Adaptive statistical iterative reconstruction for computed tomography of the spine.
The utility of evaluating a sagittal view of CT of the spine is well-known. In many clinical cases, the sagittal view includes noise generated from surrounding objects and may degrade the image quality. Iterative reconstruction (IR) techniques are useful for noise reduction; however, they can reduce spatial resolution. The aim of this study was to evaluate the effectiveness of the adaptive statistical iterative reconstruction (ASiR) for generating sagittal CT images of the spine when compared to filtered back projection (FBP). The image quality of clinical images from 25 patients were subjectively assessed. Three radiologists rated spatial resolution, image noise, and overall image quality using a five-point scale. For objective assessment, z-direction modulation transfer function (z-MTF) was measured using a custom-made phantom. Additionally, z-axis noise power spectrum (z-NPS) was measured using a water phantom. An improved adaptive statistical iterative reconstruction algorithm called ASiR-V was used in this study. Blending levels were 50%, and 100% (ASiR-V50, ASiR-V100, respectively). For subjective assessments, images using ASiR-V100 were determined to have the best overall image quality, despite having received the worst score in the assessment of spatial resolution. For objective assessments, the image using ASiR-V50 and ASiR-V100 curves were slightly degraded in terms of low contrast z-MTF when compared to FBP. ASiR-V was effective to improve the image quality when compared with FBP when reviewing sagittal reformats of the spine. This study suggests that high resolution is not the only thing that is key when reviewing sagittal CT spinal reformats. Such images should be provided as part of routine CT spine protocols, where available.


An inventory of basic research in temporal lobe epilepsy.
Temporal lobe epilepsy is a severe neurological disease, characterized by seizure occurrence and invalidating cognitive co-morbidities, which affects up to 1% of the adults. Roughly one third of the patients are resistant to any conventional pharmacological treatments. The last option in that case is the surgical removal of the epileptic focus, with no guarantee for clinical symptom alleviation. This state of affairs requests the identification of cellular or molecular targets for novel therapeutic approaches with limited side effects. Here we review some generalities about the disease as well as some of the most recent discoveries about the cellular and molecular mechanisms of TLE, and the latest perspectives for novel treatments.


Tuning of Classical Electromagnetically Induced Reflectance in Babinet Chalcogenide Metamaterials.
Metamaterials analog of electromagnetically induced reflectance (EIR) has attracted intense attentions since they can provide various applications for novel photonic devices such as optical detectors with a high sensitivity and slow-light devices with a low loss. The development of dynamic photonic devices desires a tunable EIR feature in metamaterials. However, most metamaterials-induced EIR is not spectrally controllable particularly for the near-infrared (NIR) region. Herein, a tuning of EIR is illustrated in Babinet chalcogenide metamaterials in the NIR region. The EIR response is created by weak hybridization of two dipolar (bright) modes of the paired Au slots. Such a mode interference can be engineered through non-volatile phase transition to the refractive index of the Ge2Sb2Te5 (GST), resulting in an active controlling of the reflection window. A 15% spectral tuning of the reflectance peak is observed experimentally in the NIR region as switching the GST state between amorphous and crystalline.


[Malignant meningioma with adenocarcinoma-like metaplasia: a rare entity to be not misdiagnosed].
We report on a 51-year-old woman who presented with a cervical spinal cord tumor clinically suspected to be a metastasis. Histological examination revealed an anaplastic meningioma containing epithelial nests arranged in a gland-like pattern suggestive of adenocarcinoma. This component strongly expressed cytokeratins whereas the meningothelial component was vimentin--epithelial membrane antigen--and progesterone receptor-immunoreactive, suggesting either anaplastic meningioma with adenocarcinoma-like metaplasia, or adenocarcinoma metastasis in a meningioma, but the search for a primitive neoplasia including thoracic-abdominal-pelvic computed tomography and mammography was negative. Anaplastic meningiomas with adenocarcinoma-like metaplasia are uncommon lesions, 4 cases having been reported in the literature so far. Their immunohistochemical and chromosomal characteristics are similar to those observed in secretory meningiomas. When available, fluorescence in situ hybridization detects the same chromosomal alterations in the two components, confirming a common clonal origin. This observation demonstrates the necessity to perform the correct diagnosis of malignant meningioma with adenocarcinomatous metaplasia, whose prognosis and treatment radically differ from those of metastatic adenocarcinoma located in a meningioma.


[Treatment of cancer pain in Mali: Experience of the mother-child medical oncology service of the CHU in Bamako].
Two hundred patients were refereed for advanced cancer to the oncology department of Luxembourg Hospital in Bamako. All these patients reported intense pain (88 %) which was only treated before admission by OMS level 1 analgesics. It clearly shows that cancer pain is undertreated in Malian peripheral sanitary structures. After evaluation of the pain by analog visual and verbal scales patients, the appropriate analgesic drugs such as morphine (OMS level 3) were given. A control of the pain was obtained in all the patients (100 %) with a dramatic improvement in quality of life. This study emphasizes the need for a pain control program at the Malian state level with a basic education of care givers, hospital-centric networks and access to morphine and opioids at the different levels involved in cancer management.


Exanthema after a stress Tc-99m sestamibi study: continue with a rest sestamibi study?
A mild allergic reaction assumed to be caused by injection of Tc-99m sestamibi for a stress myocardial perfusion imaging (MPI) is presented. We want to discuss the risk involved in completing the MPI with another sestamibi injection, and the precautions and possible treatment in case of a further reaction. A patient experienced a maculo-papular exanthema, i.e. a mild, probably allergic, adverse event (AE) after a stress MPI including administration of a dose of Tc-99m sestamibi. A rest MPI was needed to decide whether coronary bypass surgery should be performed. After prophylactic treatment with antihistamine and corticosteroid, an uneventful rest MPI was performed. International recommendations or guidelines related to treatment of AEs after nuclear medicine studies do not exist. Serious AEs in nuclear medicine are very rare, but anaphylactic reactions have been reported and may be life threatening. If repeated administration of the radio-pharmaceutical must be given, the prophylactic and therapeutic interventions should follow general international guidelines for allergic reactions.


Mechanical property characterization of partially crystalline Poly-Ether-Ether-Ketone.
The present study investigates the mechanical properties of partially crystalline Poly-Ether-Ether-Ketone between the glass transition and the cold crystallization. Biaxial tension, uniaxial tension, and DMA experiments were conducted to investigate the influence of temperature-induced crystallization on mechanical properties, and three stiffening behaviors are observed. Firstly, a 'U' type mechanical property is observed for all three experiments with first softening and then significant stiffening behavior with increasing temperature. Secondly, stiffening also occurs during low strain rate tests but not in higher strain rate tests. Thirdly, the stiffening behavior of the anisotropic film shows orientation dependence. Crystallinity evolution is predicted by the Nakaruma non-isothermal crystallization kinetics with optimized parameters, with which we demonstrate and explain that the stiffening behaviors are connected to the onset of crystallization. Therefore, the conclusion provides a new tool to approach and distinguish extrinsic and intrinsic properties during characterization, promoting future implementation for constitutive modeling and corresponding simulation that could replicate the influence of temperature-induced crystallization.


Safety evaluation and comparative genomics analysis of the industrial strain Aspergillus flavus SU-16 used for huangjiu brewing.
Huangjiu is a popular Chinese traditional alcoholic beverage, while its brewing processes have rarely been explored. We herein report the first gapless, near-finished genome assembly of the industrial strain Aspergillus flavus SU-16 for huangjiu brewing. This work provides insights and supports for the further industrial applications of A. flavus isolates by comprehensively studying of the safety and genomic variations of SU-16. We demonstrated that SU-16 is a non-aflatoxigenic A. flavus at both molecular and metabolic levels. Using of nanopore sequencing technology resulted in a complete genome sequence for all 8 A. flavus chromosomes, as well as the mitochondrion. Genome comparisons of SU-16 with reference strains identified the chromosomal rearrangements, revealed the adaption mechanism of SU-16 to huangjiu ecological niche, and found that SU-16 is a good repository for CAZymes and some bioactive secondary metabolites. The results will help to develop more scientific huangjiu fermentation processes, and explore metabolism pathways of desired or harmful components in huangjiu to improve its quality.


Blood pressure during sleep is associated with arterial stiffness and urine microalbumin to creatinine ratio in youth with type 1 diabetes.
To determine whether sleep blood pressure (BP) is associated with increased cardiovascular disease (CVD) risk in youth with type 1 diabetes (T1DM). We enrolled youth with T1DM, 12-21 years old. Carotid-femoral Pulse Wave Velocity (PWVcf) assessed arterial stiffness, a CVD marker. Sleep systolic and diastolic BP variables were obtained from 24-hour BP Monitoring. Linear regression models analyzed the relationship of each BP variable with PWVcf, adjusted for HbA1c. Correlation of sleep BP with urine microalbumin-to-creatinine ratio (UAC) was examined. Nocturnal hypertension was found in 36% and abnormal dipping in 48% of the 25 participants, aged 17.7 ± 2.2 years old. Sleep systolic BP [beta = 0.039, 95% Confidence Interval (CI; 0.006-0.073)], diastolic BP [beta = 0.058, 95% CI (0.003-0.114)], Mean Arterial Pressure (MAP) [beta = 0.075, 95% CI (0.018-0.131)] and MAP index [beta = 3.547, 95% CI (0.867-6.227)] were significantly associated with PWVcf. Sleep diastolic BP, load, MAP correlated with UAC. Blood pressure alterations during sleep are common in youth with T1DM and they are associated with arterial stiffness and UAC. Larger studies are needed to confirm our results and examine whether interventions that target sleep and night-time BP could decrease CVD risk.


Cationic polypeptides are required for anti-HIV-1 activity of human vaginal fluid.
Mucosal surfaces of the vagina are the portals for heterosexual transmission of HIV-1 and therefore play a fundamental role in the pathogenesis of primary infection. In the search for direct biological evidence for the role of human vaginal fluid in innate host defense, we characterized the anti-HIV-1 function of cationic polypeptides within minimally manipulated vaginal fluid. In the current study we revealed that vaginal fluid confers intrinsic anti-HIV-1 properties against both X4 and R5 strains of HIV-1 and could protect against HIV-1 infection and reduce proviral genome integration in organotypic cultures of human cervicovaginal tissue. The majority of this activity was contained in the cationic polypeptide fraction, and the depletion of cationic polypeptides using a selective cation exchange resin ablated most of the intrinsic activity against HIV-1. By adding the cationic polypeptide fraction to depleted vaginal fluid, we were able to restore activity against HIV-1. Using a proteomic approach, we identified 18 cationic polypeptides within vaginal fluid, nearly all of which are either known antimicrobials or have other purported roles in host defense. Interestingly, physiologic concentrations of 13 of the cationic polypeptides were not active alone against HIV-1, yet in concert they partially restored the anti-HIV-1 activity of cation-depleted vaginal fluid. These results suggest that synergism between cationic polypeptides is complex, and full anti-HIV-1 activity probably involves the aggregate of the cationic peptides and proteins in vaginal fluid.


Novel purine nitrile derived inhibitors of the cysteine protease cathepsin K.
Starting from the high-throughput screening hit 1a, novel cathepsin K inhibitors have been developed based on a purine scaffold. High-resolution X-ray structures of several derivatives have revealed the binding mode of these unique cysteine protease inhibitors.


Development and validation of apparent diffusion coefficient histogram-based nomogram for predicting malignant transformation of sinonasal inverted papilloma.
To develop and validate a nomogram based on whole-tumour histograms of apparent diffusion coefficient (ADC) maps for predicting malignant transformation (MT) in sinonasal inverted papilloma (IP). This retrospective study included 209 sinonasal IPs with and without MT, which were assigned into a primary cohort (n = 140) and a validation cohort (n = 69). Eight ADC histogram features were extracted from the whole-tumour region of interest. Morphological MRI features and ADC histogram parameters were compared between the two groups (with and without MT). Stepwise logistic regression was used to identify independent predictors and to construct models. The predictive performances of variables and models were assessed using the area under the curve (AUC). The optimal model was presented as a nomogram, and its calibration was assessed. Four morphological features and seven ADC histogram parameters showed significant differences between the two groups in both cohorts (all p < 0.05). Maximum diameter, loss of convoluted cerebriform pattern, ADC10th and ADCSkewness were identified as independent predictors to construct the nomogram. The nomogram showed significantly better performance than the morphological model in both the primary (AUC, 0.96 vs 0.88; p = 0.006) and validation (AUC, 0.96 vs 0.88; p = 0.015) cohorts. The nomogram showed good calibration in both cohorts. Decision curve analysis demonstrated that the nomogram is clinically useful. The developed nomogram, which incorporates morphological MRI features and ADC histogram parameters, can be conveniently used to facilitate the pre-operative prediction of MT in IPs.


Bifurcations and dynamics of a discrete predator-prey system.
In this paper, we study the dynamics behaviour of a stratum of plant-herbivore which is modelled through the following F(x, y)=(f(x, y), g(x, y)) two-dimensional map with four parameters defined by [Formula: see text] where x ≥ 0, y ≥ 0, and the real parameters a, b, r, k are all positive. We will focus on the case a ≠ b. We study the stability of fixed points and do the analysis of the period-doubling and the Neimark-Sacker bifurcations in a standard way.


Electrodiagnostic techniques in the evaluation of nerve compressions and injuries in the upper limb.
Nerve conduction studies and the needle examination of muscles (EMG) are valuable aids in the evaluation of acute and chronic focal neuropathies. A careful clinical examination, however, remains the best way to assess patients with these disorders. In an acute and apparently complete nerve lesion, the main drawbacks of electrophysiologic testing are that a full evaluation cannot usually be done before 10 days after the injury, and the differentiation between axonotmesis and neurotmesis cannot be made.


Probiotics from an industrial perspective.
Probiotic products have gained popularity with consumers that expect that the products they consume are healthy and help them maintain health. Hence, the need and preferences of the consumers are translated into a product format concept. Probiotics have been used for a long time as natural components in supplements and functional foods, mainly in fermented dairy products. Most of the strains used as probiotics belong to the genera Lactobacillus and Bifidobacterium. By definition, a strain has to have documented health benefits, in order to be called a probiotic. Although each bacterial strain is unique, there are some points that are essential when selecting a probiotic regarding the genetic stability, survival, and technical properties of a strain. Proper components, food matrices and production processes need to be selected since the matrices may affect the viability of the strain in the product and the intestine. Survival in the product is considered a requirement for the beneficial effects of probiotics.


Heat shock stress in Bacteroides fragilis.
The response to heat shock was investigated in the obligate anaerobe Bacteroides fragilis. The cells responded quickly to stress and synthesised seven heat shock proteins immediately upon exposure to heat. The apparent molecular weights of the seven proteins differed from the apparent molecular weights of the proteins induced by UV irradiation, O2 and H2O2. Heat shock did not induce phage reactivation whereas UV irradiation, O2 and H2O2 did induce phage reactivation systems. Ethanol did not elicit the heat shock response. Two heat resistant B. fragilis mutants were isolated. Both mutants lost the ability to synthesise the same two heat shock proteins. It is concluded that the heat shock response and the responses to UV irradiation, O2 and H2O2 represent two independent groups of stress responses in B. fragilis.


Electrochemical Immunosensor for the Early Detection of Rheumatoid Arthritis Biomarker: Anti-Cyclic Citrullinated Peptide Antibody in Human Serum Based on Avidin-Biotin System.
Rheumatoid arthritis (RA) is a chronic autoimmune disease that produces a progressive inflammatory response that leads to severe pain, swelling, and stiffness in the joints of hands and feet, followed by irreversible damage of the joints. The authors developed a miniaturized, label-free electrochemical impedimetric immunosensor for the sensitive and direct detection of arthritis Anti-CCP-ab biomarker. An interdigitated-chain-shaped microelectrode array (ICE) was fabricated by taking the advantage of microelectromechanical systems. The fabricated ICE was modified with a self-assembled monolayer (SAM) of Mercaptohexanoic acid (MHA) for immobilization of the synthetic peptide bio-receptor (B-CCP). The B-CCP was attached onto the surface of SAM modified ICE through a strong avidin-biotin bio-recognition system. The modified ICE surface with the SAM and bio-molecules (Avidin, B-CCP, Anti-CCP-ab and BSA) was morphologically and electrochemically characterized. The change in the sensor signal upon analyte binding on the electrode surface was probed through the electrochemical impedance spectroscopy (EIS) property of charge-transfer resistance (Rct) of the modified electrodes. EIS measurements were target specific and the sensor response was linearly increased with step wise increase in target analyte (Anti-CCP-ab) concentrations. The developed sensor showed a linear range for the addition of Anti-CCP-ab between 1 IU mL-1 → 800 IU mL-1 in phosphate buffered saline (PBS) and Human serum (HS), respectively. The sensor showed a limit of detection of 0.60 IU mL-1 and 0.82 IU mL-1 in the PBS and HS, respectively. The develop bio-electrode showed a good reproducibility (relative standard deviation (RSD), 1.52%), selectivity and stability (1.5% lost at the end of 20th day) with an acceptable recovery rate (98.0% → 101.18%) and % RSD's for the detection of Anti-CCP-ab in spiked HS samples.


Changes in the apparent localization of anterior determinants during early embryogenesis (Smittia spec., Chironomidae, Diptera).
InSmittia embryos, anterior UV irradiation causes the formation of double abdomens in which head and thorax are replaced by a mirror-image duplication of abdominal segments. The transformation is ascribed to the inactivation of cytoplasmic ribonucleoprotein particles acting as anterior determinants. During the first 5 h after egg deposition (h.a.d.), high yields of double abdomens are produced by microbeam irradiation of a small target area (diameter 20 μm) behind the anterior pole. This localization coincides with a yolk-free cytoplasmic cone observed behind the anterior pole of newly depositedSmittia eggs (Zissler and Sander 1973). Irradiation of this area becomes less efficient between 5 and 7 h.a.d., while double abdomen yields increase after irradiation of adjacent target areas. A dramatic increase in the double abdomen yield is also observed after irradiation of the entire anterior surface. Under these conditions, the UV fluence required for a given yield decreases by a factor of 3.9 between 5.5. and 7 h.a.d. This can be explained quantitatively by the assumption that the effective targets move an average distance of 8 μ from the strongly absorbing endoplasm towards the egg surface. During the period of apparent target deshielding, the distance of nuclei from the egg surface actually decreases from 11 to 3 μm. However, the timing and direction of the nuclear migration and of the apparent deshielding differ, indicating that the shift of effective targets may be triggered by, but does not exactly follow, the nuclear movement. The data suggest that a major fraction of anterior determinants shifts from a small volume behind the anterior pole to a spread-out distribution over the surface of the anterior half.


Nitrogen speciation and transformations in fire-derived organic matter.
Vegetation fires are known to have broad geochemical effects on carbon (C) cycles in the Earth system, yet limited information is available for nitrogen (N). In this study, we evaluated how charring organic matter (OM) to pyrogenic OM (PyOM) altered the N molecular structure and affected subsequent C and N mineralization. Nitrogen near-edge X-ray absorption fine structure (NEXAFS) of uncharred OM, PyOM, PyOM toluene extract, and PyOM after toluene extraction were used to predict PyOM-C and -N mineralization potentials. PyOM was produced from three different plants (e.g. Maize-Zea mays L.; Ryegrass-Lollium perenne L.; and Willow-Salix viminalix L.) each with varying initial N contents at three pyrolysis temperatures (350, 500 and 700 °C). Mineralization of C and N was measured from incubations of uncharred OM and PyOM in a sand matrix for 256 days at 30 °C. As pyrolysis temperature increased from 350 to 700 °C, aromatic C[bond, double bond]N in 6-membered rings (putative) increased threefold. Aromatic C[bond, double bond]N in 6-membered oxygenated ring increased sevenfold, and quaternary aromatic N doubled. Initial uncharred OM-N content was positively correlated with the proportion of heterocyclic aromatic N in PyOM (R2 = 0.44; P < 0.0001; n = 42). A 55% increase of aromatic N heterocycles at high OM-N content, when compared to low OM-N content, suggests that higher concentrations of N favor the incorporation of N atoms into aromatic structures by overcoming the energy barrier associated with the electronic and atomic configuration of the C structure. A ten-fold increase of aromatic C[bond, double bond]N in 6-membered rings (putative) in PyOM (as proportion of all PyOM-N) decreased C mineralization by 87%, whereas total N contents and C:N ratios of PyOM had no effects on C mineralization of PyOM-C for both pyrolysis temperatures (for PyOM-350 °C, R2 = 0.15; P < 0.27; for PyOM-700 °C, R2 = 0.22; P < 0.21). Oxidized aromatic N in PyOM toluene extracts correlated with higher C mineralization, whereas aromatic N in 6-membered heterocycles correlated with reduced C mineralization (R2 = 0.56; P = 0.001; n = 100). Similarly, aromatic N in 6-membered heterocycles in PyOM remaining after toluene extraction reduced PyOM-C mineralization (R2 = 0.49; P = 0.0006; n = 100). PyOM-C mineralization increased when N atoms were located at the edge of the C network in the form of oxidized N functionalities or when more N was found in PyOM toluene extracts and was more accessible to microbial oxidation. These results confirm the hypothesis that C persistence of fire-derived OM is significantly affected by its molecular N structure and the presented quantitative structure-activity relationship can be utilized for predictive modeling purposes.


Field and Laboratory Efficacy of Low-Impact Commercial Products in Preventing Olive Fruit Fly, Bactrocera oleae, Infestation.
The olive fruit fly, Bactrocera oleae, is the key pest of olive trees in several areas of the world. Given the need for the development of sustainable control methods, preventive tools, based on the manipulation of pest behaviour, must be considered. Here, under field and laboratory conditions, we tested the efficacy of different products in preventing B. oleae infestation. A field trial was conducted, from July to November 2020, in an olive orchard located in Central Italy. A table olive variety was selected and sprayed with rock powder, propolis, the mixture of both, copper oxychloride, or water (control). All treatments, except propolis, caused a reduction of B. oleae oviposition in olives, compared to the control. The mixture allowed the strongest reduction of fly infestation throughout the season, suggesting a synergistic effect. Behavioural no-choice assays were conducted to better understand the effects of treatments on B. oleae females. Compared to the control, females showed a lower preference for the central area of an arena containing an olive twig bearing two olive fruits, fully developed, but still green, treated with rock powder, plus propolis mixture. For all treatments, B. oleae showed lower oviposition events, suggesting deterrence to oviposition. Our results indicate that the tested products may have value against B. oleae, within integrated pest management (IPM) and organic agriculture.


Instructions for masking the taste of medication for children: Validation of a pictogram tool.
Medications that taste unpleasant can be a struggle to administer to children, most often resulting in low adherence rates. Pictograms can be useful tools to improve adherence by conveying information to patients in a way that they will understand. One-on-one structured interviews were conducted with parents/guardians and with children between the ages of 9 and 17 years at a pediatric hospital. The questionnaire evaluated the comprehension of 12 pictogram sets that described how to mask the taste of medications for children. Pictograms understood by >85% of participants were considered validated. Short-term recall was assessed by asking participants to recall the meaning of each pictogram set. There were 51 participants in the study-26 (51%) were children aged 9 to 17 years and 25 (49%) were parents or guardians. Most children (54%) had health literacy levels of grade 10 or higher. Most parents and guardians (92%) had at least a high school health literacy level. Six of the 12 pictogram sets (50%) were validated. Eleven of 12 pictogram sets (92%) had a median translucency score greater than 5. All 12 pictogram sets (100%) were correctly identified at short-term recall and were therefore validated. The addition of validated illustrations to pharmaceutical labels can be useful to instruct on how to mask the taste of medication in certain populations. Further studies are needed to assess the clinical impact of providing illustrated information to populations with low health literacy.


DNA restriction fragment length polymorphism of HLA-DR2: correlation with HLA-DR2-associated functions.
HLA-DR2 can be divided into at least 3 distinct HLA-D clusters which correlate with structural differences within the HLA-D region. Further, a functional counterpart of this subdivision has been previously identified. The presence of a particular DR beta 2 polypeptide chain correlated precisely with the susceptibility of measles virus-infected HLA-DR2 homozygous typing cell lines to lysis by measles virus-specific, HLA class II-restricted CTL clones. To determine if a genetic basis for these functional differences could be detected, the degree of polymorphism at the DNA level within the serologically defined HLA-DR2 haplotype has been examined. By using DNA probes for DR beta and DQ beta 4 of the 5 HLA-D clusters of HLA-DR2 could be distinguished and a RFLP pattern was identified which correlates with known immunological functions associated with these various D types. In addition, this technique of 'molecular genotyping' was used to investigate a limited panel of patients with multiple sclerosis (MS) who were HLA typed as either HLA-DR2,2 or HLA-DR2,blank. The RFLP profile of the HLA-DR2 Dw2 D type was found in all of these MS patients.


Multi-copy nuclear pseudogenes of mitochondrial DNA reveal recent acute genetic changes in the human genome.
Four nuclear pseudogenes homologous to the 10031-10195-bp region of the human mitochondrial genome were detected by constant denaturant capillary electrophoresis. Among them, one pseudogene is present as at least five copies in each cell, in accordance with our previous observations of multi-copy mitochondrial DNA pseudogenes. The presence of multiple identical copies of pseudogenes suggests that the human genome underwent a series of genetic changes, including gene amplifications, very recently in evolutionary history, i.e., within the last 390000 years.


Studies on the adequate composition of diphtheria and tetanus toxoids-with reference to the amounts of toxoids and aluminum adjuvant.
Immune response of man to tetanus and diphtheria-tetanus combined toxoids with different compositions was investigated, with special reference to the long-term immunity. Adsorbed tetanus toxoid with a potency of about 25 IU per human dose endowed a long-lasting immunity sufficient to prevent tetanus to the vaccines of various age groups, when administered in two doses, followed by a booster injection. Two doses of adsorbed diphtheria-tetanus combined toxoid with potencies of about 20 IU per dose for both components were sufficient to give immunity in infants against diphtheria and tetanus. However, a booster injection should be given within a year to endow a long-lasting immunity. In the case of booster immunization of children with a complete history of immunization against diphtheria and tetanus, a potent long-term immunity was endowed by a single injection of diphtheria-tetanus combined toxoid (plain) with 1 and 3.5 IU per dose, for diphtheria and tetanus components, respectively.


Developmental analysis of two wing scalloping mutantsct 6 andBx J ofDrosophila melanogaster.
The mutantscut 6 (ct6) andBeadex of Jollos (Bx J) show nicks in the wing margins as well as other malformations in different regions of the body. Clonal analysis of the wing disk's development in these mutants indicates that massive cell loss occurs during the third larval instar. Morphogenetic mosaics, originating from mitotic recombination, reveal a non-autonomous behaviour of both mutant and wild-type cells. X-rays applied during the third larval instar produce phenocopies of these mutants. A clonal and a genetic analysis of these phenocopies has been carried out.The hypothesis that scalloping mutants such asct 6, BxJ and others, as well as X-rays, affect properties of cellular interaction, such as cell adhesivity or cohesion, is discussed. Morphogenetic mosaics in the wing margin suggest that the differentiation of the marginal cuticular elements requires the interaction of the cells of the ventral and dorsal surfaces of the wing.


A new scoring system and clinical algorithm for the management of suspected foreign body aspiration in children: a retrospective cohort study.
Cases of foreign body aspiration in children may be encountered in emergency departments. A suggestive history is important in diagnosing aspirated foreign body owing to the difficulty in making a diagnosis on the basis of an abnormal physical examination or chest radiography alone. The aim of this study was to examine the sensitivity and specificity of the presenting symptoms, physical examination, and radiologic findings as predictors of foreign body aspiration in children. In addition, a feasible simple algorithm with a scoring system was generated to indicate bronchoscopic investigation. In a retrospective cohort, medical records of patients aged less than 16 years with suspected foreign body aspiration who underwent flexible or rigid bronchoscopy were included. Data including age, sex, symptoms, physical examination findings, radiological features, nature and location of the foreign body, and outcome of the bronchoscopy were collected, and multivariable binary logistic regression analysis was employed for prediction of foreign body aspiration. A total of 203 children were included, and the model showed excellent discrimination power for positive foreign body aspiration (area under the curve = 0.911) with an accuracy, sensitivity, and specificity of 86.2, 90.6, and 76.6%, respectively. The total weighted risk score at a cut-off > 2 showed a significant good power of discrimination (area under the curve = 0.879), with a sensitivity of 79.9% and specificity of 84.4%. Accordingly, a clinical algorithm was recommended. The proposed scoring system and clinical algorithm might help in decision making with regard to the need and type of bronchoscopy in children presenting with potential foreign body aspiration. However, further prospective multicenter studies should be conducted to validate this scoring system.


Effect of orbital volume in unilateral orbital fracture on indirect traumatic optic neuropathy.
This retrospective study aimed to analyze the relationship between the volume of the fractured and the normal orbit in patients with unilateral orbital fractures with and without indirect traumatic optic neuropathy (TON). Data of 25 patients with unilateral orbital fractures who underwent computer tomography between January 2016 and December 2020 were investigated. Emergency imaging was performed within 2 hours of arrival at the emergency room. The subjects were categorized into two groups: unilateral orbital fractures with and without TON. The assessment of TON was performed during a comprehensive ophthalmologic examination by an ophthalmologist. The stereographic orbit was reconstructed, and the volume was calculated. Other variables examined included age, sex, and cause of orbital trauma. The variables were compared using paired t-tests. Statistical significance was set at p < 0.05. The orbital volume of the non-fractured orbit was 27.50 ± 2.26 and 27.48 ± 2.64 cm3 in the groups with and without TON, respectively. The average volume of the fractured orbit in the TON group was 27.78 ± 2.56 cm3, and there was no significant volumetric difference between the fractured and non-fractured sides in this group. However, the average volume of the fractured orbit without TON was 28.76 ± 3.18 cm3, larger than that of the non-fractured orbit (p = 0.016). Non-expansion of the fractured orbit was a risk factor for indirect TON in patients with unilateral orbital fractures. Volumetric analysis from primary imaging would expedite the diagnosis and treatment of TON, resulting in optimal outcomes.


Vector Immunity and Evolutionary Ecology: The Harmonious Dissonance.
Recent scientific breakthroughs have significantly expanded our understanding of arthropod vector immunity. Insights in the laboratory have demonstrated how the immune system provides resistance to infection, and in what manner innate defenses protect against a microbial assault. Less understood, however, is the effect of biotic and abiotic factors on microbial-vector interactions and the impact of the immune system on arthropod populations in nature. Furthermore, the influence of genetic plasticity on the immune response against vector-borne pathogens remains mostly elusive. Herein, we discuss evolutionary forces that shape arthropod vector immunity. We focus on resistance, pathogenicity and tolerance to infection. We posit that novel scientific paradigms should emerge when molecular immunologists and evolutionary ecologists work together.


Short hairpin RNA-mediated gene silencing.
Since the first application of RNA interference (RNAi) in mammalian cells, the expression of short hairpin RNAs (shRNAs) for targeted gene silencing has become a benchmark technology. Using plasmid and viral vectoring systems, the transcription of shRNA precursors that are effectively processed by the RNAi pathway can lead to potent gene knockdown. The past decade has seen continual advancement and improvement to the various strategies that can be used for shRNA delivery, and the use of shRNAs for clinical applications is well underway. Driving these developments has been the many benefits afforded by shRNA technologies, including the stable integration of expression constructs for long-term expression, infection of difficult-to-target cell lines and tissues using viral vectors, and the temporal control of shRNA transcription by inducible promoters. The use of different effector molecule formats, promoters, and vector types, has meant that experiments can be tailored to target specific cell types and minimize cellular toxicities. Through the application of combinatorial RNAi (co-RNAi), multiple shRNA delivery strategies can improve gene knockdown, permit multiple transcripts to be targeted simultaneously, and curtail the emergence of viral escape mutants. This chapter reviews the history, cellular processing, and various applications of shRNAs in mammalian systems, including options for effector molecule design, vector and promoter types, and methods for multiple shRNA delivery.


Clinical evaluation of deep learning and atlas-based auto-segmentation for critical organs at risk in radiation therapy.
Contouring organs at risk (OARs) is a time-intensive task that is a critical part of radiation therapy. Atlas-based automatic segmentation has shown some success at reducing this time burden on practitioners; however, this method often requires significant manual editing to reach a clinically accurate standard. Deep learning (DL) auto-segmentation has recently emerged as a promising solution. This study compares the accuracy of DL and atlas-based auto-segmentation in relation to clinical 'gold standard' reference contours. Ninety CT datasets (30 head and neck, 30 thoracic, 30 pelvic) were automatically contoured using both atlas and DL segmentation techniques. Sixteen critical OARs were then quantitatively measured for accuracy using the Dice similarity coefficient (DSC) and Hausdorff distance (HD). Qualitative analysis was performed to visually classify the accuracy of each structure into one of four explicitly defined categories. Additionally, the time to edit atlas and DL contours to a clinically acceptable level was recorded for a subset of 9 OARs. Of the 16 OARs analysed, DL delivered statistically significant improvements over atlas segmentation in 13 OARs measured with DSC, 12 OARs measured with HD, and 12 OARs measured qualitatively. The mean editing time for the subset of DL contours was 50%, 23% and 61% faster (all P < 0.05) than that of atlas segmentation for the head and neck, thorax, and pelvis respectively. Deep learning segmentation comprehensively outperformed atlas-based contouring for the majority of evaluated OARs. Improvements were observed in geometric accuracy and visual acceptability, while editing time was reduced leading to increased workflow efficiency.


Tumor necrosis factor-alpha induces c-fms RNA expression in murine tissue macrophages.
The macrophage-colony stimulating factor receptor, c-fms, is induced by IL-2 in monocytes and is suppressed by LPS, LPS plus IFN-gamma, phorbol esters, and colony stimulating factor in monocytes/macrophages. Here we show that c-fms RNA is induced by treatment of murine tissue macrophages with TNF-alpha. This induction is suppressed by co-treatment with LPS, IFN-gamma, LPS plus IFN-gamma, aspirin, and ox LDL. c-fms expression is required for the proliferation, differentiation, and survival of monocytes/macrophages. Our findings indicate a way by which TNF-alpha, as well as LPS, IFN-gamma, aspirin, and ox LDL impinge upon macrophage biology.


iPSCs from cancer cells: challenges and opportunities.
Reprogramming and oncogenic transformation are stepwise processes that share many similarities, and induced pluripotent stem cells (iPSCs) generated from cancer cells could illuminate molecular mechanisms underlying the pathogenesis of human cancer. Deciphering the barriers underlying the reprogramming process of primary cancer cells could reveal information on the links between pluripotency and oncogenic transformation that would be instrumental for therapy development.


Sex differences in behavior, response to LPS, and glucose homeostasis in middle-aged mice.
Sex and age have distinct influences and roles in behavior and immune reactivity; yet, most studies use adult male rodents with little attention to middle age, a time associated with key physiological transitions in both sexes. Thus, this study investigated sex differences during middle age in behavior, immune response to lipopolysaccharide (LPS), and glucose regulation in C57BL/6 mice with GFP-tagged monocytes/microglia. Behaviorally, males performed better in tests of motor function (Open Field [OF], Grip Strength, Sticker Removal, Gait, and Pole tests) and displayed less depressive- and anxiety-like behaviors across multiple mood tests (OF, Elevated Zero Maze, Sucrose Preference, and Swim test). However, females performed better in tests of cognition (Barnes Maze and Novel Object Recognition). Following behavioral assessment, mice were given LPS to characterize sex-dependent inflammagen responses. Females displayed greater sickness behavior in the OF, higher levels of peripheral cytokines, and subtle neuroinflammation in the cortex, striatum, and hippocampus. A separate middle-aged cohort was used for glucose tolerance and insulin sensitivity testing. Both sexes had excessive blood glucose rebound after insulin challenge, but displayed differences following glucose administration, where males had higher baseline glucose and females remained hyperglycemic. This study suggests that during middle-age male mice have better emotional regulation and motor function, but not cognitive ability than females. Further, males are less sensitive than females to the acute effects of LPS peripherally and centrally, but both sexes showed sex-specific impairments in blood glucose regulation. Overall, it appears that middle age is an important transition point with multiple sex differences, some of which are unique to this stage of life.


Ionic liquids in electrokinetic chromatography.
There is an interest in the application of ionic liquids as additives into the separation media to improve achiral and chiral separations in electrokinetic chromatography (EKC). This review will critically discuss the developments on the use of ionic liquids in the different modes of EKC during the last five years (2015-mid 2020). A healthy number of 48 research articles searched through Scopus were categorised into two: ionic liquids as sole pseudophase (micelles, microemulsions, ligand exchange pseudophase or molecular pseudophase) and ionic liquids with pseudophase (achiral or chiral). More than half of the papers dealt with chiral separations that were mostly facilitated by another additive or pseudophase. The role of ionic liquids for improvement of separations were analysed, and we provided some recommendations for further investigations. Finally, the use of ionic liquids in different on-line sample concentration or stacking methods (i.e., field enhancement and sweeping) was briefly discussed.


Molecular motors: the natural economy of kinesin.
Kinesin is a molecular-scale walking machine. New analyses of its mechanism indicate that each step along a microtubule consumes one ATP molecule, and that the binding and cleavage of ATP precede detachment of the molecule's 'feet'. Directional walking ensues if ATP processing occurs preferentially on one foot.


Comparison of some methods for the detection of antigen-antibody reactions in amoebiasis.
The indirect hemagglutination test (IHA) and counterimmuno-electrophoresis (CIE) were used to test for antibodies to Entamoeba histolytica in human sera using antigens from axenic cultures of the HK9 strain. Correlation between the test was excellent with most sera from patients with amoebiasis demonstrating precipitin lines by CIE at IHA titers considered diagnostically positive, larger than or equal to 1:128. Precipitin reactions with positive sera were also compared by CIE, immunoelectrophoresis (IEP) and two-dimensional electrophoresis is (2D-IEP). The greatest number of antigen-antibody components were demonstrated by 2D-IEP. Further studies utilizing 2D-IEP should be of value in the antigenic analysis of E. histolytica.


Risk factors of meralgia paresthetica after prone position surgery: Possible influence of operating position, laminectomy level, and preoperative thoracic kyphosis.
Obesity and a prolonged surgical duration are reported risk factors for meralgia paresthetica (MP) after prone position surgery; however, this fails to explain why MP seldom occurs after prone position craniotomy. We reviewed the incidence of MP after spinal surgery and craniotomy in the prone position and investigated whether unidentified factors are involved in the mechanism of postoperative MP. Between January 2014 and March 2020, we performed 556 prone position surgeries. We excluded patients aged ≤16 years and those who were comatose or who required redo-surgery, and reviewed 446 eligible patients (124 who underwent craniotomies and 322 who underwent posterior spinal surgeries). Postoperative MP occurred in 46 (10.3%) patients with a higher incidence after spinal surgery than after craniotomy (13.7% vs. 1.6%, p < 0.001). Among the 322 patients who received posterior spinal surgery, thoracic and lumbar laminectomies were associated with a higher incidence of MP than cervical laminectomy. Analyses limited to those patients who received thoracic and lumbar laminectomies revealed that the preoperative thoracic kyphosis (TK) angle was significantly greater in patients with MP than in those without MP (average TK angle, 38.9° vs. 23.1°; p < 0.001), and that the preoperative lumbar lordosis angle did not significantly differ between the two groups. Apart from the known predisposing factors, we found that thoracolumbar-sacral laminectomy in patients with a greater TK angle is also a risk factor for MP after prone position surgery.


Reduction of impulsivity in patients receiving deep transcranial magnetic stimulation treatment for obesity.
Aims of the present study were to investigate a wide array of psychological symptoms through validated psychometric tests, before and after 5 weeks of deep Transcranial Magnetic Stimulation (dTMS) in individuals with obesity, and to identify possible relationships with neuroendocrine parameters. Forty-five patients with obesity (33 F, 12 M; age 48.8 ± 9.9 years; body wt 97.6 ± 14.2 Kg; BMI 36.2 ± 4.2) were randomized into two groups: 26 received high frequency (HF) dTMS and 19 Sham stimulation for 5 weeks. At baseline and after the 5-week treatment, all patients underwent the following psychometric evaluations: Food Cravings Questionnaire-Trait (FCQ-T) and its subscales, Barratt Impulsiveness Scale-11 (BIS-11), State and Trait Anxiety Inventory (STAI-y1 and STAI-y2), and Beck Depression Inventory (BDI). Hormonal and neuroendocrine markers were assessed at the first and last dTMS session. By adjusting for baseline variables and treatment arms, a significant decrease in body wt and BMI was found in HF group, both with univariate (p = 0.019) and multivariate analyses (p = 0.012). Impulsivity significantly decreased in HF group, both with univariate (p = 0.031) and multivariate analyses (p = 0.011). A positive association between the impulsivity score change and the leptin level variation (p = 0.031) was found. The decrease of impulsivity together with the BMI reduction in individuals with obesity, treated with real stimulation, suggests that impulsivity may be a risk factor for obesity. Treatment with dTMS revealed to be effective in reducing both BMI and impulsivity by enhancing inhibitory capacity of Pre-Frontal Cortex (PFC), and modulating neuroendocrine system, especially leptin.


The effect of the use of a TNF-alpha inhibitor in hypothermic machine perfusion on kidney function after transplantation.
One of the most important problems in transplantation medicine is the ischemia/reperfusion injury of the organs to be transplanted. The aim of the present study was to assess the effect of tumor necrosis factor-alpha (TNF-alpha) inhibitor etanercept on the machine perfusion hypothermia of renal allograft kidney function and organ perfusion. No statistically significant differences were found in the impact of the applied intervention on kidney machine perfusion during which the average flow and vascular resistance were evaluated. There were no statistically significant differences in the occurrence of delayed graft function (DGF). Fewer events in patients who received a kidney from the etanercept treated Group A compared to the patients who received a kidney from the control Group B were observed when comparing the functional DGF and occurrence of acute rejection episodes, however, there was no statistically significant difference. In summary, no effect of treatment with etanercept an inhibitor of TNF-alpha in a hypothermic machine perfusion on renal allograft renal survival and its perfusion were detected in this study. However, treatment of the isolated organ may be important for the future of transplantation medicine.


A multistate model and its standalone tool to predict hospital and ICU occupancy by patients with COVID-19.
This study aims to build a multistate model and describe a predictive tool for estimating the daily number of intensive care unit (ICU) and hospital beds occupied by patients with coronavirus 2019 disease (COVID-19). The estimation is based on the simulation of patient trajectories using a multistate model where the transition probabilities between states are estimated via competing risks and cure models. The input to the tool includes the dates of COVID-19 diagnosis, admission to hospital, admission to ICU, discharge from ICU and discharge from hospital or death of positive cases from a selected initial date to the current moment. Our tool is validated using 98,496 cases positive for severe acute respiratory coronavirus 2 extracted from the Aragón Healthcare Records Database from July 1, 2020 to February 28, 2021. The tool demonstrates good performance for the 7- and 14-days forecasts using the actual positive cases, and shows good accuracy among three scenarios corresponding to different stages of the pandemic: 1) up-scenario, 2) peak-scenario and 3) down-scenario. Long term predictions (two months) also show good accuracy, while those using Holt-Winters positive case estimates revealed acceptable accuracy to day 14 onwards, with relative errors of 8.8%. In the era of the COVID-19 pandemic, hospitals must evolve in a dynamic way. Our prediction tool is designed to predict hospital occupancy to improve healthcare resource management without information about clinical history of patients. Our easy-to-use and freely accessible tool (https://github.com/peterman65) shows good performance and accuracy for forecasting the daily number of hospital and ICU beds required for patients with COVID-19.


Identification of distinct electrocardiographic patterns from the basal left ventricle: distinguishing medial and lateral sites of origin in patients with idiopathic ventricular tachycardia.
Idiopathic ventricular tachycardias (IVTs) can originate from the basal left ventricle (LV). To determine if using magnetic electroanatomic mapping (MEAM) for accurate localization (1) unique ECG morphologies on pace maps from medial and lateral sites in basal LV could be identified and (2) this ECG information would facilitate VT localization. In 12 patients with structurally normal hearts undergoing ablation for IVT, detailed MEAM of LV was constructed in sinus rhythm and pace-mapping was done from the septal-parahisian (S-P) region, aortomitral continuity (AMC), and superior, superolateral, and lateral mitral annular (MA) locations. Pace maps were analyzed for ECG morphologies in limb leads and transition patterns in precordial leads. Medial pacing sites (S-P and AMC) compared with lateral sites (superolateral and lateral MA) demonstrated narrower QRS complexes (134 +/- 24 msec vs. 182 +/- 18 msec; P < .05) with initial negative forces in lead V1 and predominantly positive forces in lead I (amplitude 0.59 +/- 0.27 mV vs. 0.16 +/- 0.34 mV; P < .05). The ratio of QRS complexes in leads II and III was >1 for all (12 of 12) S-P pace maps and 11 of 12 lateral MA pace maps but remained < or =1 for pace maps from 10 of 12 AMC locations, 11 of 12 superior MA locations, and 10 of 11 superolateral MA locations. Using these ECG criteria, a blinded reviewer was able to accurately localize the site of origin (SOO) of clinical arrhythmia (successful ablation site on MEAM) in 10 of 12 cases (83%) of IVT originating from basal LV. Pace maps from basal LV endocardium manifest site-dependent ECG morphologies that can help differentiate medial from lateral locations and can predict the SOO of clinical arrhythmias from this region.


Updating emission inventories for vehicular organic gases: Indications from cold-start and temperature effects on advanced technology cars.
How would the organic gas emission inventories of future urban vehicles change with new features of advanced technology cars? Here, volatile organic compounds (VOCs) and intermediate volatile organic compounds (IVOCs) from a fleet of Chinese light-duty gasoline vehicles (LDGVs) were characterized by chassis dynamometer experiments to grasp the key factors affecting future inventory accuracy. Subsequently, the VOC and IVOC emissions of LDGVs in Beijing, China, from 2020 to 2035, were calculated and the spatial-temporal variations were recognized under a scenario of fleet renewal. With the tightening of emission standards (ESs), cold start contributed a larger fraction of the total unified cycle VOC emissions due to the imbalanced emission reductions between operating conditions. It took 757.47 ± 337.75 km of hot running to equal one cold-start VOC emission for the latest certified vehicles. Therefore, the future tailpipe VOC emissions would be highly dependent on discrete cold start events rather than traffic flows. By contrast, the equivalent distance was shorter and more stable for IVOCs, with an average of 8.69 ± 4.59 km across the ESs, suggesting insufficient controls. Furthermore, there were log-linear relationships between temperatures and cold-start emissions, and the gasoline direct-injection vehicles performed better adaptability under low temperatures. In the updated emission inventories, the VOC emissions were more effectively reduced than the IVOC emissions. The start emissions of VOCs were estimated to be increasingly dominant, especially in wintertime. By winter 2035, the contribution of VOC start emissions could reach 98.98 % in Beijing, while the fraction of IVOC start emissions would decrease to 59.23 %. Spatially allocation showed that the high emission regions of tailpipe organic gases from LDGVs have transferred from road networks to regions of intense human activities. Our results provide new insights into tailpipe organic gas emissions of gasoline vehicles, and can support future emission inventories and refined assessment of air quality and human health risk.


Methods for evaluating inflammation in cystic fibrosis.
Cystic fibrosis is characterized by excessive pulmonary inflammation, which presents early in life and becomes self-sustaining, eventually leading to the destruction of the lung. Treating inflammation is one of the most pressing needs in CF therapy and has been shown to slow lung function deterioration. However, it remains unclear whether excessive inflammation is a direct result of CFTR dysfunction, and thus innate, or develops in response to early stimulation of inflammatory pathways. Here, we will discuss clinically relevant studies and the methods employed by them. We will focus on investigations in cell and animal models as well as patients. Our discussion will describe the character of pulmonary inflammation in CF and present potential therapeutic approaches that can ameliorate excessive responses and improve disease prognosis.


Ultrastructural analysis of the acrosome reaction in a population of single guinea pig sperm.
Cauda epididymal guinea pig spermatozoa are arranged in rouleaux, with the sperm heads stacked one on top of the other; the plasma membranes over the apical segment of the acrosomes of adjacent sperm are linked and form non-fusigenic "junctional" zones. A complex structural and temporal sequence of membrane fusions occurs during the acrosome reaction of guinea pig sperm in rouleaux. In this study, we have devised a procedure for dispersing the rouleaux and isolating a population of single, motile guinea pig sperm, and have investigated the ultrastructural features of the acrosome reaction in single sperm to determine if the pattern of membrane fusions is different from sperm in rouleaux. The rouleaux were dispersed using trypsin, and damaged cells were removed by passing the sperm suspension through a glass bead column; a population of 70-90% motile, acrosome-intact, single sperm was obtained. Sperm were then induced to undergo lysolecithin-mediated, "synchronous" acrosome reactions, and processed for transmission electron microscopy. The acrosome reaction involved a complex sequence of membrane fusions between the plasma membrane (PM) and outer acrosomal membrane (OAM). On the convex surface of the apical segment, sheets of hybrid membrane and parallel arrays of hybrid membrane tubules formed; filaments were associated with the luminal surface of the residual OAM in these regions. Hybrid membrane vesicles were produced on the concave surface of the apical segment, but fusion was delayed relative to the convex surface. In the principal segment, branching arrays of hybrid membrane tubules formed and later vesiculated.(ABSTRACT TRUNCATED AT 250 WORDS)


Development of a quantitative antigen-specific cell-based ELISA for the 7G7/B6 monoclonal antibody directed toward IL-2Ralpha.
Interleukin-2 receptor alpha (IL-2Ralpha, CD25) has been identified as a valuable target for immunotherapy. The 7G7/B6 monoclonal antibody, a mouse IgG2a kappa, recognizes an epitope of the IL-2Ralpha peptide, other than that identified by anti-Tac. This antibody is currently being explored for potential therapeutic and diagnostic applications. Here, we show a cell-based enzyme-linked immunosorbent assay (CbELISA) method for quantitative measurement of the binding activity of the 7G7/B6 antibody to the Kit-225-iG3 cell line expressing IL-2Ralpha antigen on the cell surface. The cell- and antigen-specificity of the assay was established using specific cell lines and irrelevant control antibodies. Satisfactory binding curves were demonstrated with Kit-225-iG3 cells grown between 3 and 25 passages in culture and at seed densities of 2 x 10(5)-4 x 10(6) cells/well. The assay shows reproducible dose-response curves in the concentration range of 10-1000 ng/ml. The assay validation data presented here indicate that this CbELISA assay is quantitative, reproducible, robust, precise, and can be used to test the biological activity, lot to lot comparison, and stability of 7G7/B6 monoclonal antibody.


Theory of electric signals of membrane proteins in three dimensions.
Transmembrane ion pumps are often investigated experimentally by photoelectric measurements in model systems. In addition to the most widely used systems based on model membranes, a fundamentally different class is represented by the so-called suspension methods. In this technique the electric signal is measured on a bulk suspension of oriented ion pumps in the form of a displacement current. On this system, electric and spectroscopic experiments can be performed simultaneously. Using the information from both types of measurements, and utilizing the three-dimensional nature of the system, it is possible to follow the intramolecular charge motions in all three spatial directions. The derivable dipole moment changes associated with conformational transitions allow the verification of molecular dynamic models. In this work a theory is presented to describe the suspension method; samples with different symmetry properties and the possibilities of photoselection to obtain the desired three-dimensional information are analyzed.


The impact of COVID-19 outbreak on the Transfusion Medicine Unit of a Northern Italy Hospital and Cancer Centre.
The first wave of coronavirus disease-2019 (COVID-19) dramatically affected the Transfusion Medicine Unit of the Azienda Unità Sanitari Locale - Istituto di Ricovero e Cura a Carattere Scientifico (AUSL-IRCCS) di Reggio Emilia, which faced a total rearrangement of the procedures for donors and patients. This study aims to assess the major implications of COVID-19 on our department, focusing on the blood transfusion chain and therapies, in order to support transfusion specialists in seeking efficient ways to face similar future emergencies. This retrospective study compares our Transfusion Medicine Unit data collected between February and May 2020 with the same period in 2017-2019. Data on red blood cells and platelets donations, transfusions and clinical procedures were collected as aggregates from our internal electronic database. During the lockdown, donor centres were re-organized to reduce the risk of contagion and avoid unnecessary blood collection. Blood donations were re-scheduled to meet the decrease in elective surgery; consequently, plateletapheresis was implemented to supply the reduction of buffycoat-derived platelets. Transfusions significantly decreased together with orthopaedic and vascular surgery, while they were only marginally diminished for both cancer and onco-haematological patients. Reduced procedures for inpatients and outpatients were matched by remote medicine, addressing the need of a constant healthcare support for patients with chronic diseases. The described measures were adopted to avoid excessive blood collection and expiration, guarantee the safety of our ward (for both patients and staff) and supply the necessary transfusion therapies. These measures may support the development of appropriate risk management plans and safety procedures for other hospitals and transfusion services that have to face similar events.


Could spontaneous retroperitoneal haematoma present with scrotal mass?
Retroperitoneal haematoma could be caused by different factors. It is increasing due to an increase in the use of antithrombotic and anticoagulant therapy. Diagnosis of retroperitoneal haematoma forms a big challenge in daily clinical practice. Patients with retroperitoneal haematoma could present with leg paresis, abdominal pain, shock or abdominal compartment syndrome. Retroperitoneal haematoma could be treated conservatively but surgical interference or embolization of the bleeding vessels is always an option. To present a case with spontaneous retroperitoneal haematoma presenting with scrotal haematoma together with a mini- review of retroperitoneal haematoma. Retroperitoneal haematoma may present with a scrotal swelling and could be treated conservatively depending on the presentation and severity of the bleeding.


Phase 3 trials of aromatase inhibitors for breast cancer prevention: following in the path of the selective estrogen receptor modulators.
The third-generation aromatase inhibitors (AIs), anastrozole, exemestane, and letrozole are potential agents for preventing estrogen receptor (ER)-positive breast cancer (BC) in high-risk postmenopausal women. No AI has yet been fully evaluated for prevention. Each AI is incorporated into the design of a phase 3 randomized BC prevention trial based on hypothesis-generating contralateral breast cancer (CLBC) data from a corresponding adjuvant trial. Arimidex, tamoxifen alone or in combination (ATAC) pitted anastrozole against tamoxifen for 5 years as "initial adjuvant" therapy, showing at 33.3 months fewer CLBCs with anastrozole versus tamoxifen (odds ratio [OR] 0.42 overall; OR 0.29 ER-positive BCs), offering the hypothesis on which IBIS-II (International Breast Cancer Intervention Study) is based. "High-risk" IBIS-II compares anastrozole to placebo for the primary prevention of BC in 6000 postmenopausal women. IES (Intergroup Exemestane Study) compared exemestane to tamoxifen following 2-3 years of adjuvant tamoxifen in 4742 postmenopausal women with ER-positive BCs. The benefit from "switching" to exemestane in reducing CLBCs (HR 0.44 at 30.6 months) underlies MAP.3 (Mammary Prevention 3), which compares exemestane to placebo for primary BC risk reduction in 4560 postmenopausal women. MA.17 showed reduced CLBC incidence (HR 0.57) at 2.4 years in postmenopausal women with receptor-positive tumors receiving "extended adjuvant" letrozole compared to placebo following 5 years of tamoxifen. The Study of Letrozole and Raloxifene (STELLAR), using as the control raloxifene, the new U.S. standard drug for BC prevention, would complete the trio of AI prevention trials, but STELLAR is currently on hold.


[Experience with a double dose-monitoring system in the 18 MeV betatron therapy (author's transl)].
Correct setting of the patient dose within a range of about +/- 3% is only achieved if a second exposure monitoring system controls the output variations of a betatron beam. A sealed thimble chamber attached in the centre of the field on the patient, which switches off the betatron when a given exposure has exceeded proved as a safe device.


Screening of the heterotrophic microalgae strain for the reclamation of acid producing wastewater.
For the sustainable development of the environment, to reduce the high cost and low productivity of microalgae biofuel, nine microalgae strains were screened to study the growh and nutrient removal properties under heterotrophic culture by using the waste carbon source of volatile fatty acids (VFAs). Chlorella sorokiniana (C.sorokiniana) was selected as the best strain with the highest biomass concentration of 0.77 g L-1, specific growth rate of 0.25 d-1, biomass productivity of 91.43 mg L-1 d-1, total nitrogen removal efficiency of 95.96% and total phosphorus removal efficiency of 93.42%. To study the utilization potential of acid-producing wastewater by heterotrophic microalgae, actual acid-producing wastewater was recycled three times for the utilization of C.sorokiniana. After the three utilization cultivation, the removal rates of COD, total nitrogen, ammonia nitrogen, and total phosphorus were 74.44%, 88.05%, 79.08%, and 82.69%, respectively. The total utilization rates of acetic acid, propionic acid, and butyric acid were 58.99%, 70.54%, and 81.52%, respectively. In addition, the highest lipid content of 39.15% and protein content of 42.43% achieved at the third cultivation. After the first cultivation, the composition and diversity of the microbial community structure changed dramatically, with Protebacteria, Bacteroidota, Hydrogenophaga, and Algoriphagus becoming enriched. These results showed a promising way of coupling wastewater treatment with biomass production for long-term sustainability of microalgae lipid production.


Reliability of ultrasound to measure the distance between lumbar interspinous processes.
This study aimed to determine the reliability of ultrasound to measure the distance between interspinous processes of the lumbar spine at the segmental level (i.e., L1-L2, L2-L3, L3-L4, and L4-L5). Ten men with no history of orthopedic diseases or dysfunctions were included in this study. In total, 720 images of the lumbar spines of participants were analyzed (10 participants, 4 segments, 3 trials, 3 positions, 2 examiners). With participants in three different positions, images of each segment specifically focused on the distance between lumbar interspinous processes. Bland-Altman analysis (BAA) was used to determine intra- and inter-rater reliability. Intra-rater intraclass correlation coefficient (ICC) values (1, 1) were found to range from 0.840 to 0.988, whereas inter-rater ICC values (2, 1) ranged from 0.605 to 0.876. BAA results confirmed a fixed bias regarding the L4-L5 of the lumbar spine segment in the flexion position. Inter-rater reliability decreased throughout this study; however, results showed that using ultrasound to measure the distance between lumbar segmental interspinous processes could be applied in clinical settings to evaluate lumbar segmental mobility.


Serum Neutrophil Gelatinase-associated Lipocalin (NGAL) Is Elevated in Patients with Asthma and Airway Obstruction.
Neutrophilic airway inflammation is one of the features of severe asthma. Neutrophil gelatinase-associated lipocalin (NGAL), or lipocalin-2, is a glycoprotein associated with neutrophilic inflammation and can be detected in blood. Recently, blood NGAL levels have been reported to be elevated in chronic obstructive pulmonary disease. However, the clinical significance of serum NGAL levels in patients with asthma has not been elucidated. The aim of this study was to explore the association between serum NGAL level and clinical parameters in patients with asthma. Sixty-one non-smoking people with stable asthma were enrolled in this study. All patients underwent blood collection and pulmonary function tests. The associations between serum NGAL levels and clinical parameters were analyzed retrospectively. Serum NGAL levels in patients with asthma and obstructive ventilatory defect were higher than those in patients with asthma without obstructive ventilatory defect (76.4±51.4 ng/mL vs. 39.3±27.4 ng/mL, P=0.0019). Serum NGAL levels were correlated with forced expired flow at 50% of vital capacity %predicted and forced expired flow at 75% of vital capacity %predicted (r=-0.3373, P=0.0078 and r=-0.2900, P=0.0234, respectively). Results of a multiple regression analysis demonstrated that serum NGAL level was independently associated with obstructive ventilatory defect. Serum NGAL levels were elevated in patients with asthma and obstructive ventilatory defect. NGAL may be involved in airway remodeling possibly mediated by neutrophilic inflammation in asthma.


An engineered SARS-CoV-2 receptor-binding domain produced in Pichia pastoris as a candidate vaccine antigen.
Developing affordable and easily manufactured SARS-CoV-2 vaccines will be essential to achieve worldwide vaccine coverage and long-term control of the COVID-19 pandemic. Here the development is reported of a vaccine based on the SARS-CoV-2 receptor-binding domain (RBD), produced in the yeast Pichia pastoris. The RBD was modified by adding flexible N- and C-terminal amino acid extensions that modulate protein/protein interactions and facilitate protein purification. A fed-batch methanol fermentation with a yeast extract-based culture medium in a 50 L fermenter and an immobilized metal ion affinity chromatography-based downstream purification process yielded 30-40 mg/L of RBD. Correct folding of the purified protein was demonstrated by mass spectrometry, circular dichroism, and determinations of binding affinity to the angiotensin-converting enzyme 2 (ACE2) receptor. The RBD antigen also exhibited high reactivity with sera from convalescent individuals and Pfizer-BioNTech or Sputnik V vaccinees. Immunization of mice and non-human primates with 50 µg of the recombinant RBD adjuvanted with alum induced high levels of binding antibodies as assessed by ELISA with RBD produced in HEK293T cells, and which inhibited RBD binding to ACE2 and neutralized infection of VeroE6 cells by SARS-CoV-2. Additionally, the RBD protein stimulated IFNγ, IL-2, IL-6, IL-4 and TNFα secretion in splenocytes and lung CD3+-enriched cells of immunized mice. The data suggest that the RBD recombinant protein produced in yeast P. pastoris is suitable as a vaccine candidate against COVID-19.


The effect of hyaluronan-based delivery of stromal cell-derived factor-1 on the recruitment of MSCs in degenerating intervertebral discs.
Intervertebral disc (IVD) degeneration is the leading cause of low back pain and disability in the active population. Transplantation of mesenchymal stem cells (MSCs) in a hydrogel carrier can induce regenerative effects in degenerated IVDs. Moreover, it was found that degenerative discs release chemoattractants effective in MSC recruitment. Based on these findings, we hypothesized that an injectable hydrogel that can enhance the number of migrated MSCs in the IVD and provide a suitable matrix for their survival and differentiation would be ideal. The purpose of this study was to evaluate the potential of a thermoreversible hyaluronan-poly(N-isopropylacrylamide) (HAP) hydrogel as chemoattractant delivery system to recruit human MSCs in degenerative IVDs. The results demonstrate that HAP hydrogels containing stromal cell derived factor-1 (SDF-1) significantly increased the number of MSCs migrating into nucleotomized discs compared with discs treated with only HAP or SDF-1 in solution. HAP hydrogels releasing SDF-1 enhanced both the number of recruited cells and their migration distance in the IVD tissue. Furthermore, this phenomenon was dependent on MSC donor age. In conclusion, HAP SDF-1 is effective for the recruitment of stem cells in the IVD, thus opening new possibilities for the development of regenerative therapies based on endogenous cell migration.


Characteristics of Visual Saliency Caused by Character Feature for Reconstruction of Saliency Map Model.
Visual saliency maps have been developed to estimate the bottom-up visual attention of humans. A conventional saliency map represents a bottom-up visual attention using image features such as the intensity, orientation, and color. However, it is difficult to estimate the visual attention using a conventional saliency map in the case of a top-down visual attention. In this study, we investigate the visual saliency for characters by applying still images including both characters and symbols. The experimental results indicate that characters have specific visual saliency independent of the type of language.


Energy and environmental applications of Sn4+/Ti4+ doped α-Fe2O3@Cu2O/CuO photoanode under optimized photoelectrochemical conditions.
The most promising technique for directly converting solar energy into clean fuels and environmental remediation by organic dye degradation is photoelectrochemical (PEC) process. We introduced Sn4+/Ti4+ doped α-Fe2O3@CuxO heterojunction photoanode with complete optimization for PEC hydrogen (H2) generation and organic dye degradation. Improvement of photocurrent photo and reducing overpotentials under optimized conditions lead to enhancing PEC performances, degradation efficiency of organic compounds, and H2 generation generation rate. The optimized heterojunction photoanode (5TiFe@CuxO-D) showed IPCE exceeding 42% compared with pristine hematite (Fe0.01-8006h) nanostructures (28%). Additionally, all the optimized photoanodes showed higher PEC stability for 10 h. Time-resolved PL spectra confirm the improved average lifetime for heterojunction photoanodes, supporting the enhanced PEC performance. Optimized 5TiFe@CuxO-D material achieved PEC H2 generation of ∼300 μL h-1.cm-2 which is two times higher than pristine hematite's activity (150 μL h-1.cm-2) and almost 99% degradation efficiency within 120 min of irradiation time. Therefore, a state-of-the-art study has been explored for hematite-based heterojunction photoanodes reflecting the superior PEC performance and hydrogen, methyl orange (MO) dye degradation activities. The improved results were reported because of stable morphology and better crystallinity acquired through systematic investigation of thermal effects and hydrothermal duration, improved electrical properties by Sn/Ti doping into the lattice of α-Fe2O3 and optimization of CuxO deposition methods. The formation of well-defined heterojunction minimizes the recombination of the charge carrier and leads to effective transportation of excited electrons for the enhanced PEC performance.


Outbreak of invasive Streptococcus pneumoniae among an inner-city population in Victoria, British Columbia, 2016-2017.
Invasive pneumococcal disease (IPD) is a significant cause of morbidity and mortality; however, outbreaks of IPD are relatively rare. Homelessness and substance use are known risk factors for IPD and have been associated with several outbreaks in Canada, despite national recommendations for routine childhood and targeted adult pneumococcal vaccination. To describe the epidemiology and public health challenges related to an outbreak of novel serotype 4 IPD in a homeless and unstably housed population in Victoria, British Columbia during the autumn and winter of 2016-2017. Prospective, enhanced surveillance was initiated for laboratory confirmed cases reported to public health, including variables recording housing status and substance use. Thirty-three cases of serotype 4 IPD within the Victoria area were reported to public health between August 1, 2016 and September 1, 2017. Compared with other serotypes, these cases were more likely to be middle-aged, homeless or unstably housed, and to have a recent history of substance use. A targeted pneumococcal vaccination campaign was initiated in collaboration with external community organizations; however, these initiatives were challenged by incomplete data and staffing constraints. This report illustrates an outbreak of serotype 4 IPD among an inner-city population with multiple risk factors, including homelessness, unstable housing and substance use. Given the challenges controlling the outbreak, outreach capacity and pneumococcal vaccination coverage is needed among this marginalized population.


Sacroiliac joint injections performed with sonographic guidance.
To investigate the feasibility and effectiveness of sonographic guidance for therapeutic intra-articular sacroiliac joint injections in patients with sacroiliitis. Thirty-four consecutive patients with sacroiliitis were enrolled in this study. The synovial portions of 60 sacroiliac joints received injections under sonographic guidance. For treatment, a mixture of a corticosteroid and a local anesthetic was injected intra-articularly. Fluoroscopic spot images were obtained to assess the accuracy of the sonographically guided technique. Of the 60 sonographically guided injections, 46 (76.7%) were successful (i.e., intra-articular), and 14 (23.3%) were missed. The successful intra-articular injection rate was 60% in the first 30 injections, and it gradually improved, reaching 93.5% in the last 30 injections. The mean procedure time was 9 minutes. Our initial experience suggests that sonographically guided therapeutic injections to sacroiliac joints could be valuable alternatives to other guidance modalities in patients with sacroiliitis. In the hands of experienced radiologists, this technique is safe, rapid, and reproducible.


Association of homologous chromosomes during floral development.
Reduction in chromosome number and genetic recombination during meiosis require the prior association of homologous chromosomes, and this has been assumed to be a central event in meiosis. Various studies have suggested, however, that while the reduction division of meiosis is a universally conserved process, the pre-meiotic association of homologues differs among organisms. In the fruit fly Drosophila melanogaster, some somatic tissues also show association of homologues [1,2]. In the budding yeast Saccharomyces cerevisiae, there is some evidence for homologue association during the interphase before meiotic division [3,4], and it has been argued that such associations lead directly to meiotic homologue pairing during prophase I [5]. The available evidence for mammals suggests that homologous chromosomes do not associate in germ cells prior to meiotic prophase [6]. To study the occurrence of homologue pairing in wheat, we have used vibratome tissue sections of wheat florets to determine the location of homologous chromosomes, centromeres and telomeres in different cell types of developing anthers. Fluorescence in situ hybridization followed by confocal microscopy demonstrated that homologous chromosomes associate pre-meiotically in meiocytes (germ-line cells). Surprisingly, association of homologues was observed simultaneously in all the surrounding somatic tapetum cells. Homologues failed to associate at equivalent stages in a homologue recognition mutant. These results demonstrate that the factors responsible for the recognition and association of homologues in wheat act before the onset of meiotic prophase. The observation of homologue association in somatic tapetum cells demonstrates that this process and meiotic division are separable.


Avoiding Systematic Bias in Orthopedics Research Through Informed Variable Selection: A Discussion of Confounders, Mediators, and Colliders.
There are 3 common variable types in orthopedic research-confounders, colliders, and mediators. All 3 types of variables are associated with both the exposure (eg, surgery type, implant type, body mass index) and outcome (eg, complications, revision surgery) but differ in their temporal ordering. To reduce systematic bias, the decision to include or exclude a variable in an analysis should be based on the variable's relationship with the exposure and outcome for each research question. In this article, we define 3 types of variables with case examples from orthopedic research. Please visit the followinghttps://youtu.be/V-grpgB1ShQfor videos that explain the highlights of the article in practical terms.


A nodal EBV-positive T cell lymphoma with a T follicular helper cell phenotype.
Nodal T follicular helper (TFH) cell lymphoma (nTFHL) is a rare type of clinically aggressive T cell lymphoma. With this lymphoma type, Epstein-Barr virus (EBV) infection is frequently detected in non-neoplastic B lymphocytes, but not yet identified in neoplastic T cells. We report two cases of nTFHL showing a classic morphology and immunoprofile, with EBV-encoded small RNAs (EBER) in-situ hybridisation positivity in neoplastic TFH cells. Clonal T cell receptor (TR) gene rearrangement was detected in both cases. Whole exome sequencing identified TET2, RHOA p. G17V, as well as gene mutations unique to each case. Microdissection analysis showed EBER positivity in tumour cells and in background non-neoplastic T lymphocytes. These two immunocompetent cases of nTFHL with EBV-positive tumour cells exhibit the featured gene mutation profile and poor prognosis of this disease. This novel finding of EBV positivity in our cases expands the currently recognised spectrum of EBV-positive nodal T cell lymphomas to include rare cases of nTFHL.


The 2.8 A structure of hydroxylamine oxidoreductase from a nitrifying chemoautotrophic bacterium, Nitrosomonas europaea.
The 2.8 A crystal structure of hydroxylamine oxidoreductase of a nitrifying chemoautotrophic bacterium, Nitrosomonas europaea, is described. Twenty-four haems lie in the centre bottom of the trimeric molecule, localized in four clusters within each monomer. The haem clusters within the trimer are aligned to form a ring that has inlet and outlet sites. The inlet is occupied by a novel haem, P460, and there are two possible outlet sites per monomer formed by paired haems lying within a cavity or cleft on the protein surface. The structure suggests pathways by which electron transfer may occur through the precisely arranged haems and provides a framework for the interpretation of previous and future biochemical and genetic observations.


Nucleotide sequence determines the accelerated rate of point mutations.
Although the theory of evolution was put forth about 150 years ago our understanding of how molecules drive evolution remains poor. It is well-established that proteins evolve at different rates, essentially based on their functional role and three-dimensional structure. However, the highly variable rates of evolution of different proteins - especially the rapidly evolving ones - within a single organism are poorly understood. Using examples of genes for fast-evolving toxins and human hereditary diseases, we show for the first time that specific nucleotide sequences appear to determine point mutation rates. Based on mutation rates, we have classified triplets (not just codons) into stable, unstable and intermediate groups. Toxin genes contain a relatively higher percentage of unstable triplets in their exons compared to introns, whereas non-toxin genes contain a higher percentage of unstable triplets in their introns. Thus the distribution of stable and unstable triplets is correlated with and may explain the accelerated evolution of point mutations in toxins. Similarly, at the genomic level, lower organisms with genes that evolve faster contain a higher percentage of unstable triplets compared to higher organisms. These findings show that mutation rates of proteins, and hence of the organisms, are DNA sequence-dependent and thus provide a proximate mechanism of evolution at the molecular level.


A murine model of intracranial invasion: morphological observations on central nervous system invasion by murine melanoma cells.
We describe a model of tumour invasion in which murine melanoma/lymphocyte hybrid cells are injected into the lateral ventricle of neonatal mice. CSF circulation carries cells to the third ventricle where attachment to the ependyma and invasion of the underlying brain may be observed. At this distance from the injection site, invasion can be studied free from trauma or inflammation induced by the injection procedure. Accordingly we restricted our attention to the third ventricle. Our results reveal an unusual form of tumour invasion of the ependyma characterized by progressive attenuation of the ependymal cell layer immediately beneath tumour cell aggregates. Continuity of the ependymal cell layer is ultimately lost at a focal point immediately beneath the tumour, permitting direct contact between tumour cells and the neuropil. Subsequent deep invasion of the brain parenchyma is accomplished by pericapillary infiltration.


Comparison of complexed species of Eu in alumina-bound and free polyacrylic acid: a spectroscopic study.
The speciation of Eu complexed with polyacrylic acid (PAA) and alumina-bound PAA (PAA(ads)) was studied at pH 5 in 0.1 M NaClO(4). Structural parameters were obtained from (7)F(0) -->(5)D(0) excitation spectra measured by laser-induced fluorescence spectroscopy as well as from Eu L(III)-edge extended X-ray absorption fine structure (EXAFS) spectra. The coordination mode was also investigated by infrared spectroscopy. To elucidate the nature of the complexed species, Eu-acetate complexes were used as references. The spectroscopic techniques show that two carboxylate groups with 2-3 (EuPAA) and 4-5 (EuPAA(ads)) water molecules are coordinated to Eu in the first coordination sphere. For EuPAA(ads), the coordination between carboxylate groups and Eu appears to be bidendate. A similar coordination is probable for EuPAA but the EXAFS data indicate a slightly distorted coordination. The results show that the degree of freedom of carboxylate groups is not the same for free or adsorbed PAA. For PAA, the degree of freedom is constrained by the flexibility of the methylene chain. When PAA is adsorbed on alumina, the polymer chains cannot any more be treated as independent chains. One may rather assume formation of aggregates that form an organic layer at the mineral surface presenting a complex arrangement of carboxylate groups.


Do the terms "proximal" and "distal" cause confusion amongst radiologists and other clinicians?
To investigate the use of the terms "proximal" and "distal", and what respondents think the terms mean, when applied to certain structures within the trunk, notably the veins and the biliary tract. Fifty-three respondents were interviewed using simplified anatomical diagrams. Respondents were asked what terms they would use to describe sites at opposite ends of the superior vena cava (SVC), internal jugular vein (IJV), common bile duct (CBD), and pancreatic duct. They were also asked which end of each of these structures they would think was being referred to if they read a radiological report that used these terms. The terms "proximal" and "distal" were used by at least 50% of all respondents, and, specifically, at least 60% of radiologists at all four anatomical sites. Eighty-five percent (n=45) of all respondents and 100% (n=24) of radiologists agreed that the term "proximal" CBD referred to its superior end. However, at the other sites there was marked disagreement, 67% (n=16) of radiologists thought the superior SVC and superior IJV were "proximal", 33% (n=8) thought they were "distal". There was a 54% (n=13) to 46% (n=11) split amongst radiologists as to which end of the pancreatic duct was "proximal". The terms "proximal" and "distal" are the most frequently used terms to describe positions in veins and the biliary system, but there is widespread confusion about their meaning, which could lead to medical error and ultimately patient harm. The use of alternative terms is advised.


Association between consistent weight gain tracking and gestational weight gain: Secondary analysis of a randomized trial.
The effective components of interventions for reducing excessive gestational weight gain (GWG) remain to be identified. This study investigated the sociodemographic, physical, psychosocial, and environmental correlates of online GWG tracking and its independent association with GWG outcomes. Eight hundred ninety-eight women in the intervention arms of a randomized trial assessing the effectiveness of an integrated online and mobile phone behavioral intervention to decrease the prevalence of excessive GWG were included in this secondary analysis. Data were analyzed using χ2 analysis and modified Poisson and linear regression approaches. Only 16.5% of low-income (Medicaid-eligible) women consistently tracked GWG, as did 34.2% of not-low-income women. More highly educated, older, and white women were more likely to be consistent GWG trackers. Among not-low-income women, consistent GWG tracking was associated with 2.35 kg less GWG (95% CI: -3.23 to -1.46 kg; P < 0.0001) and a reduced risk of excessive GWG (RR 0.73; 95% CI: 0.59 to 0.89; P = 0.002). Electronic tracking of GWG is an effective component of electronic and mobile health interventions aiming to decrease the prevalence of excessive GWG in not-low-income women. Income group-specific motivators are needed to increase the prevalence of GWG tracking.


Influence of different dietary concentrations of linoleic acid on the essential fatty acid (EFA) status and functional characteristics of porcine hepatic and cardiac mitochondria.
The effect of different dietary concentrations of linoleic acid (0.2, 1.1 and 2.1% of gross energy in experiment 1 and 0.7, 1.6 and 2.3% of gross energy in experiment 2) on the EFA status and the functional characteristics of hepatic and cardiac mitochondria was investigated in pigs raised for 140 days from 10 to 105 kg live wt on their respective diets. As judged from the ratios of 20:3n9 to 20:4n6 of hepatic and cardiac mitochondrial total lipids the pigs receiving 0.2% of dietary gross energy as linoleic acid were EFA-deficient, while the pigs receiving 0.7% of dietary gross energy as linoleic acid were on the borderline of EFA deficiency. Mitochondrial protein yield and the functional parameters (endogenous respiration, respiration of exogenous NADH, state 2, 3 and 4 respiration, RCI-values, ADP/O ratios and synthetic rates of ATP) as measured in both hepatic and cardiac mitochondria with two substrates pyruvate plus malate and succinate in the presence of rotenone were not significantly (P greater than 0.05) affected by the different dietary concentrations of linoleic acid. The findings indicate a slow turnover of EFA and a low desaturation/elongation activity of the associated enzymes in the pig.


Sex and Urban-Rural Differences in the Relationship between Childhood Sexual Abuse and Mental Health among Chinese College Students.
This study aimed to reveal sex and urban-rural differences in the association between childhood sexual abuse (CSA) and mental health among Chinese college students. The study used data from the "National College Student Survey on Sexual and Reproductive Health 2019", a cross-sectional study conducted in all 31 provinces of mainland China. Weighted logistic regression analysis was conducted to determine the association between CSA (noncontact CSA, contact CSA, and penetrative CSA) and mental health (suicide attempts and mental disorders). Among 49,728 students, 39.42% of the male participants and 43.55% of the female participants had ever experienced CSA. According to the OR results of logistic regression analysis, compared to females, males in the contact CSA group (AOR: 3.49, 95% CI: 1.95-6.23) and the penetrative CSA group (AOR: 8.79, 95% CI: 3.15-24.52) had higher odds of suicide attempts. Participants from rural and suburban areas that were categorized in the penetrative CSA group were more likely to report suicide attempts (rural: AOR: 4.01, 95% CI: 1.51-10.62, suburban AOR: 4.86, 95% CI: 2.52-9.36) and mental disorders (rural: AOR: 4.01, 95% CI: 1.51-10.62, suburban: AOR: 4.86, 95% CI: 2.52-9.36). In conclusion, the findings revealed a high prevalence of CSA in both sexes and reported that males are more vulnerable to the adverse effects of CSA. In addition, we also found that undergraduates growing up in rural and suburban areas are more vulnerable to the adverse psychological effects of CSA. Policymakers should pay more attention to this vulnerable population and implement effective measures to alleviate mental trauma.


Perimetry of critical flicker frequency in human rod and cone vision.
Photopic critical flicker frequency (CFF) to green and yellow-red targets became independent of visual field location when the decrease in the density of retinal ganglion cells and increase in their receptive-field size towards the retinal periphery were compensated for by increasing stimulus area in inverse proportion to the human cortical magnification factor squared (M-scaling) and by reducing stimulus luminance in inverse proportion to Ricco's area (F-scaling). In mesopic and scotopic vision CFF to green targets increased monotonically with eccentricity despite MF-scaling. Instead, CFF to MF-scaled yellow-red targets that predominantly stimulated cones was independent of eccentricity at all luminance levels tested.


Two-dimensional patterns in bacterial veils arise from self-generated, three-dimensional fluid flows.
The behavior of collections of oceanic bacteria is controlled by metabolic (chemotaxis) and physical (fluid motion) processes. Some sulfur-oxidizing bacteria, such as Thiovulum majus, unite these two processes via a material interface produced by the bacteria and upon which the bacteria are transiently attached. This interface, termed a bacterial veil, is formed by exo-polymeric substances (EPS) produced by the bacteria. By adhering to the veil while continuing to rotate their flagella, the bacteria are able to exert force on the fluid surroundings. This behavior induces a fluid flow that, in turn, causes the bacteria to aggregate leading to the formation of a physical pattern in the veil. These striking patterns are very similar in flavor to the classic convection instability observed when a shallow fluid is heated from below. However, the physics are very different since the flow around the veil is mediated by the bacteria and affects the bacterial densities. In this study, we extend a model of a one-dimensional veil in a two-dimensional fluid to the more realistic two-dimensional veil in a three-dimensional fluid. The linear stability analysis indicates that the Peclet number serves as a bifurcation parameter, which is consistent with experimental observations. We also solve the nonlinear problem numerically and are able to obtain patterns that are similar to those observed in the experiments.


Combination immunotherapy induces distinct T-cell repertoire responses when administered to patients with different malignancies.
CTLA-4 blockade with ipilimumab is Food and Drug Administration-approved for melanoma as a monotherapy and has been shown to modulate the circulating T-cell repertoire. We have previously reported clinical trials combining CTLA-4 blockade with granulocyte-macrophage colony-stimulating factor (GM-CSF) in metastatic melanoma patients and in metastatic castration resistant prostate cancer (mCRPC) patients. Here, we investigate the effect that cancer type has on circulating T cells in metastatic melanoma and mCRPC patients, treated with ipilimumab and GM-CSF. We used next-generation sequencing of T-cell receptors (TCR) to compare the circulating T cells of melanoma and mCRPC patients receiving the same treatment with ipilimumab and GM-CSF by Wilcoxon rank sum test. Flow cytometry was utilized to investigate specific T-cell populations. TCR sequencing results were correlated with each T-cell subpopulation by Spearman's rank correlation coefficient. Of note, 14 metastatic melanoma patients had samples available for TCR sequencing and 21 had samples available for flow cytometry analysis; 37 mCRPC patients had samples available for sequencing of whom 22 have TCR data available at both timepoints; 20 of these patients had samples available for flow cytometry analysis and 16 had data available at both timepoints. While melanoma and mCRPC patients had similar pretreatment circulating T-cell counts, treatment induces greater expansion of circulating T cells in melanoma patients. Metastatic melanoma patients have a higher proportion of clones that increased more than fourfold after the treatment compared with mCRPC patients (18.9% vs 11.0%, p=0.017). Additionally, melanoma patients compared with mCRPC patients had a higher ratio of convergent frequency (1.22 vs 0.60, p=0.012). Decreases in clonality induced by treatment are associated with baseline CD8+ T-cell counts in both patient groups, but are more pronounced in the melanoma patients (r=-0.81, p<0.001 vs r=-0.59, p=0.02). NCT00064129; NCT01363206.