatment with no fear of the development of epilepsy in their children.


Association between telomere length and intima-media thickness of both common carotid arteries in patients with coronary heart disease: From the CORDIOPREV randomized controlled trial.
A critical telomere length (TL) is associated with cardiovascular mortality. Dietary habits have been demonstrated to affect cardiovascular risk. However, it remains unclear how exactly TL determines the response to specific dietary approaches in the reduction of arterial injury. We aimed to evaluate whether TL was associated with the progression of arterial injury (assessed by intima-media thickness of both common carotid arteries: IMT-CC), after long-term consumption of two healthy dietary models in patients with coronary heart disease (CHD). From the 1002 CHD patients of the CORDIOPREV study, 903 completed IMT-CC and TL evaluation at baseline and were randomized to follow a Mediterranean diet or a low-fat diet for 5 years. Patients at risk of short TL (TL < 20th percentile) presented an elevated IMT-CC, (0.79 ± 0.17 vs patients at non-risk 0.74 ± 0.17 p < 0.001). TL and IMT-CC showed an inverse association (β = -0.035, p = 0.002). Patients who consumed a Mediterranean diet, regardless of the risk of short TL, showed a significant decrease in IMT-CC, with a higher reduction in those patients with risk of short TL (-0.03 ± 0.11, p = 0.036). TL (β = 0.019, p = 0.024), age (β = -0.001, p = 0.031), energy intake (β = -0.000, p = 0.036), use of statins (β = -0.027, p = 0.028) and allocation into the Mediterranean diet (vs low-fat diet) (β = -0.024, p = 0.003) were significant contributors to changes in IMT-CC. Patients who had a reduced TL exhibited a greater decrease in IMT-CC after consuming a Mediterranean diet.


The association of food ingredients in breakfast cereal products and fumonisins production: risks identification and predictions.
Breakfast processed products are remarkably at risk of fungal contamination. This research surveyed the fumonisins concentration in different breakfast products and carried out in vitro experiments measuring fumonisins content in different substrates inoculated with Fusarium verticillioides. The pipeline started with the identification of combinations of ingredients for 58 breakfast products. Twenty-three core ingredients, seven nutritional components and production types were analyzed using a Pearson correlation, k-means clustering, and principal component analysis to show that no single factor is responsible for high fumonisins detection in processed cereals products. Consequently, decision tree regression was used as a means of determining and visualizing complex logical interactions between the same factors. We clustered the association of ingredients in low, medium, and high risk of fumonisin detection. The analysis showed that high fumonisins concentration is associated with those products that have high maize concentrations coupled especially with high sodium or rice. In an in vitro experiment, different media were prepared by mixing the ingredients in the proportion found in the first survey and by measuring fumonisins production by Fusarium verticillioides. Results showed that (1) fumonisins production by F. verticillioides is boosted by the synergistic effect of maize and highly ready carbohydrate content such as white flour; (2) a combination of maize > 26% (w/w), rice > 2.5% (w/w), and NaCl > 2.2% (w/w) led to high fumonisins production, while mono-ingredient products were more protective against fumonisins production. The observations in the in vitro experiments appeared to align with the decision tree model that an increase in ingredient complexity can lead to fumonisins production by Fusarium. However, more research is urgently needed to develop the area of predictive mycology based on the association of processing, ingredients, fungal development, and mycotoxins production.


Systemic chemotherapy promotes HIF-1α-mediated glycolysis and IL-17F pathways in cutaneous T-cell lymphoma.
Systemic chemotherapy is often the last resort of advanced cutaneous T-cell lymphoma (CTCL). Tumor recurrence and adverse effects of systemic chemotherapy are the main limitations. We aim to investigate the metabolic alterations in tumor cells after CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone) chemotherapy. In advanced CTCL, CHOP chemotherapy has no survival benefit and the duration of response is significantly inferior to other canonical treatments. HIF-1α is significantly elevated in lesions of advanced MF patients as well as tumor cell line Hut78 and tumor xenograft mice model. CHOP therapy also increased glycolytic activities in a HIF-1α-dependent manner. In CTCL xenograft tumor mice model, lesional cells showed a significant increase in IL-17F after chemotherapy, shifting toward a Th17 phenotype, which process is also regulated by HIF-1α. Echinomycin, HIF-1α inhibitor, was co-administered in xenograft tumor mouse models with CHOP and showed a significant reduction in tumor growth. CHOP chemotherapy promotes glycolysis and IL-17 pathways in a HIF-1α-dependent fashion. Furthermore, HIF-1α blockade is promising as an accompanying agent in systemic chemotherapy for patients with advanced CTCL.


Structural basis for the design of allosteric inhibitors of the Aurora kinase A enzyme in the cancer chemotherapy.
Aurora kinases are essential enzymes for the control of cell cycle. The specific role of aurora kinase A (AURKA) is the regulation of spindle assembly and stability by promoting centrosome maturation and separation. Because AURKA is an essential protein for the normal occurrence of the cycle, mutations and deregulations in the activities of this protein are associated with several cancers. The kinase activity of AURKA is controlled by autocatalytic phosphorylation, which is facilitated after binding to a regulator protein, the Target Protein for Xenopuskinesin-like protein 2 (TPX2). This review highlights the physiological and pathophysiological properties of AURKA, the structure of the AURKA/TPX2 complex and the main structural features that can be explored for the design of selective AURKA inhibitors. The design of selective AURKA inhibitors remains as a challenge as most of the currently available inhibitors target only the ATP binding cleft and are nonselective among kinases. However, by exploring the inactive form of the kinase, researchers get access to an adjacent hydrophobic pocket, allowing the design of more selective inhibitors. Additionally, the possibility of designing potent allosteric AURKA inhibitors look very promising from the clinical perspective, since it tends to yield the most selective class of compounds. Herein we detailed the binding modes of the most selective AURKA inhibitors currently reported. We believe this will aid researchers in defining the structural patterns necessary for selective AURKA inhibition, guiding the design of more potent compounds to be therapeutically explored in cancer patients.


Analytical solution to transport in three-dimensional heterogeneous well capture zones.
Solute transport is investigated in a heterogeneous aquifer for combined natural-gradient and well flows. The heterogeneity is associated with the spatially varying hydraulic conductivity K(x, y, z), which is modelled as a log-normal stationary-random function. As such, the conductivity distribution is characterized by four parameters: the arithmetic mean K(A), the variance sigma(Y)(2) (Y=lnK), the horizontal integral scale I of the axisymmetric log-conductivity autocorrelation and the anisotropy ratio e=I(v)/I (I(v) is the vertical integral scale). The well fully penetrates an aquifer of constant thickness B and has given constant discharge QB, while the background aquifer flow is driven by an uniform mean head-gradient, - J. Therefore, for a medium of homogeneous conductivity K(A), the steady-state capture zone has a width 2L=Q/(K(A)|J|) far from the well (herein the term capture zone is used to refer both to the zone from which water is captured by a pumping well and the zone that captures fluid from an injecting well). The main aim is to determine the mean concentration as a function of time in fluid recovered by a pumping well or in a control volume of the aquifer that captures fluid from an injecting well. Relatively simple solutions to these complex problems are achieved by adopting a few assumptions: a thick aquifer B>>I(v) of large horizontal extent (so that boundary effects may be neglected), weak heterogeneity sigma(Y)(2)<1, a highly anisotropic formation e<0.2 and neglect of pore-scale dispersion. Transport is analyzed to the first-order in sigma(Y)(2) in terms of the travel time of particles moving from or towards the well along the steady streamlines within the capture zone. Travel-time mean and variance to any point are computed by two quadratures for an exponential log-conductivity two-point covariance. Spreading is reflected by the variance value, which increases with sigma(Y)(2) and I/L. For illustration, the procedure is applied to two particular cases. In the first one, a well continuously injects water at constant concentration. The mean concentration as function of time for different values of the controlling parameters sigma(Y)(2) and I/L is determined within control volumes surrounding the well or in piezometers. In the second case, a solute plume, initially occupying a finite volume Omega(0), is drawn towards a pumping well. The expected solute recovery by the well as a function of time is determined in terms of the previous controlling parameters as well as the location and extent of Omega(0). The methodology is tested against a full three-dimensional simulation of a multi-well forced-gradient flow field test ([Lemke, L., W.B. II, Abriola, L., Goovaerts, P., 2004. Matching solute breakthrough with deterministic and stochastic aquifer models. Ground Water 42], SGS simulations). Although the flow and transport conditions are more complex than the ones pertinent to capture zones in uniform background flow, it was found that after proper adaptation the methodology led to results for the breakthrough curve in good agreement with a full three-dimensional simulation of flow and transport.


Duffy blood group system and ocular toxoplasmosis.
Duffy blood group phenotypes [Fy(a + b-), Fy(a-b+), Fy(a + b+), Fy(a-b-)], characterized by the expression of Fya, and Fyb antigens, are present in red blood cells. Therefore, we hypothesize that the non-hematopoietic expression of these antigens might influence cell invasion by T. gondii. 576 consecutive patients from both genders were enrolled. The presumed OT clinical diagnosis was performed. Duffy phenotyping was performed by hemagglutination in gel columns and for the correct molecular characterization Fy(a-b-) phenotype, using PCR-RFLP. Anti-T. gondii IgG antibodies were detected by ELISA. Chi-square, Fisher's exact tests were used to compare the proportions. OT was present in 22.9% (n = 132) and absent in 77.1% (n = 444) of patients. The frequencies of anti-T. gondii IgG antibodies were higher in OT (127/132, 96.2%) than those without this disease (321/444, 72.3%) (p < .0001). None of the Duffy antigens or phenotypes were associated with T. gondii infection (χ2: 2.222, GL: 3, p = .5276) as well as the risk of OT (χ2: 0.771, GL: 3, p = .8566). Duffy blood group system phenotypes and their antigens do not constitute risk factors for infection by T. gondii infection and the development of OT.


A direct thrombin inhibitor, dabigatran etexilate protects from renal fibrosis by inhibiting protease activated receptor-1.
Chronic kidney disease (CKD) involves interstitial fibrosis as an influential underlying pathological process associated with compromised renal function regardless of etiological cause of the injury. The tubulointerstitial fibrosis is found to be well correlated with declining renal function and its subsequent culmination into renal failure. Given the prominent role of thrombin in multiple diseases, it was tempting for us to investigate the outcome of a direct thrombin inhibitor in renal injury. We investigated the involvement of thrombin in renal injury and fibrosis by using an FDA approved orally active, direct thrombin inhibitor, dabigatran etexilate (DB). We used a robust experimental model of unilateral ureteral obstruction (UUO)-induced renal injury which shows progressive tubulointerstitial fibrosis (TIF) along with tubular injury and inflammation. The obstructed kidney showed severe TIF as compared to control kidneys. The administration of DB significantly inhibited UUO-induced collagen-1 and TIF by inhibition of thrombin activated protease activated receptor (PAR)-1 expression in fibrotic kidney. In addition, DB administration improved histoarchitecture of obstructed kidney, inhibited TGF-β and SNAI2-induced epithelial-mesenchymal transition (EMT) program. Our study highlights the importance of thrombin signalling in TIF and provides strong evidences to support the notion that a direct thrombin inhibitor ameliorates TIF by PAR-1 mediated mechanism.


A Virtual Reality Platform for Context-Dependent Cognitive Research in Rodents.
Animal survival necessitates adaptive behaviors in volatile environmental contexts. Virtual reality (VR) technology is instrumental to study the neural mechanisms underlying behaviors modulated by environmental context by simulating the real world with maximized control of contextual elements. Yet current VR tools for rodents have limited flexibility and performance (e.g., frame rate) for context-dependent cognitive research. Here, we describe a high-performance VR platform with which to study contextual behaviors immersed in editable virtual contexts. This platform was assembled from modular hardware and custom-written software with flexibility and upgradability. Using this platform, we trained mice to perform context-dependent cognitive tasks with rules ranging from discrimination to delayed-sample-to-match while recording from thousands of hippocampal place cells. By precise manipulations of context elements, we found that the context recognition was intact with partial context elements, but impaired by exchanges of context elements. Collectively, our work establishes a configurable VR platform with which to investigate context-dependent cognition with large-scale neural recording.


Metabolism of N-nitroso-1,3-thiazolidine in the rat.
[2-14C]N-nitroso-1,3-thiazolidine (125 mg/kg body weight) administered by gavage to rats was excreted mostly (81% of the dose) in the urine with a smaller amount (7%) in respired air. The major metabolite in the urine (77.2%) was 2-hydroxy-1,3-thiazolidine and minor quantities of the isomers 4- and 5-hydroxy-1,3-thiazolidine were also detected. The presence of hydroxy-1,3-thiazolidine, determined using mass spectrometry and high-performance liquid chromatography, indicated that alpha-hydroxylation and denitrosation are major metabolic pathways of N-nitroso-1,3-thiazolidine. Analysis of the non-acidic urine extract with gas chromatography-mass spectrometry (GC-MS) using untreated on-column injection and heated split injection gave differing results. Compounds detected using the latter technique may have been artefacts formed by pyrolysis in the heated injection port. Analysis of the metabolites by direct probe mass spectrometry (unheated) and Fourier transform infra-red spectroscopy supported the results seen with on-column GC-MS.


Service planning implications of estimating Primary Health Organisation enrolment rate based on a Health Service Utilisation population rather than a Census-derived population.
Estimating Primary Health Organisation (PHO) enrolment rates with a census-derived estimated resident population denominator may provide misleading results because of numerator and denominator mismatch. This study uses the Health Service Utilisation (HSU) population denominator as an alternative. A HSU population was generated by record linkage of routinely collected datasets from the Ministry of Health via encrypted National Health Index (NHI). We compare PHO enrolment rates by age and ethnicity in Counties Manukau District Health Board (CMDHB) in 2013. In CMDHB, 98% of people who had utilised publicly-funded health services in 2013 were enrolled in a PHO in 2013. Using the HSU population as a denominator, PHO enrolment rates for Maaori, Pacific, Asian, New Zealand European/Other population groups were 98.3%, 97.7%, 97.6%, and 98.3% respectively. Just under 4% of people discharged from CMDHB inpatient facilities were not enrolled in a PHO within a month from the day of discharge in 2013. Using the HSU population as a proxy of health services need, PHO enrolment rates were similar across ethnicities in the CMDHB population. Support to improve PHO enrolment coverage would be more efficient if the HSU population were used to target people who are not yet enrolled in a PHO.


Systematic sequencing of chloroplast transcript termini from Arabidopsis thaliana reveals >200 transcription initiation sites and the extensive imprints of RNA-binding proteins and secondary structures.
Chloroplast transcription requires numerous quality control steps to generate the complex but selective mixture of accumulating RNAs. To gain insight into how this RNA diversity is achieved and regulated, we systematically mapped transcript ends by developing a protocol called Terminome-seq. Using Arabidopsis thaliana as a model, we catalogued >215 primary 5' ends corresponding to transcription start sites (TSS), as well as 1628 processed 5' ends and 1299 3' ends. While most termini were found in intergenic regions, numerous abundant termini were also found within coding regions and introns, including several major TSS at unexpected locations. A consistent feature was the clustering of both 5' and 3' ends, contrasting with the prevailing description of discrete 5' termini, suggesting an imprecision of the transcription and/or RNA processing machinery. Numerous termini correlated with the extremities of small RNA footprints or predicted stem-loop structures, in agreement with the model of passive RNA protection. Terminome-seq was also implemented for pnp1-1, a mutant lacking the processing enzyme polynucleotide phosphorylase. Nearly 2000 termini were altered in pnp1-1, revealing a dominant role in shaping the transcriptome. In summary, Terminome-seq permits precise delineation of the roles and regulation of the many factors involved in organellar transcriptome quality control.


In non-small cell lung cancer mitogenic signaling leaves Sprouty1 protein levels unaffected.
Sprouty1 protein belongs to a family of receptor tyrosine kinase-mediated signaling inhibitors, whose members are usually regulated by growth factors to form a negative feedback loop. Correspondingly fluctuations of Sprouty1 mRNA in response to single growth factors have been observed. In this report, we investigate Sprouty1 protein levels and show that in non-small cell lung carcinoma-derived cells, the expression levels are unaffected by the serum content in the cellular environment. Although cells harboring K-Ras mutations express insignificant higher Sprouty1 levels, ectopic expression of constitutive active Ras in normal human lung fibroblasts fails to augment Sprouty1 protein content. Furthermore, serum starvation for three days has no influence on Sprouty1 expression and addition of serum or of singular growth factors leaves Sprouty protein levels unchanged. Cell cycle analysis reveals that Sprouty1 levels remain constant throughout the whole cell cycle. These data demonstrate that Sprouty1 expression is not connected with mitogenic signaling and cell proliferation.


Usefulness of the total iron binding capacity in the evaluation and treatment of acute iron overdose.
The ingestion of iron-containing products is a potential toxicologic emergency. The total iron binding capacity (TIBC) has been used widely as a predictor of end-organ toxicity and a guide to the need for deferoxamine therapy. When the TIBC is greater than the serum iron concentration (SIC), it is held that no free iron is present to cause toxicity. The TIBC fails as a marker of toxicity for several reasons. First, the laboratory methods used to measure TIBC are inaccurate in the setting of iron overload. Second, the presence of deferoxamine, the antidote for iron poisoning, has been shown to make the TIBC measurement inaccurate. Third, TIBC measurements have been shown to be variable. Finally, studies and case reports demonstrate toxicity even when the TIBC is greater than the SIC. These shortcomings of the TIBC invalidate it as a predictor of toxicity in iron poisoning.


Stereoselective total synthesis of Oxylipin from open chain gluco-configured building block.
Total synthesis of naturally occurring Oxylipin has been achieved from open chain gluco-configured building block which is readily assembled from inexpensive and commercially available D-(+)-gluconolactone. Grignard reaction and Wittig olefination reactions are key steps for the requisite CC bond formation.


[The effect of epsilon-aminocaproic acid on the normalization of embolizing fatty matter in the rabbit lung following experimental fractures. A polarized light study].
It has been confirmed that epsilon-aminocaproic acid (EACA), an inhibitor of fibrinolysis, reduced the incidence of fat embolism in the lung of rabbits with experimental bone fractures. Microscopic specimens of lungs, examined under polarized light, demonstrated the reduced amounts of lipoid materials that were prevalently undergraded. The action of the drug is owed to the inhibition of some primary mechanisms, involved in the genesis and diffusion of post-traumatic fat embolism.


Electrophysiological and behavioural processing of complex acoustic cues.
To examine behavioural and neural processing of pitch cues in adults with normal hearing (NH) and adults with sensorineural hearing loss (SNHL). All participants completed a test of behavioural sensitivity to pitch cues using the TFS1 test (Moore and Sek, 2009a). Cortical potentials (N1, P2 and acoustic change complex) were recorded in response to frequency shifted (deltaF) tone complexes in an 'ABA' pattern. The SNHL group performed more poorly than the NH group for the TFS1 test. P2 was more reflective of pitch differences between the complexes than N1. The presence of acoustic change complex in response to the TFS transitions in the ABA stimulus varied with deltaF. Acoustic change complex amplitudes were reduced for the group with SNHL compared to controls. Behavioural performance and cortical responses reflect pitch processing depending on the salience of pitch cues. These data support the use of cortical potentials and behavioural sensitivity tests to measure processing of complex acoustic cues in people with hearing loss. This approach has potential for evaluation of benefit from auditory training and hearing instrument digital signal processing strategies.


Rational selection of an ideal oncolytic virus to address current limitations in clinical translation.
Oncolytic virus therapy (OVT) is a promising modality that leverages the propensity of natural or engineered viruses to selectively replicate in and kill cancer cells. Over the past decade, (pre)clinical studies have focused on the development and testing of adenovirus, herpes simplex virus, and vaccinia virus-based vectors. These studies have identified barriers to success confronting the field. Here, we propose a set of selection criteria or ideal properties of a successful oncolytic virus, which include lack of pathogenicity, low seroprevalence, selectivity (infection and replication), transgene carrying capacity, and genome stability. We use these requirements to analyze the oncolytic virus landscape, and then identify a potentially optimal species for platform development - vesicular stomatitis virus.


Management of fetal endocrine disorders.
A number of maternal endocrine disorders, when active during pregnancy, can have adverse effects on the newborn. Frequently, these affects can be anticipated as in Graves' disease, or the adverse effect can be prevented as in macrosomia in the infant of the diabetic mother. Occasionally, there are opportunities for prenatal treatment of a fetal endocrine disorder. For instance, a large goitre that may cause problems during delivery can be treated with thyroid hormones administered intra-amniotically or as analogues that cross the placenta. A uniquely effective form of treatment for prevention of a major birth defect is administration of dexamethasone to the mother to avoid virilisation of a female fetus with congenital adrenal hyperplasia (CAH). However, such treatment should only be conducted within the framework of a clinical trial as the long-term effects of exposure to potent glucocorticoids in utero are unknown. Intrauterine growth retardation, which affects about 5% of newborns, is currently not amenable to direct pharmacological treatment before birth. However, there are more practical options for managing this condition, including improved maternal nutrition and avoidance of toxins injurious to fetal growth.


Early and late outcomes in patients excluded from same-day home discharge after transradial stenting and maximal antiplatelet therapy.
To develop a safe practice of same-day discharge after percutaneous coronary intervention (PCI), it is important to identify early the patients who need to remain hospitalized and potentially require more careful follow-up. In the EASY trial, a large number of patients with acute coronary syndromes were enrolled prior to PCI to be randomized between same-day discharge or overnight hospitalization. Based on a few angiographic criteria, suboptimal results, or clinical complications, some patients were excluded from randomization after PCI. We report the early and late outcomes of those patients, and evaluate the use of simple criteria precluding same-day discharge. The rate of major adverse cardiac events including death, myocardial infarction, and target vessel revascularization in patients excluded from randomization (n = 343) was significantly higher at 30 days (10.2% vs. 1.6%), 6 months (17.5% vs. 5.6%), and 12 months (24.5% vs. 9%) compared with randomized patients (n = 1,005; P < 0.0001). At 12 months, only transient vessel closure (HR 1.78, 95% CI 1.10-2.65, P = 0.023) and a residual dissection >or= grade B post-PCI (HR 1.53, 95% CI 1.11-2.05, P = 0.011) were independent predictive factors of adverse outcomes. Criteria associated with angiographic suboptimal results or clinical complications are useful to identify patients ineligible for same-day discharge after PCI, regardless of the clinical presentation. Patients excluded from same-day discharge after PCI for safety concerns have worse early and late outcomes. Transient vessel closure and persisting moderate dissection after PCI remain independent predictors of late adverse outcomes after PCI with maximal antiplatelet therapy.


Interpretation of fundus autofluorescence changes in choriocapillaritis: a multi-modality imaging study.
We aimed to describe imaging findings in primary inflammatory choriocapillaropathies (PICCPs) after a photobleaching process. 2Images from six consecutive cases of patients affected by PICCPs (four with multiple evanescent white dot syndrome and two with multifocal choroiditis) were reviewed. Patients underwent fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA), and spectral-domain optical coherence tomography (SD-OCT) by means of the Spectralis HRA (Heidelberg Engineering, Heidelberg, Germany). FAF images were acquired at the beginning of the examination in partially dark-adapted conditions followed by light adapted conditions. During the active phase of the diseases, all patients showed areas of increased FAF that became isoautofluorescent after photobleaching. Simultaneously with increased FAF, the ICGA showed typical hypofluorescent dark areas that were more evident in the late phase. SD-OCT showed disruptions in the hyper-reflective band at the ellipsoid zone. FAF and SD-OCT are complementary imaging techniques that show alterations in the outer retina of patients affected by PICCPs.


A community of marine bacteria with potential to biodegrade petroleum-based and biobased microplastics.
The biodegradability conditions for both, petroleum-based plastics and bioplastics needs to be evaluated under environmentally realistic conditions. We assessed the biodegradability of low-density polyethylene and biobased polyethylene terephthalate microplastic films by a consortium of marine bacteria during 45 days. Bacterial growth and pH were higher in the samples inoculated with bacteria, compared to the controls. Fourier Infrared spectroscopy-Attenuated Total Reflectance and scanning electron microscopy indicated changes in the chemical functional groups, and the presence of fractures and biofilms in the surface of both plastics exposed to the bacterial community, respectively. The chemical oxygen demand further indicated signs of biodegradation of both polymers. Specific groups of bacteria showed preference for each type of microplastic. Overall, our results show signs of biodegradation, or at least biodeterioration and biofragmentation, of both types of plastics, when subjected to the selected bacterial community. Biobased PET was no more prone to biodegradation than conventional, petroleum-based LDPE.


Preferences for Palliative and End-of-Life Care: A Systematic Review of Discrete Choice Experiments.
Understanding what matters most to patients and their caregivers is fundamental to delivering high-quality care. This systematic review aimed to characterize and appraise the evidence from discrete choice experiments eliciting preferences for palliative care. A systematic literature search was undertaken for publications up until August 2022. Data were synthesized narratively. Thematic analysis was applied to categorize attributes into groups. Attribute development, frequency, and relative importance were analyzed. Subgroup analyses were conducted to compare outcomes between patient and proxy respondents. Seventeen studies spanning 11 countries were included; 59% of studies solely considered preferences for patients with cancer. A range of respondent groups were represented including patients (76%) and proxies (caregivers [35%], health providers [12%], and the public [18%]). A total of 117 individual attributes were extracted and thematically grouped into 8 broad categories and 21 subcategories. Clinical outcomes including quality of life, length of life, and pain control were the most frequently reported attributes, whereas attributes relating to psychosocial components were largely absent. Both patients and proxy respondents prioritized pain control over additional survival time. Nevertheless, there were differences between respondent cohorts in the emphasis on other attributes such as access to care, timely information, and low risk of adverse effects (prioritized by patients), as opposed to cost, quality, and delivery of care (prioritized by proxies). Our review underscores the vital role of pain control in palliative care; in addition, it shed light on the complexity and relative strength of preferences for various aspects of care from multiple perspectives, which is useful in developing personalized, patient-centered models of care for individuals nearing the end of life.


Investigating the associations of glycemic load and glycemic index with lung cancer risk in the Southern Community Cohort Study.
Diets with a high glycemic load (GL) or glycemic index (GI) may increase cancer risk. Findings from prior studies on the relationship between GL, GI, and lung cancer risk are inconsistent. We investigated this relationship in a large prospective cohort. We analyzed data from the Southern Community Cohort Study, a prospective cohort that includes diverse racial groups predominantly low-income adults aged 40-79 in 12 southeastern states of the USA. We estimated dietary GL and GI values using data collected from food frequency questionnaires at baseline. Dietary GL and GI were energy adjusted by residual method and categorized into sex-specific quintiles. Cox proportional hazard regression was used to assess the associations between dietary GL, GI, and lung cancer risk. We further performed stratified analyses by various factors. Intakes of individual food items or food groups that commonly contribute to GL were similar between blacks and whites in the cohort. After excluding the first two years of follow-up, 947 incident lung cancers were ascertained among 55,068 participants. Neither dietary GL nor GI was significantly associated with incident lung cancer risk in the overall population (GL: Q5 vs. Q1, HR = 0.88, 95% CI 0.72-1.07, ptrend = 0.29; GI: Q5 vs. Q1, HR = 1.06, 95% CI 0.86-1.30, ptrend = 0.71), nor in subgroups of populations (ptrend > 0.05), in multivariable-adjusted analyses. Dietary GL and GI were not independently associated with incident lung cancer risk in a large understudied population.


Fluorescence Spectroscopy for the Diagnosis of Endometritis in the Mare.
By exploiting the PMN property to produce high quantities of oxygen peroxide to neutralize pathogens, the oxygen peroxide content of uterine cells was measured to diagnose endometritis. After preliminary in vitro studies in which endometrial cells from slaughtered mares were mixed with leukocytes from peripheral blood, endometrial samples were collected by uterine flushing from mares before insemination. Staining endometrial cells with H2DCF-DA was combined with hydroethidine to normalize the fluorescence intensity with the cellular content of the sample. Stained cell smears were assumed as the gold standard of endometritis, and based on this assay, the samples were considered positive (C+) and negative (C−) for endometritis. The amount and the turbidity of fluid recovered by uterine flushing were significantly (p < 0.01) higher in C+ than in C−. Moreover, the oxygen peroxide content of the endometrial cells was significantly higher in the C+ than in the C− group (6.31 ± 1.92 vs. 3.12 ± 1.26, p = 0.001). Using the value of 4.4 as the cutoff level of this fluorescence cytology assay, it was found that only one C− sample exceeded the cutoff level (false positives = 7.7%) while three C+ samples showed values below the cutoff level (false negative = 11.5%).


Duration of stunting impacts compensatory growth and carcass quality of farmed milkfish, Chanos chanos (Forsskal, 1775) under field conditions.
An 18-months field trial was performed to explore the effect of duration of stunting on growth, digestive enzymes and carcass quality in Chanos chanos. Milkfish fry (weight of 1.25 ± 0.03 g and length of 5.53 ± 0.03 cm) were stocked in earthen ponds of 0.02 ha, in triplicate, for different duration of stunting, viz., 4 months (Treatment-1; T4), 8 months (Treatment-2; T8) and 12 months (Treatment-3; T12) and a normal seed (Control; C) separately. In the stunting phase, fish were stocked at higher stocking density (0.2 million/ha) and fed de-oiled rice bran at sub-optimal level. Post-stunting or re-feeding phase commenced immediately after completion of respective stunting duration and fish were reared for the rest of the period to complete the total rearing period of 18 months. In post-stunting, fish stocking density was adjusted to (5000 pieces/ha) and fed at an optimum level (3%). At the end of stunting phase, the study found a significant reduction in growth, survival, digestive enzymes activity, except protease in the T4 group, and carcass nutrients composition of stunted fish. However, in the initial phase of post-stunting, T8 group exhibited an elevated specific growth rate (5.00 ± 0.092%/day), body weight gain (80.82 ± 1.28 g), amylase (0.585 ± 0.021 U/mg protein), protease (5.48 ± 0.13 U/mg protein), and lipase activity (7.92 ± 0.32 U/mg protein). All stunted fish groups displayed a compensatory growth response in post-stunting, but a complete growth compensation was observed in T8 group, which resulted in better feed conversion ratio (3.03 ± 0.04) feed efficiency ratio (0.33 ± 0.01), protein efficiency ratio (1.91 ± 0.03), survival (91.38 ± 0.07%) and digestive enzyme activities. Similarly, at the end of post-stunting, carcass analysis revealed a complete restoration of nutrients in stunted fish and significantly higher protein content in T8 group. Further, the study found lower meat and higher bone contents in normally reared fish than the post-stunted fish which revealed the carcass quality improvement in post-stunted fish thus indicates superiority of the stunting process over normal rearing. Overall, the study suggests that stunting of milkfish, for 8 months (T8), positively affects its growth, survival, digestive enzyme activities and carcass quality which in turn, shall help to overcome the contemporary challenges in milkfish culture.


Recurrent lip swelling as a late presentation of Kawasaki disease: Case report and review of literature.
Kawasaki Disease (KD) is an acute systemic vasculitis of unknown etiology. In many developed countries, KD has replaced rheumatic heart disease as the leading cause of acquired heart disease in children. Among the classical criteria for a diagnosis of KD are oral manifestations such as strawberry tongue, erythematous cracked lip, and oropharyngeal mucositis. We report the case of a 24-year-old Saudi female with a history of Kawasaki disease who presented to our oral medicine clinic with recurrent painless swelling of the upper lip. As lip swelling has not previously been reported as an oral manifestation of KD, this case represents a novel presentation of recurrent Kawasaki disease in an adult female.


Evolution and regulation of the downstream gene of hypoxia-inducible factor-1alpha in naked carp (Gymnocypris przewalskii) from Lake Qinghai, China.
The naked carp (Gymnocypris przewalskii) is a native teleost of Lake Qinghai (altitude, 3.2 km) on the Qinghai-Tibet Plateau in China. Hypoxia-inducible factor (HIF)-1alpha of Gymnocypris przewalskii was cloned and a phylogenetic tree for vertebrate HIF-1alpha was constructed. By analysis of maximum likelihood models of codon substitutions for HIF-1alpha, three positive sites in the branch lineages of crucian carp, eelpout, and flounder, and a higher proportion of neutral sites in naked carp, antarctic eelpout, rainbow trout, and grayling, were detected among all teleosts. It seems that low habitat temperatures relax the purifying selection of HIF-1alpha in these stenothermal coldwater fish, and both cold and hypoxic lake water contributed to the evolution of the HIF-1alpha gene in the naked carp. Furthermore, Glut 1 mRNA, a gene downstream from HIF-1alpha, has a time-course- and tissue-specific dependent response to hypoxic challenge.


Randomized controlled exploratory study comparing the usefulness of two types of metallic stents with different axial forces for the management of duodenal obstruction caused by pancreatobiliary cancer.
Very few studies have examined effectiveness of duodenal stent placement (DSP) for duodenal obstruction (DO) caused specifically by pancreatobiliary cancer. We compared two types of stents with different axial forces (AF) for DO with pancreatobiliary cancer. The patients were randomly assigned to two stent groups with different AF (high AF stent, WallFlex™: W-group or low AF stent, Niti-S™: N-group). The primary endpoint was improvement in the Gastric Outlet Obstruction Scoring System (GOOSS) score. This study was registered at UMIN000009061. The GOOSS scores significantly improved in both W-group (0.9 before vs. 2.7 after; P = 0.002) and N-group (1.0 before vs. 2.5 after; P = 0.001). The change in the GOOSS score after DSP did not differ significantly between the groups (P = 0.482). The median time to recurrent DO (RDO) was significantly shorter in W-group than in N-group (89 days vs. 421 days; P = 0.025). The incidence of RDO was significantly higher in W-group than in N-group (64% vs. 24%; P = 0.027). Stent kinking occurred only in W-group. The GOOSS scores significantly improved after DSP, but effectiveness did not differ significantly between groups. The use of stents with high AF was related to short-term stent patency, but did not influence survival time.


Central benzodiazepine receptors in human brain: estimation of regional Bmax and KD values with positron emission tomography.
Studies of central benzodiazepine receptors in the human brain in vivo are now possible using positron emission tomography (PET) and [11C]flumazenil. With the aim of measuring Bmax and Kd in brain regions, we used a two-injection [11C]flumazenil (at high and low specific radioactivity, respectively) pseudo-equilibrium paradigm to evaluate, in seven unmedicated healthy volunteers, the relative merits of three 'reference' structures (pons, hemispheric white matter and corpus callosum) in which the free radioligand concentration in brain tissue was estimated 15-40 min after i.v. injection of the radioligand. By means of high-resolution PET, the Bmax and Kd were calculated for each subject in 18 gray matter structures, based on a two-point Scatchard plot. We found that the use of the corpus callosum as reference often resulted in spurious Bmax and Kd values. The pons was the best reference structure because it provided satisfactory Bmax values (closest to in vitro data) and most consistent Kd values, and was the region easiest to sample on PET images. The pattern of regional Bmax was consistent with that expected from in vitro studies, with values highest in the cerebral cortex, intermediate in the cerebellum, and lowest in the striatum and the thalamus. The Kd values were uniform among regions and were consistent with earlier in vitro and in vivo data. This work documents the feasibility of estimating Bmax and Kd of central benzodiazepine receptors in multiple brain regions for clinical research.


Fluorescence-Based High-Throughput and Targeted Image Acquisition and Analysis for Phenotypic Screening.
Applying the right acquisition method in a fluorescence imaging-based screening context is of great importance to obtain an appropriate readout and to select the right scale of the screen. In order to save imaging time and data, we have developed routines for multiscale targeted imaging, providing both a broad overview of a sample and additional in-depth information for targets of interest identified within the screen. These objects can be identified and acquired on-the-fly by an interconnection of image acquisition and image analysis.


Phentolamine mesylate relaxes penile corpus cavernosum tissue by adrenergic and non-adrenergic mechanisms.
We investigated the biochemical and physiological mechanisms of action of phentolamine mesylate (Vasomax) in regulating erectile tissue smooth muscle contractility in human and rabbit corpus cavernosum. The binding activity of phentolamine was investigated in a cell-free system by displacement of specific and selective radiolabelled ligands to alpha 1 and 2 adrenergic receptors. The physiologic activity of phentolamine-mediated relaxation of adrenergic and non-adrenergic pre-contracted erectile tissue strips of human and rabbit corpus cavernosum were studied in organ bath chambers. In corpus cavernosum membranes, phentolamine displaced binding of the selective alpha 1 receptor antagonists [125I]HEAT and [3H]prazosin and the alpha 2 receptor antagonists [3H]rauwolscine and [3H]RX 821002 with relatively high affinity. Phentolamine caused concentration dependent relaxation in erectile tissue strips pre-contracted with adrenergic agonists phenylephrine, norepinephrine, oxymetazoline and UK 14,304, as well as with non-adrenergic contractile agents endothelin and KCl. Biochemical and physiologic studies reveal that the concentration of phentolamine required to displace half maximal binding or to produce half-maximal relaxation was similar to that found in human plasma 30 min after ingestion of 40 mg of Vasomax. Reversible inhibition of nitric oxide synthase by L-nitroarginine or mechanical disruption of endothelium diminished non-adrenergic phentolamine-mediated erectile tissue relaxation. Phentolamine mesylate induced relaxation of corpus cavernosum erectile tissue by direct antagonism of alpha 1 and 2 adrenergic receptors and by indirect functional antagonism via a non-adrenergic, endothelium-mediated mechanism suggesting nitric oxide synthase activation.


Detection, isolation, and characterization of alpha-fetoprotein-specific T cell populations and clones using MHC class I multimer magnetic sorting.
alpha-fetoprotein (AFP) is a fetal protein specifically reexpressed in 50% of hepatocellular carcinomas. This protein could serve as a tumor-associated antigen for immunotherapy purpose. The aim of our work was to analyze the presence of AFP-specific T cell populations in peripheral blood mononuclear cells (PBMCs) from cirrhotic patients with or without hepatocellular carcinoma. Using peptide-major histocompatibility complex class I multimers, AFP-specific populations corresponding to 3 previously described human leukocyte antigen (HLA)-A*0201 major histocompatibility complex class I epitopes (AFP137, AFP158, and AFP325) were sorted magnetically from CD8 positive cells without prior stimulation with the target antigen. T cell populations specific for 1 peptide (AFP158) were frequent, whereas populations corresponding to peptide AFP137 were rare and absent for peptide AFP325. We also isolated and fully characterized T cell clones specific for AFP137 and AFP158 peptides. We show that these clones can be used to monitor dendritic cell loading with peptides and could be useful for future immunotherapy protocols.


The psychological meaning of job insecurity and job loss: results of a longitudinal study.
This paper presents some results from a longitudinal intensive study of 26 shipyard workers during a period of two years. Unemployment was found to comprise a process consisting of a series of psychological crisis due to loss of important factors contributing to identity. The anticipatory phase was found to be a very burdening phase of unemployment due to the prolonged uncertainty. Despite good economic compensation depressive reactions were noticed. Other psychological reactions were irrational job seeking behaviour. The attitudes towards work were investigated. The central concepts of meaning of work was found to be unconscious and mediated early during childhood and to change very slowly. The shipyard workers tried to maintain an old working identity but especially the old, single men had difficulties to stand firm to it. Some of them intensifies alternative to work, like fishing, hunting and other activities and, in a way, continue to work. The single, older unemployed men were found to be a risk group.


An ultrasensitive biosensor for prostate specific antigen detection in complex serum based on functional signal amplifier and designed peptides with both antifouling and recognizing capabilities.
The development of biosensors capable of averting biofouling and detecting biomarkers in complex biological media remains a challenge. Herein, an ultralow fouling and highly sensitive biosensor based on specifically designed antifouling peptides and a signal amplification strategy was designed for prostate specific antigen (PSA) detection in human serum. A low fouling layer of poly(ethylene glycol) (PEG) doped the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) was electrodeposited on the electrode surface, followed by the immobilization of streptavidin and further attachment of biotin-labelled peptides. The peptide was designed to include PSA specific recognition domain (HSSKLQK) and antifouling domain (PPPPEKEKEKE), and the terminal of the peptide was functionalized with -SH group. DNA functionalized gold nanorods (DNA/AuNRs) were then attached to the electrode, and methylene blue (MB) molecules were adsorbed to the DNA to form the signal amplifier. In the presence of PSA, the peptide was specifically cleaved and resulted in the loss of AuNRs together with DNA and MB, and thus significant decrease of the current signal. The biosensor exhibited a low limit of detection (LOD) of 0.035 pg mL-1 (S/N = 3), with a wide linear range from 0.10 pg mL-1 to 10.0 ng mL-1, and it was able to detect PSA in real human serum owing to the presence of the antifouling peptides, indicating great potential of the constructed biosensor for practical application.


Complexation of labile aluminium species by chelating resins Iontosorb--a new method for Al environmental risk assessment.
The utilization of chelating ion-exchange by the method based on binding strength and kinetic discrimination for aluminium fractionation was studied. Two chelating cellulose resins, Iontosorb Oxin (IO) and Iontosorb Salicyl (IS), were used for the determination of quickly reacting labile aluminium species. The possibilities of aluminium fractionation on these chelating resins were investigated by a solid phase extraction technique. The study of the pH (2.5-6.0) influence on the Al complexation by both resins indicates that at low pH the IS has lower sorption capacity but better adsorptive kinetic properties than IO. The optimal resin complexation time for reactive Al species was experimentally found after aluminium sorption study at pH 4.0 in synthetic solutions containing some inorganic and organic ligands, which simulate the composition of analysed acid soil and water samples. The negative influence of sulphate and iron on the Al complexation by IS resin was found and investigated. The flame atomic absorption spectrometry was used for the aluminium quantification.


Growth phase dependent alterations in the surface coat of Acanthamoeba castellanii.
Application of ruthenium red, cationized ferritin and concanavalin A to exponentially growing trophozoites reveals on their plasma membrane negatively charged surface coat bearing sugar residues. In the coat of trophozoites from advanced stationary growth phase no sugar residues can be visualized. In mature cysts the external layer of their wall is negatively charged, however, on their protoplast surface no terminals reacting with the 2 polycations, or with concanavalin A can be revealed, even though the penetration of the reagents has been ensured by enzymatic impairing of the cyst wall. The results are confronted with the known facts concerning alterations of physiological properties of plasma membrane occurring during the life cycle of Acanthamoeba.


A systematic review of the prevalence of pathogenic or likely pathogenic germline variants in individuals with FOXO1 fusion-positive rhabdomyosarcoma.
Several cancer predisposition syndromes (CPS) are reported to predispose to rhabdomyosarcoma, most frequently in children with embryonal rhabdomyosarcoma. There are lingering questions over the role of CPS in individuals with alveolar rhabdomyosarcoma (ARMS), which are frequently driven by FOXO1 fusion oncoproteins. We conducted a systematic review to identify patients with FOXO1 fusion-positive ARMS (FP-ARMS) who underwent germline DNA sequencing. We estimated the prevalence of pathogenic/likely pathogenic (P/LP) variants in cancer predisposing genes (CPGs) and of CPSs. We included 19 publications reporting on 191 patients with FP-ARMS. P/LP variants in CPGs were identified in 26/191 (13.6%) patients, nine (4.9%) of which were associated with a CPS diagnosis. Evidence for causal associations between CPSs and FP-ARMS could not be assessed with available data from this review. Only one patient was affected with a CPS known to predispose to rhabdomyosarcoma, Li-Fraumeni syndrome. Typical CPS associations with rhabdomyosarcoma are rare, but not nonexistent, in patients with FP-ARMS. FOXO1 fusion status, alone, is insufficient for clinicians to rely on to distinguish between patients with/without CPS.


Concordance between karyotyping and in situ hybridization procedures in the detection of monosomy 9 in bladder cancer.
Twenty-three cases of transitional cell carcinoma (TCC) with a diploid model chromosome count as selected after karyotyping were analyzed by fluorescence in situ hybridization (FISH), using a probe for the heterochromatic region of chromosome 9. A monosomy for chromosome 9 was detected in 50% by karyotyping and after FISH in 52% of the cases. A full concordance between FISH and conventional karyotyping was found. We concluded that FISH can be reliably applied to interphase nuclei of TCC for the detection of numerical chromosome 9 aberrations.


Amylopectin molecular structure in relation to physicochemical properties of quinoa starch.
Structure-function relationships of starch components remain a subject of research interest. Quinoa starch has very small granules (∼2μm) with unique properties. In this study, nine quinoa starches varied greatly in composition, structure, and physicochemical properties were selected for the analysis of structure-function relationships. Pearson correlation analysis revealed that the properties related to gelatinization such as swelling power, water solubility index, crystallinity, pasting, and thermal properties are much affected by the amylopectin chain profile and amylose content. The parameters of gel texture and amylose leaching are much related to amylopectin internal structure. Other properties such as enzyme susceptibility and particle size distribution are also strongly correlated with starch composition and amylopectin structure. Interesting findings indicate the importance of amylopectin internal structure and individual unit chain profile in determining the physicochemical properties of starch. This work highlights some relationships among composition, amylopectin structure and physicochemical properties of quinoa starch.


Fetal liver micronucleus assay in mice of 5-fluorouracil and related compounds.
The cytogenetic effects of 5-fluorouracil (5-FU), 1-hexyl-carbamoyl-5- fluorouracil (HCFU) and 1-(2-tetrahydrofuryl)-5-fluorouracil (TF) were examined with the fetal liver micronucleus assay in mice. The frequencies of micronucleated polychromatic erythrocytes (MNPCEs) in fetal liver peaked at 27, 24 and 27 h, respectively, after single intraperitoneal injections into pregnant mice on day 13 of gestation. The highest frequency of MNPCEs by 5-FU treatment in fetal liver was 13.6%, whereas the frequency in maternal bone marrow was only 0.4%. The micronucleus frequency and the number of micronuclei per individual polychromatic erythrocyte were clearly dose-dependent. These results suggest that the micronucleus test in fetal liver has particular advantages compared to maternal bone marrow for evaluating the cytogenetic effects of 5-FU and related compounds after a single treatment. The cytogenetic effect was ranked 5-FU = HCFU > TF, in both a time-course study and a dose-response study of micronucleus distribution.


Comparative Clustering (CompaCt) of eukaryote complexomes identifies novel interactions and sheds light on protein complex evolution.
Complexome profiling allows large-scale, untargeted, and comprehensive characterization of protein complexes in a biological sample using a combined approach of separating intact protein complexes e.g., by native gel electrophoresis, followed by mass spectrometric analysis of the proteins in the resulting fractions. Over the last decade, its application has resulted in a large collection of complexome profiling datasets. While computational methods have been developed for the analysis of individual datasets, methods for large-scale comparative analysis of complexomes from multiple species are lacking. Here, we present Comparative Clustering (CompaCt), that performs fully automated integrative analysis of complexome profiling data from multiple species, enabling systematic characterization and comparison of complexomes. CompaCt implements a novel method for leveraging orthology in comparative analysis to allow systematic identification of conserved as well as taxon-specific elements of the analyzed complexomes. We applied this method to a collection of 53 complexome profiles spanning the major branches of the eukaryotes. We demonstrate the ability of CompaCt to robustly identify the composition of protein complexes, and show that integrated analysis of multiple datasets improves characterization of complexes from specific complexome profiles when compared to separate analyses. We identified novel candidate interactors and complexes in a number of species from previously analyzed datasets, like the emp24, the V-ATPase and mitochondrial ATP synthase complexes. Lastly, we demonstrate the utility of CompaCt for the automated large-scale characterization of the complexome of the mosquito Anopheles stephensi shedding light on the evolution of metazoan protein complexes. CompaCt is available from https://github.com/cmbi/compact-bio.


[Endoscopic diagnosis, treatment, and follow-up of polyps of the lower gastrointestinal tract].
The endoscopic management of polyps of the lower gastrointestinal tract (l-GIT) has emerged in recent years as a result of numerous technological innovations. However, proven expertise and experience are essential. Presentation of novel and standard techniques and best-practice recommendations for the characterization and resection of l‑GIT polyps. Recent specialist literature and current guidelines. High-definition endoscopy should be the standard when performing colonoscopy. The (virtual) chromoendoscopy can improve detection and characterization of polyps, but always requires special expertise and experience of the endoscopist in advanced endoscopic imaging. In this regard, computer-aided-diagnosis (CAD) systems have the potential to support endoscopists in the future. Pedunculated polyps should be removed with a hot snare. Small flat polyps can be resected by cold snare or large forceps. Large, non-pedunculated polyps should be treated in an interdisciplinary approach at a referral center with long-standing experience depending on its malignancy potential. After complete resection of small adenoma without high grade dysplasia, surveillance endoscopy is recommended after 5-10 years. Patients with large adenoma or high grade dysplasia should undergo endoscopy after 3 years and patients with multiple adenoma earlier than 3 years. After incomplete or piecemeal resection or insufficient bowel preparation, near-term endoscopy is recommended. Adequate characterization and treatment are essential for the appropriate management of l‑GIT polyps.


Integrative taxonomy reveals three new species of European Lepidocyrtus lignorum-group (Collembola, Entomobryidae).
Lepidocyrtus is one of the genera of springtails with the largest number of species in the world. Molecular studies carried out to date on this genus have revealed the existence of a large number of cryptic species. Molecular and morphological studies done with four European populations of the genus have allowed us to describe three new species within the L. lignorum-group: L. fuscocephalus sp. nov., L. milagrosae sp. nov. and L. semicoloratus sp. nov. One of these species is made up of two geographically separate populations that represent two clearly separate but morphologically indistinguishable haplotypes.


Host metabolome predicts the severity and onset of acute toxicities induced by CAR T-cell therapy.
Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is a highly effective treatment option for patients with relapsed/refractory large B-cell lymphoma. However, widespread use is deterred by the development of clinically significant acute inflammatory toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), that induce significant morbidity and require close monitoring. Identification of host biochemical signatures that predict the severity and time-to-onset of CRS and ICANS may assist patient stratification to enable timely mitigation strategies. Here, we report pretreatment host metabolites that are associated with CRS and ICANS induced by axicabtagene ciloleucel or tisagenlecleucel therapy. Both untargeted metabolomics analysis and validation using targeted assays revealed a significant association between the abundance of specific pretreatment biochemical entities and an increased risk and/or onset of clinically significant CRS (q < .1) and ICANS (q < .25). Higher pretreatment levels of plasma glucose and lower levels of cholesterol and glutamate were associated with a faster onset of CRS. In contrast, low baseline levels of the amino acids proline and glycine and the secondary bile acid isoursodeoxycholate were significantly correlated with clinically significant CRS. Lower concentration of the amino acid hydroxyproline was associated with higher grade and faster onset of ICANS, whereas low glutamine was negatively correlated with faster development of ICANS. Overall, our data indicate that the pretreatment host metabolome has biomarker potential in determining the risk of clinically significant CRS and ICANS, and may be useful in risk stratification of patients before anti-CD19 CAR T-cell therapy.