A novel quinazolinone derivative induces cytochrome c interdependent apoptosis and autophagy in human leukemia MOLT-4 cells.
Crosstalk between apoptosis and autophagy is budding as one of the novel strategies in the cancer therapeutics. The present study tinted toward the interdependence of autophagy and apoptosis induce by a novel quinazolinone derivative 2,3-dihydro-2-(quinoline-5-yl) quinazolin-4(1H)-one structure [DQQ] in human leukemia MOLT-4 cells. DQQ induces cytochrome c arbitrated apoptosis and autophagy in MOLT-4 cells. Apoptosis induces by DQQ was confirmed through a battery of assay e.g. cellular and nuclear microscopy, annexin-V assay, cell cycle analysis, loss of mitochondrial membrane potential and immune-expression of cytochrome c, caspases and PARP. Furthermore, acridine orange staining, LC3 immunofluorescence and western blotting of key autophagy proteins revealed the autophagic potential of DQQ. A universal caspase inhibitor, Z-VAD-FMK and cytochrome c silencing, strongly inhibited the DQQ induce autophagy and apoptosis. Beclin1 silencing through siRNA partially reversed the cell death, which was not as significant as by cytochrome c silencing. Although, it partially reversed the PARP cleavage induced by DQQ, indicating the role of autophagy in the regulation of apoptosis. The present study first time portrays the negative feedback potential of cytochrome c regulated autophagy and the importance of quinazolinone derivative in discovery of novel anticancer therapeutics.


Regulatory T cells and immunodeficiency in mycosis fungoides and Sézary syndrome.
Cutaneous T-cell lymphoma (CTCL) is the term for diseases characterized by primary accumulation of malignant T cells in the skin. Patients with the two predominant clinical forms of CTCL called mycosis fungoides (MF) and Sézary syndrome (SS) characteristically develop severe immunodeficiency during disease progression and consequently patients with advanced disease frequently die of infections and not from the tumor burden. For decades, it has been suspected that the malignant T cells actively drive the evolving immunodeficiency to avoid antitumor immunity, yet, the underlying mechanisms remain unclear. The identification of a subset of highly immunosuppressive regulatory T cells (Tregs) triggered a variety of studies investigating if MF and SS are malignant proliferations of Tregs but seemingly discordant findings have been reported. Here, we review the literature to clarify the role of Tregs in MF and SS and discuss the potential mechanisms driving the immunodeficiency.


Desloratadine citrate disodium injection, a potent histamine H(1) receptor antagonist, inhibits chemokine production in ovalbumin-induced allergic rhinitis guinea pig model and histamine-induced human nasal epithelial cells via inhibiting the ERK1/2 and NF-kappa B signal cascades.
Chemokines have chemotactic properties on leukocyte subsets whose modulation plays a pivotal role in allergic inflammatory processes. Our present study was designed to investigate the anti-allergic and anti-inflammatory properties of desloratadine citrate disodium injection (DLC) and elucidate the molecular mechanisms of its anti-inflammatory properties. The anti-allergic effects of DLC were evaluated based on allergic symptoms, serological marker production and histological changes of the nasal mucosa in guinea pigs model of allergic rhinitis. The anti-inflammatory properties and molecular mechanisms of DLC were explored by studying the regulation of a set of chemokines and extracellular signal-regulated kinase (ERK)1/2 and nuclear factor-kappa B (NF-κB) pathways, after DLC treatment in guinea pigs model of allergic rhinitis in vivo and histamine-activated human nasal epithelial cells (HNECs) in vitro. In vivo model in guinea pigs, DLC alleviated the rhinitis symptoms, inhibited inflammatory cells infiltration in nasal lavage fluid (NLF) and histamine, monocyte chemotactic protein (MCP)-1, regulated on activation normal T cell expressed, and presumably secreted (RANTEs) and interleukin (IL)-8 release in sera and P-ERK1/2 and NF-κB activation in nasal mucosa. In vitro, DLC markedly inhibited histamine-induced production of MCP-1, RANTEs and IL-8 and suppressed c-Raf, mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) and ERK1/2 activation in HNECs. These results provide evidence that DLC possesses potent anti-allergic and anti-inflammatory properties. The mechanism of action underlying DLC in allergic inflammation appears to be inhibition of the phosphorylation of ERK1/2, in addition to blocking of the NF-κB pathway.


Antioxidant properties of scopoletin isolated from Sinomonium acutum.
Scopoletin was isolated from Sinomonium acutum and studied using four experimental models designed to assess antioxidant properties. The results indicated that scopoletin scavenged superoxide anion in the xanthine/xanthine oxidase reaction system in a concentration-dependent manner, but did not inhibit xanthine oxidase. Scopoletin may therefore be responsible for the superoxide anion scavenging activity seen in Sinomonium acutum extracts and may be of use in preventing superoxide anion-induced damage in vivo.


Air quality assessment in biosphere reserves close to emission sources. The case of the Spanish "Tablas de Daimiel" national park.
This work shows that biosphere reserves, national parks and other protected natural areas require in situ tools to monitor and detect local and remote air pollution sources which are a threat to flora, fauna water and soil. Industries in surrounding areas, traffic and long-range transport of air pollution, can change with time and meteorology and so each national park should also have a historical database of the air quality in the site. This study reports surface measurements of ozone, NO, NO2, CO, SO2 and PM2.5 acquired from March 2020 to July 2021 in "Las Tablas de Daimiel", a wetland Mediterranean National Park bordered by different cities and new industries in the field of the revalorization of agricultural wastes. Simultaneous data from a background station in a rural area isolated from air pollution are considered as reference. Twelve campaigns of one week duration were also performed to sample air in sorbent tubes to analyse volatile organic compounds from anthropogenic sources. Data are discussed considering meteorology, especially wind speed and direction together with the assessment of back-trajectories of air masses from distant sources. The results show that the effects of pollution from local and faraway sources on air quality in the park were weak. Thus, except for the high levels of ozone, with a mean value of 71 μg.m-3, measured mass loadings for pollutants were low and not in exceedance of the air quality standards. Saharan dust events were frequent and contributed to PM2.5 levels in the site. NOx and SO2 average concentrations (3.2 and 0.4 μg.m-3, respectively) were below the recommended critical levels for vegetation and all the quantified VOCs were found in average concentration levels below 0.5 μg.m-3.


Effects of weight bearing and non-weight bearing exercises on bone properties using calcaneal quantitative ultrasound.
This study was designed to investigate bone properties using heel quantitative ultrasound (QUS) in young adults participating in various sports. A cross sectional study was performed on Chinese male students (n = 55), aged 18-22 years. Subjects with previous fractures or suffering from any diseases known to affect bone metabolism or taking any medication with such an effect, were not included. The subjects were categorised according to their main sporting activities, including soccer (n = 15) (a high impact, weight bearing exercise), dancing (n = 10) (a low impact, weight bearing exercise), and swimming (n = 15) (non-weight bearing exercise). A sedentary group acted as controls (n = 15). A reproducibility study of the velocity of sound (VOS) and the broadband ultrasound attenuation (BUA) measurement was performed and analysed using the intraclass correlation coefficient (ICC). There was good intra-investigator and inter-investigator agreement (ICC > or = 0.8; p < 0.05) in the measurement of BUA and VOS. No significant differences in BUA and VOS (p > 0.05) were found between the dominant and non-dominant heel. Soccer players (137 +/- 4.3 dB/MHz; 1575 +/- 56 m/s; 544.1 +/- 48.4) and dancers (134.6 +/- 3.7 dB/MHz; 1538 +/- 46 m/s; 503.0 +/- 37.0) had significantly higher BUA, VOS, and stiffness index (SI) scores (p < 0.05), respectively, than swimmers (124.1 +/- 5.1 dB/MHz; 1495 +/- 42 m/s; 423.3 +/- 46.9) and the sedentary control group (119.9 +/- 6.1 dB/MHz; 1452 +/- 41 m/s; 369.9 +/- 46.4). A trend of a significant linear increase with the weight bearing and high impact exercise was revealed in all QUS parameters (p < 0.05). This cross sectional study indicated that regular participation in weight bearing exercise in young people might be beneficial for accruing peak bone mass and optimising bone structure.


Uncovering the antimalarial potential of toad venoms through a bioassay-guided fractionation process.
Malaria remains to date one of the most devastating parasitic diseases worldwide. The fight against this disease is rendered more difficult by the emergence and spread of drug-resistant strains. The need for new therapeutic candidates is now greater than ever. In this study, we investigated the antiplasmodial potential of toad venoms. The wide array of bioactive compounds present in Bufonidae venoms has allowed researchers to consider many potential therapeutic applications, especially for cancers and infectious diseases. We focused on small molecules, namely bufadienolides, found in the venom of Rhinella marina (L.). The developed bio-guided fractionation process includes a four solvent-system extraction followed by fractionation using flash chromatography. Sub-fractions were obtained through preparative TLC. All samples were characterized using chromatographic and spectrometric techniques and then underwent testing on in vitro Plasmodium falciparum cultures. Two strains were considered: 3D7 (chloroquine-sensitive) and W2 (chloroquine-resistant). This strategy highlighted a promising activity for one compound named resibufogenin. With IC50 values of (29 ± 8) μg/mL and (23 ± 1) μg/mL for 3D7 and W2 respectively, this makes it an interesting candidate for further investigation. A molecular modelling approach proposed a potential binding mode of resibufogenin to Plasmodium falciparum adenine-triphosphate 4 pump as antimalarial drug target.


Risk factors for osteomyelitis.
An approach that is useful in classifying the risk factors for the development of acute osteomyelitis is the same as one commonly employed to discuss the mechanisms responsible for pathogenesis: hematogenous dissemination, direct inoculation, and contiguous spread from an adjacent area of soft tissue infection. Acute hematogenous osteomyelitis is predominantly a disease of children. Factors that favor the development of acute bone infection are those that predispose to bacteremia. These include indwelling intravascular catheters, distant foci of infection, and intravenous drug abuse. The distant sites of focal infection that are most commonly associated with acute osteomyelitis include the skin as well as urinary and respiratory tracts. Two patient groups with an usual susceptibility to acute skeletal infections are those with sickle cell anemia and chronic granulomatous disease. The second major mechanism for the development of acute osteomyelitis is by direct inoculation. Injuries due to penetrating bites and puncture wounds of the food may serve to infect bone directly. Diagnostic procedures (lumbar puncture, fetal monitoring electrodes, suprapubic aspiration, and heel sticks) may result inadvertently in the inoculation of a neighboring osseous structure. Surgical procedures such as internal fixation of long bone fractures and skeletal traction may cause an infection of the bone. Osteomyelitis may develop as a consequence of contiguous spread of infection from adjacent soft tissue, particularly if vascular insufficiency complicates the clinical picture. Infection of the mandible, maxilla, and frontal or mastoid bones may result from persistent or neglected infection of the teeth, paranasal sinuses, or middle ear cavity, respectively. The major risk factor for chronic infection of bone is inadequate or delayed management of acute osteomyelitis or completely unrecognized bone infection.


SjO2/SvO2 correlation during pediatric cardiac surgery with cardiopulmonary bypass.
To compare the SjO2 (cerebral oxygenation indicator) and SvO2 (cardiac output indicator) during pediatric cardiac surgery with cardiopulmonary bypass (CPB). Retrospective study. Data of SjO2 and SvO2 measured simultaneously at critical time periods during cardiac surgery with CPB were analyzed by the Spearman correlation test and Bland- Altman plot. Regression analysis of the pooled data showed poor correlation between SjO2 and SvO2 (r²=0.14, P=0.03) and Bland- Altman plot had a high bias (-7.9), indicating independency of the two variables. SjO2<50% (indicative of cerebral ischemia-hypoxia) were observed in 50% of the measurements after rewarming during hypothermic CPB. SvO2 is not a good predictor of SjO2 during pediatric cardiac surgery with CPB, and low SjO2 can be undetected measuring SvO2 only.


Effect of using vacutainers with cartoon characters on the pain and fear levels of preschoolers during bloodletting.
Our study aims to analyse the effect of using a vacutainer with cartoon characters on preschoolers' pain and fear levels during the bloodletting process. The experimental, randomised controlled clinical trial was conducted with 102 children aged 3-6 years, randomised into control and experimental groups. The bloodletting routine was applied to the control group. The vacutainer of each child in the experimental group was covered with the illustration of their chosen cartoon character and blood was drawn with it. The fear and pain levels during the bloodletting procedure were examined in both groups. Pain and fear levels were significantly lower in the experimental group than in the experimental group (P < 0.05). Our research highlighted that using a cartoon character sticker with a vacutainer can reduce preschoolers' pain and fear during bloodletting.


Detection and recognition of radial frequency patterns.
Detection thresholds for radial deformations of circular contours were measured using a range of radii and contour peak spatial frequencies. For radial frequencies above two cycles, thresholds were found to be a constant fraction of the mean radius across a four-octave range of pattern radii and peak spatial frequencies (mean Weber fraction: 0.003-0.004). At low radial frequencies, thresholds were unaffected by contrast reduction. In 167 ms presentations, subjects were able to identify radial frequencies of six cycles and below with an accuracy of over 90% correct even when phase was randomized. The extreme sensitivity of subjects to these radial deformations (as low as 2-4 s of arc) cannot be explained by local orientation or curvature analysis, and points instead to the global pooling of contour information at intermediate levels of form vision.


Corrigendum: Comparison of Ceramic-on-Ceramic vs. Ceramic-on-Polyethylene for Primary Total Hip Arthroplasty: A Meta-Analysis of 15 Randomized Trials.
[This corrects the article DOI: 10.3389/fsurg.2021.751121.].


[Electron microscopy of spermatozoa. Indications and results].
Electron microscopy of spermatozoa is required in cases of important and persistent disorders of motility. Within the frame of fertility investigations, it can also prove useful in cases of in vitro fertilisation failures where structural defects of acrosome may be detected. Lastly subclinical seminal infections are diagnosed in more than 20% and account for a substantial number of acquired head anomalies and necrospermia.


Prosthodontics dental materials: From conventional to unconventional.
New inventions and innovations in the field of dentistry have potential applications to satisfy the patient's demand. In prosthodontics, a dental prosthesis plays a major role in improving the quality of oral health care. Currently, the trends have shifted towards the implants and implant-supported prosthesis for the replacement of missing teeth. Conventional dentures are patient's preference mainly due to financial constraints. In an attempt to find solutions to current problems, we have come across new materials zirconium, titanium and new inventions like flexible dentures, fenestrated dentures, and CAD/CAM fabricated dentures. Using the progress of past five years in the field of prosthodontics, this comprehensive review focuses on denture base materials, denture liners, removable partial dentures, fixed prosthesis such as crown and bridge materials, implant-supported a fixed denture, artificial teeth materials, impression materials, and ingenious alternatives to conventional dentures. This article also sheds some light on the current promising researches and gives insight into the problems that can be the focus of future researches.


Site-Specific Incorporation of Two ncAAs for Two-Color Bioorthogonal Labeling and Crosslinking of Proteins on Live Mammalian Cells.
The pyrrolysyl-tRNA/pyrrolysyl-tRNA synthetase (PylT/RS) pair from the archaeon Methanosarcina mazei (Mma) is widely used in protein engineering to site-specifically introduce noncanonical amino acids (ncAAs) through nonsense codon suppression. Here, we engineer the PylT/RS pair encoded by Methanogenic archaeon ISO4-G1 (G1) to be orthogonal to Mma PylT/RS and alter the G1 PylRS active site to accept a complementary ncAA spectrum. We combine the resulting mutual orthogonal pairs for site-specific dual ncAA incorporation of two lysine analogs with high selectivity and efficiency. Demonstrating the robustness of the system, we incorporate two ncAAs with compatible bioorthogonal reactivity into a Notch receptor, as well as a G protein-coupled receptor. We show that selective and site-specific incorporation of two ncAAs allows for two-color bioorthogonal labeling as well as chemical-controlled crosslinking of surface proteins on live mammalian cells.


Misoprostol dose selection in a controlled-release vaginal insert for induction of labor in nulliparous women.
The purpose of this study was to identify the maximum tolerable dose and to determine the efficacy of different misoprostol dose reservoirs in an intravaginal controlled-release hydrogel polymer. Nulliparous women at > or = 37 weeks' gestation requiring cervical ripening and induction of labor were treated with misoprostol in a controlled-release, retrievable hydrogel polymer vaginal insert. Sequential cohorts of 6 patients were to be treated with escalating dose reservoirs of 25, 50, 100, 200, and 300 mug. The insert was to be removed upon onset of active labor, at 24 hours, or earlier if treatment-related adverse events occurred. The safety end point was determination of the maximum tolerable dose (MTD) based on occurrence of hyperstimulation syndrome. Our primary efficacy end point was time to vaginal delivery. Increasing reservoir doses of misoprostol up to 100 microg produced more rapid increases in modified Bishop scores, less need for oxytocin, and a shorter time to vaginal delivery. Doses above 100 microg did not further enhance cervical ripening or shorten time to vaginal delivery. The median time to vaginal delivery was 14.2 hours using the 100 microg dose. Uterine hyperstimulation and adverse fetal heart rate effects occurred with the 200 and 300 microg inserts. The 100 microg vaginal insert resulted in successful cervical ripening and rapid vaginal delivery with an acceptable safety profile for future randomized clinical trials.


Normal radiographic heart volume in the neonate. 1. Dependence of ductal closure.
The hypothesis that the normal distribution of relative heart volume in the neonatal period is a mixture of two different populations, with different means and variances, has been tested. The definition of the two populations was (i) normally patent ductus and (ii) closed ductus arteriosus. The assumed frequencies of the patency in different age-groups were taken from Gentile et coll. [5]. A material consisting of 100 neonates found to be normal has been analysed radiologically during the first 360 hours after birth. The results strongly supports the hypothesis and explains the large normal range of relative heart volume during the first 48 hours of life.


In vivo development of vitrified rabbit embryos: effects of vitrification device, recipient genotype, and asynchrony.
This study was designed to evaluate the effects of vitrification device, recipient genotype, and recipient asynchrony on implantation rate, offspring rate at birth, and fetal losses of rabbit embryos. Morphologically normal embryos (N = 787) recovered at 72 hours of gestation were kept at room temperature until transfer or vitrification. Vitrified embryos in Cryotop and ministraw devices were transferred into females induced to ovulate 60 hours (asynchrony) or 72 hours (synchrony) before transfer. In addition, recipient genotypes were analyzed (maternal and paternal genotype). The number of implanted embryos was estimated by laparoscopy as number of implantation sites at day 14 of gestation. At birth, total kits born were recorded. Fetal losses were calculated as the difference between total born at birth and implanted embryos. Our data show that a combination of Cryotop device and recipient asynchrony at -12 hours provides the most successful rate of offspring at birth, although a similar implantation rate was obtained with both devices. Thus, low fetal loss rates were observed for embryos vitrified in Cryotop independently of recipient synchrony, and embryos vitrified in straws revealed a two-fold higher rate of fetal losses. Moreover, when an asynchrony between vitrified embryo and recipients was applied, higher rates of embryos developed to term were obtained regardless of the device used. Finally, we found a highly significant association of the recipient genotype with implantation rate, offspring rate at birth, and fetal losses. In conclusion, the current study findings show that Cryotop enhances offspring rate because it is associated with a lower rate of fetal loss. This study thus provides additional evidence that recipient genotype and recipient asynchrony affect offspring rate at birth and indicates that the genotype of the recipient and the recipient asynchrony have a significant effect on implantation rate and fetal losses after vitrification.


Hierarchically porous graphene-like biochar for efficient removal of aromatic pollutants and their structure-performance relationship: A combined experimental, MD and DFT study.
Development of high-efficiency adsorbents and exploration of the structure-performance relationship holds exciting implications for removal of aromatic pollutants (APs) from water. Herein, hierarchically porous graphene-like biochars (HGBs) were successfully prepared by K2CO3 simultaneous graphitization and activation of Physalis pubescens husk. The HGBs possess high specific surface area (1406-2369.7 m2/g), hierarchically meso-/microporous structure and high graphitization degree. The optimized HGB-2-9 sample exhibits rapid adsorption equilibrium time (te) and high adsorption capacities (Qe) for seven widely-used persistent APs with different molecular structures (e.g., phenol: te = 7 min, Qe = 191.06 mg/g; methylparaben: te = 12 min Qe = 482.15 mg/g). HGB-2-9 also shows a wide pH (3-10) suitability and good ionic strength (0.01-0.5 M NaCl) resistance properties. The effects of the physicochemical properties of HGBs and APs on the adsorption performance were deeply investigated by the adsorption experiments, molecular dynamics (MD) and density functional theory (DFT) simulation. The results demonstrate that the large specific surface area, high graphitization degree and hierarchically porous structure of HGB-2-9 can supply more active sites on accessible surface and facilitate the transport of APs. And the aromaticity and hydrophobicity of APs play the more crucial roles during the adsorption process. Besides, the HGB-2-9 presents good recyclability and high removal efficiency for APs in various real water, which further confirms its potential for practical applications.


Theory predicts UV/vis-to-IR photonic down conversion mediated by excited state vibrational polaritons.
This work proposes a photophysical phenomenon whereby ultraviolet/visible (UV/vis) excitation of a molecule involving a Franck-Condon (FC) active vibration yields infrared (IR) emission by strong coupling to an optical cavity. The resulting UV/vis-to-IR photonic down conversion process is mediated by vibrational polaritons in the electronic excited state potential. It is shown that the formation of excited state vibrational polaritons (ESVP) via UV/vis excitation only involve vibrational modes with both a non-zero FC activity and IR activity in the excited state. Density functional theory calculations are used to identify 1-Pyreneacetic acid as a molecule with this property and the dynamics of ESVP are modeled. Overall, this work introduces an avenue of polariton chemistry where excited state dynamics are influenced by the formation of vibrational polaritons. Along with this, the UV/vis-to-IR photonic down conversion is potentially useful in both sensing excited state vibrations and quantum transduction schemes.


BRAF copy number gains in thyroid tumors detected by fluorescence in situ hybridization.
Point mutation of the BRAF gene is a common genetic event in papillary thyroid carcinomas. More recently, it has been found that BRAF can also participate in chromosomal rearrangement. In this study, we explore yet another possible mechanism of BRAF alteration, which involves copy number gain. Using fluorescence in situ hybridization with BRAF specific and chromosome 7 centromeric probes, we studied 62 follicular thyroid tumors and 32 papillary carcinomas. We found that numerical changes in BRAF copy number were rare in papillary thyroid carcinomas, while they occurred in 16-45% of follicular tumors of conventional and oncocytic (Hürthle cell) types. They were due to amplification of the gene or gain of one or more copies of chromosome 7. Tetrasomy for chromosome 7 was overall the most common finding. The changes in BRAF copy number did not overlap with RAS mutations in follicular tumors. In a group of follicular carcinomas, tumors with BRAF copy number gain were significantly more often widely invasive (67%) compared to tumors with no copy number change (18%). By Western blotting, the tumors carrying four copies of the gene revealed higher expression of BRAF protein, suggesting that copy number gain may represent another mechanism of BRAF activation in thyroid tumors.


Effect of maternal micronutrients (folic acid and vitamin B12) and omega 3 fatty acids on indices of brain oxidative stress in the offspring.
Our earlier studies have shown that a maternal diet imbalanced with micronutrients like folic acid, vitamin B12 has adverse effects on fatty acid metabolism, global methylation patterns and levels of brain neurotrophins in the offspring at birth. However, it is not clear if these effects are mediated through oxidative stress. The role of oxidative stress in influencing epigenetic mechanisms and thereby fetal programming is not well studied. Pregnant female rats were divided into six treatment groups at two levels of folic acid both in the presence and absence of vitamin B12. Omega 3 fatty acid supplementation was given to the vitamin B12 deficient groups. Following delivery, 8 dams from each group were randomly shifted back to control and the remaining 8 continued on the same treatment diet. Our results indicate for the first time that an imbalance in maternal micronutrients reduces the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) (p<0.05 for both) at birth. At d21 of life, the levels of MDA and GPx (p<0.05 for both) in pup brain from the micronutrient imbalanced group were higher as compared to control while omega 3 fatty acid supplementation normalizes the levels of GPx. Our data shows that maternal micronutrient imbalance adversely affects antioxidant defense mechanisms while omega 3 fatty acid supplementation ameliorates some of the negative effects. Our study throws light on the role of oxidative stress in fetal brain programming and consequential risk for neurodegenerative disorders in later life.


Idiopathic facial nerve palsy in children and the effect of treatment with steroids.
During a 10-year period 228 children were seen with Bell's Palsy. In half of them the palsy was incomplete. Overall the recovery rate was 96%. There was a strong female preponderance but no difference in incidence between right of left sides. Twenty-eight reported a previous episode of facial palsy. When separated into categories based on clinical assessment and evidence of nerve fibre degeneration it was evident that all children without degeneration recovered. Those with incomplete palsies recovered in about half the time taken by those with complete palsies. Only two thirds of those children in whom degeneration was evident recovered. One hundred children were treated with a course of high dose steroid. This did not influence recovery either by improving recovery rate or by decreasing the time period to recovery.


Seminal vesicle growth induced by Ascaris suum infection.
This study was designed to determine the effect of Ascaris suum infection upon growth of mouse vesicular glands. Mice were infected with varying dosages of A. suum eggs and killed after six weeks. Results indicated a dose dependent increase in seminal vesicle weight, independent of total body weight.


Spoligotyping of Mycobacterium africanum, Burkina Faso.
Using Ziehl-Neelsen-positive slides collected from tuberculosis diagnostic centers in Burkina Faso, we showed that 20% of 80 spoligotyping-positive DNA samples had a characteristic Mycobacterium africanum-specific genomic signature. This result suggests that M. africanum is still present in Burkina Faso at almost the same prevalence as 15-20 years ago.


Plasma concentration and urinary excretion of N epsilon-(carboxymethyl)lysine in breast milk- and formula-fed infants.
Industrial processing of infant formulas (IFs) induces the formation of Maillard products, namely N epsilon-(carboxymethyl)lysine (CML). CML content is expected to be several times higher in IFs than in fresh human breast milk. To elucidate whether CML is absorbed from IFs into the bloodstream, CML concentration in the plasma and urine were analyzed in 6-month-old infants (34 breast fed and 25 fed exclusively with IFs) and in 56 samples of human breast milk and 16 commercial IFs. We found that IFs contain higher amounts of CML compared to mother's milk (median: 70-fold; range: 28- to 389-fold), and CML content was higher in hydrolyzed IFs than in nonhydrolyzed IFs (P < 0.03). Plasma CML levels were 46% higher (P < 0.01) and urinary excretion of CML was 60-fold higher (P < 0.001) in the formula-fed infants than in the breast-fed group. Infants fed with hydrolyzed IFs displayed significantly higher plasma CML levels than those on nonhydrolyzed formulations. We conclude that CML from IFs is absorbed into the circulatory system and is rapidly excreted in the urine.


Breast cancer subtypes: two decades of journey from cell culture to patients.
Recent molecular profiling has identified six major subtypes of breast cancers that exhibit different survival outcomes for patients. To address the origin of different subtypes of breast cancers, we have now identified, isolated, and immortalized (using hTERT) mammary stem/progenitor cells which maintain their stem/progenitor properties even after immortalization. Our decade long research has shown that these stem/progenitor cells are highly susceptible to oncogenesis. Given the emerging evidence that stem/progenitor cells are precursors of cancers and that distinct subtypes of breast cancer have different survival outcome, these cellular models provide novel tools to understand the oncogenic process leading to various subtypes of breast cancers and for future development of novel therapeutic strategies to treat different subtypes of breast cancers.


Ocular Perfusion Pressure and Severity of Glaucoma: Is There a Link?
To establish the association between 12-month inter-visits ocular perfusion pressure (OPP) and severity of glaucoma. A total of 164 eyes (60 primary open-angle glaucoma, 52 normal-tension glaucoma, and 52 primary angle-closure glaucoma) of 164 patients were analyzed in this prospective cohort study. Patients who demonstrated good compliance to treatment were recruited. The severity of glaucoma was stratified according to the Advanced Glaucoma Intervention Study (AGIS) score based on reliable and reproducible visual field analysis at baseline. OPP was obtained at baseline and a 3-monthly follow-up visit over a 12-month duration. The pattern and fluctuation of mean OPP were studied. Repetitive measure ANOVA and one-way ANOVA were used for statistical analysis. The inter-visits mean OPP (p = 0.010), systolic OPP (p = 0.020), diastolic OPP (p = 0.010), systolic blood pressure (p = 0.040), and diastolic blood pressure (p = 0.006) showed significant difference with severity of glaucoma. There was no significant difference between mean inter-visits intraocular pressure (IOP) and severity of glaucoma (p = 0.410). The end-stage glaucoma group had the lowest mean OPP and widest inter-visit mean OPP fluctuation. Early and mild glaucoma patients demonstrated higher mean OPP compared with moderate, severe, and end-stage glaucoma. There is a significant association between OPP and the severity of glaucoma. Balancing blood pressure and IOP is important in optimizing adequate perfusion and prevent further damage to the optic nerve head. Ch'ng TW, Chua CY, Ummi Kalsom MA, et al. Ocular Perfusion Pressure and Severity of Glaucoma: Is There a Link? J Curr Glaucoma Pract 2021;15(2):78-85.


Relationship between a Low-Carbohydrate, High-Fat Diet and Risk of Metabolic Syndrome in Korean Women.
Prevalence of metabolic syndrome with aging is higher in women than in men, and it increases after menopause. Interventions to reduce the risk of metabolic syndrome in women are important. A low-carbohydrate, high-fat diet is effective in weight loss and improvement cardiovascular risk factors including abdominal circumference, blood pressure, and blood lipid profile. We aimed to determine the relationship between a low-carbohydrate, high-fat diet and the risk of metabolic syndrome in Korean women. This cross-sectional study was conducted using secondary data from the 2014-2018 Korean National Health and Nutrition Examination Survey. Overall, 8,222 women aged >19 yr were included. The effect of a low-carbohydrate, high-fat diet on the risk of metabolic syndrome was analyzed by multiple logistic regression analysis using a complex sampling procedure. The diet significantly reduced the likelihood of metabolic syndrome development (P=0.044). In addition, regardless of the fat type, the diet significantly reduced the likelihood of low high-density lipoprotein cholesterolemia (low-carbohydrate, high-total fat, P=0.013; low-carbohydrate, high-unsaturated fat, P=0.006; low-carbohydrate, high-saturated fat, P=0.006). A low-carbohydrate, high-fat diet is an important intervention that can reduce the risk of metabolic syndrome, and the reduced consumption of carbohydrates can decrease the risk of low high-density lipoprotein cholesterolemia regardless of fat type. Therefore, it is necessary to actively explore the potential of this diet, targeting Asians, including Koreans.


Effect of altering the reciprocation range on the fatigue life and the shaping ability of WaveOne nickel-titanium instruments.
The purpose of this study was to investigate the effect of altering the reciprocation range of the WaveOne instrument (Dentsply Maillefer, Ballaigues, Switzerland) on its fatigue life and shaping ability regarding tendency for canal transportation, the canal centering ratio, and preparation time. Thirty primary WaveOne instruments were divided into 3 equal groups according to the reciprocation range used: G1: 150 counterclockwise (CCW)-30 clockwise (CW), G2: 120 CCW-30 CW, and G3: 90 CCW-45 CW. They were activated in a cyclic fatigue testing device until fracture. The time to fracture and the length of the fractured tip were recorded and registered. To assess the shaping ability, 30 mesiobuccal canals of mandibular molars were prepared using the same reciprocation ranges. Canals were scanned using cone-beam computed tomography scanning before and after preparation to evaluate root canal transportation and the canal centering ratio at 1, 4, and 7 mm from the apex. The time taken to complete canal preparation was also recorded. The mean ± standard deviation values were analyzed using analysis of variance and the Tukey post hoc test. The significance level was set at P < .05. The time to fracture recorded increased as the reciprocation range decreased, and this was significant for the 90 CCW-45 CW group (P < .05). Regarding preparation time, it increased significantly as the reciprocation range was decreased (P < .05). Results for canal transportation and the canal centering ratio showed that at 1 mm from the apex there were no significant differences between the experimental groups. For the other studied levels, the 150 CCW-30 CW group had the highest mean for canal transportation and the lowest mean for the canal centering ratio, which was statistically significant in comparison with the other experimental groups (P < .05). Decreasing the reciprocation range of WaveOne instruments resulted in an increased cyclic fatigue resistance with less canal transportation and more centered preparations but with longer preparation times.


Biochemical and biological studies on the lipopolysaccharide of Bacteroides nodosus.
Lipopolysaccharides (LPS) were extracted from three Bacteroides nodosus isolates by the aqueous phenol method and purified by ultracentrifugation. The structure of B nodosus LPS appears to be similar to enterobacterial LPS, with the polysaccharide component joined to the lipid A moiety through an acid-labile 2-keto-3-deoxyoctonic acid (KDO) linkage. B nodosus LPS contained glucose, galactose, hexosamine, KDO and heptose and no sugars apart from ribose, which was possibly a nucleic acid contaminant, were unique to any of the isolates. Electron microscopic examination indicated a similar morphology to LPS derived from other Gram-negative bacteria. B nodosus LPS was found to exhibit biological properties characteristic of endotoxins, such as pyrogenicity, leucopenic and leucocytotic activity, production of the primary inflammatory response in rabbit skin and Shwartzman reactivity. However, the toxicity of B nodosus LPS was low.


Expression of interfering RNAs from an HIV-1 Tat-inducible chimeric promoter.
The therapeutic value of antiviral interfering RNAs could be improved by technologies that limit their expression to the infected cell population. The HIV-1 Tat-inducible viral LTR and LTR-containing chimeric promoters have previously been used to drive expression of antiviral RNAs and proteins directed against HIV-1. Here, we characterize an alternative promoter, consisting of a chicken β-actin core promoter fused to the viral TAR element, for the conditional expression of interfering RNAs. This promoter, that we refer to as the CK-TAR promoter, can induce levels of silencing comparable to the viral LTR in response to Tat produced from co-transfected plasmids or during viral replication. While the CK-TAR promoter shows a modest level of basal activity, similar to the viral LTR, it is less responsive to the extracellular stimuli tested including LPS, TNFα, and PMA. The CK-TAR promoter is an alternative Tat-inducible promoter with the potential to minimize the risk of vector mobilization and to drive polycistronic expression of interfering RNAs.


HDAC4 mediates IFN-γ induced disruption of energy expenditure-related gene expression by repressing SIRT1 transcription in skeletal muscle cells.
Metabolic homeostasis is achieved through balanced energy storage and output. Impairment of energy expenditure is a hallmark event in patients with obesity and type 2 diabetes. Previously we have shown that the pro-inflammatory cytokine interferon gamma (IFN-γ) disrupts energy expenditure in skeletal muscle cells via hypermethylated in cancer 1 (HIC1)-class II transactivator (CIITA) dependent repression of SIRT1 transcription. Here we report that repression of SIRT1 transcription by IFN-γ paralleled loss of histone acetylation on the SIRT1 promoter region with simultaneous recruitment of histone deacetylase 4 (HDAC4). IFN-γ activated HDAC4 in vitro and in vivo by up-regulating its expression and stimulating its nuclear accumulation. HIC1 and CIITA recruited HDAC4 to the SIRT1 promoter and cooperated with HDAC4 to repress SIRT1 transcription. HDAC4 depletion by small interfering RNA or pharmaceutical inhibition normalized histone acetylation on the SIRT1 promoter and restored SIRT1 expression in the presence of IFN-γ. Over-expression of HDAC4 suppressed the transcription of genes involved in energy expenditure in a SIRT1-dependent manner. In contrast, HDAC4 knockdown/inhibition neutralized the effect of IFN-γ on cellular metabolism by normalizing SIRT1 expression. Therefore, our data reveal a role for HDAC4 in regulating cellular energy output and as such provide insights into rationalized design of novel anti-diabetic therapeutics.


Combined transcriptome sequencing reveals the photoperiod insensitivity mechanism of oats.
Avena sativa L. is the most important cultivated oat species worldwide. Although photoperiod-insensitive oat varieties exist, the molecular mechanisms underlying their photoperiod sensitivity are poorly understood. This study investigated the effects of day length on the fioral transition of oats and the mechanisms underlying oat photoperiod insensitivity. Photoperiod-sensitive and photoperiod-insensitive varieties, including gp012, were used in shading experiments, and the developing leaves and main shoot apices (MSAs) of the HONGQI2 and gp012 varieties were used for sequencing. Leaves and MSAs were collected in 2016, and their transcriptomes were sequenced. The photoperiod-insensitive varieties headed under both short-day and long-day conditions, while the photoperiod-sensitive varieties headed only under long-day conditions. A total of 60673 transcript sequences were obtained, 7932 of which were differentially expressed; 3194 and 4738 transcripts were differentially expressed in the leaves and MSAs, respectively. A total of 25793 transcripts were classified into 123 pathways based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The carbon metabolism pathways were dominant, followed by ribosome and protein processing in the endoplasmic reticulum. In addition, 203 transcripts were classified into the circadian rhythm pathway. Compared with the expression of pseudo-response regulator protein 37 (PRR37) in photoperiod-sensitive varieties, that in photoperiod-insensitive varieties was upregulated. Among the differentially expressed transcripts (DETs), 8 MADS-box genes were identified. PRR37 is a key regulator of oat photoperiod insensitivity. The obtained transcriptome dataset may provide a reference for analyzing oat transcript expression, and the results should be used as a reference for oat breeding and production.


Indications for cardiac surgery in patients with active infective endocarditis.
Currently, absolute indications for valve replacement during active infective endocarditis include severe heart failure, the presence of an infecting microorganism that is not susceptible to available antimicrobial agents, and, in patients with an infected prosthetic valve, an unstable device. Relative indications include an etiologic microorganism other than a susceptible Streptococcus, relapse after presumed effective therapy, evidence of intracardiac extension of the infection, two or more systemic emboli, vegetations large enough to be demonstrated by echocardiography, and, in patients with an infected prosthetic device, early disease and periprosthetic leak. With use of data from the medical literature, a study generated by the cardiovascular surgical group at the University of Alabama School of Medicine, and a brief cost analysis, a point system was constructed to assist in decision-making concerning surgery in patients with active infective endocarditis. The usefulness of this system will depend on experience generated from its utilization in a larger number of patients as well as new data relative to a more complete understanding of the risks and benefits of surgery in this condition.


Possible locations of pH-dependent central chemoreceptors: intramedullary regions with acidic shift of extracellular fluid pH during hypercapnia.
Using liquid membrane pH microelectrodes, we evaluated rapid and transient changes in extracellular fluid (ECF) pH within the medulla during vertebral artery injections of CO2-saturated saline (0.5 ml) in anesthetized (Dial-urethane), spontaneously breathing cats. We found intramedullary regions where ECF pH shifted to the acid side in the time course analogous to respiratory excitation during the CO2 loadings: the acidic shift occurred just before the respiratory excitation. Since most of the tested regions showed no or few changes in ECF pH, the responsive regions are thought to be specific local environments fitting the central chemoreceptors. Forty (85%) out of the 47 responsive regions were found to be scattered in the ventrolateral medulla, i.e. a long narrow zone extending from the ventrolateral surface to the ventral respiratory group (VRG) areas where inspiratory or expiratory activity was frequently recorded. The responsive regions were not necessarily restricted to the superficial ventral layers. We were also able to find the responsive regions in the dorsal area ventral to the nucleus tractus solitarii, though they were fewer in number (7/47). The distributions corresponded rougly to the areas where we had previously identified the tonically firing neurons excited exclusively by stimulation of the central chemoreceptors. These results indicate a possibility that the pH-dependent central chemoreceptors, if any, would be located within the regions demonstrated in this study.


Decreased fetal movements with sustained maternal hyperglycemia using the glucose clamp technique.
The purpose of this study was to evaluate the effect of sustained maternal hyperglycemia (120 mg/dl) on fetal activity. The glucose infusion study group was comprised of nine healthy gravidas between 36 and 40 weeks' gestation, and six patients served as controls. The protocol design included an overnight fast for all patients. Fetal movements were evaluated by external fetal monitoring. A 2-hour preinfusion evaluation of fetal activity served as the baseline control for each patient studied. Study patients then received a glucose infusion by a glucose clamp technique to maintain a sustained hyperglycemia of 120 mg/dl for 3 hours. After the glucose infusion, fetal movements were observed for 1 hour. Control patients received a saline infusion for 2 hours after a 2-hour baseline evaluation. Maternal hyperglycemia was associated with a significant decrease of fetal movements greater than 1 second duration during the first hour of glucose infusion. Fetal movements returned to baseline during the second and third hours of glucose infusion. Saline infusion was not associated with a decrease in fetal activity. We conclude that sustained maternal hyperglycemia is associated with a transient decrease in fetal movement during the first hour of glucose infusion followed by a return to the control (preinfusion) level of fetal activity. These data may have implications in the study of fetal behavior in diabetes mellitus.


Novel insight into Y-box binding protein 1 in the regulation of vascular smooth muscle cell proliferation through targeting GC box-dependent genes.
Abnormal proliferation of vascular smooth muscle cells (VSMCs) is a key event in atherosclerosis and restenosis. In this paper, we report that Y-box binding protein 1 (YB1) functions as a phenotypic regulator in VSMC proliferation-differentiation switching through targeting GC box-dependent genes. Oligo pull-down assays demonstrated that YB1 binds directly to GC boxes via amino acids 125-220. YB1 C-terminal tail domain (CTD, amino acids 125-324) regulates GC box-dependent target gene transcription and suppresses VSMC proliferation. These findings provide a novel insight into the regulation of GC box-related genes by YB1, and provide a new understanding of VSMC proliferation regulation.


Friendly fire against neutrophils: proteolytic enzymes confuse the recognition of apoptotic cells by macrophages.
Physiologically the only acceptable fate for almost all damaged or unwanted cells is their apoptotic death, followed by engulfment of the corpses by healthy neighbors or professional phagocytes. Efficient clearance of cells that have succumbed to apoptosis is crucial for normal tissue homeostasis, and for the modulation of immune responses. The disposal of apoptotic cells is finely regulated by a highly redundant system of receptors, bridging molecules and 'eat me' signals. The complexity of the system is reflected by the term: 'engulfment synapse', used to describe the interaction between a phagocytic cell and its target. In healthy humans, dying neutrophils are the most abundant and important targets for such recognition and engulfment. In inflammation the scope and importance of this complicated task is further increased. Paradoxically, despite growing evidence highlighting the priority of neutrophils clearance, the recognition of these cells by phagocytes is not as well understood as the recognition of other apoptotic cell types. New findings indicate that the interaction of phosphatidylserine (PS) on apoptotic neutrophils with its receptor on macrophages is not as critical for the specific clearance of neutrophil corpses it was previously believed. In this review we focus on recent findings regarding alternative, PS-independent "eat me" signals expressed on neutrophils during cell death and activation. Based on our own research, we emphasize the clearance of dying neutrophils, especially at the focus of bacterial infection; and the associated inflammatory reaction, which occurs in a highly proteolytic milieu containing both host and bacteria-derived proteinases. In these environments, eat-me signals expressed by neutrophils are drastically modified; arguing against the phospholipid-based detection of apoptotic cells, but supporting the importance of proteinaceous ligand(s) for the recognition of neutrophils by macrophages. In this context we discuss the effect of the gingipain R (Rgp) proteinases from Porphyromonas gingivalis on neutrophils interactions with macrophages. Since the recognition of apoptotic neutrophils is an important fundamental process, serving multiple functions in the regulation of immunity and homeostasis, we hypothesize that many pathogenic bacteria may have developed similar strategies to confuse macrophage-neutrophil interaction as a common pathogenic strategy.


Surgical management of concurrent lateral ankle instability and osteochondral lesions of the talus increases dynamic sagittal ankle range of motion.
A biomechanical study, in which imaging modalities are used to strictly include patients with concurrent lateral ankle instability (LAI) and osteochondral lesions of the talus (OLT), is needed to demonstrate the static and dynamic ankle range of motion (ROM) restriction in these patients, and determine whether ankle ROM restriction can be corrected postoperatively. Eight patients with concurrent LAI and OLT treated with the arthroscopic modified Broström procedure and microfracture were recruited from June 2019 to January 2020. Patients were assessed using outcome scales, static ankle ROM, and a stair descent gait analysis for dynamic ankle ROM, a day prior to surgery and one year postoperatively. Eight healthy subjects were assessed using the same modalities upon recruitment. Operative outcomes and variables during stair descent were documented and compared among the preoperative, postoperative, and healthy groups. A curve analysis, one-dimensional statistical parametric mapping, was performed to compare the dynamic ankle kinematics and muscle activation curves over the entire normalised time series. The functional outcomes of patients with concurrent LAI and OLT were significantly worse than those of healthy subjects preoperatively, but were partially improved postoperatively. Patients had decreased static and dynamic ROM preoperatively, and static ROM did not significantly increase postoperatively (preoperative, 39.6 ± 11.3; postoperative, 44.9 ± 7.1; healthy, 52.0 ± 4.6; p = 0.021). Patients showed increased dynamic ankle flexion ROM (preoperative, 41.2 ± 11.6; postoperative, 53.6 ± 9.0; healthy, 53.9 ± 3.4; p = 0.012) postoperatively, as well as increased peroneus longus activation (preoperative, 35.8 ± 12.0; postoperative, 55.4 ± 25.1; healthy, 71.9 ± 13.4; p = 0.002) and muscle co-contraction of the tibialis anterior and peroneus longus (preoperative, 69.4 ± 23.4; postoperative, 88.4 ± 9.3; healthy, 66.2 ± 18.1; p = 0.045). Patients with concurrent LAI and OLT had decreased static and dynamic sagittal ankle ROM and altered neuromuscular activation patterns. The arthroscopic modified Broström procedure and microfracture did not significantly increase the static sagittal ankle ROM. However, the dynamic sagittal ankle ROM, peroneus longus activation and muscle co-contraction of the tibialis anterior and peroneus longus increased postoperatively. IV.


Anesthetic management of the first pediatric bilateral hand transplant.
The purpose of this case report is to describe the anesthetic and case management of the first vascularized composite allograft pediatric bilateral hand transplant. Our patient was an eight-year-old male with a medical history of Staphylococcus aureus sepsis at one year of age that resulted in end-stage renal disease as well as bilateral upper and lower extremity amputations. After referral for bilateral hand transplantation, the transplantation team, with expertise in all aspects of perioperative care (surgery, anesthesiology, nephrology, renal transplantation, pediatric intensive care, and therapeutic pharmacy), was consulted to help develop anesthetic and other perioperative protocols for surgery. Prior to activation of the transplantation team, the lead surgeon evaluated potential donors by comparing a three-dimensional printed model of the recipient's forearm with the donor's upper extremities to ensure an adequate match. The anesthesia team inserted bilateral ultrasound-guided infraclavicular catheters to provide a sympathetic block to facilitate blood flow to the upper extremities and to provide both intraoperative and postoperative pain control. The patient remained in the operating room for 13 hr 37 min for a surgical time of ten hours 39 min. He remained in the hospital for 34 days after the procedure and was then transferred to an inpatient rehabilitation facility for a further 15 days. The patient is currently doing well in a postoperative rehabilitation program. He has demonstrated motor power to the hands using the forearm muscles but is not expected to reach his maximum sensory function for at least one to two years. This report describes the anesthetic management of the first pediatric bilateral hand transplant. This procedure required considerable preoperative planning and communication between various teams to ensure all resources needed to deliver the care for this complex and novel transplant surgery were readily available.


Cardiovascular profile of Ro 13-6438, a novel positive inotropic agent with vasodilating properties.
The cardiovascular properties of Ro 13-6438 (R-6-chloro-1,5-dihydro-3- methylimidazo -[2,1-b] quinazolin -2[ 3H]-one), a novel nonglycoside , noncatechol cardiotonic agent, were investigated in vitro and in vivo by both intravenous and oral administration. Ro 13-6438 increased tension development of isolated guinea pig left atria in a concentration-dependent manner with an EC50 of 30 microM, but had no stimulant effect on the spontaneous rate of right atria. The positive inotropic effect of Ro 13-6438 was additive to that of ouabain (0.1 microM); Ro 13-6438 suppressed the arrhythmogenic activity of high concentrations of ouabain (10 microM). IN anesthetized open-chest dogs 10-300 micrograms/kg Ro 13-6438 i.v. produced a significant and dose-dependent increase in myocardial force, with a duration of action exceeding 60 min following the highest dose. It also slightly increased heart rate, cardiac output, and blood flow. Ro 13-6438 decreased systolic and diastolic blood pressure, left ventricular end-diastolic pressure, and total peripheral resistance. Thus, the direct positive inotropic effects of Ro 13-6438 were supported by a decrease in preload and afterload. In chronically instrumented, conscious dogs Ro 13-6438 increased myocardial contractility after administration of 0.03-0.3 mg/kg i.v. or 3-10 mg/kg p.o. The effects persisted for greater than 8 h after oral administration of 10 mg/kg. The inotropic effects were accompanied by a modest increase in heart rate, which, however, had a clearly shorter duration of action than the former.(ABSTRACT TRUNCATED AT 250 WORDS)


Comprehension by Caregivers and Adolescents of Clinical Trial Information Delivered via Multimedia Video Versus Conventional Practice: Nonrandomized Controlled Trial.
Research participants often misunderstand the required elements of informed consent information, whether provided in written or oral format. Informed consent instruments with embedded evidence-based learning theory principles administered in multimedia electronic formats may improve comprehension and retention. This study aims to determine whether study information comprehension and retention using an interactive multimedia video consent process was noninferior to comprehension and retention after an in-person face-to-face interaction with a conventional written consent document for caregivers and adolescents enrolled in a clinical trial. Participants were caregivers and children aged 12 to 17 years who were enrolled in a clinical trial of asthma treatment. Consent information was presented as a multimedia web-based video consent interaction or as a conventional written consent document with in-person interaction between the prospective participants and the study staff. The trial used a parallel nonrandomized noninferiority design that compared the 2 consent methods. Caregivers and adolescents completed a 17-item open-ended comprehension questionnaire (score range 17-51) at enrollment and at the end of the study 20 weeks later. Comprehension and retention were compared between the consent formats. Noninferiority was established if the 95% CI upper bound of the difference in scores (conventional format minus web-based) was less than the noninferiority margin of 2.4; superiority was established if the upper bound of the CI was <0. In total, 54 caregiver and adolescent dyads completed the interactive multimedia web-based video consent, and 25 dyads completed the conventional consent. Overall, 33% (26/79) of all adolescents were Black, 57% (45/79) were male, and 61% (48/79) had a household income of <US $60,000 per year. For caregivers, the interactive multimedia web-based format was noninferior to the conventional format at enrollment (difference between the conventional and web-based formats: mean -0.30, 95% CI -2.52 to 1.92) and was superior at the end of the study 20 weeks later (mean -2.20, 95% CI -3.9 to -0.5). There was a loss of comprehension over 20 weeks (mean -1.65, 95% CI -3.1 to -0.19) with the conventional format but not with the multimedia web-based format (mean 0.14, 95% CI -0.84 to 1.12). For adolescents, the noninferiority of the multimedia web-based format was not established. Caregivers who are considering enrolling their adolescent in an asthma clinical trial have similar comprehension of study information when delivered through an interactive multimedia web-based platform, which incorporates evidence-based learning theory principles, compared with having a conventional in-person, face-to-face discussion. The retention of study information over time was better with the multimedia format for caregivers. ClinicalTrials.gov NCT02061280; https://clinicaltrials.gov/ct2/show/NCT02061280 and NCT01437995; https://clinicaltrials.gov/ct2/show/NCT01437995.


Patterns of taxonomic, phylogenetic diversity during a long-term succession of forest on the Loess Plateau, China: insights into assembly process.
Quantifying the drivers underlying the distribution of biodiversity during succession is a critical issue in ecology and conservation, and also can provide insights into the mechanisms of community assembly. Ninety plots were established in the Loess Plateau region of northern Shaanxi in China. The taxonomic and phylogenetic (alpha and beta) diversity were quantified within six succession stages. Null models were used to test whether phylogenetic distance observed differed from random expectations. Taxonomic beta diversity did not show a regular pattern, while phylogenetic beta diversity decreased throughout succession. The shrub stage occurred as a transition from phylogenetic overdispersion to clustering either for NRI (Net Relatedness Index) or betaNRI. The betaNTI (Nearest Taxon Index) values for early stages were on average phylogenetically random, but for the betaNRI analyses, these stages were phylogenetically overdispersed. Assembly of woody plants differed from that of herbaceous plants during late community succession. We suggest that deterministic and stochastic processes respectively play a role in different aspects of community phylogenetic structure for early succession stage, and that community composition of late succession stage is governed by a deterministic process. In conclusion, the long-lasting evolutionary imprints on the present-day composition of communities arrayed along the succession gradient.


The demonstration of a change in responsiveness of mice to physostigmine and atropine after withdrawal from long-term haloperidol pretreatment.
Mice, administered haloperidol 3 mg/kg/day, in their drinking water for 21 days, were tested for their responsiveness to cholinergic and anticholinergic drugs 4 days after withdrawal from haloperidol (or vehicle). Haloperidol-treated animals administered methylhyoscine (1 mg/kg i.p.) and various doses of physostigmine (5 to 1215 microgram/kg) displayed significantly less depression of locomotor activity than vehicle-treated animals. Atropine, 5 mg/kg, whilst ineffective in producing locomotor stimulation in vehicle-treated animals, produced marked stimulation in haloperidol-treated animals. Methylatropine (5 mg/kg) did not produce significant stimulation in either group. Dopamine receptor supersensitivity was present in these animals as haloperidol-treated mice, pretreated with alpha-methyltyrosine and reserpine, displayed a significantly greater locomotor response to apomorphine than did vehicle-treated animals. The data support the hypothesis that long-term administration of haloperidol produces an apparent hyposensitivity of central muscarinic receptors.


Contragestion with RU 486: a new approach to postovulatory fertility control.
The steroidal derivative RU 486 (17 beta-hydroxy-11 beta-(4-dimethyl-aminophenyl)-17 alpha-(prop-1-ynyl) ester-4, 9-dien-3-one) is the first potent antiprogestin to be used clinically. RU 486 blocks the action of progesterone by a reversible inhibition of the action of progesterone on its own receptors. This reversibility allows endocrine functions to return quickly to normal after discontinuation of treatment. However, target cells which depend upon a continuity of progesterone action will be irreversibly disrupted by receptor blockade. In normal women, RU 486 acts during the luteal phase in the endometrium, provoking bleeding, and decreasing pituitary luteinizing hormone (LH) secretion and hence luteolysis. In pregnant women, it affects the decidua, increases myometrial contractility and ripening of the cervix and ultimately leads to termination of pregnancy. Detachment of the trophoblast leads to a further fall in gonadotropin production. Clinical studies indicate that RU 486 can be a very efficient agent for the termination of early pregnancy, and as a postcoital menstrual regulator. In about 20% of cases when RU 486 is given alone, termination of pregnancy fails. This can be overcome by taking in addition a small amount of prostaglandin.


Megestrol acetate: phase II study of a single daily administration in advanced breast cancer.
A new formulation of megestrol acetate, a semisynthetic oral progestin used in the hormonal treatment of breast cancer, allows the administration of 160 mg of the drug in a single daily dose. Sixty-nine postmenopausal patients with advanced breast cancer have been treated with this regimen: five patients received megestrol acetate as first-line treatment of their metastatic disease, while all the others had been previously treated with one or more regimens of chemotherapy and/or hormone therapy. The median duration of the treatment for evaluable patients was 3 months (range 1-13+). Among 65 evaluable patients 2 complete responses and 12 partial responses (objective response rate 21.5%; 95% confidence limits 12.31%-33.49%) were observed. Median duration of response was 7 months (range 2-12+). Responses were observed both in visceral and in non-visceral sites of disease. Twenty-nine patients obtained a stabilization of disease (44.7%), and twenty-two progressed (33.8%). Median duration of stabilization was 4 months (range 3-13+). Median survival for all patients from the start of megestrol acetate was 9 months (range 1-22+). The most common side effect of therapy was weight gain, occurring in 36% of patients. Megestrol acetate on a single-daily-dose schedule can be considered as an interesting hormonal treatment for advanced breast cancer, especially in the clinical instance of patients who, after having obtained a remission or stabilization of disease with tamoxifen, need further palliative treatment.


Rheumatic diseases associated with alveolar hemorrhage: analysis of the national inpatient sample.
Diffuse alveolar hemorrhage (DAH) is a severe pulmonary complication of numerous diseases, including rheumatic conditions. We have conducted an observational study using inpatient data from the National Inpatient Sample to study the relationship of DAH with rheumatic conditions along with their descriptive characteristics. An observational study was conducted on hospitalizations in 2016-2018 with a principal diagnosis of DAH from the United States National Inpatient Sample database. A multivariate logistic regression analysis was performed to calculate adjusted odds ratios (ORadj) for risk factors of DAH. A total of 5420 DAH hospitalizations were identified among 90 million hospitalizations. Mortality in this group was found to be 24.3%. Majority of patients admitted with DAH were white and male, with a mean age of 61.8 years and a mean LOS of 10.6 days. Multivariate analysis showed that multiple rheumatic diseases were associated with DAH, including anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) (ORadj 72.56) (95% C.I. 50.607-104.043), antiphospholipid antibody syndrome (APLS) (ORadj 6.51) (95% C.I. 3.734-11.366), eosinophilic granulomatosis with polyangiitis (EGPA) (ORadj 7.13) (95% C.I. 1.886-26.926), Goodpasture's (ORadj 30.58) (95% C.I. 16.360-57.176), rheumatoid arthritis (RA) (ORadj 1.60) (95% C.I. 1.158-2.212), sarcoidosis (ORadj 3.99) (95% C.I. 2.300-6.926), and systemic lupus (SLE) (ORadj 5.82) (95% C.I. 3.993-8.481). Although DAH is a relatively rare entity, it carries a very high mortality. Multiple rheumatic diseases were associated with DAH hospitalizations including AAV, APLS, EGPA, Goodpasture's, RA, sarcoidosis, and SLE. Key points • It is known that DAH carries a high morbidity and mortality based on prior literature. However, large datasets on the association of rheumatic diseases with DAH are lacking • This study identifies the descriptive characteristics of patients admitted to the hospital with DAH • This study also identifies the strength of association of rheumatic diseases with DAH.


A selective decrease in the relative density of parvalbumin-immunoreactive neurons in the hippocampus in schizophrenia.
Neuropathological studies have demonstrated deficits of GABAergic interneurons in the hippocampus in schizophrenia. and selective deficits in some GABAergic sub-populations defined by calcium-binding proteins (CBPs) have been reported in the cortex in schizophrenia. In the present study, the relative densities of cells immunoreactive for the CBPs parvalbumnin (PV) and calretinin (CR) were determined in hippocampal tissue sections taken from patients with schizophrenia, bipolar disorder and major depression and from matched control subjects (15 per group). No significant difference in the density of CR-immunoreactive neurons was found between subject groups. Relative to normal controls, schizophrenic patients showed a significant and profound deficit in the relative density of PV-immunoreactive neurons in all hippocampal sub-fields. These reductions were more apparent in male than female schizophrenic patients, and were unrelated to antipsychotic drug treatment, age or duration of illness. The density of PV-immunoreactive neurons did not differ significantly from controls in the depression group, although a trend toward decreased relative density of PV-immunoreactive neurons was apparent in bipolar disorder that reached significance in one sub-field. The findings provide further evidence to support a profound and selective abnormality of a sub-population of GABAergic neurons in the hippocampus in schizophrenia.


[Usefulness of regional cerebral oxygen saturation monitoring in balloon test occlusion].
Recently, temporary balloon test occlusion (BTO) of the internal carotid artery (IC) has become a well accepted procedure for preoperative evaluation of patients with IC large aneurysms. However, it might be dangerous to move patients fitted with a balloon catheter to the room for single-photon emission computed tomography (SPECT). We attempted to clarify the usefulness of regional cerebral oxygen saturation (rSO2) monitoring during BTO, comparing cerebral blood flow (CBF) obtained from SPECT. Eight patients with an IC large aneurysm underwent BTO with rSO2 monitoring. Regions of interest in the SPECT were defined in the area below the rSO2 sensor of each hemisphere. Correlations among rSO2, CBF, stump pressure and appearance of symptoms were discussed. The rSO2 significantly reduced during BTO (74.1 +/- 1.2 to 60.4 +/- 2.7%, p < 0.001). The individual decreases in rSO2 correlated with decreases of CBF from SPECT (r = 0.966, P < 0.001). Four patients with deltarSO2 (baseline rSO2 - rSO2 during IC occlusion) less than 12 points had no symptoms, but 4 patients with deltarSO2 more than 14 points had some symptoms. The stump pressure had no correlation with CBF and rSO2. The rSO2 significantly correlated with CBF from SPECT and related with appearance of symptoms. Our results revealed that rSO2 monitoring was useful in BTO, and SPECT could be skipped in some cases to determine the strategies for treatment of IC large aneurysms.


Comparison of Cardiorespiratory Demand and Rate of Perceived Exertion During Propulsion in a Natural Environment With and Without the Use of a Mobility Assistance Dog in Manual Wheelchair Users.
The aim of this study was to compare cardiorespiratory demand during manual wheelchair (MWC) propulsion among MWC users with a spinal cord injury (SCI) in a natural environment with and without the use of a trained mobility assistance dog (MAD). In this quasi-experimental repeated-measures analysis of difference, 13 experienced MWC users with an SCI propelled themselves with and without their trained MAD at a self-selected natural speed along a standardized 630-m course in a natural environment. Participants were equipped with a portable gas analyzer to measure their oxygen consumption, ventilation, tidal volume, respiratory quotient, respiratory rate, and heart rate before, during, and after completing the course. Participants also rated their perceived exertion on a modified Borg scale following each trial. All cardiorespiratory outcome measures decreased significantly with the use of a MAD (P ≤ 0.013; mean difference, -9% to -38%). Furthermore, most participants completed the course significantly faster (P ≤ 0.001; mean difference, -34%), while reporting considerably lower perceived exertion rates (P = 0.007; mean difference, -65%). A trained MAD decreases cardiorespiratory demand and rate of perceived exertion during MWC propulsion on a 630-m course among experienced MWC users with SCI. Trained MADs represent a valuable mobility assistive technology option for MWC users.


IMPAD-22: a checklist for authors of qualitative nursing research manuscripts.
The aim of this paper is to develop a checklist for authors preparing qualitative nursing research manuscripts, specifically focusing on the method section. Literature review. 15 articles were purposefully selected from three different nursing journals. Evans' four step process was used to synthesize the method sections of the included articles. Four main categories were identified 1) Ingress and Methodology, 2) Participants, 3) Approval, and 4) DATA: Collection and Management. Based on the categories and sub-categories, a 22-item checklist was developed. Earlier guidelines for formal reporting were developed for qualitative research in general. The main advantage and contribution of IMPAD is that it provides a 22-item checklist specifically aimed towards the method section, and furthermore, it was developed specifically for authors within the field of nursing research.


Effect of externally added carnitine on the synthesis of acetylcholine in rat cerebral cortex cells.
Acetylcholine synthesis from radiolabelled glucose was monitored in cerebral cortex cells isolated from brains of suckling and adult rats. Acetylcholine synthesis was found much higher in suckling animals, both in the absence and presence of acetylcholinesterase (acetylcholine hydrolase, EC 184.108.40.206) inhibitor, paraoxon. Together with choline (20 microM), carnitine was found to stimulate acetylcholine synthesis in a synergistic way in cortex cells from adult rats (18%). Choline, however, was incapable of reversing an inhibitory effect exerted by carnitine on acetylcholine synthesis in cortex cells from suckling animals. Distribution of carnitine derivatives was found significantly different in the cells from young and old animals, the content of acetylcarnitine decreased with age with a corresponding increase of free carnitine. The observed differences in carnitine effect on acetylcholine synthesis suggested that high acetylcarnitine in cells capable of beta-oxidation might be correlated with the lower level of acetylcholine synthesis.


Involvement of chromosome 22 in a Merkel cell carcinoma in a patient with a previous meningioma.
The relatively simple cytogenetic findings in an aggressive metastatic Merkel cell carcinoma are reported. Deletion 2p was found in 100% of the cells. Nevertheless, this was considered a secondary (metastatic?) change because the same aberration has been found in several other kinds of malignancy. The involvement of chromosome 22 [del(22q) and -22] in 85% of the cells seemed more intriguing, considering the fact that the Merkel cell carcinoma followed a previous meningioma.


The effect of E type prostaglandins on the proliferation of haemopoietic stem cells in vivo.
The ability of protaglandins E1 and E2 to stimulate the proliferation of haemopoietic stem cells (CFUS) was studied in vivo. PGE2, in a dose range of 10(-4) to 10(-1) microgram/g body weight and PGE1 in a dose range of 10(-5) to 10(-1) microgram/g body weight, produced a rapid cycling wave of CFUS. The increase in the number of CFUS in S phase was not followed by a rise in the femoral CFUS content, and except for a transient increase in femoral CFUC level, no increase in differentiation was found either. Therefore, it is proposed that haemopoiesis after PG-induced CFU stimulation is ineffective. PGE2 did not stimulate regeneration of CFUS in a perturbed state (after sublethal irradiation). All these findings support the idea that PGEs might represent potent stimulators of the haemopoietic stem cells acting in physiological doses. However, if acting concurrently with physiological control systems PGs lead to ineffective haemopoiesis (under normal conditions) or do not exert any measurable effect (after sublethal irradiation).


The Characteristics, Distribution, Function, and Origin of Alternative Lateral Horse Gaits.
This article traces the characteristics, origin, distribution, and function of alternative lateral horse gaits, i.e., intermediate speed lateral-sequence gaits. Such alternative lateral gaits (running walk, rack, broken pace, hard pace, and broken trot) are prized by equestrians today for their comfort and have been found in select horse breeds for hundreds of years and even exhibited in fossil equid trackways. After exploring the evolution and development of alternative lateral gaits via fossil equid trackways, human art, and historical writings, the functional and genetic factors that led to the genesis of these gaits are discussed. Such gaited breeds were particularly favored and spread by the Scythians, Celts, Turks, and Spaniards. Fast and low-swinging hard pacing gaits are common in several horse breeds of mountainous areas of East and North Asia; high-stepping rack and running walk gaits are often displayed in European and North and South American breeds; the broken pace is found in breeds of Central Asia, Southeast Asia, West Asia, Western North America, and Brazil in South America; and the broken trot occurs in breeds of North Asia, South Asia, the Southern United States, and Brazil in South America, inhabiting desert or marshy areas.


Identification and sequencing of the HLA-B*4106 allele.
We report a novel HLA-B*41 allele (HLA-B*4106) initially detected by an unusual sequence-specific oligonucleotide (SSO) hybridization pattern and identified by sequence-based HLA typing. Molecular cloning and sequencing determined that the new HLA-B allele was identical to the HLA-B*4101 in exon 2 and 3 except for a single nucleotide substitution in the exon 3 changing codon 204 from Glu to Gln (GAG-->CAG). In addition, intron 2 was identical to the published HLA-B*4104 intron 2, except for the base 509 (C-->G).


The prognostic value of the preoperative lung immune prognostic index in patients with urothelial bladder cancer undergoing radical cystectomy.
The lung immune prognostic index (LIPI) predicts the prognosis of patients with advanced non-small-cell lung cancer and is a prognostic biomarker for renal cell carcinoma and melanoma; however, no study has evaluated its potential as a preoperative biomarker for patients with bladder cancer (BC). We investigated the LIPI as a preoperative prognostic biomarker in patients undergoing radical cystectomy. We retrospectively analyzed the clinical records of 105 patients with BC who underwent radical cystectomy from January 2013 to June 2019. The LIPI was evaluated based on the preoperatively derived neutrophil-lymphocyte ratio and the lactate dehydrogenase levels. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and decision curve analysis (DCA) were performed to assess the disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) rates. The patients were classified into the good, intermediate, and poor LIPI groups [71 (67.6%), 28 (26.7%), and 6 (5.7%) patients, respectively]. IPTW-adjusted Kaplan-Meier curve analyses showed that patients with intermediate to poor LIPI had worse DFS, CSS, and OS rates than those with good LIPI. The LIPI combined with pT3/4 and lymph node metastasis could better assess the prognosis of DFS at 24 months postoperatively by DCA. The preoperative LIPI can predict the prognosis of patients with BC undergoing radical cystectomy and has a better predictive ability when combined with pT3/4 and lymph node metastasis.


How useful is the lung-to-head ratio in predicting outcome in the fetus with congenital diaphragmatic hernia? A systematic review and meta-analysis.
Fetal surgery to improve lung growth comprises tracheal occlusion in selected 'high-risk' fetuses with congenital diaphragmatic hernia (CDH). Sonographically measured fetal lung-to-head ratio (LHR) is utilized to recruit candidates for fetal surgery. This study provides a meta-analysis of the evidence regarding the prognostic use of lung-to-head ratio measurements in fetal CDH. MEDLINE, SCOPUS and ISI PROCEEDINGS databases were searched for MeSH terms: lung, head, hernia and ratio. References in retrieved studies were also searched. Studies were categorized as follows: Phase I studies measured normal fetal LHR; Phase II studies compared fetal LHR in CDH survivors and non-survivors (if LHR informed therapy decisions or LHR was not measured during the window for intervention (< 32 weeks' gestation), studies were excluded); Phase III studies used LHR to guide selection for fetal surgery (non-randomized trials were excluded); Phase IV studies measured CDH survival before and after LHR application in clinical practice. The one Phase I study showed that LHR varied substantially with gestation and technique. No complete studies met the selection criteria for Phase II: meta-analysis of subgroups revealed similar LHR in CDH survivors and non-survivors. A single Phase III study revealed no benefit for LHR-directed fetal surgery. No Phase IV studies were identified. The prognostic use of LHR in fetal CDH entered clinical practice prior to publication of robust normal data and is not supported by current evidence. Application of a structured approach to any 'new' prognostic test could improve its validity and clinical application.


Correction: Kim, N.K., et al. Study of the Association between microRNA (miR-25T>C, miR-32C>A, miR-125C>T, and miR-222G>T) Polymorphisms and the Risk of Recurrent Pregnancy Loss in Korean Women. Genes 2020, 11, 354.
The authors wish to make a correction to the published version of their paper [...].


Causal reasoning about epidemiological associations in conversational AI.
We present a Socratic dialogue with ChatGPT, a large language model (LLM), on the causal interpretation of epidemiological associations between fine particulate matter (PM2.5) and human mortality risks. ChatGPT, reflecting probable patterns of human reasoning and argumentation in the sources on which it has been trained, initially holds that "It is well-established that exposure to ambient levels of PM2.5 does increase mortality risk" and adds the unsolicited remark that "Reducing exposure to PM2.5 is an important public health priority." After patient questioning, however, it concludes that "It is not known with certainty that current ambient levels of PM2.5 increase mortality risk. While there is strong evidence of an association between PM2.5 and mortality risk, the causal nature of this association remains uncertain due to the possibility of omitted confounders." This revised evaluation of the evidence suggests the potential value of sustained questioning in refining and improving both the types of human reasoning and argumentation imitated by current LLMs and the reliability of the initial conclusions expressed by current LLMs.


The limit spin current in a time-dependent Rashba spin-orbit coupling system.
The generation of spin current in a one dimensional electron gas (1DEG) system is studied, where the Rashba spin-orbit coupling (RSOC) is modulated by a time-varying gate voltage. With a simple unitary transformation, we show the appearance of an additional spin-dependent potential which results in a spin-dependent effective electric field. We include the scattering interaction by taking a relaxation approximation. The formula for the induced spin current is derived, the limit value accessible by time-varying RSOC is obtained and the order of magnitude is estimated. We find that the maximum of a pulsed spin current can reach that limit value. The results in 1DEG are extended to 2DEG. In addition, we study the spin current in a metal-quantum dot-metal system.


What is the optimal management of a loose glenoid component after anatomic total shoulder arthroplasty: a systematic review.
Total shoulder arthroplasty (TSA) provides excellent long-term clinical outcomes in the treatment of glenohumeral arthritis. However, symptomatic glenoid polyethylene loosening can be seen at intermediate follow-up and can lead to shoulder pain and dysfunction. The purpose of this study was to perform a systematic review of the available literature to determine the optimal management of symptomatic glenoid loosening with regard to reoperation and patient satisfaction following various approaches to symptomatic glenoid loosening. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies investigating revision arthroplasty for the treatment of glenoid loosening with clinical outcomes were identified. Clinical failure was defined as a repeat procedure after revision arthroplasty. Overall, 14 studies met inclusion criteria that included 483 patients with a mean age of 66.5 ± 3.0 years who underwent revision arthroplasty for symptomatic glenoid loosening. There were 8 studies that discussed conversion to a hemiarthroplasty (HA, 148 patients), 7 studies that discussed glenoid reimplantation in a single setting (1-stage TSA, 157 patients), 2 studies that discussed glenoid reimplantation in a staged setting (2-stage TSA, 18 patients), and 2 studies that discussed conversion to a reverse shoulder arthroplasty (RSA, 164 patients). All patients underwent glenoid component removal. The length of follow-up was significantly shorter in the RSA group (41 months for RSA vs. 56 months for HA vs. 55 months for 1-stage TSA vs. 62 months for 2-stage TSA, P < .001). The reoperation rate at the final follow-up was 19% for the HA cohort, 20% for the 1-stage TSA cohort, 22% for the 2-stage TSA cohort, and 21% for the RSA cohort (P = .971). Patient satisfaction rate at the final follow-up was 62% for the HA cohort, 66% for the 1-stage TSA cohort, 71% for the 2-stage TSA cohort, and 86% for the RSA cohort (P = .045). Positive cultures were noted in 15% of patients with Cutibacterium acnes comprising 72% of positive cultures. Overall, the optimal management of symptomatic glenoid loosening remains unclear. All 4 types of revision arthroplasty (HA, 1-stage TSA, 2-stage TSA, and RSA) had a similar reoperation rate (20%) at the latest follow-up. Conversion to RSA provided a higher proportion of patients satisfied with the procedure. However, the length of follow-up was significantly shorter than other groups, and therefore longer-term follow-up of this group is needed to determine if results are durable.


Lepidimoide Promotes Light-Induced Chlorophyll Accumulation in Cotyledons of Sunflower Seedlings.
The effect of disaccharide lepidimoide on light-induced chlorophyll accumulation was studied in cotyledons of sunflower (Helianthus annuus L.) seedlings and detached cucumber (Cucumis sativus L.) cotyledons. From studies on the structure-activity relationships of lepidimoide, its analogs, and sucrose with respect to light-induced chlorophyll accumulation in the cotyledons of sunflower seedlings, both lepidimoide and the free carboxylic acid of lepidimoide (lepidimoic acid) showed the highest promoting activity, whereas the hydrogenated lepidimoide, which lacks a double bond in the C4, 5 position in uronic acid, showed lower activity than lepidimoide; however, sucrose exhibited very weak activity. These results suggest that lepidimoide acts as a new type of plant growth regulator, not simply as a carbon source providing energy. Lepidimoide promoted not only light-induced chlorophyll accumulation in sunflower cotyledons but also light-induced 5-aminolevulinic acid content, which is considered to be a rate-limiting step in chlorophyll biosynthesis. Lepidimoide with cytokinin stimulated the accumulation of chlorophyll and 5-aminolevulinic acid additively. In detached cucumber cotyledons, lepidimoide also promoted light-induced chlorophyll accumulation. These results indicate that lepidimoide, in cooperation with cytokinin, causes light-induced chlorophyll accumulation in the cotyledons of several dicot plant species by affecting the level of 5-aminolevulinic acid. Key Words. 5-Aminolevulinic acid accumulation-Chlorophyll accumulation-Cucumis sativus-Cytokinin-Helianthus annuus-Lepidimoic acid-Lepidimoide-Structure-activity relationship


Contribution of Cerebellar Loops to Action Timing.
Recent studies of sensorimotor processing have benefited from decision-making paradigms that emphasize the selection of appropriate movements. Selecting when to make those responses, or action timing, is important as well. Although the cerebellum is commonly viewed as a controller of movement dynamics, its role in action timing is also firmly supported. Several lines of research have now extended this idea. Anatomical findings have revealed connections between the cerebellum and broader timing circuits, neurophysiological results have suggested mechanisms for timing within its microcircuitry, and theoretical work has indicated how temporal signals are processed through it and decoded by its targets. These developments are inspiring renewed studies of the role of the cerebellar loops in action timing.


A complex balanced chromosomal rearrangement in repeated abortions.
A double balanced reciprocal translocation involving four chromosomes, t(1;19;6;14) (1p11; 19p11; 6q25; 14q21), was found in the phenotypically normal husband in a couple referred because of repeated abortions. Reciprocal translocations, t(6;14), had been transmitted by his mother, his father being apparently homozygous for a translocation comprising pairs 1 and 19--t(1;19)(1;19). The genetic consequences of this complex chromosomal rearrangement are analyzed.


Correction: Boronate based fluorescence (ESIPT) probe for peroxynitrite.
Correction for 'Boronate based fluorescence (ESIPT) probe for peroxynitrite' by Adam C. Sedgwick et al., Chem. Commun., 2016, 52, 12350-12352.


Surfactants: their role in preventing the precipitation of proteins by tannins in insect guts.
Much more tannic acid or pin oak tannin is required to precipitate the abundant leaf protein, ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBPC), from Manduca sexta gut fluid adjusted to pH 6.5 than is required to precipitate this protein from an aqueous buffer at the same pH. This finding demonstrates that some characteristic of M. sexta gut fluid, in addition to its basicity, counteracts the potential of tannins to precipitate ingested proteins. Gut fluid of M. sexta has a surface tension of 36-39 dynes/cm, indicating the presence of surfactants. Lysolecithin and linoleoylglycine, surfactants known to be present in insect gut fluids, also interfere with the precipitation of RuBPC by tannins at pH 6.5. It is concluded that detergency is a widespread property of insect gut fluids that counteracts the potential of tannins to precipitate die ary proteins, and it is argued that there is no longer any justification for continuing to refer to tannins as digestibility-reducing-substances. Finding that there has been no formidable barrier to the evolution of mechanisms that counter a generalized antidigestive action by tannins is difficult to reconcile with the idea that reduced digestibility is an evolved anti-herbivore adaptation of apparent plants.


A Diagnostic Prediction Model to Distinguish Multisystem Inflammatory Syndrome in Children.
Features of multisystem inflammatory syndrome in children (MIS-C) overlap with other syndromes, making the diagnosis difficult for clinicians. We aimed to compare clinical differences between patients with and without clinical MIS-C diagnosis and develop a diagnostic prediction model to assist clinicians in identification of patients with MIS-C within the first 24 hours of hospital presentation. A cohort of 127 patients (<21 years) were admitted to an academic children's hospital and evaluated for MIS-C. The primary outcome measure was MIS-C diagnosis at Vanderbilt University Medical Center. Clinical, laboratory, and cardiac features were extracted from the medical record, compared among groups, and selected a priori to identify candidate predictors. Final predictors were identified through a logistic regression model with bootstrapped backward selection in which only variables selected in more than 80% of 500 bootstraps were included in the final model. Of 127 children admitted to our hospital with concern for MIS-C, 45 were clinically diagnosed with MIS-C and 82 were diagnosed with alternative diagnoses. We found a model with four variables-the presence of hypotension and/or fluid resuscitation, abdominal pain, new rash, and the value of serum sodium-showed excellent discrimination (concordance index 0.91; 95% confidence interval: 0.85-0.96) and good calibration in identifying patients with MIS-C. A diagnostic prediction model with early clinical and laboratory features shows excellent discrimination and may assist clinicians in distinguishing patients with MIS-C. This model will require external and prospective validation prior to widespread use.


Prognostic models for short-term annual risk of severe complications and mortality in patients living with type 2 diabetes using a national medical claim database.
Prognostic models in patients living with diabetes allow physicians to estimate individual risk based on medical records and biological results. Clinical risk factors are not always all available to evaluate these models so that they may be complemented with models from claims databases. The objective of this study was to develop, validate and compare models predicting the annual risk of severe complications and mortality in patients living with type 2 diabetes (T2D) from a national claims data. Adult patients with T2D were identified in a national medical claims database through their history of treatments or hospitalizations. Prognostic models were developed using logistic regression (LR), random forest (RF) and neural network (NN) to predict annual risk of outcome: severe cardiovascular (CV) complications, other severe T2D-related complications, and all-cause mortality. Risk factors included demographics, comorbidities, the adjusted Diabetes Severity and Comorbidity Index (aDSCI) and diabetes medications. Model performance was assessed using discrimination (C-statistics), balanced accuracy, sensibility and specificity. A total of 22,708 patients with T2D were identified, with mean age of 68 years and average duration of T2D of 9.7 years. Age, aDSCI, disease duration, diabetes medications and chronic cardiovascular disease were the most important predictors for all outcomes. Discrimination with C-statistic ranged from 0.715 to 0.786 for severe CV complications, from 0.670 to 0.847 for other severe complications and from 0.814 to 0.860 for all-cause mortality, with RF having consistently the highest discrimination. The proposed models reliably predict severe complications and mortality in patients with T2D, without requiring medical records or biological measures. These predictions could be used by payers to alert primary care providers and high-risk patients living with T2D.


[Antibacterial Activity of Alkylated and Acylated Derivatives of Low-Molecular Weight Chitosan].
A number of alkylated (quaternized) and acylated derivatives of low-molecular weight chitosan were obtained. The structure and composition of the compounds were confirmed by the results of IR and PMR spectroscopy, as well as conductometric titration. The effect of the acyl substituent and the degree of substitution of N-(2-hydroxy-3-trimethylammonium) with the propyl fragment appended to amino groups of the C2 atom of polymer chains on antibacterial activity against typical representatives of gram-positive and gram-negative microorganisms (Staphylococcus epidermidis and Escherichia coli) was studied. The highest activity was in the case of N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan chloride with the maximal substitution (98%). The minimal inhibitory concentration of the derivative was 0.48 µg/mL and 3.90 µg/mL for S. epidermis and E. coli, respectively.


The circumferential margin in rectal cancer. Recommendations based on the Dutch Total Mesorectal Excision Study.
A very low local recurrence rate in rectal cancer is possible with optimal staging, preoperative radiotherapy and the use of total mesorectal excision (TME). Data from a study where patients were randomised for preoperative radiotherapy (or not) and complete removal of the tumour and mesorectum were examined. A consensus meeting was held to discuss the data in which the following guidelines for implementation were made. Adequate imaging is necessary to increase the likelihood of a R0 resection. Advances cases (possible margin to the endopelvicfascie less than 2 mm) need a long course of preoperative radiotherapy. Primary resectable cases benefit from a short course of radiation directly followed by surgery. A continuous quality control of surgery is mandatory in order to maintain the skill for a TME. A complete pathology report is important for the quality control of the surgical treatment and to predict the outcome of treatment. All of the involved disciplines in the diagnosis and treatment of rectal cancer should focus on the circumferential margin to guide for optimal treatment. Multidisciplinary teams are important for the achievement of optimal treatment planning of rectal cancer patients and maintenance of the highest level of quality control.