The clinical application of aspiration deoxyribonucleic acid flow cytometry to neurologically impaired men entering an electroejaculation program.
For the neurologically impaired patient electroejaculation with a rectal probe can furnish sperm for artificial insemination. However, documentation of pregnancies in this patient group has been limited. Deoxyribonucleic acid flow cytometry has been shown to be a reproducible quantitative method with which to evaluate spermatogenesis. We assessed the ability of deoxyribonucleic acid flow cytometry on testicular aspirates to predict the quality of sperm production in 13 men undergoing electroejaculation. Semen analysis was performed on antegrade and retrograde specimens. Deoxyribonucleic acid histograms from testicular aspirates were evaluated for the relative proportions of haploid, diploid and tetraploid cells. These ratios were compared to the means reported for our own series of 25 patients who at vasovasostomy had sperm intraoperatively and to the similar figures from a group of 10 accident victims. Five patients had normal testicular ploidy compartments defined as within 2 standard deviations from control means. Of the 5 patients 4 had normal sperm counts and motilities (30 per cent or greater). Two patients have contributed sperm for artificial insemination; 1 has resulted in pregnancy. Three patients had moderately abnormal (2 to 4 standard deviations) testicular ploidy classes. These patients had adequate sperm counts but low motilities (5 per cent or less). Of the 5 patients with markedly abnormal (greater than 4 standard deviations) histograms 4 remained azoospermic despite repeated attempts at electroejaculation. Our data support the use of deoxyribonucleic acid flow cytometry on testicular aspirates as a predictor of which patients might succeed and those who are unlikely to succeed in an electroejaculation program.


Applying community health systems lenses to identify determinants of access to surgery among mobile & migrant populations with hydrocele in Zambia: A mixed methods assessment.
Hydrocele which is caused by long term lymphatic filariasis infection can be treated through the provision of surgery. Access to surgeries remains low particularly for hard to reach populations. This study applied community health system lenses to identify determinants to the adoption, implementation and integration of hydrocele surgeries among migrants &mobile populations in Luangwa District, Zambia. A concurrent mixed methods design consisting of cross-sectional survey with hydrocele patients (n = 438) and in-depth interviews with different community actors (n = 38) was conducted in October 2021. Data analysis was based on the relational and programmatic lenses of Community Health Systems. Under the Programmatic lens, insufficient resources resulted in most health facilities being incapable of providing the minimum package of care for lymphatic filariasis. The absence of cross border collaborative structures limits the continuity of care for patients moving across the three countries. Other programmatic barriers include language barriers, inappropriate appointment systems, direct and indirect costs. In the relational lens, despite the key role that community leaders play their engagement in service delivery was low. Community actors including patients were rarely included in planning, implementation or evaluation of hydrocele services. Some patients utilized their power within to act as champions for the surgery but local groups such as fishing associations remained underutilized. Community health systems provide a potential avenue through which access amongst mobile and migrant populations can be enhanced through strategies such engagement of patient groups, knowledge sharing across borders and use of community monitoring initiatives.


A feasibility study on the prediction of tumour location in the lung from skin motion.
The system for predicting tumour location from skin motion induced by respiration was designed to reduce the effects of target movement. Fluoroscopic studies on 34 sites in the lungs and 14 sites in the diaphragm were performed so that the motions of skin markers and organs could be observed simultaneously. While patients were lying down in the simulator with radio-opaque markers on their skin, fluoroscopic images both in the anterior-posterior (AP) view and in the lateral view were sent to an analysing computer and recorded. The results that showed a strong correlation (0.77+/-0.12) between the patients' skin and tumour movement, especially for the sites located in the lower lung fields or in the diaphragm. With the prediction from skin motion, the uncertainties of the position of tumours due to respiratory movement could be reduced by up to 1.47 cm in the lower lung fields in the superior-inferior (SI) direction. This study revealed that it is possible to trace the exact location of tumours in the lungs by observing skin motion in most cases (up to 88%).


Drug delivery targets and systems for targeted treatment of rheumatoid arthritis.
Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease that selectively attacks human joints. The common non-targeted treatment approaches lead to obvious side effect and systemtic complication for RA patients. Therefore, targeted drug delivery for treatment of RA has gained much attetntion in the past few years. In this paper, we reviewed the potential targets (folate receptor, angiogenesis, matrix metalloproteases, selectins, vasoactive intestinal peptide receptor andFc-γ receptor) that could be utilised to facilitate the specific delivery of drugs to the inflammed synovium and also presented different drug delivery systems for targeting RA, including the liposomes, various types of nanoparticles, polymeric micelles and the macromolecular prodrugs. The strategies combining nanotechnologies and ligand mediated active targeting for RA would be emphatically illustrated, which was expected to be helpful for identifying technologies and drug delivery methods for targeted treatment of RA.


LDL apheresis and inflammation--implications for atherosclerosis.
Low-density lipoprotein (LDL) apheresis is an extracorporeal treatment modality used in high-risk patients when LDL cholesterol levels cannot be reduced adequately with medication. The treatment is highly effective, but could be affected by potential unwanted effects on pro- and anti-inflammatory biomarkers. In this paper, we review the literature regarding the effect of LDL apheresis on pro- and anti-inflammatory biomarkers important in atherosclerosis, also as patients in LDL apheresis have high risk for atherosclerotic complications. We discuss the effect of LDL apheresis on complement, cytokines and finally a group of other selected pro- and anti-inflammatory biomarkers. The complement system is affected by LDL apheresis, and there are differences between different LDL apheresis systems. The plasma separation columns seem to trigger the formation of proinflammatory complement factors including C3a and C5a, while the same anaphylatoxins are adsorbed by the LDL apheresis columns, however, to varying degree. Proinflammatory cytokines are to some extent adsorbed by the LDL apheresis columns, while some of the anti-inflammatory cytokines increase during treatment. Finally, we discuss the effect of apheresis on different biomarkers including C-reactive protein, fibrinogen, adhesion molecules, myeloperoxidase and HDL cholesterol. In conclusion, even if there are differences between pro- and anti-inflammatory biomarkers during LDL apheresis, the consequences for the patients are largely unknown and larger studies need to be performed. Preferably, they should be comparing the effect of different LDL apheresis columns on the total inflammatory profile, and this should be related to clinical endpoints.


TBC-YOLOv7: a refined YOLOv7-based algorithm for tea bud grading detection.
Accurate grading identification of tea buds is a prerequisite for automated tea-picking based on machine vision system. However, current target detection algorithms face challenges in detecting tea bud grades in complex backgrounds. In this paper, an improved YOLOv7 tea bud grading detection algorithm TBC-YOLOv7 is proposed. The TBC-YOLOv7 algorithm incorporates the transformer architecture design in the natural language processing field, integrating the transformer module based on the contextual information in the feature map into the YOLOv7 algorithm, thereby facilitating self-attention learning and enhancing the connection of global feature information. To fuse feature information at different scales, the TBC-YOLOv7 algorithm employs a bidirectional feature pyramid network. In addition, coordinate attention is embedded into the critical positions of the network to suppress useless background details while paying more attention to the prominent features of tea buds. The SIOU loss function is applied as the bounding box loss function to improve the convergence speed of the network. The results of the experiments indicate that the TBC-YOLOv7 is effective in all grades of samples in the test set. Specifically, the model achieves a precision of 88.2% and 86.9%, with corresponding recall of 81% and 75.9%. The mean average precision of the model reaches 87.5%, 3.4% higher than the original YOLOv7, with average precision values of up to 90% for one bud with one leaf. Furthermore, the F1 score reaches 0.83. The model's performance outperforms the YOLOv7 model in terms of the number of parameters. Finally, the results of the model detection exhibit a high degree of correlation with the actual manual annotation results ( R2 =0.89), with the root mean square error of 1.54. The TBC-YOLOv7 model proposed in this paper exhibits superior performance in vision recognition, indicating that the improved YOLOv7 model fused with transformer-style module can achieve higher grading accuracy on densely growing tea buds, thereby enables the grade detection of tea buds in practical scenarios, providing solution and technical support for automated collection of tea buds and the judging of grades.


Effect of hydrogenation on the structure and magnetic properties of an iron oxide cluster.
The structure and properties of the Fe8O12Hn clusters (n = 0-18) are computed using the all-electron density functional theory with the generalized gradient approximation for the exchange-correlation potential. The ground state of Fe8O12 is found to be a singlet state having a bi-capped octahedron geometry. Upon hydrogenation, the octahedral framework of Fe is retained in Fe8O12Hn up to n < 7, beyond which point the iron octahedron transforms into a cube. Hydrogen atoms are bound to oxygen atoms up to n = 12, but they bind to the faces of the Fe8 cube when n > 12. The total spin magnetic moment of a Fe8O12Hn cluster is larger than 6 μB for 1 ≤ n ≤ 18, except for n = 8 and 10, where the lowest total energy states are antiferromagnetic singlets. The reason for this deviation from the general behavior in the Fe8O12Hn series is attributed to the collective superexchange phenomenon. Surprisingly, the total spin magnetic moment of a Fe8O12Hn cluster is found to be substantially larger than the total spin magnetic moment of the bare Fe8 cluster when n = 12-18. All of the Fe8O12Hn clusters are stable with respect to an abstraction of a single hydrogen atom but are unstable toward the abstraction of an H2 dimer when n =10 and n = 14-18.


Metabolic fluxes in an illuminated Arabidopsis rosette.
Photosynthesis is the basis for life, and its optimization is a key biotechnological aim given the problems of population explosion and environmental deterioration. We describe a method to resolve intracellular fluxes in intact Arabidopsis thaliana rosettes based on time-dependent labeling patterns in the metabolome. Plants photosynthesizing under limiting irradiance and ambient CO2 in a custom-built chamber were transferred into a (13)CO2-enriched environment. The isotope labeling patterns of 40 metabolites were obtained using liquid or gas chromatography coupled to mass spectrometry. Labeling kinetics revealed striking differences between metabolites. At a qualitative level, they matched expectations in terms of pathway topology and stoichiometry, but some unexpected features point to the complexity of subcellular and cellular compartmentation. To achieve quantitative insights, the data set was used for estimating fluxes in the framework of kinetic flux profiling. We benchmarked flux estimates to four classically determined flux signatures of photosynthesis and assessed the robustness of the estimates with respect to different features of the underlying metabolic model and the time-resolved data set.


A Novel 7H-[1,2,4]Triazolo[3,4-b]thiadiazine-based Cystic Fibrosis Transmembrane Conductance Regulator Potentiator Directed toward Treatment of Cystic Fibrosis.
Cystic fibrosis (CF) is an autosomal genetic disorder caused by disrupted anion transport in epithelial cells lining tissues in the human airways and digestive system. While cystic fibrosis transmembrane conductance regulator (CFTR) modulator compounds have provided transformative improvement in CF respiratory function, certain patients exhibit marginal clinical benefit or detrimental effects or have a form of the disease not approved or unlikely to respond using CFTR modulation. We tested hit compounds from a 300,000-drug screen for their ability to augment CFTR transepithelial transport alone or in combination with the FDA-approved CFTR potentiator ivacaftor (VX-770). A subsequent SAR campaign led us to a class of 7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines that in combination with VX-770 rescued function of G551D mutant CFTR channels to approximately 400% above the activity of VX-770 alone and to nearly wild-type CFTR levels in the same Fischer rat thyroid model system.


Resting state fast brain dynamics predict interindividual variability in motor performance.
Motor learning features rapid enhancement during practice then offline post-practice gains with the reorganization of related brain networks. We hypothesised that fast transient, sub-second variations in magnetoencephalographic (MEG) network activity during the resting-state (RS) reflect early learning-related plasticity mechanisms and/or interindividual motor variability in performance. MEG RS activity was recorded before and 20 min after motor learning. Hidden Markov modelling (HMM) of MEG power envelope signals highlighted 8 recurrent topographical states. For two states, motor performance levels were associated with HMM temporal parameters both in pre- and post-learning resting-state sessions. However, no association emerged with offline changes in performance. These results suggest a trait-like relationship between spontaneous transient neural dynamics at rest and interindividual variations in motor abilities. On the other hand, transient RS dynamics seem not to be state-dependent, i.e., modulated by learning experience and reflect neural plasticity, at least on the short timescale.


Experimental Analysis of the Mechanical Response of Masonry Columns Partially Confined with PBO FRCM (Fabric Reinforced Cementitious Mortar) Composites.
An experimental investigation on partially PBO (short of Polyparaphenylenebenzobisthiazole) FRCM (Fiber Reinforced Cementitious Mortar) confined clay brick masonry columns has been conducted. Ten small-scale specimens measuring 445 mm high with a square cross-section of the 250 mm side have been tested under monotonic axial loading until collapse. Two columns were unconfined, while the remaining ones were confined with single-layer PBO FRCM jackets varying the geometric configuration along their height. The vertical spacing ratio sf'/sf, being sf' and sf the center-to-center and the net spacings between two consecutive jackets, respectively, was considered as the key parameter of the confinement configuration. The failure modes, stress-strain curves and peak axial stress and strain values are reported. The experimental results have been compared to the predictions of models found in the Italian guidelines CNR DT 215/2018 and the American ACI 549-R20 standards. The main aspects analyzed involved (i) the evaluation of the effectiveness of partial confinement on the mechanical response of columns, (ii) the definition of the mechanical and geometrical parameters that influence the structural response of partially confined columns, and (iii) the development of appropriate analytical models for the prediction of the resisting capacity of masonry columns partially confined with PBO FRCM.


New developments in intrauterine device use: focus on the US.
Many more women in the US today rely upon intrauterine devices (IUDs) than in the past. This increased utilization may have substantially contributed to the decline in the percentage of unintended pregnancies in the US. Evidence-based practices have increased the number of women who are medically eligible for IUDs and have enabled more rapid access to the methods. Many women enjoy freedom to use IUDs without cost, but for many the impact of the Affordable Care Act has yet to be realized. Currently, there are three hormonal IUDs and one copper IUD available in the US. Each IUD is extremely effective, convenient, and safe. The newer IUDs have been tested in populations not usually included in clinical trials and provide reassuring answers to older concerns about IUD use in these women, including information about expulsion, infection, and discontinuation. On the other hand, larger surveillance studies have provided new estimates about the risks of complications such as perforation, especially in postpartum and breastfeeding women. This article summarizes significant features of each IUD and provides a summary of the differences to aid clinicians in the US and other countries in advising women about IUD choices.


[Roundworm infection (Toxocara and Toxascaris) in dogs in the Netherlands (author's transl)].
The incidence of roundworm infections was determined by examination of the faeces in a total number of 544 adult dogs in the Netherlands during the period from 1972 to 1977. The incidence of roundworm infections varied from 13 to 34 per cent (average 22.9 per cent) during this period, from 2 to 31 per cent (average 14.5 per cent) for Toxocara canis infections, from 8 to 15 per cent (average 11.2 per cent) for Toxascaris leonina infections and from 0 to 11 per cent (average 2.8 per cent) for combined T. canis and T. leonina infections.


Laser acquisition experimental demonstration for space gravitational wave detection missions.
The laser acquisition-pointing technique is one of the most important techniques for space gravitational wave detection missions, like the Taiji program and the LISA (Laser Interferometer Space Antenna) program. The laser acquisition system suppresses the laser deviation angle to 1 µrad at the receiving aperture. Corresponding to 80 times of telescope magnification, the acquisition accuracy should reach 80 µrad at the acquisition camera. In order to verify the feasibility of the laser acquisition scheme, a laser acquisition ground simulation experimental system is designed and constructed. The experimental system simulates the actual acquisition process of the Taiji from three aspects: optical path, acquisition accuracy and acquisition scanning process. In the experiment, the coupling between the laser acquisition system and the laser pointing system is considered by introducing the DWS (Differential Wave-front Sensing) technique to calibrate the reference position of the acquisition camera and read out the acquisition precision. Due to limited beam propagation distance in the ground experiment, the in-flat top properties of the transmitting beam will greatly affect the acquisition precision. Based on the analysis of the influence, an improved acquisition ground simulation scheme is introduced. The experimental results indicate that the experimental system can achieve the acquisition accuracy of sub-10 µrad magnitude at the acquisition camera. The experimental system realizes methodological demonstration of the acquisition scheme. The results offer the experimental foundation and theoretical basis for the acquisition system of the Taiji/LISA program.


The mitogenome of Paphia euglypta (Bivalvia: Veneridae) and comparative mitogenomic analyses of three venerids.
Extraordinary variation has been found in mitochondrial (mt) genome inheritance, gene content and arrangement among bivalves. However, only few bivalve mt genomes have been comparatively analyzed to infer their evolutionary scenarios. In this study, the complete mt genome of the venerid Paphia euglypta (Bivalvia: Veneridae) was firstly studied and, secondly, it was comparatively analyzed with other venerids (e.g., Venerupis philippinarum and Meretrix petechialis) to better understand the mt genome evolution within a family. Though several common features such as the AT content, codon usage of protein-coding genes, and AT/GC skew are shared by the three venerids, a high level of variability is observed in genome size, gene content, gene order, arrangements and primary sequence of nucleotides or amino acids. Most of the gene rearrangement can be explained by the "tandem duplication and random loss" model. From the observed rearrangement patterns, we speculate that block interchange between adjacent genes may be common in the evolution of mt genomes in venerids. Furthermore, this study presents several new findings in mt genome annotation of V. philippinarum and M. petechialis, and hence we have reannotated the genome of these two species as: (1) the ORF of the formerly annotated cox2 gene in V. philippinarum is deduced by using a truncated "T" codon and a second cox2 gene is identified; (2) the trnS-AGN gene is identified and marked in the mt genome of both venerids. Thus, this study demonstrated a high variability of mt genomes in the Veneridae, and showed the importance of comparative mt genome analysis to interpret the evolution of the bivalve mt genome.


Epidemiology and risk factors for premature physeal closure in distal femur fractures.
Premature physeal closure (PPC) is a common and concerning complication to distal femoral fractures as the distal growth plate accounts for 70% of the growth of the femur. The literature is not unanimous in determining the risk factors of PPC, and the epidemiological characterization of these fractures is limited. Our aim was to calculate the population-based incidence and investigate risk factors for PPC in these fractures. In this register-based study, between 2014 and 2021, 70 children with distal femoral physeal fractures presented to our hospital. Demographic data, and fracture- and treatment-related details were collected using the Kids' Fracture Tool. A directed acyclic graph (DAG) was constructed to determine confounding factors used in the risk analysis. Physeal fractures of the distal femur occurred with an annual incidence of 6/105 children, and a resulting PPC occurred in 16/70 (23%) with an annual incidence of 1.3/105 children. In multivariable analysis, dislocation exceeding 10 mm was a risk factor for PPC (OR 6.3, CI 1.4-22). One-fourth of distal femoral physeal fractures developed PPC. Greater dislocation and higher injury energy were significant risk factors, whereas choice of fracture treatment was not an independent risk factor. All patients with PPC belonged in the age group 11-16 years.


Efficacy of motor imagery additional to motor-based therapy in the recovery of motor function of the upper limb in post-stroke individuals: a systematic review.
Background. Motor imagery (MI) consists of the mental simulation of repetitive movements with the intention of promoting the learning of a motor skill. It seems to be an additional useful tool for motor-based therapy to potentiate the rehabilitation of the upper limb function of post-stroke individuals. Objective. To investigate whether MI combined with motor-based therapy is effective in recovering motor deficits of upper limbs from post-stroke individuals. Method. A systematic review of the literature was performed in the PEDro, LILACS, Cochrane, SCOPUS, Medline/PubMed and SciELO databases. Randomized controlled trials (RCTs) investigating the efficacy of MI associated with motor-based therapy compared with isolated motor-based therapy were included. The included outcomes were gross motor function and functional activities of the upper limb of post-stroke individuals. The physiotherapy evidence database scale was applied for evaluation of methodological quality. Results. Four RCTs were included, with a total of 104 participants, with methodological quality varying from moderate to high. There was a statistically significant improvement in upper limb motor function in all studies. Gross motor function was higher in MI associated with motor-based therapy compared to controls, but only in one study there was superiority in the results of functional activities of the upper limb. Conclusion. There is evidence showing that MI associated with motor-based therapy is an effective tool in improving the motor function of upper limbs of post-stroke individuals. However, more studies are needed to establish criteria for frequency and duration of intervention, and what better type of MI should be used.


Dietary phylloquinone intakes and metabolic syndrome in US young adults.
The relationship between dietary intake of vitamin K and metabolic syndrome (MetS) has not been investigated previously. The aim of this study was to examine whether and to what extent vitamin K intake measured as phylloquinone is related to MetS. We performed a cross-sectional analysis on data from 5800 adults aged 20 to 45 years who participated in the National Health and Nutrition Examination Survey (NHANES) 1999-2004. MetS was defined according to Adult Treatment Panel III criteria. Dietary phylloquinone intakes were obtained from 24-hour dietary recall. Prevalence and odds ratios (OR) of MetS and its components were assessed by quartiles of dietary phylloquinone intake. The lowest prevalence of MetS and its 5 components was observed in individuals with the highest phylloquinone intake. The prevalence of low high-density lipoprotein cholesterol (HDL) and elevated blood pressure progressively decreased with increasing phylloquinone intake (p < 0.05 for trend). HDL and C-reactive protein (CRP) levels improved gradually with increasing dietary phylloquinone intake (p < 0.05 for trend). In general, participants who had MetS or its element consumed less phylloquinone from diet compared those who did not. In comparison with the lowest phylloquinone intake quartile, the highest quartile of intake was associated with significantly reduced risks of low HDL level, hypertriglyceridemia, and hyperglycemia after adjustment was made for various nondietary confounding factors (OR, 0.73, 95% confidence interval [CI], 0.45-0.98; OR, 0.51, 95% CI, 0.25-0.97; and OR, 0.18, 95% CI, 0.05-0.73, respectively). Only the association between hyperglycemia and phylloquinone intake remained significant after further adjustment for dietary confounders (OR, 0.18, 95% CI, 0.05-0.73). Mean reported dietary phylloquinone intakes suggested that most US young adults consume an insufficient amount of vitamin K from their diet. A high intake of phylloquinone may favorably affect MetS or its components, probably through an overall more heart-healthy dietary pattern. The pathogenesis of MetS is profoundly complex and may involve other factors and/or mechanisms, in addition to vitamin K nutriture. Although our data suggest a potential role of vitamin K in MetS, the biological mechanisms underlying the observed associations must be elucidated.


Vitamin D and Demyelinating Diseases: Neuromyelitis Optica (NMO) and Multiple Sclerosis (MS).
Vitamin D deficiency is prevalent in all ages regardless of climate or geographical location and evidence is emerging that the incidence of autoimmune diseases is increasing worldwide. Women make up a large proportion of autoimmune disease diagnoses, underscoring the importance of fully elucidating the complex synergistic relationships between estrogens and vitamin D. Vitamin D receptor-activating drugs appear to enhance remyelination in patients diagnosed with multiple sclerosis (MS) and other demyelinating diseases such as neuromyelitis optica (NMO). This review is intended to update health practitioners about the potential role of vitamin D deficiency demyelination and to motivate future research on dietary recommendations for vitamin D in preventing and treating demyel1nating diseases.


Calcium effect on the membrane preparation of segmented poly(ether/urethane/amide) (PEUN) as a biomedical material.
Poly(ether/urethane/amide) (PEUN), a segmented polyurethane, was characterized concerning phase relationship, viscosity in solution, hydraulic permeability, mechanical properties, and in vivo biocompatibility with tissue and blood. PEUN was dissolved at the highest concentration of 0.5% in N,N-dimethylformamide (DMF). Addition of calcium chloride at concentrations up to 3.1% progressively increased the solubility of PEUN in DMF PEUN2 membrane was prepared by casting from mixtures of PEUN, 3% calcium chloride, and DMF, from which calcium chloride was sufficiently removed. The PEUN2 membrane thus obtained was compared with PEUN membrane which was prepared by casting from DMF solution without the addition of calcium chloride. The water permeability across PEUN2 membrane was higher than that across PEUN membrane. PEUN2 membrane in the swollen state exhibited a lower tensile modulus and much greater elastic property than PEUN membrane. Tissue compatibility of PEUN2 membrane was better than that of PEUN membrane. Thromboresistance of PEUN membrane was good, while PEUN2-coated surface was thrombogenic to some extent in vivo. Our characterization suggested that PEUN2 membrane is more hydrophilic than PEUN membrane, possibly because of the assembly of polar groups on the segments of PEUN molecules which show affinity to calcium chloride in membrane processing.


Effect of irradiation on DNA synthesis, NBN gene expression and chromosomal stability in cells with NBN mutations.
The NBN gene product is part of the MRE11/RAD50/NBN complex, which plays an essential role in genomic stability. In the study we try to answer the question what is the effect of irradiation on DNA synthesis, NBN gene expression and chromosomal stability in cells with homozygous c.657-661del, and heterozygous c.657-661del, p.I171V and p.R215W NBN gene mutations. Immortalized B-lymphocytes with NBN gene mutations were X-ray irradiated at doses of 1, 2, 5 and 8 Gy/min. Radioresistant DNA synthesis rate and the percentage of cells in phase S was analyzed by 3H thymidine and BrdU incorporation assays. NBN gene expression was quantified by real-time PCR with TaqMan fluorescent probe. Increasing the irradiation dose resulted in gradual decrease of 3H thymidine incorporation in all cells, but significantly only in homo- and heterozygous c.657-661del cells (p-values < 0.0001). After irradiation the relative expression of NBN was significantly higher in homozygous c.657-661del and heterozygous p.R215W cells as compared to heterozygous c.657-661del, p.I171V and control cells (p < 0.01). All cells with NBN gene mutations showed significantly higher total number of chromosomal aberrations per metaphase as compared to control cells, with the highest number of aberrations in homozygous c.657-661del cells (p < 0.001). The results obtained indicate that homozygous c.657-661del mutation affects cell sensitivity to irradiation. Moreover, homozygous variant is associated with disturbance in the activation of cell cycle checkpoints and with defects in DNA repair. In turn, heterozygous c.657-661del, p.R215W and p.I171V mutations do not substantially alter the radiosensitivity.


Measuring anterior loop length of the inferior alveolar nerve to estimate safe zone in implant planning: A CBCT study in a Malaysian population.
The inferior alveolar nerve (IAN) frequently loops backward before exiting from the mental foramen and spreads several millimeters medially to the foramen. Implant placement in this area may damage the nerve if the anterior loop area is not carefully identified in a radiographic or computed tomography (CT) evaluation. The purpose of this observational study was to measure the prevalence of the presence of the anterior loop and to estimate sex and ethnicity-related variations in anterior loop length in the Malaysian population. A total of 100 cone beam computed tomography (CBCT) Digital Imaging and Communications in Medicine (DICOM) files were selected from a pool of 810 ongoing or completed patients in 3 different ethnic groups: Malay (33), Indian (33), and Chinese (34). The DICOM data were imported into commercial software. The IAN was traced with software along with the anterior loop and part of the incisive nerve. The vertical length of the nerve was estimated from the canal to the opening of the mental foramen from the cross-sectional view and translated to the panoramic view. Measurement was made from this point to the most anterior point of the anterior loop by following the trajectory of the nerve and was repeated on the opposite side. A 2-way mixed analysis of variance (ANOVA) test was carried out to evaluate the sex- and ethnicity-related variations (α=.05). The anterior loop was present in 94% of the 100 participants. Overall anterior loop length (AnLL) ranged between 0.73 and 7.99 mm with a mean length of 3.69 ±1.75 mm on the left side and 3.85 ±1.73 mm on the right side. Among all participants, no statistically significant differences were found between the left and right sides of the mandible (P=.379). Overall, no significant main effect of ethnicity (P=.869) or sex (P=.576) was found on AnLL measurements. Also, with multiple comparisons, no significant effect was found between each pair of ethnic groups. Men in all 3 ethnic groups had greater AnLL than women. The anterior loop was present in 94% of the 100 participants among the 3 major ethnic groups of Malaysia. Overall AnLL ranged between 0.73 and 7.99 mm and mean lengths of 3.69 ±1.75 mm on the left side and 3.85 ±1.73 mm on the right side, with no significant ethnicity- or sex-related variations.


Evaluation of Biofilm Formation in Candida tropicalis Using a Silicone-Based Platform with Synthetic Urine Medium.
Molecular mechanisms of biofilm formation in Candida tropicalis and current methods for biofilm analyses in this fungal pathogen are limited. (2) Methods: Biofilm biomass and crystal violet staining of the wild-type and each gene mutant strain of C. tropicalis were evaluated on silicone under synthetic urine culture conditions. (3) Results: Seven media were tested to compare the effects on biofilm growth with or without silicone. Results showed that biofilm cells of C. tropicalis were unable to form firm biofilms on the bottom of 12-well polystyrene plates. However, on a silicone-based platform, Roswell Park Memorial Institute 1640 (RPMI 1640), yeast nitrogen base (YNB) + 1% glucose, and synthetic urine media were able to induce strong biofilm growth. In particular, replacement of Spider medium with synthetic urine in the adherence step and the developmental stage is necessary to gain remarkably increased biofilms. Interestingly, unlike Candida albicans, the C. tropicalis ROB1 deletion strain but not the other five biofilm-associated mutants did not cause a significant reduction in biofilm formation, suggesting that the biofilm regulatory circuits of the two species are divergent. (4) Conclusions: This system for C. tropicalis biofilm analyses will become a useful tool to unveil the biofilm regulatory network in C. tropicalis.


An evaluation of the clinical pathologic findings in experimentally induced urinary bladder rupture in pre-ruminant calves.
The purpose of this project was to study the biochemical abnormalities that develop over time in preruminant calves with experimentally induced uroperitoneum. Uroperitoneum was produced by incising the bladder via a standing left flank laparotomy. Serum and peritoneal concentrations sodium, chloride, potassium, phosphate and creatinine were determined at 0, 2, 4, 8, 24, and 40 h. Serum creatinine concentration was increased by 8 h post-bladder rupture. Peritoneal concentrations of potassium and phosphate were significantly elevated 2 h after bladder rupture and peritoneal creatinine was significantly elevated by 4 h. Serum to peritoneal fluid ratios for potassium, phosphate and creatinine exceeded 2:1 within 2 h of bladder rupture. Pre-ruminant calves with experimentally induced uroperitoneum did not become hyperkalemic during the 40 h experiment.


[The pharmacogenomics of CFH Y402H and wet age-related macular degeneration].
Age-related macular degeneration(AMD) is one of the main leading causes of irreversible vision damage in patients over 50 years old. Genetic factors play an important role in the occurrence and development of AMD. Since the significant correlation between complement factor H (CFH) gene and AMD was found, the pharmacogenomics of CFH polymorphism was paid close attention by academic circles. Among which, studies concerning CFH Y402H were more deeply. Studies have found CFH Y402H genotypes might lead to differences toward the outcome of PDT and anti-VEGF treatment. In this article, we review the researches on the pharmacogenomics of CFH Y402H in wet AMD treatment. (Chin J Ophthalmol, 2017, 53: 144-147).


Extraordinary Strengthening Effect of Carbon Nanotubes in Metal-Matrix Nanocomposites Processed by Molecular-Level Mixing.
Carbon-nanotube-reinforced Cu matrix nanocomposites have been fabricated by molecular-level mixing of functionalized carbon nanotubes (CNTs) with Cu ions, followed by spark plasma sintering. The compressive strengths and Young's moduli of CNT-reinforced nanocomposites are considerably higher than those of the Cu matrix due to the homogeneously dispersed CNTs embedded in the Cu matrix.


Setting the research agenda for living with and beyond cancer with comorbid illness: reflections on a research prioritisation exercise.
People living with and beyond cancer are more likely to have comorbid conditions and poorer mental and physical health, but there is a dearth of in-depth research exploring the psychosocial needs of people experiencing cancer and comorbid chronic conditions. A patient partnership approach to research prioritisation and planning can ensure outcomes meaningful to those affected and can inform policy and practice accordingly, but can be challenging. We aimed to inform priorities for qualitative inquiry into the experiences and support needs of people living with and beyond cancer with comorbid illness using a partnership approach. A three-step process including a patient workshop to develop a consultation document, online consultation with patients, and academic expert consultation was carried out. The research prioritisation process was also appraised and reflected upon. Six people attended the workshop, ten responded online and eight academic experts commented on the consultation document. Five key priorities were identified for exploration in subsequent qualitative studies, including the diagnostic journey, the burden of symptoms, managing medications, addressing the needs of informal carers, and service provision. Limitations of patient involvement and reflections on procedural ethics, and the challenge of making measurable differences to patient outcomes were discussed. Findings from this research prioritisation exercise will inform planned qualitative work to explore patients' experiences of living with and beyond cancer with comorbid illness. Including patient partners in the research prioritisation process adds focus and relevance, and feeds into future work and recommendations to improve health and social care for this group of patients. Reflections on the consultation process contribute to a broadening of understanding the field of patient involvement.


[Pathogenicity of avian adenoviruses in chickens].
In the last years avian adenoviruses have caused diseases with similar symptoms and high losses in four countries. The causative viruses could be grouped by cross-neutralization tests and restriction enzyme analysis into four serotypes. Within the serotypes there exist strains with pathogenic properties as well as strains without pathogenicity. Epidemiologic investigations demonstrated that not only immunosuppression or co-infections produce diseases after adenovirus infections. Vertical transmission of the virus from parent stocks and deficiency of specific maternal antibodies in the chickens contribute to the development of diseases. Parent stocks, which were infected with different serotypes of adenovirus during their rearing period, produce chickens with maternal antibodies. These chickens are protected against early infections with avian adenoviruses.


Automated external defibrillators: design considerations.
Biphasic defibrillation waveforms are now the standard of care in clinical use for defibrillation with implantable cardioverter-defibrillators (ICDs), due to the superior performance demonstrated over that of comparable monophasic waveforms. To better understand these significantly different outcomes, ICD research has developed cardiac cell response models to defibrillation. Waveform design criteria have been derived from these first principles and have been applied to monophasic and biphasic waveforms to optimize their parameters. These principles-based design criteria have produced significant improvements over the current art of waveforms. Monophasic defibrillation waveforms remain the standard of care in clinical use for transthoracic defibrillation. Waveform design has not yet been influenced by the important gains made in ICD research. The limitations of present transthoracic waveforms may be due in part to a lack of application of these design principles to determine optimal waveform characteristics. To overcome these limitations, design principles based on cell response have recently been developed for external defibrillation waveforms. The transthoracic model incorporates elements into a cell response model that extends it to external defibrillation. External waveform design principles demonstrate reductions in capacitance, voltage, duration, and delivered energy. Therefore, design principles based on cardiac electrophysiology may provide a means to significantly reduce the energy required for safe and efficacious external defibrillation. Footnotes, formulae, and figures augment this presentation in order to clarify the defibrillation waveform theory.


The Screening of Combinatorial Peptide Libraries for Targeting Key Molecules or Protein-Protein Interactions in the NF-κB Pathway.
Peptides are emerging as an increasingly dependable class of therapeutics in the treatment of cancer and metabolic and cardiovascular diseases, which are all areas of high interest to the pharmaceutical industry. The global market for peptide therapeutics was valued at about 25 billion USD in 2018 and is estimated to reach 57.2 billion USD by the end of 2027. Here, we describe a method for the screening and deconvolution of combinatorial peptide libraries to discover compounds that target discrete signaling components of the NF-κB pathway. Recently, we used this approach to specifically disrupt the interaction between the JNK-activating kinase, MKK7, and the NF-κB-regulated antiapoptotic factor, GADD45β, in multiple myeloma (MM). We showed that the GADD45β/MKK7 complex is a functionally critical survival module downstream of NF-κB in MM cells and as such provides an attractive therapeutic target to selectively inhibit NF-κB antiapoptotic signaling in cancer cells. By integrating the library screening and deconvolution methods described here with a rational chemical optimization strategy, we developed the first-in-class GADD45β/MKK7 inhibitor, DTP3 (a D-tripeptide), which is now being trialed in MM and diffuse large B-cell lymphoma (DLBCL) patients. The same drug discovery approach may be generally applied to therapeutically target other key components of the NF-κB pathway in cancers beyond MM and DLBCL, as well as in non-malignant NF-κB-driven diseases.


Effectiveness of intervention strategies exclusively targeting reductions in children's sedentary time: a systematic review of the literature.
An increasing number of interventions targeting sedentary behaviour in children have emerged in recent years. Recently published reviews included sedentary behaviour and physical activity interventions. This review critically summarizes evidence on the effectiveness of intervention strategies that exclusively targeted reducing sedentary time in children and adolescents. We performed a systematic literature search in Pubmed, Embase and the Cochrane Library through November 2015. Two independent reviewers selected eligible studies, extracted relevant data and rated the methodological quality using the assessment tool for quantitative studies. We included 21 intervention studies, of which 8 studies scored moderate on methodological quality and 13 studies scored weak. Four out of eight moderate quality studies reported significant beneficial intervention effects.Although descriptions of intervention strategies were not always clearly reported, we identified encouragement of a TV turnoff week and implementing standing desks in classrooms as promising strategies. Due to a lack of high quality studies and inconsistent findings, we found no convincing evidence for the effectiveness of existing interventions targeting solely sedentary behaviour. We recommend that future studies apply mediation analyses to explore which strategies are most effective. Furthermore, to increase the effectiveness of interventions, knowledge of children's motives to engage in sedentary behavior is required, as well as their opinion on potentially effective intervention strategies.


Musculoskeletal injuries and pain in dancers: a systematic review update.
The objective of this study was to assemble and synthesize the best available literature from 2004 to 2008 on musculoskeletal injury and pain in dancers. MEDLINE and CINAHL were the primary sources of data. Indexed terms such as dance, dancer, dancing, athletic injuries, occupational injuries, sprains and strains, musculoskeletal diseases, bone density, menstruation disturbances, and eating disorders were used to search the databases. Citations were screened for relevance using a priori criteria, and relevant studies were critically reviewed for scientific merit by the best-evidence synthesis method. After screening, 19 articles were found to be scientifically admissible. Data from accepted studies were abstracted into evidence tables relating to: prevalence and associated factors; incidence and risk factors; intervention; and injury characteristics and prognosis of musculoskeletal injury and pain in dancers. Principal findings included: a high prevalence and incidence of lower extremity, hip and back injuries; preliminary evidence that psychosocial and psychological issues such as stress and coping strategies affect injury frequency and duration; history of a previous lateral ankle sprain is associated with an increased risk of ankle sprain in the contralateral ankle in dance students; fatigue may play a role in ACL injury in dancers; acute hamstring strains in dancers affect tendon more than muscle tissue, often resulting in prolonged absence from dance. It is concluded that, while there are positive developments in the literature on the epidemiology, diagnosis, prognosis, treatment, and prevention of MSK injuries and pain in dancers, much room for improvement remains. Suggestions for future research are offered.


Ceramo-Metal Crown or Cad-Cam Rehabilitation: Patient and Practitioner Appraisal.
Crowns produced using CAD-CAM technology must be evaluated so they can be integrated in the dentist's therapeutic arsenal. To this end, an evaluation tool for the fixed element units was developed and tested in a randomized cross-over pilot study. At a hospital centre, 10 single crowns from the same dental preparation and produced using CEREC technology were compared to Ceramo-Metal Crowns produced using a conventional procedure. Practitioners generally evaluated CEREC crowns more positively, corroborating the subjects' preference for these crowns. The CEREC technology used in a hospital setting meets the requirements of both patients and practitioners.


[Phosphodiesterase type 5 inhibitors for pulmonary arterial hypertension].
The therapeutic effects of phosphodiesterase type 5 inhibitors in patients with pulmonary arterial hypertension (PAH) were reviewed. A double-blind, placebo-controlled study named SUPER-1 showed that sildenafil improved exercise capacity, WHO functional class, hemodynamics, and quality of life. Two randomized, double-blind, crossover studies, showed that sildenafil improved exercise tolerance and quality of life, and reduced estimated pulmonary artery systolic pressure. The dose independent effects of sildenafil on PAH are controversial. There are few case-reports that show vardenafil and tadalafil have benefits in PAH patients. A double-blind study of tadalafil in PAH patients is ongoing.


Contributions of the Ah receptor to bilirubin homeostasis and its antioxidative and atheroprotective functions.
Abstract The homeostasis and atheroprotective function of bilirubin could be an appealing model to investigate one of the many physiologic functions of the human aryl hydrocarbon receptor (AhR). Several clinical and epidemiological studies have been carried out on key enzymes generating and eliminating bilirubin (heme oxygenase-1 and UDP-glucuronosyltransferase UGT1A1, respectively) and their regulation by the AhR. Studies with AhR-deficient mice strongly suggest a role of the AhR in vascular biology. Atherosclerosis, a major cause of premature death, is initiated by pro-oxidative insults of the vascular endothelium. The strong antioxidant and activator of AhR bilirubin is generated in vascular endothelial cells, smooth muscles and macrophages. It acts mostly in the lipid environment, thereby complementing other antioxidants such as glutathione which act mostly on water-soluble proteins. In conclusion, the atheroprotective functions of bilirubin might not only provide models to study physiologic functions of the human AhR but also provide opportunities to improve prevention and treatment of a major life-threatening disease.


[Intramuscular vascular malformations as a differential diagnosis of focal myositis].
Focal myositis constitutes an original and rare pathological entity, characterized by a localized inflammation within skeletal muscle, presenting as a soft tissue painful tumefaction. Diagnosis requires histological confirmation because of its non-specific clinical feature and the numerous differential diagnoses. We report a 27 year-old man who presented with suggestive symptoms of focal myositis. MR imaging and echography were compatible with this diagnosis but also demonstrated the existence of a vascular component within the tumefaction. The diagnosis of a benign vascular malformation with intramuscular development was made by a surgically guided biopsy. Vascular malformations are histologically heterogeneous with extremely variable clinical expressions. When they develop within skeletal muscle, they may mimic focal myositis. Hence, their diagnosis has to be evoked before performing muscle biopsy, because of the potential hemorrhagic risk.


Ephrin-mediated cis-attenuation of Eph receptor signaling is essential for spinal motor axon guidance.
Axon guidance receptors guide neuronal growth cones by binding in trans to axon guidance ligands in the developing nervous system. Some ligands are coexpressed in cis with their receptors, raising the question of the relative contribution of cis and trans interactions to axon guidance. Spinal motor axons use Eph receptors to select a limb trajectory in response to trans ephrins, while expressing ephrins in cis. We show that changes in motor neuron ephrin expression result in trajectory selection defects mirrored by changes in growth cone sensitivity to ephrins in vitro, arguing for ephrin cis-attenuation of Eph function. Furthermore, the relative contribution of trans-signaling and cis-attenuation is influenced by the subcellular distribution of ephrins to membrane patches containing Eph receptors. Thus, growth cone ephrins are essential for axon guidance in vivo and the balance between cis and trans modes of axon guidance ligand-receptor interaction contributes to the diversity of axon guidance signaling responses.


Loss of glial fibrillary acidic protein (GFAP) impairs Schwann cell proliferation and delays nerve regeneration after damage.
Axonal loss causes disabling and permanent deficits in many peripheral neuropathies, and may result from inefficient nerve regeneration due to a defective relationship between Schwann cells, axons and the extracellular matrix. These interactions are mediated by surface receptors and transduced by cytoskeletal molecules. We investigated whether peripheral nerve regeneration is perturbed in mice that lack glial fibrillary acidic protein (GFAP), a Schwann-cell-specific cytoskeleton constituent upregulated after damage. Peripheral nerves develop and function normally in GFAP-null mice. However, axonal regeneration after damage was delayed. Mutant Schwann cells maintained the ability to dedifferentiate but showed defective proliferation, a key event for successful nerve regeneration. We also showed that GFAP and the other Schwann-cell-intermediate filament vimentin physically interact in two distinct signaling pathways involved in proliferation and nerve regeneration. GFAP binds integrin alphavbeta8, which initiates mitotic signals soon after damage by interacting with fibrin. Consistently, ERK phosphorylation was reduced in crushed GFAP-null nerves. Vimentin instead binds integrin alpha5beta1, which regulates proliferation and differentiation later in regeneration, and may compensate for the absence of GFAP in mutant mice. GFAP might contribute to form macro-complexes to initiate mitogenic and differentiating signaling for efficient nerve regeneration.


Structure of a functional amyloid protein subunit computed using sequence variation.
Functional amyloid fibers, called curli, play a critical role in adhesion and invasion of many bacteria. Unlike pathological amyloids, curli structures are formed by polypeptide sequences whose amyloid structure has been selected for during evolution. This important distinction provides us with an opportunity to obtain structural insights from an unexpected source: the covariation of amino acids in sequences of different curli proteins. We used recently developed methods to extract amino acid contacts from a multiple sequence alignment of homologues of the curli subunit protein, CsgA. Together with an efficient force field, these contacts allow us to determine structural models of CsgA. We find that CsgA forms a β-helical structure, where each turn corresponds to previously identified repeat sequences in CsgA. The proposed structure is validated by previously measured solid-state NMR, electron microscopy, and X-ray diffraction data and agrees with an earlier proposed model derived by complementary means.


Oscillations of IgM antibody affinity at the level of single immunocytes.
IgM antibody affinity was measured by hemolytic plaque inhibition assays on spleen cells from mice immunized with a single injection of DNP-dextran. Maturation of affinity was found to occur with time after 1 to 1000 microgram of immunogen and to be characterized by rapid oscillations independent from changes inFC number/spleen and in antibody secretion rate. Analysis of affinity heterogeneity showed that such oscillations occur in higher affinity PFC subpopulations. The origin of affinity oscillations was discussed in terms of interactions among antigen and the elements of the immune network.


Endotoxinaemia in sickle cell disease.
Fifty-nine children with sickle cell anaemia (HbSS) or associated haemoglobinopathies were studied prospectively using a chromogenic Limulus amoebocyte lysate assay to detect circulating endotoxin. The 41 children with HbSS (mean age 8 years 9 months) had more serious disease than the 18 with HbSC disease (n = 14) or HbS-beta-thalassaemia (n = 4) (mean age 7 years 2 months), with a greater degree of splenomegaly, lower haemoglobin, and higher white cell counts, platelet counts and bilirubin values (P less than 0.05 for all). Twenty-nine children with HbSS had evidence of poor reticuloendothelial function, with red cell pitting of greater than or equal to 2%. Three of these 29 had low levels of endotoxin in plasma (0.12-0.24 endotoxin units (EU)/ml); two were clinically well, one had a painful crisis. Eight of 18 children with other sickle haemoglobinopathies had greater than or equal to 2% pitted red cells; none was endotoxinaemic. Therefore, in 37 patients with reticuloendothelial dysfunction, three were endotoxinaemic; all had sickle cell anaemia. Although not statistically significant, this suggests that endotoxinaemia may occur predominantly in patients with reticuloendothelial dysfunction, and is compatible with the hypothesis that systemic endotoxinaemia can derive from the intestine especially when reticuloendothelial function is depressed.


The influence of pH on the convertogenic activity of plant phenolics.
The genotoxicity of plant phenolics, including pyrogallol, gallic acid, resorcinol and catechin, and a water extract and tannin fraction of betel nut (Areca catechu) was examined at pH levels ranging from 5 to 10. Strain D7 of Saccharomyces cerevisiae was used since the cells can withstand a wide range of pH levels without any loss of viability. At alkaline pH ranges, the examined phenolics and betel nut extracts induced mitotic conversion, whereas they lacked this capacity at acid pH levels. This phenomenon may be due to the rapid autoxidation of phenolics under alkaline conditions, which leads to the generation of H2O2 and free radicals. The results indicate that plant phenolics may pose a genotoxic hazard during chewing of lime-containing betel quid and tobacco which causes the salivary pH to rise above 8.


3D evaluation of composite resin restoration at practical training using swept-source optical coherence tomography (SS-OCT).
Internal adaptation of restorations to the cavity wall is one of the important topics in clinical dentistry. The purpose of this study was to investigate the possibility to utilize the non-invasive tomographic imaging system for teaching the importance of cavity adaptation at dental school pre-clinical training. Swept-source optical coherence tomography (SS-OCT) was used for detection of marginal and internal defects in the composite resin restorations as an educational device. Class 1 and Class 2 composite restorations to melamine resin molar tooth were assigned to the students and prepared during the skill test, and SS-OCT imaging was performed to evaluate students' works. SS-OCT could detect the internal gaps and voids within the restorations in tomography images synthesized based on the backscatter signal from within the restoration. It is suggested that the SS-OCT is promising diagnostic modality, as well as educational imaging device for the detection of internal gaps in adhesive restorations.


Value of Dynamic Contrast-enhanced and Diffusion-weighted MR Imaging in the Detection of Pathologic Complete Response in Cervical Cancer after Neoadjuvant Therapy: A Retrospective Observational Study.
Purpose To evaluate the association between dynamic contrast material-enhanced (DCE) and diffusion-weighted (DW) magnetic resonance (MR) imaging with pathologic complete response after preoperative combined chemotherapy and radiation therapy for cervical carcinoma and evaluate the risk of local recurrence. Materials and Methods The institutional ethics committee approved the study and waived the requirement to obtain informed consent. The study comprised 52 patients with locally advanced carcinoma, treated first with combined chemotherapy and radiation therapy, who underwent MR imaging before final surgery between June 2011 and July 2015. Three radiologists evaluated conventional, DW, and DCE MR images to identify a complete response. The standard of reference was surgical-pathologic findings. Results An initial increase in signal intensity on DCE MR images that was greater in the cervical lesion than in the myometrium was defined as time-signal intensity curve type B and showed a significant association with incomplete response (P = .0004). DCE MR imaging parameters (ie, maximum slope enhancement, area under the gadolinium concentration-time curve during the first 90 seconds after gadolinium injection [AUGC90], and volume transfer constant [Ktrans]) and a low signal intensity on apparent diffusion coefficient (ADC) maps were significantly associated with an incomplete response (P = .027, P = .041, P = .037, and P = .032, respectively). A mean ADC of 0.0014 m2/sec or less (hazard ratio [HR] = 8.3), low ADC signal intensity (HR = 7.3), high signal intensity at DW imaging (HR = 7.1), and time-signal intensity curve type B (HR = 4.3) were associated with earlier recurrence (P < .05). Excellent agreement between readers was found for time-signal intensity curve analysis (κ > 0.9) and the following parameters: AUGC90, Ktrans, and maximum slope enhancement (intraclass correlation coefficient, >0.9). Conclusion DCE MR imaging parameters, especially the time-signal intensity curve, and DW imaging are associated with complete response and incomplete response and could potentially help oncologists with management decisions. Moreover, DCE and DW MR imaging could help oncologists accentuate the follow-up for patients with a high risk of local recurrence to assess for recurrence. © RSNA, 2017 Online supplemental material is available for this article.


Robot-assisted urologic procedures.
Surgical robotics, the result of the combined efforts of engineers, computer scientists, entrepreneurs, and surgeons, has enabled the surgeon to execute precise technical maneuvers while seated at a remote console. The capability to perform sophisticated surgical operations by means of a robot is today's reality. The combination of laparoscopy and robotics has the potential to enhance operative performance and the outcomes of laparoscopy, and expand the clinical application of laparoscopy while reducing patient morbidity. In this article, we review initial pioneering and laboratory research, early clinical investigations, and current clinical applications of robotics in urologic surgery.


Mathematical Modelling of Immune Parameters in the Evolution of Severe Dengue.
Aims. Predicting the risk of severity at an early stage in an individual patient will be invaluable in preventing morbidity and mortality caused by dengue. We hypothesized that such predictions are possible by analyzing multiple parameters using mathematical modeling. Methodology. Data from 11 adult patients with dengue fever (DF) and 25 patients with dengue hemorrhagic fever (DHF) were analyzed. Multivariate statistical analysis was performed to study the characteristics and interactions of parameters using dengue NS1 antigen levels, dengue IgG antibody levels, platelet counts, and lymphocyte counts. Fuzzy logic fundamentals were used to map the risk of developing severe forms of dengue. The cumulative effects of the parameters were incorporated using the Hamacher and the OWA operators. Results. The operator classified the patients according to the severity level during the time period of 96 hours to 120 hours after the onset of fever. The accuracy ranged from 53% to 89%. Conclusion. The results show a robust mathematical model that explains the evolution from dengue to its serious forms in individual patients. The model allows prediction of severe cases of dengue which could be useful for optimal management of patients during a dengue outbreak. Further analysis of the model may also deepen our understanding of the pathways towards severe illness.


Neuronal death during combined intermittent hypoxia/hypercapnia is due to mitochondrial dysfunction.
Breathing-disordered states, such as in obstructive sleep apnea, which are cyclical in nature, have been postulated to induce neurocognitive morbidity in both pediatric and adult populations. The oscillatory nature of intermittent hypoxia, especially when chronic, may mimic the paradigm of ischemia-reperfusion in that tissues and cells are exposed to episodes of low and high O(2) and this may lead to oxidant stress. Therefore, we decided to explore the potential contribution of oxidant stress in our intermittent hypoxia/hypercapnia animal model and the role that mitochondria might play in this stress. Neonatal mice were exposed to intermittent hypoxia/hypercapnia for 10 days and 2 wk. Combined intermittent hypoxia/hypercapnia led to a marked increase in apoptotic cell death in the cerebral cortex. Oxygen consumption studies in isolated mitochondria from intermittent hypoxia/hypercapnia-exposed brains demonstrated significant reductions in both state 4 and state 3 respiratory activities by approximately 60% and 75%, respectively. Electron paramagnetic resonance spectroscopy registered a significant increase in superoxide production during nonphosphorylating state 4 by 37%, although superoxide leakage during state 3 did not increase upon treatment. Neuronal superoxide-specific dihydroethidium oxidation was also greater in exposed animals. These studies indicate that intermittent hypoxia/hypercapnia leads to oxidative stress due to mitochondrial response within the mouse central nervous system.


Murine allergic rhinitis and nasal Th2 activation are mediated via TSLP- and IL-33-signaling pathways.
Thymic stromal lymphopoietin (TSLP) and IL-33 are epithelium-derived proallergic cytokines that contribute to allergic diseases. Although the involvement of TSLP in allergic rhinitis (AR) is suggested, the exact role of TSLP in AR is poorly understood. Furthermore, the relative contribution of TSLP and IL-33 in nasal allergic responses has not been described. In this study, we examined the roles of TSLP and IL-33 in AR by analyzing acute and chronic AR models. Acute AR mice were intraperitoneally immunized with ragweed, then intranasally challenged with ragweed pollen for four consecutive days. Chronic AR mice were nasally administrated ragweed pollen on consecutive days for 3 weeks. In both models, TSLP receptor (TSLPR)-deficient mice showed defective sneezing responses and reduced serum ragweed-specific IgE levels compared with wild-type (WT) mice. Analyses of bone-marrow chimeric mice demonstrated that hematopoietic cells were responsible for defective sneezing in TSLPR-deficient mice. In addition, FcεRI(+)-cell-specific TSLPR-deficient mice showed partial but significant reduction in sneezing responses. Of note, Th2 activation and nasal eosinophilia were comparable between WT and TSLPR-deficient mice. ST2- and IL-33-deficient mice showed defective Th2 activation and nasal eosinophilia to acute, but not chronic, ragweed exposure. TSLPR and ST2 double-deficient mice showed defective Th2 activation and nasal eosinophilia even after chronic ragweed exposure. These results demonstrate that TSLPR signaling is critical for the early phase response of AR by controlling the IgE-mast-cell/basophil pathway. The IL-33/ST2 pathway is central to nasal Th2 activation during acute allergen exposure, but both TSLPR and ST2 contribute to Th2 responses in chronically allergen-exposed mice.


Preeclampsia and maternal heart rate variability.
Maternal heart rate variability was evaluated by means of 24-hour Holter ECG monitoring in three groups of patients (15 preeclamptic, 15 women hospitalized due to other complications and 15 normal ambulatory pregnant women) in the 28th-33rd week of gestation. Heart rate variability was estimated by time and frequency domain measures. Patients with preeclampsia had significantly longer NN intervals during daytime compared to the other groups studied. With regard to frequency domain measures such as very-low-frequency, low-frequency and high-frequency power, the groups did not differ. Nor did they differ with regard to day and nighttime. We conclude that during pregnancy, the power of the maternal heart rate spectrum is markedly depressed, which affects the power of the method to separate normal pregnancies from pregnancies affected by preeclampsia.


Pigeons (Columba livia) are a suitable experimental model for Neospora caninum infection in birds.
Neospora caninum infections in chickens have been recently described by epidemiological and experimental approaches, and these birds may be considered natural intermediate hosts of the parasite. It has been postulated that other bird species might perform this role in wildlife as well. To better understand the sylvatic life cycle of N. caninum, further studies are required. In that sense, this work aimed to observe infection kinetics in pigeons experimentally infected with N. caninum. Experimental infections were conducted in parallel with a related protozoan, Toxoplasma gondii, which has been already described as able to infect pigeons in nature. Our results demonstrated that N. caninum disseminated through various tissues of this host and induced parasite-specific IgG seroconversion. Infection parameters were similar to that observed in the T. gondii infected group, although N. caninum-infected pigeons presented lower IgG titers during acute phase. The results herein described demonstrate that pigeons are a suitable model for N. caninum infection, considering that these data are in agreement with those observed in chickens experimentally infected with this parasite. As pigeons may be revealed as important reservoirs for N. caninum infection in nature, future studies are necessary to determine the real prevalence of this parasite in this and other birds in wildlife.


Hiccups as a Rare Presentation of Thyrotoxicosis Triaged by an Epidural Steroid Injection.
Thyrotoxicosis manifests when excess levels of thyroid hormone act on different tissues throughout the body. Excess hormone levels can be related to endogenous production or exogenous ingestion and can present differently in patients. It has been theorized that high levels of thyroxine can irritate the neuroanatomical hiccup center leading to persistent hiccups. Although extremely rare, physicians should be aware of this entity to allow for proper diagnosis and management. Here, we discuss a rare case of thyrotoxicosis after an epidural steroid injection presenting with intractable hiccups.


Locked nucleic acid (LNA) recognition of RNA: NMR solution structures of LNA:RNA hybrids.
Locked nucleic acids (LNAs) containing one or more 2'-O,4'-C-methylene-linked bicyclic ribonucleoside monomers possess a number of the prerequisites of an effective antisense oligonucleotide, e.g. unprecedented helical thermostability when hybridized with cognate RNA and DNA. To acquire a detailed understanding of the structural features of LNA giving rise to its remarkable properties, we have conducted structural studies by use of NMR spectroscopy and now report high-resolution structures of two LNA:RNA hybrids, the LNA strands being d(5'-CTGAT(L)ATGC-3') and d(5'-CT(L)GAT(L)AT(L)GC-3'), respectively, T(L) denoting a modified LNA monomer with a thymine base, along with the unmodified DNA:RNA hybrid. In the structures, the LNA nucleotides are positioned as to partake in base stacking and Watson-Crick base pairing, and with the inclusion of LNA nucleotides, we observe a progressive change in duplex geometry toward an A-like duplex structure. As such, with the inclusion of three LNA nucleotides, the hybrid adopts an almost canonical A-type duplex geometry, and thus it appears that the number of modifications has reached a saturation level with respect to structural changes, and that further incorporations would furnish only minute changes in the duplex structure. We attempt to rationalize the conformational steering induced by the LNA nucleotides by suggesting that the change in electronic density at the brim of the minor groove, introduced by the LNA modification, is causing an alteration of the pseudorotational profile of the 3'-flanking nucleotide, thus shifting this sugar equilibrium toward N-type conformation.


Exploring Key Physiological System Profiles at Rest and the Association with Depressive Symptoms in Autism Spectrum Disorder.
Depression is often associated with dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS). Individuals with autism spectrum disorder (ASD) may experience physiological dysregulation and psychological comorbidities; however, the extent to which the interactions between these systems predict internalizing symptoms in ASD has not been investigated. The study examined interactions with the HPA axis and ANS in 10-13-year-old children with ASD (n = 41) and typical development (TD; n = 46). The interrelated systems uniquely contributed to depressive symptoms in ASD above and beyond any system in isolation. A reciprocal, parasympathetic-dominant ANS was related to fewer affective symptoms in ASD. Findings highlight the importance of examining arousal across multiple systems to more precisely identify profiles associated with maladaptive psychiatric outcomes in ASD.


Healthy Aging in Times of Extreme Temperatures: Biomedical Approaches.
Climate extremes and rising energy prices present interconnected global health risks. Technical solutions can be supplemented with biomedical approaches to promote healthy longevity in hot and cold conditions. In summer, reducing basal metabolic rate through mild caloric restriction or CR mimetics, such as resveratrol, can potentially be used to lower body temperature. In winter, activating brown adipose tissue (BAT) for non-shivering thermogenesis and improved metabolic health can help adaptation to colder environments. Catechins found in green tea and in other food could be alternatives to drugs for these purposes. This review examines and discusses the biomedical evidence supporting the use of CR mimetics and BAT activators for health benefits amid increasingly extreme temperatures.


Inhibition of HDAC3 prevents diabetic cardiomyopathy in OVE26 mice via epigenetic regulation of DUSP5-ERK1/2 pathway.
Inhibition of total histone deacetylases (HDACs) was phenomenally associated with the prevention of diabetic cardiomyopathy (DCM). However, which specific HDAC plays the key role in DCM remains unclear. The present study was designed to determine whether DCM can be prevented by specific inhibition of HDAC3 and to elucidate the mechanisms by which inhibition of HDAC3 prevents DCM. Type 1 diabetes OVE26 and age-matched wild-type (WT) mice were given the selective HDAC3 inhibitor RGFP966 or vehicle for 3 months. These mice were then killed immediately or 3 months later for cardiac function and pathological examination. HDAC3 activity was significantly increased in the heart of diabetic mice. Administration of RGFP966 significantly prevented DCM, as evidenced by improved diabetes-induced cardiac dysfunction, hypertrophy, and fibrosis, along with diminished cardiac oxidative stress, inflammation, and insulin resistance, not only in the mice killed immediately or 3 months later following the 3-month treatment. Furthermore, phosphorylated extracellular signal-regulated kinases (ERK) 1/2, a well-known initiator of cardiac hypertrophy, was significantly increased, while dual specificity phosphatase 5 (DUSP5), an ERK1/2 nuclear phosphatase, was substantially decreased in diabetic hearts. Both of these changes were prevented by RGFP966. Chromatin immunoprecipitation (ChIP) assay showed that HDAC3 inhibition elevated histone H3 acetylation on the DUSP5 gene promoter at both two time points. These findings suggest that diabetes-activated HDAC3 inhibits DUSP5 expression through deacetylating histone H3 on the primer region of DUSP5 gene, leading to the derepression of ERK1/2 and the initiation of DCM. The present study indicates the potential application of HDAC3 inhibitor for the prevention of DCM.


Patient education and mind diversion in supportive care.
Cancer is a growing health problem worldwide. Common treatments include surgery, chemotherapy and radiation therapy. Systemic anti-cancer medications often result in an array of physical and psychological side effects. Supportive care assists patients with cancer in managing multidimensional symptoms that result from treatment or the illness itself. This review discusses supportive care and examines patient counselling and mind-diversion activities, which are safe and cost-effective strategies. Improving cancer patients' health and wellbeing should be encouraged in oncology nursing practice and by teaching students the knowledge and skills needed to provide supportive care.


Modulation of placental protein expression of OLR1: implication in pregnancy-related disorders or pathologies.
The lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (OLR1) is a newly described receptor for oxidatively modified LDL. The human pregnancy is associated with hyperlipidemia and oxidative stress. It has been reported that modification in maternal lipid profile can induce disturbance during pregnancy. In this study, we have evaluated the expression protein level of OLR1 in human term placenta of women having plasma cholesterol level lower to 7 mM or higher to 8 mM and women of gestational diabetes mellitus (GDM) by western blot analysis. The present study demonstrates that the maternal lipid profile is associated with placental protein expression of OLR1. A significant increase in the protein expression of OLR1 was observed in placenta of women with elevated plasmatic total cholesterol level (>8 mM). In addition, the placental protein expression of OLR1 is increased in mothers having the highest pre-pregnancy body mass index (BMI) and low (<7 mM) plasmatic total cholesterol level at term. Interestingly, the placental protein expression of OLR1 is increased in the presence of GDM pregnancies compared with normal lipids level pregnancies, without the modification of mRNA expression. In conclusion, placental OLR1 protein expression is associated with maternal lipid profile, pre-pregnancy BMI, and pathology of GDM.


Histological and parasitological distinctive findings in clinically-lesioned and normal-looking skin of dogs with different clinical stages of leishmaniosis.
Normal-looking skin of dogs with leishmaniosis frequently shows microscopic lesions along with the presence of Leishmania amastigotes. However, histological lesions with or without detection of amastigotes might not occur in less severe clinical cases. In addition, comparative studies between paired clinically-lesioned and normal-looking skin samples from dogs with different disease severity are lacking. The objective of this study was to compare histological and parasitological findings by Leishmania immunohistochemistry (IHC) and quantitative PCR (qPCR) on paired clinically-lesioned and normal-looking skin biopsies from 25 dogs with different clinical stages of leishmaniosis, 11 with stage I-mild disease (papular dermatitis) and 14 with stage II-III (ulcerative or exfoliative dermatitis). The study demonstrated microscopic lesions in 14 out of 25 (56%) samples from normal-looking skin biopsies. In those samples, perivascular to interstitial dermatitis composed by macrophages with lymphocytes and plasma cells was observed mainly in the superficial and mid-dermis. The intensity of the dermatitis was mild to moderate and always less prominent than in the clinically-lesioned skin. In normal-looking skin samples, the presence of parasites was detected by histology, IHC and qPCR in 5/25 (20%), 8/25 (32%) and 18/25 (72%), respectively. Leishmania was encountered in 11/25 (44%), 23/25 (92%) and 25/25 (100%) of clinically-lesioned skin samples by histology, IHC and qPCR, respectively. Normal-looking skin from dogs with stage I-mild disease was less frequently inflamed (P = 0.0172). Furthermore, Leishmania was more easily demonstrated by histology (P = 0.0464), IHC (P = 0.0421) or qPCR (P = 0.0068) in normal-looking skin of dogs with stage II-III-moderate to severe disease. In addition, in the latter group, there was a significantly higher parasite load studied by means of qPCR than in dogs with less severe disease (P = 0.043). Clinically-lesioned skin from dogs with stage I disease was more frequently characterised by the nodular to diffuse pattern and granuloma formation (P = 0.0166) and by a lower parasite load studied by means of qPCR (P = 0.043) compared with more diseased dogs. Normal-looking skin from dogs with stage I is less likely to present histological lesions as well as harbour the parasite when compared with dogs with moderate to severe leishmaniosis.


Delayed-onset cytomegalovirus infection is frequent after discontinuing letermovir in cord blood transplant recipients.
Cytomegalovirus (CMV)-seropositive umbilical cord blood transplantation (CBT) recipients have a high incidence of CMV-associated complications. There are limited data regarding the efficacy of letermovir for preventing clinically significant CMV infection (CS-CMVi), and the impact of letermovir prophylaxis on delayed-onset CMV reactivation after letermovir discontinuation, in CBT recipients. We compared the cumulative incidence of CS-CMVi and CMV detection in 21 CMV-seropositive CBT recipients receiving letermovir prophylaxis with a historical cohort of 40 CBT recipients receiving high-dose valacyclovir prophylaxis. Letermovir was administered on day +1 up to day +98. The cumulative incidence of CS-CMVi was significantly lower by day 98 in the letermovir cohort (19% vs 65%). This difference was lost by 1 year due to a higher incidence of delayed-onset CMV reactivation in the letermovir cohort. No patients developed CMV disease in the letermovir cohort within the first 98 days compared with 2 cases (2.4%) in the high-dose valacyclovir cohort; 2 patients developed CMV enteritis after discontinuing letermovir. Median viral loads were similar in both cohorts. Thus, letermovir is effective at preventing CS-CMVi after CBT, but frequent delayed-onset infections after letermovir discontinuation mandate close monitoring and consideration for extended prophylaxis.


Mathematical analysis of a power-law form time dependent vector-borne disease transmission model.
In the last few years, fractional order derivatives have been used in epidemiology to capture the memory phenomena. However, these models do not have proper biological justification in most of the cases and lack a derivation from a stochastic process. In this present manuscript, using theory of a stochastic process, we derived a general time dependent single strain vector borne disease model. It is shown that under certain choice of time dependent transmission kernel this model can be converted into the classical integer order system. When the time-dependent transmission follows a power law form, we showed that the model converted into a vector borne disease model with fractional order transmission. We explicitly derived the disease-free and endemic equilibrium of this new fractional order vector borne disease model. Using mathematical properties of nonlinear Volterra type integral equation it is shown that the unique disease-free state is globally asymptotically stable under certain condition. We define a threshold quantity which is epidemiologically known as the basic reproduction number (R0). It is shown that if R0 > 1, then the derived fractional order model has a unique endemic equilibrium. We analytically derived the condition for the local stability of the endemic equilibrium. To test the model capability to capture real epidemic, we calibrated our newly proposed model to weekly dengue incidence data of San Juan, Puerto Rico for the time period 30th April 1994 to 23rd April 1995. We estimated several parameters, including the order of the fractional derivative of the proposed model using aforesaid data. It is shown that our proposed fractional order model can nicely capture real epidemic.


Prevalence of Risk Factors of Chronic Rhinosinusitis With Nasal Polyps Among the Saudi Population.
Background The burden of chronic rhinosinusitis symptoms experienced by Saudi citizens is considered an important factor in getting an overall insight of the problem in the region, therefore our study aimed to determine the prevalence of risk factors of chronic rhinosinusitis with nasal polyps and correlate the risk factors with various sociodemographic parameters among Saudi population. Methods This study analyzed five-year cross-sectional data from 2017-2021. A total of 386 participants were enrolled and subsequently divided into four groups: aged 18-25 years, 26-35 years, 36-45 years, and > 45 years. A study was conducted utilizing non-probability sampling targeting a population of Saudi nationality living in selected regions of Saudi Arabia. Data was collected through an online questionnaire which had been distributed through social media and had been analyzed accordingly using a statistical package for social sciences. Results In this study, 272 (70.5%) participants were female and 114 (29.5%) were male. A total of 374 (96.9%) participants were Saudis while 12 (3.1%) were non-Saudis. Risk factors were compared by age and gender of study participants. Having polyps in the nose (p-value 0.016) and a family history of polyps (p-value 0.049) showed a significant association with the gender of study participants. The frequency of having nasal polyps was significantly higher among male participants, however, having a family history of nasal polyps was significantly higher among female participants. The educational status of study participants showed a significant association with the use of cortisone (p-value 0.032) and having a broken nose (p-value 0.032). Having a family history of nasal polyps showed a significant (p-value 0.017) association with the socioeconomic status of study participants. Conclusion Nasal polyps are more common in males than females, however, having a family history of nasal polyps was significantly higher among female participants.


Free the Bun: Prevalence of Alopecia Among Active Duty Service Women, Fiscal Years 2010-2019.
Active duty service women (ADSW) constitute 16% of the force. The prevalence of alopecia, a dermatologic condition characterized by hair loss, is understudied in regard to hairstyle regulations across the U.S. military services. Alopecia has several causes; one of which is due to tension on the scalp secondary to tight hairstyles. In the U.S., alopecia has a lifetime prevalence of 1.7-2.1%; no previous studies which evaluated this condition in service women were found. We used the Military Health System Data Repository to perform a retrospective study to assess the prevalence of alopecia in ADSW from fiscal years (FYs) 2010 to 2019. Statistical analyses included descriptive statistics on patient demographics and trend analysis on the prevalence of alopecia over the 10-year study period. A total of 498,219 ADSW were identified over the 10-year study period, of which 2.40% had a diagnosis of alopecia. Overall, the prevalence of alopecia decreases over the 10-year period, with two observed periods of slight increase (FY 2013 to 2014 and FY 2018 to 2019) when comparing prevalence year-to-year. Of those diagnosed, the majority were young, Black, with a senior enlisted rank, and in the U.S. Army. The prevalence of alopecia in ADSW is slightly higher than that in civilian populations and is most likely underreported. It is more commonly diagnosed in Black women than would be expected based on ratios of this population in military service. Policy changes to ensure that traction alopecia is a qualifying medical condition for Veterans Affairs disability compensation, mechanisms are in place for more specific coding in the electronic medical record, and treatment options to be covered by TRICARE are recommended. All U.S. military services should consider updating and evaluating regulations to improve the health and quality of life of ADSW.


Maintenance of Low-Pressure Carburising Furnaces: A Source of PAH Exposure.
Low-pressure carburising is a new technology used to harden steel; the process has been shown to be a source of considerable polycyclic aromatic hydrocarbons (PAH) pollution. Some PAH are carcinogenic, and activities such as furnace maintenance may thus represent a risk to workers. Occupational exposure during these operations should therefore be assessed. In this study, the PAH-related carcinogenic risk associated with furnace maintenance was assessed by monitoring atmospheric levels of benzo[a]pyrene (BaP), a representative marker, alongside urinary levels of 3-hydroxybenzo[a]pyrene (3-OHBaP), one of its metabolites. PAH exposure levels were monitored during seven sampling campaigns in four different factories specialized in heat-treatment of mechanical workpieces for the automotive and helicopter industries. Two types of furnace were studied, and 37 individuals were monitored. Values up to 20-fold the French regulatory value of 150 ng/m3 for atmospheric BaP, and, for urinary 3-OHBaP values up to 40-fold the French biological limit value (BLV) of 0.35 nmol/mol of creatinine were detected. Very high concentrations of BaP, close to or even exceeding those found in coal-tar pitch (up to about 20 g/kg), were measured in residues (tars, dusts) deposited inside the furnace. Even when adequate and suitable personal protective equipment was used, urinary 3-OHBaP values often exceeded the BLV. We hypothesize that this exposure is linked to insidious and fortuitous dermal contamination through contact with factory equipment and staining.


A two gene-based risk score predicts alcoholic cirrhosis development in males with at-risk alcohol consumption.
Alcoholic cirrhosis represents 1% of all cause-of-deaths worldwide. Its incidence is higher in males and results from the combination of environmental and genetic factors. Among all the genetic determinants of alcoholic cirrhosis, the patatin-like phospholipase domain protein 3 (PNPLA3) rs738409 represents the most widely validated determinant. Recent cross-sectional studies on alcohol abusers identified transmembrane-6 superfamily member 2 (TM6SF2) rs58542926, membrane bound O-acyltransferase domain containing 7 (MBOAT7) rs641738, and cluster of differentiation 14 (CD14) rs2569190 as new genetic risk factors for alcoholic cirrhosis. We aimed to develop a gene-based risk score to predict the incidence of alcoholic cirrhosis in males with at-risk alcohol consumption. A total of 416 male at-risk alcohol drinkers were retrospectively examined. The association between alcoholic cirrhosis incidence and PNPLA3, CD14, TM6SF2, and MBOAT7 variants was tested. Age at onset of at-risk alcohol consumption, age, and body mass index (BMI) were included as covariates to determine the prediction score for alcoholic cirrhosis incidence by evaluating time-dependent receiver operating characteristic curves. We found that PNPLA3, CD14, and TM6SF2 were associated with alcoholic cirrhosis prevalence. PNPLA3 and CD14 were also associated with its incidence. The best predictive score formula was (age at onset of at-risk alcohol consumption × 0.1) + (number of CD14 allele T) + (number of PNPLA3 allele M) + (BMI × 0.1). A threshold of 7.27 was identified as cutoff for the predictive risk of alcoholic cirrhosis development in 36 years from the onset of at-risk alcohol consumption with 70.1% sensitivity and 78.7% specificity. We developed the first score for alcoholic cirrhosis prediction that combines clinical and genetic factors.


Mutation frequency decline in MMS-treated Escherichia coli K-12 mutS strains.
It has been shown that the decline in mutant frequency (MFD) (argE3(ochre)-->Arg+) which occurs in MMS-treated and then transiently starved AB1157 Escherichia coli K-12 cells concerns revertants which arose by supL suppressor formation in a process which is umuDC dependent. Here we have examined whether MMS-induced Arg+ revertants are susceptible to decline when bacteria are deficient in mismatch repair. We show that there is an absence of MFD in MMS-treated M1 (mutS) and in EC2416 (mutS delta umuDC) cells defective in mismatch repair which is associated with a change in the spectrum of MMS-induced mutations formed. In contrast to AB1157, transformation of M1 (mutS) bacteria with plasmids harbouring various combinations of umuD(D')C genes does not enhance the level of MMS-induced mutations but may influence the proportion of supL mutations. These supL mutations show MFD. Repair processes under MFD conditions were confirmed by analysis of plasmid DNA isolated from MMS-treated bacteria at different stages of their starvation and digestion with Fpg protein.


Pulsed blue light inactivates two strains of human coronavirus.
Emerging evidence suggests that blue light has the potential to inactivate viruses. Therefore, we investigated the effect of 405 nm, 410 nm, 425 nm and 450 nm pulsed blue light (PBL) on human alpha coronavirus HCoV-229 E and human beta coronavirus HCoV-OC43, using Qubit fluorometry and RT-LAMP to quantitate the amount of nucleic acid in irradiated and control samples. Like SARS-CoV-2, HCoV-229E and HCoV-OC43 are single stranded RNA viruses transmitted by air and direct contact; they have similar genomic sizes as SARS-CoV-2, and are used as surrogates for SARS-CoV-2. Irradiation was carried out either at 32.4 J cm-2 using 3 mW cm-2 irradiance or at 130 J cm-2 using 12 mW cm-2 irradiance. Results: (1) At each wavelength tested, PBL was antiviral against both coronaviruses. (2) 405 nm light gave the best result, yielding 52.3% (2.37 log10) inactivation against HCoV-OC43 (p < .0001), and a significant 1.46 log 10 (44%) inactivation of HCoV-229E (p < .01). HCoV-OC43, which like SARS-CoV-2 is a beta coronavirus, was more susceptible to PBL irradiation than alpha coronavirus HCoV-229E. The latter finding suggests that PBL is potentially antiviral against multiple coronavirus strains, and that, while its potency may vary from one virus to another, it seems more antiviral against beta coronaviruses, such as HCoV-OC43. (3) Further, the antiviral effect of PBL was better at a higher irradiance than a lower irradiance, and this indicates that with further refinement, a protocol capable of yielding 100% inactivation of viruses is attainable.


Trichoblastoma Arising From the Nevus Sebaceus of Jadassohn.
Trichoblastoma is a rare benign skin adnexal tumour, belonging to the category of trichogenic tumours. The clinical and histological findings may often be confused with basal cell carcinoma, a malignant epidermal skin tumour. We report here a case of a 70-year-old man presented with a dome-shaped, dark-pigmented nodule within a yellowish hairless plaque on the scalp. The plaque had existed since childhood. However, the central pigmented nodule began appearing three months ago and enlarging gradually. The patient had no medical history. Furthermore the physical examination revealed a translucent, verrucous, and yellowish plaque, with central and pigmented nodule measuring 0.7 × 0.5 cm. Also basal cell carcinoma and trichoblastoma's diagnosis were discussed. The patient was subsequently referred to the plastic surgery department, where he underwent a total excision. The histological examination was in favour of trichoblastoma arising from the nevus sebaceus. After 24 months of checking, no recurrence was observed. Trichoblastoma is a benign adnexal tumour. Its progression to malignant trichoblastoma (or trichoblastic carcinoma) is possible, but remains exceptional. Therefore, complete excision should be proposed to the patient at the time of diagnosis.


Connective tissue activation. XXX: Isoelectric point microheterogeneity of CTAP-III, a human platelet-derived growth factor.
Connective tissue activating peptide (CTAP-III) is one of the growth factors found in the alpha granules of human platelets. This small cationic platelet protein shows several apparent isoelectric point variants after the preparative isoelectric focusing step in large scale preparations from multiple donors. Analytical isoelectricfocusing techniques under denaturing conditions, coupled with Western blotting and immunodetection, now show that CTAP-III prepared rapidly from single donors also has multiple isoelectric point variants, suggesting that this finding is more likely related to post-translational modification than preparative artifact or genetic polymorphism.


The Pilocarpine Model of Temporal Lobe Epilepsy and EEG Monitoring Using Radiotelemetry System in Mice.
Temporal lobe epilepsy (TLE) is a common neurological disorder in adulthood. For translational studies of chronic epilepsy, pilocarpine-induced status epilepticus (SE) is frequently selected to recapitulate spontaneous recurrent seizures (SRS). Here we present a protocol of SE induction by intraperitoneal (i.p.) injection of pilocarpine and monitoring of chronic recurring seizures in live animals using a wireless telemetry video and electroencephalogram (EEG) system. We demonstrated notable behavioral changes that need attention after pilocarpine injection and their correlation with hippocampal neuronal loss at 7 days and 6 weeks post-pilocarpine. We also describe the experimental procedures of electrode implantation for video and EEG recording, and analysis of the frequency and duration of chronic recurrent seizures. Finally, we discuss the possible reasons why the expected results are not achieved in each case. This provides a basic overview of modeling chronic epilepsy in mice and guidelines for troubleshooting. We believe this protocol can serve as a baseline for suitable models of chronic epilepsy and epileptogenesis.