Comparative study of silicon and selenium to modulate chloroplast pigments levels, Hill activity, photosynthetic parameters and carbohydrate metabolism under arsenic stress in rice seedlings.
Arsenic (As) in groundwater severely harms global economic development by affecting growth and productivity of agricultural crops that causes human health risk. The comparative influence of silicon (Si) and selenium (Se) to modulate pigments levels, photosynthetic parameters using LI-6400XT Portable Photosynthesis System and carbohydrate metabolism under arsenate (As-V) stress in rice cv. MTU-1010 were evaluated. As(V) stress significantly decreased chlorophyll-a (32% on an average), chlorophyll-b (58% on an average), total chlorophyll (46% on an average), fluorescence intensity (31% on an average), carotene (39% on an average), xanthophyll (33% on an average), Hill activity (47% on an average) and the photosynthetic parameters, viz. intercellular CO2 concentration (52% on an average), net photosynthesis (54% on an average), transpiration rate (36% on an average) and stomatal conductance (38% on an average) in the test seedlings. As(V) + Si treatments enhanced the stated occurrences more than As(V) + Se treatments in rice seedlings. Sugar contents, viz. reducing (85% on an average) and non-reducing sugar (61% on an average), were increased, but starch content (57% on an average) was decreased in only As(V)-treated rice seedlings. The activities of carbohydrate metabolizing enzymes were increased, while sucrose synthase activity was decreased due to As(V) toxicity in the test seedlings. Co-application of Si and As(V) as well as Se and As(V) showed ameliorative effects on sugar and starch contents along with the activities of carbohydrate metabolizing enzymes, but more potential effect was observed under combined application of Si and As(V) in rice seedlings. Thus, it is an important purpose of this paper to compare the ability of Se and Si to alleviate As(V) toxicity in rice seedlings which will be an effective approach to develop possible strategies in As-contaminated agricultural soil to improve normal growth and productivity of rice plants.


A clue to the basis of allelic enhancement: occurrence of the Ax subgroup in the offspring of blood group O parents.
Apparent deviation from Mendelian rules of blood group inheritance is rarely observed. Blood group O parents with children expressing weak A subgroups have occasionally been described but not explained. A detailed serological investigation of such a family is described here. The ABO locus was analysed by PCR-ASP/restriction fragment length polymorphism genotyping and DNA sequencing. The propositus' RBCs were very weakly agglutinated with monoclonal anti-A but distinctly with polyclonal anti-A,B, i.e. typical for Ax. Serum anti-A1 (titre 4) and -B were present. Her parents' blood groups were both clearly O, with titres of serum anti-A1, and -A at 16 and 4, respectively. Adsorption/ elution studies demonstrated A antigen on the daughter's cells only. The ABO genotypes were: mother, AxO1; father, O1vO2; and propositus, AxO2. The Ax allele was an A1-O1v hybrid allele with a crossing-over breakpoint between positions 235 and 446 in intron 6 (Ax-4). Compared to the A1 glycosyltransferase, this allele predicts a protein with two amino acid substitutions (Phe216Ile and Met277Val) known to yield either weakly expressed or no A antigen on RBCs. This study suggests that the nature of the ABO allele in trans can influence A antigen expression, a phenomenon previously described as allelic enhancement (or reinforcement). Potential mechanisms for this are discussed.


Risks of maternal prepregnancy overweight/obesity, excessive gestational weight gain, and bottle-feeding in infancy rapid weight gain: evidence from a cohort study in China.
Rapid weight gain (RWG) in infants is associated with numerous health problems, and its risk factors are still unclear. We assessed 98,097 maternal-infant pairs from a population-based cohort study and followed up with them until the infants were 6 months old. We assessed the associations between maternal prepregnancy weight status; gestational weight gain; feeding pattern; and infants' RWG at 0-1, 0-3, 1-3, and 3-6 months using multivariate unconditional logistic regression models, with controlled confounders. We found that maternal prepregnancy weight status, gestational weight gain, and feeding pattern at the 1st, 3rd, and 6th months had significant impacts on the infants' RWG at each time period (P<0.05). Infants with overweight/obese mothers had a higher risk of RWG after birth, whereas those of mothers who experienced excessive gestational weight gain had higher risks of RWG from birth than the other groups (P<0.01). Infants who were formula-fed had a higher risk of RWG than breastfed infants at the same time point (P<0.01). In conclusion, maternal prepregnancy obesity, excessive gestational weight gain, and formula-feeding were risk factors for infants' RWG during the first 6 months of life.


Microdosimetric calculation of penumbra for biological dose in wobbled carbon-ion beams with Monte Carlo Method.
In carbon-ion radiotherapy, it is important to evaluate the biological dose because the relative biological effectiveness values vary greatly in a patient's body. The microdosimetric kinetic model (MKM) is a method of estimating the biological effect of radiation by use of microdosimetry. The lateral biological dose distributions were estimated with a modified MKM, in which we considered the overkilling effect in the high linear-energy-transfer region. In this study, we used the Monte Carlo calculation of the Geant4 code to simulate a horizontal port at the Heavy Ion Medical Accelerator in Chiba of the National Institute of Radiological Sciences. The lateral biological dose distributions calculated by Geant4 were almost flat as the lateral absorbed dose in the flattened area. However, in the penumbra region, the lateral biological dose distributions were sharper than the lateral absorbed dose distributions. Furthermore, the differences between the lateral absorbed dose and biological dose distributions were dependent on the depth for each multi-leaf collimator opening size. We expect that the lateral biological dose distribution presented here will enable high-precision calculations for a treatment-planning system.


Segmental facial hemangioma accompanied by brain anomalies: report of a case.
Hemangioma of infancy (HOI) is the most common tumor of infancy. Initial rapid proliferation is generally followed by gradual involution and resolution. However, some HOI may be associated with congenital structural abnormalities. We describe a case of HOI associated with hypoplasia of the left cerebellum and arachnoid cyst.


[Acute pancreatitis and post-traumatic pseudocysts of the pancreas. Report of 12 cases (author's transl)].
The authors report 12 personal cases and a bibliographic study showing the authenticity of acute pancreatitis and pancreatic pseudo-cyst following trauma. The clinico-pathological aspects, the course and the treatment are not specific. The medico-legal aspect is the most important for the secondary or late manifestations raise the problem of the imputability to the accident. Surgeons and judicial experts should be aware of the post-traumatic risk.


Ultra-high molecular weight pullulan-based material with high deformability and shape-memory properties.
Most shape-memory polymers (SMPs) are derived from petroleum feedstocks, which have limitations due to their challenging manufacturing process. Accordingly, herein, a novel SMP based on microbially produced ultrahigh-molecular-weight (UHMW) pullulan was developed. UHMW pullulan cross-linked with 1,4-butanediol diglycidyl ether was wet-spun into fibers with high stretchability (1365 % strain) and excellent shape-memory properties. Furthermore, using three-dimensional (3D) printing, UHMW pullulan-based structures with highly complex shapes (for example, square, cruciform, pentagram and tubular structures), large deformability, and shape memory properties were fabricated. These 3D-printed structures exhibited four-dimensional (4D) programmable deformation under solvent stimulation, enabling the 4D printing of pullulan. The sustainable and eco-friendly approach proposed in this study for the production of pullulan-based SMPs promised to address the current limitations of petroleum-based SMPs.


A dysmorphic child with myelodysplasia characterized by a duplication of 1q and multiple duplications of 3q.
Multiple inserted duplications of bands 3q21 through 3q27 and a duplication of the chromosome 1 long arm are reported in a karyotypically altered clone from a dysmorphic child with myelodysplasia.


Structural insight into the human SID1 transmembrane family member 2 reveals its lipid hydrolytic activity.
The systemic RNAi-defective (SID) transmembrane family member 2 (SIDT2) is a putative nucleic acid channel or transporter that plays essential roles in nucleic acid transport and lipid metabolism. Here, we report the cryo-electron microscopy (EM) structures of human SIDT2, which forms a tightly packed dimer with extensive interactions mediated by two previously uncharacterized extracellular/luminal β-strand-rich domains and the unique transmembrane domain (TMD). The TMD of each SIDT2 protomer contains eleven transmembrane helices (TMs), and no discernible nucleic acid conduction pathway has been identified within the TMD, suggesting that it may act as a transporter. Intriguingly, TM3-6 and TM9-11 form a large cavity with a putative catalytic zinc atom coordinated by three conserved histidine residues and one aspartate residue lying approximately 6 Å from the extracellular/luminal surface of the membrane. Notably, SIDT2 can hydrolyze C18 ceramide into sphingosine and fatty acid with a slow rate. The information presented advances the understanding of the structure-function relationships in the SID1 family proteins.


Ultrasound therapy effect in carpal tunnel syndrome.
To investigate the overall effect of repeated ultrasound treatment in carpal tunnel syndrome (CTS). Patient-blinded, placebo-controlled, before-after treatment trial. University hospital PM&R department outpatient clinic and neurology department electromyography laboratory. Eighteen women with diagnosis of CTS in 30 hands. Three groups, each with 10 cases of CTS, were randomly established. Continuous ultrasound therapy, with intensities of 1.5W/cm2 (group A), 0.8W/cm2 (group B), and 0.0W/cm2 (group C), was applied to palmar carpal tunnel area for 5 minutes, 5 days a week, for 2 weeks. Patients were evaluated clinically and electrophysiologically before and after the treatment. At the end of treatment, statistically significant improvement was obtained in clinical parameters in all groups: pain (p < .05), pain/paresthesia at night/day (p < .05), and frequency of awakening at night (p < .05). Although there was no statistically significant before-after difference in electrophysiologic studies, slightly decreased motor nerve conduction velocity and increased motor distal latency were noted in groups A and B, but not in group C. Ultrasound therapy in CTS was comparable to placebo ultrasound in providing symptomatic relief, and the probability of a negative effect on motor nerve conduction needs to be considered.


Studies on extraction of fumonisins from rice, corn-based foods and beans.
Different solvent mixtures were examined for extraction of fumonisins from various naturally contaminated and spiked foods and foodstuffs: rough rice, retail rice, rice flour, white corn flour, corn meal, corn starch, corn flakes, tortilla/corn chips, white bean flour, white beans, mung beans, adzuki beans and infant cereals. Most of the naturally contaminated samples were analyzed using the extraction solvent mixtures methanol-acetonitrile-water (25:25:50) (solvent A) and methanol-water (75:25 or 80:20) (solvents B, BB); some were extracted with 0.1 M sodium hydrogen phosphate-acetonitrile (1:1, adjusted to pH 3.0 with o-phosphoric acid) (solvent C) and methanol-0.025 M borate buffer (3:1, adjusted to pH 9.2 with 1 N sodium hydroxide) (solvent D). A 1-ml SAX solid phase extraction column was used for the cleanup in all cases except for infant cereals, for which immunoaffinity chromatography was used; fumonisin concentrations were determined by liquid chromatography.Solvent A gave slightly better extraction of fumonisins from one of two samples of naturally contaminated rough rice than solvent B (fumonisin B1: 4080 ng/g versus 3150 ng/g; fumonisin B2:1100 ng/ g versus 922 ng/g) and much better extraction than solvent C (1210 ng/g fumonisin B1 and 315 ng/g fumonisin B2) or solvent D (372 ng/ g fumonisin B1 and 191 ng/g fumonisin B2). However, spike recoveries on a similar rice naturally contaminated at a lower level were only in the 43-53% range (solvent A). Recovery of fumonisins was very poor from spiked white rice flour but satisfactory from other rice foods.Solvent A similarly gave slightly better extraction of fumonisins from a sample of naturally contaminated white corn flour than solvent B (fumonisin B1 1260 ng/g versus 931 ng/g; fumonisin B2: 511 ng/g versus 447 ng/g ) and better extraction than solvents C and D. Solvent A was also a better solvent for extraction of fumonisins from naturally contaminated tortilla chips and infant cereals. Study of naturally contaminated corn starch was confounded by instability of fumonisins in this food. Recovery of fumonisins from spiked corn meal, tortilla chips, corn flakes, various types of beans and infant cereals with solvent A and/or solvent B (or BB) was satisfactory.


Effects of chronic ethanol on cholinergic actions in rat hippocampus: electrophysiological studies and quantification of m1-m5 muscarinic receptor subtypes.
The effects of chronic ethanol treatment (CET) on cholinergic modulation of CA1 evoked field potentials and recurrent inhibition were investigated in rat hippocampal slices. Densities of muscarinic receptor subtypes were quantified in remaining hippocampal tissue by immunoprecipitation. Iontophoretic application of ACh in stratum pyramidale results in facilitation of single evoked population spikes; application in stratum radiatum results in depression of field EPSPs. CET decreased cholinergic facilitation of population spikes, while cholinergic inhibition of field EPSPs remained unaffected. Integrity of feedback (recurrent) inhibitory circuitry was evaluated by paired-pulse stimulation. As previously demonstrated, recurrent inhibition was significantly reduced after CET; cholinergic disinhibition was also significantly reduced. Thus, CET appears to disrupt a subset of cholinergic effector systems within hippocampal neurons. The reductions in cholinergic function produced by CET does not appear to be due to receptor loss, since muscarinic receptor subtype densities were not found to be significantly altered in this tissue. These results support the hypothesis that muscarinic receptor function is impaired in CA1 pyramidal cells through a disruption of intracellular signal transduction mechanisms. While it is unclear whether cholinergic function is reduced in interneurons directly, these results suggest that modulation of neuronal firing in the hippocampus is markedly altered following CET due to impairment of both cholinergic and GABAergic systems.


Development and validation of a sensitive enantiomeric separation method for new single enantiomer drug levornidazole by CD-capillary electrophoresis.
A fast and sensitive chiral capillary electrophoresis method has been developed to determine levornidazole and its enantiomeric impurity at a 0.05% level in levornidazole injection solution. Several chemical and instrumental parameters which have an effect on chiral separation were investigated, including chiral selectors, buffer composition and pH, applied voltage, capillary length, temperature and rinsing procedure. After optimizing all the effective parameters, the ideal separation conditions were 20 mM Tris phosphate buffer at pH 2.1, containing 2.0% (w/v) sulfated-α-cyclodextrin with short end injection at 0.5 psi for 5.0 s. Online UV detection was performed at 277 nm. A voltage of 30 kV was applied and the capillary temperature was kept at 25 °C. 2,4,6-triaminopyrimidine was chosen as internal standard to improve the injection precision. The total analysis time is less than 7 min, which is faster than the existing chiral HPLC method (65 min). The validation of the method was performed in terms of factorial analysis, stability of the solution, different cyclodextrin batches study, selectivity, linearity (from 2.5 μg/mL to 6000 μg/mL, y=0.0015 x+0.0304; R(2)=0.9999 and the residuals were randomly scattered around 0), LOD and LOQ (0.3 and 1.0 μg/mL, respectively), precision and accuracy. The proposed method was then applied to the enantiomeric purity control of the starting material and injection solution of levornidazole (0.5 mg/100 mL).


Ontogenesis of gastrin cells in the pyloric antrum and duodenum of the mouse.
Ontogenesis of gastrin cells was studied in the pyloroduodenal mucosa of the mouse using anti-human G17 serum, R-1301, and anti-human G34(1-15) serum, R-2703. R-1301-immunostained cells first appeared in the pyloric mucosa of 14-day-old fetuses. Cells stained with both R-1301 and R-2703 appeared immediately after birth, and gradually increased in number to the adult level. Most R-1301-reactive cells were also reactive to R-2703, whereas some cells that reacted with R-1301 exhibited very weak or no reaction with R-2703. The discrepancy between these two immunoreactivities is discussed. In the duodenum, a considerable number of R-1301-reactive cells were present from the perinatal stage and through out adult development. A few R-2703-reactive cells were seen in the duodenum of young mice but not of the adult.


Factors associated with improvement in disability-adjusted life years in patients with HIV/AIDS.
The epidemic of HIV/AIDS and treatments that have emerged to alleviate, have brought about a shift in the burden of disease from death to quality of life/disability. The aim was to determine which factors are associated with improvements in the level of health of male and female patients with HIV/AIDS in Andalusia, in terms of disability-adjusted life years. Descriptive study based on a sample group of 8800 people on the Andalusian AIDS register between 1983 and 2004. Life lost due to premature mortality (YLL), years lost due to disability (YLD) and disability-adjusted life years (DALY). vital state, sex, age at the time of diagnosis, age at the time of death, transmission category, province of residence, AIDS-indicator disease and the period of diagnosis. A bivariate analysis was carried out to find out if the health level variables changed in accordance with the independent variables. Using the independent variables which had a statistically significant link with the level of health variables, a multivariate linear regression model, disaggregated by gender, was constructed. Amongst the women, we found a model which explained the level of health of 64.9%: a link was found between a higher level of health (lower DALYs) and not intravenous drug use, the province of residence, being diagnosed during the HAART era and older age at the time of diagnosis. Amongst the men, we found a model which explained the level of health of 64.4%: a link was found between a higher level of health (lower DALYs) and intravenous drug use, the province of residence, being diagnosed during the HAART era and older age at the time of diagnosis. A higher level of health (lower DALY) amongst both men and women was found to be linked to not be intravenous drug user, the province of residence, being diagnosed during the HAART era and older age at the time of diagnosis.


[States of preadjustment under conditions of prolonged activation according to evoked potential findings in schizophrenic patients].
The paper deals with a psychophysiological study of the states of disposition, expectation with the aid of the method of evoked potentials as one of the indices of peculiarities in activation processes in schizophrenic patients in conditions of active senso-motor activity. The study demonstrated significant differences in the schizophrenic patients in EP changes of cerebral cortex antecentral zones in situations of mental activity associated with expectation, active disposition. Moreover, in conditions of long-term stable activation schizophrenic patients show differences from normals by a character of dynamics of EP changes in the frontal brain areas, as the tension increases. The obtained data can testify to the fact that the given trend of psychophysiological studies may serve as an aspect of search and analysis of factors that are the basis of changes in a selective form of activation in schizophrenia.


Effective of metastasis-directed therapy for de novo metastatic nasopharyngeal carcinoma: A propensity score matched analysis.
Our objective was to establish a prognostic model for patients with de novo metastatic nasopharyngeal carcinoma (NPC) who received chemotherapy followed by locoregional radiotherapy (LRRT) to identify candidates for metastasis-directed therapy (MDT). De novo metastatic NPC patients who received chemotherapy followed by LRRT were enrolled. Propensity score matching (PSM) method was used to compare overall survival (OS) for patients receiving LRRT alone and MDT plus LRRT. We developed a predictive model to predict survival and estimate the outcome of stratified therapy and identify suitable candidates for MDT. A total of 107 patients received MDT plus LRRT and 178 received LRRT alone were enrolled. PSM analysis identified 107 patients in each cohort and showed that MDT plus LRRT was associated with a significant survival benefit (HR: 0.640; 95% CI, 0.29-0.956; p = 0.027). Based on five independent prognostic factors, including metastases number, serum lactate dehydrogenase, liver metastasis, C-reactive protein, and tumor response, a prognostic model was established. All patients were stratified according to the prognostic score obtained by the prognostic model. In the low-risk group, MDT plus LRRT group revealed a significant improvement for OS compared with LRRT alone group (5-year OS, 69.9% vs. 57.8%, p = 0.020). However, no significant difference was observed between MDT plus LRRT group and LRRT alone in the high-risk group (p = 0.75). MDT plus LRRT was associated with improved OS in patients with de novo metastatic NPC, especially low-risk patients identified with a newly developed prognostic model.


Identification of factors affecting meropenem pharmacokinetics in critically ill patients: Impact of inflammation on clearance.
The purpose of this study was to explore factors influencing meropenem pharmacokinetics (PKs) in critically ill patients by developing a population PK model and to determine the optimal dosing strategy. This prospective observational study involved 12 critically ill patients admitted to the intensive care unit and treated with meropenem 1 g infused over 1 h every 8 h. Blood samples were collected on days 1, 2, and 5 immediately prior to dosing, and at 1, 2, 4, and 6 h after the start of infusion. Population PK parameters were estimated using nonlinear mixed-effects model software. Meropenem PK was adequately described using a two-compartment model. Typical values of total and inter-compartmental clearance were 9.30 L/h and 9.70 L/h, respectively, and the central and peripheral compartment volumes of distribution were 12.61 L and 7.80 L, respectively. C-reactive protein (CRP) was identified as significant covariate affecting total meropenem clearance. The probability of target attainment (PTA) predicted by Monte Carlo simulations varied according to the patients' CRP. The PTA of 100% time above the minimum inhibitory concentration ≤2 mg/L for bacteria was achieved after a dose of 1 and 2 g infused over 4 h every 8 h in patients with CRP of 30 and 5 mg/dL, respectively. The findings of this study suggest that CRP might be helpful in managing meropenem dosing in critically ill patients. Higher doses and extended infusion may be required to achieve optimal pharmacodynamic targets.


The trend and future projection of technology-assisted total knee arthroplasty in the United States.
As technology-assisted surgery has boosted in the last decades, we aimed to investigate the factors affecting adoption and to predict the future utilization of technology among patients who underwent total knee arthroplasty (TKA). Patients underwent TKA in 2017-2019 in the MarketScan Database were included. Percentage of technology-assisted surgery was calculated. Multivariable logistic regression models were performed to analyse the factors and make the prediction. Of 112,161 TKA procedures, 7.2% were technology-assisted. The proportion of technology-assisted TKA is expected to reach 50% by 2032. The West showed the highest proportion of technology-assisted TKA (12.3%), while the South had the lowest (5.7%). Over time, the Midwest showed the greatest increase in technology adoption (OR = 1.26 compared to the Northeast, 95% CI [1.15, 1.38]). Technology adoption rate of TKA will continue to increase for the next 20 years in the United States with a slight geographical variation.


Somatic transgenesis using retroviral vectors in the chicken embryo.
The avian embryo is an excellent model system for experimental studies because of its accessibility and ease of microsurgical manipulations. While the complete chicken genome sequence will soon be determined, a comprehensive germ cell transmission-based genetic approach is not available for this animal model. Several techniques of somatic cell transgenesis have been developed in the past decade. Of these, the retroviral shuttle vector system provides both (1) stable integration of exogenous genes into the host cell genome, and (2) constant expression levels in a target cell population over the course of development. This review summarizes retroviral vectors available for the avian model and outlines the uses of retroviral-mediated gene transfer for cell lineage analysis as well as functional studies of genes and proteins in the chick embryo.


Insulin/IGF-1 receptor signaling enhances biosynthetic activity and fat mobilization in the initial phase of starvation in adult male C. elegans.
Upon nutrient deprivation, cells are thought to suppress biosynthesis but activate catabolic pathways to provide alternative energy sources and nutrients. However, here we provide evidence that in adult male C. elegans, both biosynthesis and degradation activities, including ribosome biogenesis and turnover, are enhanced during early starvation and appear to depend on the availability of intestinal lipid stores. Upon depletion of the intestinal lipids, further food deprivation results in a significant reduction in metabolic activity in the starved male worms. Our data show that adult C. elegans exhibits a two-phase metabolic response to starvation stress: an initial phase with enhanced metabolic activity that rapidly exhausts the lipid stores, followed by a phase with low metabolic activity, which outlasts the life of fed control worms. DAF-2 insulin/IGF-1 receptor signaling to the RAS pathway is required for the starvation-induced ribosome biogenesis and rapid lipid depletion in the initial phase of starvation.


Lung transplantation for post-COVID-19 pulmonary fibrosis.
COVID-19 has affected over a billion people around the world, with over 2 million losing their lives (Worldometer). About 10% of patients infected with COVID-19 develop a serious illness, including respiratory failure, that require advanced life-supporting measures. Mortality among this subgroup exceeds 60%. We present a case of an otherwise healthy 34-year-old male who developed end-stage pulmonary fibrosis following COVID-19 infection. He achieved haemodynamic stability with mechanical ventilation and extracorporeal membrane oxygenation (ECMO) but did not show any sign of weaning off ECMO; however, he successfully underwent bilateral lung transplantation.


Elucidation of a complete mechanical signaling and virulence activation pathway in enterohemorrhagic Escherichia coli.
Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is an important extracellular human pathogen. The initial adherence of EHEC to host cells is a major cue for transcriptional induction of the locus of enterocyte effacement (LEE) genes to promote colonization and pathogenesis, but the mechanism through which this adherence is sensed and the LEE is induced remains largely elusive. Here, we report a complete signal transduction pathway for this virulence activation process. In this pathway, the outer-membrane lipoprotein NlpE senses a mechanical cue generated from initial host adherence and activates the BaeSR two-component regulatory system; the response regulator BaeR then directly activates the expression of airA located on O-island-134 and encoding a LEE transcriptional activator. Disruption of this pathway severely attenuates EHEC O157:H7 virulence both in vitro and in vivo. This study provides further insights into the evolution of EHEC pathogenesis and the host-pathogen interaction.


Percutaneous drainage for post-traumatic hepatic abscess in children under ultrasound imaging.
Hepatic abscess is rare in children. A patient with a post-traumatic hepatic abscess was successfully treated by ultrasound-guided percutaneous drainage. Although he underwent a drainage operation for the perihepatic abscesses, high fever continued. It was then considered that the traumatic hematoma had been infected and had become an abscess. Sonographically-guided percutaneous aspiration is useful for the definite diagnosis of hepatic abscess. Subsequent percutaneous drainage under ultrasound imaging is a safe and useful therapeutic method even in a poor-risk patient.


Chitosan/benzyloxy-benzaldehyde modified ZnO nano template having optimized and distinct antiviral potency to human cytomegalovirus.
Utilization of biomolecules encapsulated nano particles is currently originating ample attention to generate unconventional nanomedicines in antiviral research. Zinc oxide nanoparticle has been extensively studied for antimicrobial, antifungal and antifouling properties due to high surface to volume ratios and distinctive chemical as well as physical properties. Nevertheless, still minute information is available on their response on viruses. Here, in situ nanostructured and polysaccharide encapsulated ZnO NPs are fabricated with having antiviral potency and low cytotoxicity (%viability ~ 90%) by simply controlling the formation within interspatial 3D networks of hydrogels through perfect locking mechanism. The two composites ChH@ZnO and ChB@ZnO shows exceedingly effective antiviral activity toward Human cytomegalovirus (HCMV) having cell viability 93.6% and 92.4% up to 400 μg mL-1 concentration. This study brings significant insights regarding the role of ZnO NPs surface coatings on their nanotoxicity and antiviral action and could potentially guide to the development of better antiviral drug.


Resolutions of control episodes between well and affectively ill mothers and their young children.
Control interactions between 87 well and affectively ill mothers and their 15- to 51-month-old children were studied. Spontaneously occurring control interventions (conceptualized as episodes of interaction between mother and child) were coded from 90 minutes of videotaped interactions in a naturalistic laboratory apartment setting. The results suggest developmental changes in mother-child interaction in the 2nd to 4th years of life: the increase of the rate of immediate maternal success (p less than .05) and compromise (p less than .05), on the decrease in maternal use of power (ultimate success by enforcement, p less than .01). Well mothers achieved compromise with their children, particularly daughters, more often than did affectively ill mothers (p less than .05). Affectively ill mothers more often than well mothers avoided confrontation with their children (p less than .05). The impairments in control interventions of affectively ill mothers were exacerbated by the severity of the disorder.


The Diversity and Metabolism of Culturable Nitrate-Reducing Bacteria from the Photic Zone of the Western North Pacific Ocean.
To better understand bacterial communities and metabolism under nitrogen deficiency, 154 seawater samples were obtained from 5 to 200 m at 22 stations in the photic zone of the Western North Pacific Ocean. Total 634 nitrate-utilizing bacteria were isolated using selective media and culture-dependent methods, and 295 of them were positive for nitrate reduction. These nitrate-reducing bacteria belonged to 19 genera and 29 species and among them, Qipengyuania flava, Roseibium aggregatum, Erythrobacter aureus, Vibrio campbellii, and Stappia indica were identified from all tested seawater layers of the photic zone and at almost all stations. Twenty-nine nitrate-reducing strains representing different species were selected for further the study of nitrogen, sulfur, and carbon metabolism. All 29 nitrate-reducing isolates contained genes encoding dissimilatory nitrate reduction or assimilatory nitrate reduction. Six nitrate-reducing isolates can oxidize thiosulfate based on genomic analysis and activity testing, indicating that nitrate-reducing thiosulfate-oxidizing bacteria exist in the photic zone. Five nitrate-reducing isolates obtained near the chlorophyll a-maximum layer contained a dimethylsulfoniopropionate synthesis gene and three of them contained both dimethylsulfoniopropionate synthesis and cleavage genes. This suggests that nitrate-reducing isolates may participate in dimethylsulfoniopropionate synthesis and catabolism in photic seawater. The presence of multiple genes for chitin degradation and extracellular peptidases may indicate that almost all nitrate-reducing isolates (28/29) can use chitin and proteinaceous compounds as important sources of carbon and nitrogen. Collectively, these results reveal culturable nitrate-reducing bacterial diversity and have implications for understanding the role of such strains in the ecology and biogeochemical cycles of nitrogen, sulfur, and carbon in the oligotrophic marine photic zone.


Endometrial cancer in patients with preoperative diagnosis of atypical endometrial hyperplasia.
Atypical endometrial hyperplasia (AEH) has been associated with the presence of concomitant endometrial carcinoma (EC). The aim of this study is to examine the frequency of coexisting endometrial carcinoma when atypical endometrium hyperplasia was found upon biopsy. We also evaluated the influence of preoperative diagnostic techniques (pipelle and dilation and curettage (D&C)), and the value of transvaginal ultrasound in detecting unexpected tumor invasion. Between January 1992 and December 2003, at the Department of Obstetrics and Gynecology, University of Parma, and Policlinico S. Matteo, Pavia, 70 consecutive patients subjected to total hysterectomy with a histological diagnosis of AEH were retrospectively selected. 52/70 patients underwent vaginal hysterectomy, with bilateral salpingo-oophorectomy (BSO) whereas 18/70 had abdominal hysterectomy with BSO within 8 weeks since the diagnosis of AEH. We found in 30 of the 70 patients with atypical endometrial hyperplasia in the biopsy coexisting endometrial carcinoma (43%). No differences in diagnostic accuracy between the pipelle method and D&C were found. Transvaginal ultrasound was not a feasible method for predicting EC. After a follow-up of an average of 5 years there was, neither in the abdominal operated patients nor in the vaginal operated patients, a recurrence of disease.


A network approach can improve eating disorder conceptualization and treatment.
Eating disorders are severe mental illnesses with the second highest mortality rate of all psychiatric illnesses. Eating disorders are exceedingly deadly because of their complexity. Specifically, eating disorders are highly comorbid with other psychiatric illnesses (up to 95% of individuals with an eating disorder have at least one additional psychiatric illness), have extremely heterogeneous presentations, and individuals often migrate from one specific eating disorder diagnosis to another. In this Perspective, we propose that understanding eating disorder comorbidity and heterogeneity via a network theory approach offers substantial benefits for both conceptualization and treatment. Such a conceptualization, strongly based on theory, can identify specific pathways that maintain psychiatric comorbidity, how diagnoses vary across individuals, and how specific symptoms and comorbidities maintain illness for one individual, thereby paving the way for personalized treatment.


Heparan Sulfate Proteoglycans Are Important for Islet Amyloid Formation and Islet Amyloid Polypeptide-induced Apoptosis.
Deposition of β cell toxic islet amyloid is a cardinal finding in type 2 diabetes. In addition to the main amyloid component islet amyloid polypeptide (IAPP), heparan sulfate proteoglycan is constantly present in the amyloid deposit. Heparan sulfate (HS) side chains bind to IAPP, inducing conformational changes of the IAPP structure and an acceleration of fibril formation. We generated a double-transgenic mouse strain (hpa-hIAPP) that overexpresses human heparanase and human IAPP but is deficient of endogenous mouse IAPP. Culture of hpa-hIAPP islets in 20 mm glucose resulted in less amyloid formation compared with the amyloid load developed in cultured islets isolated from littermates expressing human IAPP only. A similar reduction of amyloid was achieved when human islets were cultured in the presence of heparin fragments. Furthermore, we used CHO cells and the mutant CHO pgsD-677 cell line (deficient in HS synthesis) to explore the effect of cellular HS on IAPP-induced cytotoxicity. Seeding of IAPP aggregation on CHO cells resulted in caspase-3 activation and apoptosis that could be prevented by inhibition of caspase-8. No IAPP-induced apoptosis was seen in HS-deficient CHO pgsD-677 cells. These results suggest that β cell death caused by extracellular IAPP requires membrane-bound HS. The interaction between HS and IAPP or the subsequent effects represent a possible therapeutic target whose blockage can lead to a prolonged survival of β cells.


Chronic graft-versus-host disease-related polymyositis and myocarditis: A case report and review of the literature.
Chronic graft-versus-host disease (cGVHD) is a major late complication of hematopoietic stem cell transplantation (HSCT). Polymyositis (PM) has been reported to be an uncommon presentation of cGVHD. Myocarditis is an even rarer manifestation of cGVHD-associated PM. Here, we report a 38-year-old male patient developed cGVHD-related PM twelve years post-transplantation, which was confirmed by muscle biopsy and immunological study. The presence of pain in the chest area, dynamic changes in the electrocardiogram, as well as elevated troponin and myocardial enzyme levels with improvement after immunotherapy all pointed to cardiac involvement. Ruxolitinib in combination with tachlimus and methylprednisolone successfully treated cGVHD associated PM with myocarditis. The literature on cGVHD-related PM and myocarditis is briefly reviewed.


The expanded role of the transplant pharmacist: A 10-year follow-up.
The role of the transplant pharmacist is recognized by transplant programs, governmental groups, and professional organizations as an essential part of the transplant multidisciplinary team. This role has evolved drastically over the last decade with the advent of major advances in the science of transplantation and the growth of the field, which necessitate expanded pharmacy services to meet the needs of patients. Data now exist within all realms of the phases of care for a transplant recipient regarding the utility and benefit of a solid organ transplant (SOT) pharmacist. Furthermore, governing bodies now have the opportunity to use Board Certification in Solid Organ Transplant Pharmacotherapy as a mechanism to identify and recognize specialty knowledge and expertise within the field of SOT pharmacotherapy. The purpose of this paper is to provide an overarching review of the current and future state of SOT pharmacy while also identifying major changes to the profession, forthcoming challenges, and expected areas of growth.


Changes in skeletal muscle qualities during enzyme replacement therapy in late-onset type II glycogenosis: temporal and spatial pattern of mass vs. strength response.
Muscle quality is defined as muscle strength generated per unit muscle mass. If enzyme replacement therapy (ERT) has some effects on type II glycogenosis (GSDII) skeletal muscle pathology, we should be able to measure a change in strength and mass. We conducted a prospective study including 11 patients aged 54.2 ± 11.2 years, referring to a single institution and receiving ERT for ≥2 years. Median Walton score was 3 (2.5-6). Lower limb skeletal muscles were assessed by dynamometry and quantitative muscle MRI. Three segments (anterior thigh, posterior thigh, leg) were analysed separately. Clinical-MRI correlations were searched for at T0, T6/T8, and T18/24. Changes in lean and fat body composition were assessed by bioelectrical impedance analysis. We found that the anterior thigh showed the best therapeutic response, with an improvement in muscle quality (muscle mass: +7.5%, p = 0.035; strength: +45%, p = 0.002). BMI and lean body mass increased (p = 0.007). Patients with low BMI showed a better outcome. Intramuscular fat accumulation significantly progressed in spite of ERT (+3.7%, p = 0.001), especially in the poorly responsive posterior thigh muscles. Both clinical assessment and MRI revealed a definite improvement in the anterior thigh muscles. However, progression of intramuscular fat accumulation during ERT, as well as the limited responsiveness of posterior thigh muscles, suggests the necessity for early treatment intervention. The better outcome of patients with low BMI, if confirmed, may indicate that dietary protocols could be adopted as adjuvant measures to ERT in adult GSDII.


Cardiovascular comorbidities in amyotrophic lateral sclerosis: A systematic review.
To summarize the prevalence of the cardiovascular comorbidities in patients with amyotrophic lateral sclerosis (ALS) and explore the impacts of cardiovascular diseases on ALS. PubMed, EMBASE, OVID and Web of Science were searched systematically until July 2021 for studies on the prevalence of cardiovascular diseases among ALS patients or quantitatively investigating the effects of cardiovascular comorbidities on incidence, progression or survival of ALS. We conducted a fixed-effects or random-effects meta-analysis to calculate the summary rate or ORs (odds ratios) with 95 %CIs (confidence intervals). The comorbidity of hypertension in France (56.9%) was the highest, followed by Portugal (48%). Only 15% of Chinese ALS patients suffered from hypertension. A quarter of ALS patients in America had coronary heart disease while only 4-5% of patients with ALS in Australia or the Netherlands suffered from coronary heart disease. There was significant relationship between hypertension and survival of ALS (OR: 1.04, 95%CI: 1.01, 1.07). Coronary heart disease was considerably related to ALS onset (OR: 1.19, 95%CI: 1.14, 1.24) and heart failure could noticeably accelerate the progression rate of ALS (OR: 6.33, 95%CI: 1.55, 24.84). Cardiovascular comorbidities in ALS patients varied significantly with different regions. Hypertension could reduce the survival of ALS so the intensive treatment of chronic hypertension should be recommended to ALS patients in clinical practice. Coronary heart disease could increase the risk of ALS and heart failure was a negative prognostic factor for ALS, which deserved more attention of clinicians.


A role for nerve growth factor in collateral reinnervation from sensory nerves in the guinea pig.
We have investigated whether chronic nerve growth factor (NGF) depletion affects the development of a transmedian collateral reinnervation. The extent of transmedian innervation of the skin supplied by the left inferior alveolar nerve (IAN) was determined either immediately, 2 days or 7-9 weeks after sectioning and preventing regeneration of the contralateral IAN and in another group of animals left to recover for 7-9 weeks but also autoimmunised against NGF. Transmedian innervation was measured by recording the area from which a jaw-opening reflex could be evoked and by recording activity in the left IAN during mechanical and electrical stimulation of the skin. Nerve recording during electrical stimulation revealed extensive transmedian collateral reinnervation 7-9 weeks after denervation but this was prevented by NGF autoimmunisation. No change in transmedian innervation could be detected in any of the groups by nerve recording during mechanical stimulation and reflex responses revealed changes in the anaesthetic area which could not be attributed to collateral reinnervation. These results suggest that NGF plays an important role in collateral reinnervation from high-threshold sensory nerves.


Optimized Method of 3D Scaffold Seeding, Cell Cultivation, and Monitoring Cell Status for Bone Tissue Engineering.
The cultivation of cells in 3D systems is commonly regarded to be more physiological than in 2D as it comes much closer to the natural situation in tissues in many different aspects. However, 3D cell culture is much more complex. Cells within the pores of a printed 3D scaffold face a special situation concerning cell-material interaction and cell adhesion, cell proliferation, and supply of medium and oxygen into the core of the scaffolds. Biological assays (for cell proliferation, viability, and activity) have been validated primarily for 2D cell cultures and need to be adapted for 3D cultures. Likewise, in imaging, a number of points need to be taken into account in order to get a clear picture of the cells in 3D scaffolds, preferably with the method of multiphoton microscopy. Here, we describe a method for pretreatment and cell seeding of porous inorganic composite scaffolds (α-TCP/HA) for bone tissue engineering and for cultivation of the cell-scaffold constructs. The analytical methods described are the cell proliferation assay and the ALP activity assay. A step-by-step protocol is provided here that safely tackles typical difficulties that arise with this 3D cell-scaffold setting. In addition, MPM imaging of cells is described both with and without labeling. The combination of biochemical assays and imaging provides valuable insights into the possibilities of analysis with this 3D cell-scaffold system.


Rapidly progressive glomerulonephritis in a patient with renal amyloidosis: Case report and review of the literature.
Renal amyloidosis is characterized by progressive deposition of extracellular material, most commonly in the glomeruli. Most often, patients present with nephrotic range proteinuria and the disease progresses gradually to renal failure. Rapid worsening of renal functions is rare. We report a case of crescentic glomerulonephritis superimposed on amyloidosis, clinically presenting as rapidly progressive renal failure, and present a review of the literature.


Tumor vascularity evaluated by transrectal color Doppler US in predicting therapy outcome for low-lying rectal cancer.
To evaluate the impact on T downstaging of the vasculature supplying blood flow to rectal cancer evaluated by color Doppler ultrasound. Color Doppler images were graded in 29 T3-staged rectal carcinoma patients sonographically just before chemoradiation. Any arterial vessels detected in rectal masses were assigned one of two grades: vascularity was considered as grade 1 for vessels feeding the periphery and as grade 2 for vessels coursing in all rectal masses within its peripheral and central portions. The pulsatility indices (PI = peak systolic velocity - end-diastolic velocity/time-averaged maximum velocity) were calculated in the central and peripheral portions. The pathologic observations showed a change in stage in 15 of the 23 patients graded 2, positive predictive value 65.2% (p = 0.047), and in one of the six rectal cancers graded 1 (negative predictive value, 83.3%). The minimal peripheral PI values in rectal cancer graded 2 were higher in nonresponding (2.2 +/- 1.3) than in responding lesions (1.6 +/- 0.7) p = 0.01. Vascularity graded 2 associated with low peripheral PI values are indicators of therapy outcome. Vascularity graded 1 and high peripheral PI values in graded 2 have negative predictive value.


Proximate, mineral, and anti-nutrient compositions of underutilized plants of Ethiopia: Figl (Raphanus sativus L.), Girgir (Eruca sativa L) and Karkade (Hibiscus sabdariffa): Implications for in-vitro mineral bioavailability.
In Ethiopia, particularly in the Benishangul-Gumuz region, there are several underutilized plants like Figl (Raphanus sativus), Girgir (Eruca sativa) and Karkade (Hibiscus sabdariffa) which are cultivated and consumed only by the local communities. However, information on nutrient, anti-nutrient contents and mineral bioavailability of edible parts of these plants are limited. Given this, leaves and roots of Figl, leaves of Girgir, calyces and seeds of Karkade were evaluated for their proximate, mineral and anti-nutrient contents following the standard analytical methods. The result on dry matter basis revealed that protein contents (26.32 g/100 g) were high for brown seeds of Karkade, dried leaves of Figl (26.71 g/100 g) and Girgir (24.23 g/100 g). The fat and energy contents were high for seeds of Karkade (15.58-18.00 g/100 g; 371.64-376.69 kcal/100 g). The fiber content was high for dried leaves of Figl (28.39 g/100 g) and low for calyces of Karkade (15.33-16.54 g/100 g). There was a significant difference (p < 0.05) in terms of mineral contents. The dried leaves of Figl were high in calcium, sodium, potassium, and phosphorus contents while dried leaves of Girgir were high in iron and zinc contents. With exception of oxalate content, seeds of Karkade were low in tannin, phytate and alkaloid. The phytate: mineral ratio analysis showed the bioavailability of iron is likely to be inhibited from roots of Figl and calyces of Karkade; zinc bioavailability from calyces of Karkade which suggests processing for phytate reduction is important. The result showed the seeds of Karkade are good sources of protein, fat and energy with low antinutritional contents that may favor mineral bioavailability with potential for utilization in baby food formulations to alleviate protein energy malnutrition. The leaves of Figl and Girgir can also be exploited in different food formulations to improve macro and micronutrient deficiency.


Associations of sleep problems with non-physical bullying perpetration and victimization among adolescents: A cross-lagged panel study.
The current study attempted to explore the possible temporal direction of the relationship between sleep problems and non-physical bullying perpetration as well as non-physical bullying victimization among adolescents. The study used a longitudinal panel survey design with a 6-month interval. A cluster random sampling method was conducted to recruit students from junior high schools in Northern Taiwan. Eight hundred twenty-two students (46.6% were boys) completed a survey at 2 waves. Adolescents reported their sleep problems, non-physical bullying perpetration, and non-physical bullying victimization in both waves. The results from cross-lagged panel models revealed that sleep problems at time 1 significantly predicted non-physical bullying victimization at time 2, but not in the opposite direction. In addition, non-physical bullying perpetration at time 1 significantly predicted sleep problems at time 2, but not in the opposite direction. No significant differences emerged between male and female adolescents in the cross-lagged model of sleep problems with non-physical bullying perpetration and non-physical bullying victimization. This study advances the literature by revealing that sleep problems may be a consequence, not a precursor, of adolescent non-physical bullying perpetration and a precursor, not a consequence, of non-physical bullying victimization. Intervention programs aimed at preventing adolescents from being non-physically bullied may consider improving their sleep quality. Reducing adolescents' non-physical bullying perpetration may also improve sleep quality along the way.


Amino acid sequence of the carboxy-terminal part of an acidic type I cytokeratin of molecular weight 51 000 from Xenopus laevis epidermis as predicted from the cDNA sequence.
The DNA sequence of a clone from a cDNA library made from Xenopus laevis skin is described. This sequence represents the 3'-terminal end of an mRNA which codes for an epidermal cytokeratin polypeptide of mol. wt. 51 000 of the acidic (type I) subfamily as identified by hybridization-selection of mRNAs, followed by gel electrophoretic identification of the polypeptides synthesized by translation in vitro. The partial amino acid sequence of the amphibian cytokeratin shows strong similarity to type I cytoskeletal keratins from human (mol. wt. 50 000) and murine (mol. wt. 59 000) epidermis. In the non alpha-helical tail region the human and the non-mammalian (Xenopus) keratins are more similar to each other than to the murine protein, indicating that the former are equivalent cytokeratin polypeptides and belonging to a special subclass of type I keratin polypeptides devoid of glycine-rich regions in the carboxy-terminal portion. The evolutionary conservativity of the genes coding for cytokeratins is discussed.


Variables that regulate production of insulin-like peptide(s) in human leukemia cell line (HL-60).
A human myeloid leukemia cell line (HL-60) produces a peptide or peptides with insulin-like activity which is distinct from insulin or insulin-like growth factors (somatomedins). Factors regulating the production of this peptide (HL-ILP) were explored in the present study. The production of HL-ILP was maximal in the early log phase of cell growth and declined with increasing cell density. Differentiation of HL-60 cells to macrophages, induced by dihydroxyvitamin D3 or phorbol esters, was also associated with a decrease in HL-ILP production. Glucose consumption by the cells in the early log phase was closely related with HL-ILP production, and HL-ILP was found to stimulate glucose consumption by HL-60 cells. Production of HL-ILP was dependent on glucose concentrations in the culture medium and glucose concentrations higher than 1mg/d1 suppressed the release of HL-ILP. These observations are not inconsistent with a hypothesis that HL-ILP is involved in the glucose metabolism of the HL-60 cells that produce this peptide.


The association between operative hysteroscopy prior to assisted reproductive technology and cervical insufficiency in second trimester.
To assess the association between operative hysteroscopy prior to assisted reproductive technology (ART) cycle and cervical insufficiency (CI) in the second trimester of pregnancy. A retrospective cohort study was conducted. The charts of all women who got pregnant following an ART cycle between January 2015 and June 2018 were reviewed. The study group consisted of pregnant women who underwent operative hysteroscopy within 6 months before conception. The control group consisted of pregnant women who did not undergo hysteroscopy or any type of cervical surgical procedure before conception. The primary outcome measure was CI during the second trimester (13-27 weeks of gestation). A total of 363 pregnancies achieved by ART cycles were assessed. After the exclusion of multiple pregnancies (n = 19), previous surgical procedures (n = 4) and first-trimester pregnancy losses (n = 80), there were 29 women in the study group and 231 women in the control group. The mean ages of the study and control groups were 31.2 ± 4.06 and 29.82 ± 4.71 years, respectively (P = 0.13). The indications for operative hysteroscopy were uterine septum (n = 19), T-shaped uterus (n = 4), endometrial polyp (n = 4), and submucosal fibroids (n = 2). The rates of CI in the study and control groups were 13.7% (4/29) and 3.4% (8/231), respectively (P = 0.012). The term delivery rates in the study and control groups were 79.3 and 91.8%, respectively (P = 0.044). Operative hysteroscopy prior to ART cycles is significantly associated with CI between 13 and 27 weeks of gestation. Further investigation with larger cohorts is urgently needed to clarify this issue.


Mycophenolate mofetil.
Mycophenolate mofetil (MMF) is a relatively new systemic immunosuppressive agent whose use is rapidly increasing within the field of dermatologic. Originally used in the 1970s for the treatment of psoriasis, MMF has demonstrated efficacy in multiple types of inflammatory skin diseases. Although the safety data within the dermatologic literature is sparse, MMF's extensive use within the field of organ transplantation has demonstrated a favorable safety profile. MMF's lack of hepatic or renal toxicity is a significant advantage over immunosuppressive medications currently used in dermatology and make MMF an attractive candidate for multidrug regimens. In this review the present authors discuss the pharmacology, mechanisms of action, side effects and current uses of MMF reported within the dermatologic literature. The present authors also provide practical information regarding the use of the MMF culled from the literature as well as from the present authors' own clinical experience with the medication.


Torsional moment to failure for carbon fibre polysulphone expandable rivets as compared with stainless steel screws for carbon fibre-reinforced epoxy fracture plate fixation.
A method of securing carbon fibre-reinforced epoxy bone plates with carbon fibre polysulphone expanding rivets was investigated. Six carbon fibre-reinforced epoxy bone plates were secured to rods with carbon fibre polysulphone rivets and six were secured with standard cortical stainless steel screws. These constructions were then subjected to pure torsional load to failure. The carbon fibre expandable rivets failed at a greater torsional moment.


Author Correction: Kinesiologist-guided functional exercise in addition to intradialytic cycling program in end-stage kidney disease patients: a randomised controlled trial.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Longitudinal changes in depressive symptoms associated with social isolation after the Great East Japan Earthquake in Iwate Prefecture: findings from the TMM CommCohort study.
Whether past disaster experiences affect the association between changes in social isolation and depressive symptoms is largely unknown. This study examined the association between changes in social isolation and depressive symptoms among survivors who experienced earthquake damage in the aftermath of the Great East Japan Earthquake (GEJE). We analyzed longitudinal data from 10,314 participants who responded to self-report questionnaires on the Lubben Social Network Scale-6 (LSNS-6) and the Center for Epidemiological Studies-Depressive Scale (CES-D) in both the baseline survey (FY2013 to FY2015) and follow-up survey (FY2017 to FY2019) after the GEJE. According to changes in the presence of social isolation (< 12 of LSNS-6) at two time points, participants were categorized into four groups: "not socially isolated," "improved socially isolated," "newly socially isolated," and "continuously socially isolated." At the follow-up survey, a CES-D score of ≥ 16 indicates the presence of depressive symptoms. The adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were estimated using the logistic regression analysis to examine the influence of the change in social isolation over four years on depressive symptoms. Participants who were newly socially isolated had a significantly higher prevalence of depressive symptoms than those who were not socially isolated (AOR = 1.89, 95% CI = 1.61 - 2.23). In addition, AORs were highest for those who were continuously socially isolated and had experienced house damage (AOR = 2.17, 95% CI = 1.73 - 2.72) and those who were newly socially isolated and had not experienced the death of family members due to the GEJE (AOR = 1.88, 95%CI = 1.60 - 2.22). Our longitudinal findings suggest that being newly or continuously socially isolated is associated with a risk of depressive symptoms, not only among those who had experienced house damage or the death of a family member, but also those who had not, in the disaster-affected area. Our study underlines the clinical importance of social isolation after a large-scale natural disaster and draws attention to the need for appropriate prevention measures.


Catalytic Arylsulfonyl Radical Triggered 1,7-Enyne Bicyclizations.
A new metal-free bicyclization reaction of 1,7-enynes anchored by α,β-conjugates with arylsulfonyl radicals generated in situ from sulfonyl hydrazides has been established using tert-butyl hydroperoxide and tetrabutylammonium iodide. The reactions occurred through sulfonylation/6-exo-dig/6-exo-trig bicyclization/in situ desulfonylation/5-exo-trig cyclization/alkyl or alkenyl migration cascade mechanism to give benzo[j]phenanthridines regioselectively.


Particulate and non-particulate fractions of soil organic carbon under pastures in the Southern Piedmont USA.
Pasture management can be effective at sequestering soil organic C. We determined the depth distribution of particulate organic C (POC), non-particulate organic C (NPOC), particulate-to-total organic C (POC-to-TOC) ratio, and particulate organic C-to-N (POC-to-N) ratio under pastures near Watkinsville, GA, USA. POC was highly related with total organic C (TOC), but became an increasingly larger portion of TOC near the soil surface, where both pools were greatest. POC and NPOC were (i) greater under pasture than under conservation-tillage cropland, (ii) greater when pasture was grazed than when hayed, (iii) marginally greater with higher fertilization of pasture, (iv) greater with higher frequency of endophyte infection of tall fescue, and (v) greater under increasing stand age of grass. Soil under pasture comparisons that had greater TOC content had (i) larger improvements in POC than in NPOC and (ii) lower POC-to-N ratios, suggesting improvement in biochemical soil quality, as well as soil C sequestration.


A case of malignant pleural mesothelioma with unexpectedly long survival without active treatment.
Malignant pleural mesothelioma (MPM) is a disease with a very dismal prognosis. A median survival of 6-18 months is expected in most patients. Rarely, patients may survive unexpectedly long. We present the case of a patient with MPM who survived for more than 10 years without active treatment after the disease had been diagnosed.


Generation of Induced Pluripotent Stem Cells from Human Bone Marrow-Derived Mesenchymal Stem Cells.
Adult somatic cells can be reprogrammed and become pluripotent called induced pluripotent stem cells (iPSC) when they are induced by the stemness genes. The iPSCs have been representing a research and development platform for cell-based therapies, and even in gene editing technologies as they provide the ability to differentiate almost all cell types. The efficiency of the protocols for the iPSC development defines the success of the experiments' outcome. Here, we describe the optimized protocol for obtaining human iPSCs derived from mesenchymal stem cells of bone-marrow origin to shed a light on the hurdles in the research laboratories.


Differentiation of Erwinia amylovora and Erwinia pyrifoliae strains with single nucleotide polymorphisms and by synthesis of dihydrophenylalanine.
Fire blight has spread from North America to New Zealand, Europe, and the Mediterranean region. We were able to differentiate strains from various origins with a novel PCR method. Three Single Nucleotide Polymorphisms (SNPs) in the Erwinia amylovora genome were characteristic of isolates from North America and could distinguish them from isolates from other parts of the world. They were derived from the galE, acrB, and hrpA genes of strains Ea273 and Ea1/79. These genes were analyzed by conventional PCR (cPCR) and quantitative PCR (qPCR) with differential primer annealing temperatures. North-American E. amylovora strains were further differentiated according to their production of L: -2,5-dihydrophenylalanine (DHP) as tested by growth inhibition of the yeast Rhodotorula glutinis. E. amylovora fruit tree (Maloideae) and raspberry (rubus) strains were also differentiated by Single Strand Conformational Polymorphism analysis. Strains from the related species Erwinia pyrifoliae isolated in Korea and Japan were all DHP positive, but were differentiated from each other by SNPs in the galE gene. Differential PCR is a rapid and simple method to distinguish E. amylovora as well as E. pyrifoliae strains according to their geographical origin.


RETRACTED: Immunization of mice with autolysin adhesin (Aaa) provides protection against Staphylococcus aureus and Staphylococcus epidermidis infection.
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Theophylline neurotoxicity in pregnant rats.
The purpose of this investigation was to determine whether the neurotoxicity of theophylline is altered in advanced pregnancy. Sprague-Dawley rats that were 20 days pregnant and nonpregnant rats of the same age and strain received infusions of aminophylline until onset of maximal seizures which occurred after 28 and 30 minutes respectively. Theophylline concentrations at this endpoint in serum (total) and CSF were similar but serum (free) and brain concentrations were slightly different in pregnant rats. Theophylline serum protein binding determined by equilibrium dialysis was lower in pregnant rats. Fetal serum concentrations at onset of seizures in the mother were similar to maternal brain and CSF concentrations and correlated significantly with the former. It is concluded that advanced pregnancy has a negligible effect on the neurotoxic response to theophylline in rats.


Cellular and Molecular Regulation of Exercise-A Neuronal Perspective.
The beneficial effects of exercise on the proper functioning of the body have been firmly established. Multi-systemic metabolic regulation of exercise is the consequence of multitudinous changes that occur at the cellular level. The exercise responsome comprises all molecular entities including exerkines, miRNA species, growth factors, signaling proteins that are elevated and activated by physical exercise. Exerkines are secretory molecules released by organs such as skeletal muscle, adipose tissue, liver, and gut as a function of acute/chronic exercise. Exerkines such as FNDC5/irisin, Cathepsin B, Adiponectin, and IL-6 circulate through the bloodstream, cross the blood-brain barrier, and modulate the expression of important signaling molecules such as AMPK, SIRT1, PGC1α, BDNF, IGF-1, and VEGF which further contribute to improved energy metabolism, glucose homeostasis, insulin sensitivity, neurogenesis, synaptic plasticity, and overall well-being of the body and brain. These molecules are also responsible for neuroprotective adaptations that exercise confers on the brain and potentially ameliorate neurodegeneration. This review aims to detail important cellular and molecular species that directly or indirectly mediate exercise-induced benefits in the body, with an emphasis on the central nervous system.


Protestant clergy marriage in the congregational context: a report from the field.
The author reports on in-depth interviews with fourteen clergy--both male and female--along with their spouses to determine how they experience the stressors and marriages. These responses are compared with the literature currently available on clergy couples in relation to congregational systems. Recommendations are made for strengthening clergy marriage by identifying initiatives that may be taken during seminary and continued by local congregations and judicatories.


Minimally Invasive Radical Hysterectomy for Cervical Cancer: A Systematic Review and Meta-analysis.
To compare recurrence rate, progression-free survival (PFS), and overall survival for early-stage cervical cancer after minimally invasive (MIS) vs abdominal radical hysterectomy. MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Library databases. We identified studies from 1990 to 2020 that included women with stage I or higher cervical cancer treated with primary radical hysterectomy and compared recurrence and/or PFS and overall survival with MIS vs abdominal radical hysterectomy. (The review protocol was registered with the International Prospective Register of Systematic Reviews: CRD4202173600). We performed random-effects meta-analyses overall and by length of follow-up. Fifty articles on 40 cohort studies and 1 randomized controlled trial that included 22 593 women with cervical cancer met the inclusion criteria. Twenty percent of the studies had <36 months of follow-up, and 24% had more than 60 months of follow-up. The odds of PFS were worse for women undergoing MIS radical hysterectomy (odds ratio 1.54; 95% CI [confidence interval], 1.24-1.94; 14 studies). When limited to studies with longer follow-up, the odds of PFS were progressively worse with MIS radical hysterectomy (HR [hazard ratio] 1.48 for >36 months; 95% CI, 1.21-1.82; 10 studies; HR 1.69 for >48 months; 95% CI, 1.26-2.27; 5 studies; and HR 2.020 for >60 months; 95% CI, 1.36-3.001; 3 studies). For overall survival, the odds were not significantly different for MIS vs abdominal hysterectomy (odds ratio 0.94; 95% CI, 0.66-1.35; 14 studies) (HR 0.99 for >36 months; 95% CI, 0.66-1.48; 9 studies; HR 1.05 for >48 months; 95% CI, 0.57-1.94; 4 studies; and HR 1.35 for >60 months; 95% CI, 0.73-2.51; 3 studies). In our meta-analysis of 50 studies, MIS radical hysterectomy was associated with worse PFS than open radical hysterectomy for early-stage cervical cancer. The emergence of this finding with longer follow-up highlights the importance of long-term, high-quality studies to guide cancer and surgical treatments.


Methotrexate enhances 3T3-L1 adipocytes hypertrophy.
Methotrexate (MTX) is broadly used in the treatment of chronic inflammatory diseases such as rheumatoid arthritis (RA). The prevalence of metabolic syndrome (MeS) in patients with this condition is relatively high. Given the importance of adipose tissue in the development of obesity metabolic complications, this study aimed to investigate the effect of methotrexate on preadipocyte proliferation, adipogenesis, and glucose uptake by adipocytes. 3T3-L1 preadipocytes proliferation was evaluated by sulforhodamine B staining and (3)H-thymidine incorporation, after 24 or 48 h of treatment with MTX (0.1 and 10 μM). Preadipocytes were induced to differentiate with an appropriate adipogenic cocktail in the presence or absence of MTX. Adipogenesis was determined by measuring lipid accumulation after staining with oil red O. (3)H-Deoxyglucose ((3)H-DG) uptake was determined by liquid scintillation counting. MTX treatment reduced culture protein content in a concentration-dependent manner and (3)H-thymidine incorporation (P < 0.05). MTX (0.1 μM) treatment increased lipid accumulation and basal (3)H-DG uptake by adipocytes (P < 0.05). In 0.1 μM MTX-treated adipocytes, insulin stimulation did not result in an increase of (3)H-DG uptake, contrarily to what was observed in control cells. These results demonstrate that methotrexate interferes with adipocyte proliferation and promotes the hypertrophic growth of adipocytes. These molecular effects may have implications on metabolic profile of RA patients treated with MTX.


Small azobenzene derivatives active against bacteria and fungi.
ATP synthase and protein kinase (PKs) are prime targets for drug discovery in a variety of diseases. It is well known that numerous stilbenes are capable to interact and inhibit ATP synthase and PKs. This work focuses on a series of azobenzene based molecules having high structural similarity with antimicrobial stilbenes. An investigation was carried out analyzing the potential toxicity of a large set of molecules by means of computational analysis. A small selection of potential low toxic molecules have been therefore synthesized, characterized and finally microbiologically tested. The synthesized compounds show potent bactericidal activity against Gram+ and a fungus, and are capable of inhibiting biofilm formation. Finally, the compounds demonstrated a thermal stability that makes them potential candidates for incorporation in polymer matrix for application as biomedical devices and food packaging.


Analysis of postoperative complications and risk factors in patients with permanent pacemaker implantation.
Permanent pacemaker implantation (PPI) is widely used for the treatment of chronic arrhythmia. The aim of the present study was to investigate the incidence of postoperative complications and the risk factors in patients with PPI. The clinical data of 124 patients who underwent PPI in our hospital from January 2014 to January 2018 were collected and analyzed retrospectively. Data on sex, age, status of disease, and related complications of all patients were recorded, and differences were compared. The factors affecting postoperative complications in patients with PPI were analyzed. The incidence of postoperative complications in 124 patients with PPI was 8.06% (10/124), including 4 cases with capsular hematoma (3.23%), 2 cases with capsular rupture (1.61%), 3 cases with capsular infection (2.42%) and 1 case with venous thrombosis (0.81%). Unconditional single-factor logistic regression model showed that the incidence of postoperative complications in patients with PPI was significantly greater with older age, high body mass index (BMI), smoking history, poor nutritional status, and decreased platelet counts (P<0.05). Results of the unconditional multivariate logistic regression analysis showed that older age, high BMI, smoking history, poor nutritional status, and decreased platelet counts were all independent risk factors of postoperative complications in patients with PPI (P<0.05). The incidence of postoperative complications in patients with PPI was low, and the complications were mainly related to capsular bag. Factors, such as older age, high BMI, smoking history, poor nutritional status, and decreased platelet counts, were independent risk factors resulting in postoperative complications in patients with PPI.


Secretagogue effect of barium on output of melanocyte-stimulating hormone from pars intermedia of the mouse pituitary.
Ba ions caused an intense and prolonged discharge of melanocyte-stimulating hormone (MSH) from perifused neurointermediate lobes of mouse pituitaries and dispersed pars intermedia cells. The effect persisted in chronically cultured lobes or cells. It did not require Ca, but, like the Ca-dependent response to excess K, was blocked by cyanide combined with glucose lack. The secretagogue effect of Ba was blocked or prevented by Co or by excess Ca, both of which can reduce inward Ba currents through Ca channels. Prior exposure to excess K partially reduced the secretagogue effect of Ba, suggesting that depolarization caused some inactivation of Ba current. In contrast to Ba, excess K elicited secretion that was transient, and prior exposure of preparations to excess K (in the absence of Ca) profoundly suppressed the secretagogue effect of Ca. The evidence is consistent with the view that inward Ca current rapidly inactivates in these cells. It is concluded that Ba ions have a potent and persistent direct secretagogue effect on the melanotrophs that may reflect, in part, their ability to penetrate Ca channels more easily than Ca ions. The strong secretagogue effects of Ba on melanotrophs may be of considerable utility in studies on MSH secretion since a physiological secretagogue has yet to be discovered. Moreover, since the responses of melanotrophs (and other endocrine cells) to Ba can be distinguished from those of various other secretory cells and neurones, it is suggested that Ba may provide a tool for characterizing the distinctive membrane properties of the Ba-responsive endocrine cells.


Validation of the Arabic version of the score for allergic rhinitis tool.
Allergic rhinitis (AR) is a common inflammation of the nasal mucosa in response to allergen exposure. We translated and validated the Score for Allergic Rhinitis (SFAR) into an Arabic version so that the disease can be studied in an Arabic population. SFAR is a non-invasive self-administered tool that evaluates eight items related to AR. This study aimed to translate and culturally adapt the SFAR questionnaire into Arabic, and assess the validity, consistency, and reliability of the translated version in an Arabic-speaking population of patients with suspected AR. Cross-sectional. Tertiary care hospital in Riyadh. The Arabic version of the SFAR was administered to patients with suspected AR and control participants. Comparison of the AR and control groups to determine the test-retest reliability and internal consistency of the instrument. The AR (n=173) and control (n=75) groups had significantly different Arabic SFAR scores (P < .0001). The instrument provided satisfactory internal consistency (Cronbach's alpha value of 0.7). The test-retest reliability was excellent for the total Arabic SFAR score (r =0.836, P < .0001). These findings demonstrate that the Arabic version of the SFAR is a valid tool that can be used to screen Arabic speakers with suspected AR. The absence of objective allergy testing.


Long-term uveal and capsular biocompatibility of a new fluid-filled, modular accommodating intraocular lens.
To evaluate long-term uveal and capsular biocompatibility of a new fluid-filled modular accommodating intraocular lens (IOL) consisting of base and fluid lenses. John A. Moran Eye Center, University of Utah, Salt Lake City, UT, USA. Experimental study. Bilateral phacoemulsification was performed on 8 rabbits; 1 eye received the test IOL (Juvene) and the other a hydrophobic acrylic control IOL (SA60AT). Slitlamp examinations were performed at postoperative weeks 1 and 4, and at months 2, 3, and 6. The rabbits were killed humanely at 6 months. After gross examination from the Miyake-Apple view, IOLs were removed for implant cytology. All globes were then processed for histopathologic examination. Uveal biocompatibility was similar between test and control IOLs up to 6 months postoperatively. Anterior capsule opacification appeared absent in the test group, and posterior capsule opacification (PCO) was significantly less in comparison with the control group throughout the study. At 6 months, central PCO was scored as 0.12 ± 0.23 with test IOLs and as 4.0 ± 0 with control IOLs (P < .0001, 2-tailed t test: paired 2-sample for means). Histopathologic examination confirmed the relative lack of capsular opacification in test eyes in comparison to controls and the absence of toxicity in any eye. Six weeks in the rabbit model corresponds to approximately 2 years in the human eye for PCO. In this model, the Juvene IOL maintained an open and expanded capsular bag, preventing overall capsular bag opacification while retaining excellent uveal and capsular biocompatibility.


Low body mass index is associated with ectopic pregnancy following assisted reproductive techniques: a retrospective study.
To investigate the association between body mass index (BMI) and ectopic pregnancy (EP) following embryo transfer (ET). Retrospective cohort study. University-affiliated hospital. A total of 16 378 pregnancies derived from either fresh ET or frozen-thawed ET between January 2008 and December 2017. We used the generalised estimating equation (GEE) to analyse the association between BMI categories and EP, as one woman may contribute to more than one pregnancy. Generalised additive models were also used to demonstrate the non-linear association. Models were adjusted for age, parity, gravidity, previous history of ectopic pregnancy, duration of infertility, polycystic ovary syndrome, endometriosis, diagnosis of tubal problems, ovarian reserve markers, ovarian stimulation parameters, insemination protocol, endometrial thickness and embryo transfer policies. Ectopic pregnancy. According to the WHO criteria, the number of cycles with low (<18.5 kg/m2 ), normal (18.5-24.9 kg/m2 ) and high (≥25 kg/m2 ) BMI were 2155, 13 447 and 776, respectively. In comparison with the normal BMI group, the rate of EP was significantly increased in the low BMI group (2.92% versus 2.02%, relative risk 1.45, 95% CI 1.11-1.90), but not in the high BMI group (2.84%, relative risk 1.41, 95% CI 0.92-2.20). Adjusted for confounding factors, the odds ratio for EP comparing low BMI versus normal BMI was 1.61 (95% CI 1.19-2.16) and that comparing high BMI versus normal BMI was 1.12 (95% CI 0.72-1.76). Low BMI is associated with an increased risk of EP. The ectopic pregnancy rate after embryo transfer for lean women is higher than that for women of normal weight.


A study of the interaction between clonidine and morphine on analgesia and blood pressure during continuous intrathecal infusion in the rat.
In the rat, the continuous intrathecal (i.t.) infusion of clonidine (0.4 microgram/hr) significantly increased the tail-flick latency (TF) and the threshold for paw pressure (PP) withdrawal for 5 days and decreased the systolic blood pressure (up to 24 mm Hg) for 7 days. The antinociceptive effect of continuous intrathecal infusion of clonidine (0.4 microgram/hr) in the tail flick and paw pressure tests was not attenuated in rats that were tolerant to morphine. The acute intrathecal administration of clonidine (2.7 micrograms) and morphine (1.0 microgram) resulted in a synergistic interaction in the tail-flick and paw pressure tests. A synergistic interaction was also observed during the continuous intrathecal infusion of morphine (1.25 micrograms/hr) and clonidine (0.2 microgram/hr) in the tail-flick and paw pressure tests. Individually, these doses of morphine and clonidine had no antinociceptive effect. However, intrathecal infusion together yielded peak tail-flick and paw pressure responses comparable to that of 0.4 microgram/hr clonidine alone, without affecting systolic blood pressure. No delay in the onset of tolerance to the analgesic effect was observed with the combination as compared with clonidine (0.4 microgram/hr) alone. The data indicate that clonidine-induced spinal analgesia is independent of endogenous opioid systems linked to mu-receptors in the spinal cord, and that optimization of spinal analgesia (e.g. synergism) can be achieved during continuous intrathecal infusion without affecting cardiovascular activity.


Proteoglycans in the nervous system.
Proteoglycans are ubiquitous cell-surface and secreted glycoproteins that are involved in diverse cellular behaviors. The identities of several nervous system proteoglycans, including many of the major species in the mammalian brain, have recently come to light. In addition, recent studies have given new insights into the roles of proteoglycans in nervous system development and function.


Does mild paravalvular regurgitation post transcatheter aortic valve implantation affect survival? A meta-analysis.
To assess the impact of post transcatheter aortic valve implantation (TAVI) mild paravalvular regurgitation (PVR) on mortality. More than moderate PVR after TAVI has decreased with the advent of new-generation prosthetic valves. However, mild PVR remains common and its clinical impact has been inconsistent. We aimed to assess the impact of mild PVR through meta-analysis. A systematic literature search was conducted through PUBMED and EMBSE. Manuscripts that reported hazard ratio (HR) with 95% confidence interval (CI) for clinical outcome of interest (all-cause and cardiac mortality) has been included. Random-effects model was used for calculation of HR. A total of 25 articles including total of 21,018 patients were finally included for quantitative synthesis (meta-analysis). Our pooled analysis demonstrated higher all-cause mortality in patients with mild PVR compared to none/trivial PVR (HR 1.26, 95%CI 1.11-1.43, I2 =45%, p < 0.001) (follow up duration range 6 months to 5 years). Significant heterogeneity among studies was observed (p for heterogeneity = 0.005). Egger's test showed no evidence of publication bias. Cardiovascular mortality was increased in patients with mild PVR compared with none/trivial PVR (HR 1.28, 95%CI 1.05-1.57, I2 =8%, p = 0.02) (follow up duration range 1-3 years). Mild PVR was associated with increased all-cause and cardiovascular mortality after TAVI. Whether further interventions in mild PVR is of benefit, has yet to be determined.


Intussusception of the bowel: a new sonographic pattern.
The ultrasonic findings in a case of small bowel intussusception in an adult patient are presented. The sonographic features vary with the scanning plane. Scans along the longitudinal axis of the involved segment show a diagnostic pattern, not previously described: three parallel stripes of low echogenicity delineating two reflective areas.


Unspecific interactions of estrogen receptors with immunoglobulins and their absence in the tryptic receptor fragment.
Immunoglobulin G preparations align unspecifically with all naturally occurring forms of the estradiol receptor, giving rise to soluble complexes of moderately increased sedimentation velocities. This interaction is not shown by the tryptic receptor fragment, which still contains the high affinity steroid binding site and the dimerization links of the native receptor.


Synthesis of novel neutrophil-specific imaging agents for Positron Emission Tomography (PET) imaging.
A neutrophil-specific peptide, cinnamoyl-F(D)LF(D)LFK (cFLFLFK), was conjugated consecutively with a polyethylene glycol moiety (3.4K) and 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA) to form cFLFLFK-PEG-DOTA. After (64)Cu labeling, Positron Emission Tomography (PET) imaging was successfully able to detect mouse lung inflammation.


The variable conversion of neutralizing anti-SARS-CoV-2 single-chain antibodies to IgG provides insight into RBD epitope accessibility.
Monoclonal antibody (mAb) therapies have rapidly become a powerful class of therapeutics with applications covering a diverse range of clinical indications. Though most widely used for the treatment of cancer, mAbs are also playing an increasing role in the defense of viral infections, most recently with palivizumab for prevention and treatment of severe RSV infections in neonatal and pediatric populations. In addition, during the COVID-19 pandemic, mAbs provided a bridge to the rollout of vaccines; however, their continued role as a therapeutic option for those at greatest risk of severe disease has become limited due to the emergence of neutralization resistant Omicron variants. Although there are many techniques for the identification of mAbs, including single B cell cloning and immunization of genetically engineered mice, the low cost, rapid throughput and technological simplicity of antibody phage display has led to its widespread adoption in mAb discovery efforts. Here we used our 27-billion-member naïve single-chain antibody (scFv) phage library to identify a panel of neutralizing anti-SARS-CoV-2 scFvs targeting diverse epitopes on the receptor binding domain (RBD). Although typically a routine process, we found that upon conversion to IgG, a number of our most potent clones failed to maintain their neutralization potency. Kinetic measurements confirmed similar affinity to the RBD; however, mechanistic studies provide evidence that the loss of neutralization is a result of structural limitations likely arising from initial choice of panning antigen. Thus this work highlights a risk of scFv-phage panning to mAb conversion and the importance of initial antigen selection.


Fluorescent in situ hybridization studies of lymphocytes and neutrophils in chronic granulocytic leukemia.
Using immunomagnetic cell separation and fluorescent in situ hybridization (FISH), we studied nine patients who had chronic granulocytic leukemia (CGL) for the proportion of interphase nuclei with Mbcr/abl fusion in a direct preparation of the bone marrow and also in the mononuclear cell (MNC), neutrophil, and B- and T-cell fractions of the peripheral blood. In five untreated patients, conventional cytogenetics revealed 97% to 100% Philadelphia chromosome (Ph)+ metaphases. In three of these five patients, FISH studies on bone marrow direct preparations and peripheral blood MNCs indicated that an Mbcr/abl fusion occurred in 62% to 69% of the cells. We observed 69% to 88% of nuclei with Mbcr/abl fusion within the neutrophil fractions. In contrast, the values were 12% to 39% within the T-cell fractions in the four patients we studied. B-cell fractions were studied in three patients, and only one had an abnormal value (58%). In the four patients receiving alpha-interferon therapy, the degree of conventional cytogenetic remission correlated best with the degree of FISH remission observed in the peripheral blood neutrophil fraction. Our results are in agreement with earlier studies in that both B and T lymphocytes may be involved with the clonal process in CGL. The FISH-based detection of Mbcr/abl fusion in the peripheral blood neutrophil compartment provided the best estimate for the proportion of Ph metaphases determined by conventional cytogenetics.


Categorization of COVID-19 severity to determine mortality risk.
Algorithms for classification of inpatient COVID-19 severity are necessary for confounding control in studies using real-world data. Using Healthverity chargemaster and claims data, we selected patients hospitalized with COVID-19 between April 2020 and February 2021, and classified them by severity at admission using an algorithm we developed based on respiratory support requirements (supplemental oxygen or non-invasive ventilation, O2/NIV, invasive mechanical ventilation, IMV, or NEITHER). To evaluate the utility of the algorithm, patients were followed from admission until death, discharge, or a 28-day maximum to report mortality risks and rates overall and by stratified by severity. Trends for heterogeneity in mortality risk and rate across severity classifications were evaluated using Cochran-Armitage and Logrank trend tests, respectively. Among 118 117 patients, the algorithm categorized patients in increasing severity as NEITHER (36.7%), O2/NIV (54.3%), and IMV (9.0%). Associated mortality risk (and 95% CI) was 11.8% (11.6-12.0%) overall and increased with severity [3.4% (3.2-3.5%), 11.5% (11.3-11.8%), 47.3% (46.3-48.2%); p < 0.001]. Mortality rate per 1000 person-days (and 95% CI) was 15.1 (14.9-15.4) overall and increased with severity [5.7 (5.4-6.0), 14.5 (14.2-14.9), 32.7 (31.8-33.6); p < 0.001]. As expected, we observed a positive association between the algorithm-defined severity on admission and 28-day mortality risk and rate. Although performance remains to be validated, this provides some assurance that this algorithm may be used for confounding control or stratification in treatment effect studies.


Cytokinin dehydrogenase differentially regulates cytokinin and indirectly affects hydrogen peroxide accumulation in tomato leaf.
Cytokinin dehydrogenase (CKX) catalyzes the irreversible degradation of cytokinins (CKs). CKs play a role in the regulation of hydrogen peroxide (H(2)O(2)) accumulation while H(2)O(2) is involved in chlorophyll degradation. Here, we elucidated how CKX differentially regulates representative CK levels and indirectly influence H(2)O(2) accumulation in tomato leaves. We induced drought, salt and iron-deficiency stresses in tomato plants and found that chlorosis-inducing stresses (salt and iron-deficiency) induced lower chlorophyll levels as compared to drought stress and control. Protein gel blot analysis detected two CKXs in tomato leaves: a 35 kDa protein (CKX35) found in chlorotic leaves associated with a reduction in representative CK levels and high H(2)O(2) concentrations, and a 37 kDa protein (CKX37) found in green leaves associated with representative CKs and H(2)O(2) at normal levels. In summary, CKX isoforms in the tomato leaf appear to have distinct roles in differentially regulating CK levels and indirectly influencing H(2)O(2) accumulation.


Increased vasoconstrictor response to noradrenaline in femoral vascular bed of diabetic dogs. Is thromboxane A2 involved?
The aim was to determine the role of cyclo-oxygenase products in the vasoconstrictor response of femoral arterial bed to noradrenaline and to analyse the role of vascular adrenoceptors in the synthesis of cyclo-oxygenase products. The influence of intra-arterially injected cyclo-oxygenase inhibitors indomethacin and acetylsalicylic acid on alterations in conductance of femoral arterial bed induced by noradrenaline was compared in metabolically healthy and alloxan diabetic dogs. PGI2 and TXA2 synthesising ability of isolated femoral arterial rings was measured with and without inhibition of alpha adrenoceptors by phentolamine. 18 metabolically healthy and 18 alloxan (560 mumol.kg-1) diabetic dogs of either sex, weight 16-28 kg, were studied. Noradrenaline produced greater (p less than 0.01) pressor effects in the femoral arterial bed of alloxan diabetic dogs than in the hind limb of control animals. Blockade of cyclo-oxygenase either by indomethacin 10 mumol.kg-1 or by acetylsalicylic acid 140 mumol.kg-1 markedly reduced the response to noradrenaline in alloxan treated animals, but not in controls, thereby eliminating the different responsiveness of the two groups. Femoral arterial rings from diabetic animals synthesised similar amounts of PGI2 as control rings but formed more TXA2 (p less than 0.05). Phentolamine pretreatment (5 mumol.litre-1) markedly reduced the production of TXA2, but not of PGI2, in diabetic vessels. The results show an increased release of TXA2 by isolated diabetic femoral arteries. It is therefore suggested that an alpha adrenoceptor mediated increase in TXA2 biosynthesis may play a part in the vascular hyperreactivity of the diabetic femoral arterial bed.


Dual-Mode Electrochemical Assay of Prostate-Specific Antigen Based on Antifouling Peptides Functionalized with Electrochemical Probes and Internal References.
Sensitive and selective detection of target analytes in complex biological samples is currently a major challenge. Herein we constructed a dual-mode antifouling electrochemical sensing platform for the detection of prostate-specific antigen (PSA) based on two kinds of antifouling peptides functionalized with a graphene oxide-Fe3O4-thionine (GO-Fe3O4-Thi) probe and internal reference ferrocene (Fc), respectively. The longer peptide (Pep1) modified with the GO-Fe3O4-Thi probe was designed to contain a peptide sequence (HSSKLQK) capable of being recognized and cut by PSA. The GO-Fe3O4-Thi probe functions not only as a peroxidase mimick (GO-Fe3O4) but also works as an electrochemical probe due to the presence of thionine (Thi). The concentration of PSA can be measured through both the increase of differential pulse voltammetry (DPV) signal change of Thi and the decrease of chronoamperometry (CA) signal of the reduction of H2O2 electrocatalyzed by GO-Fe3O4. The shorter peptide (Pep2) was tagged with Fc, whose DPV signal remained constant and was independent of the presence of PSA, and it was used as an internal reference to ensure the reliability and accuracy of the measurement. The dual-mode PSA sensor exhibits a wide linear range from 5 pg/mL to 10 ng/mL, with low detection limits of 0.76 and 0.42 pg/mL through DPV and CA modes, respectively. More importantly, owing to the antifouling capability of the designed peptides, the biosensor performances remained operable even in human serum, indicating feasibility of the electrochemical biosensor for practical PSA quantification in complex samples.


Gangliosides and phospholipids in human thyroids responsive and unresponsive to thyrotropin.
The patterns of gangliosides and phospholipids and their relation to TSH response were examined in twenty-six malignant thyroid tumors (4 follicular, 6 papillary, 5 medullary, 11 anaplastic carcinomas) and thirty-six hyperplastic goiters. Thirteen thyroid tissues adjacent to benign tumors with no evidence of macroscopic or microscopic abnormalities were used as normal tissue. In normal thyroids the major ganglioside was GD3 (44%) and GM3 was the second ganglioside (20%). In minor amounts GD1a (8.6%), GD1b (6.2%), GT1b (5.7%) and GM1 (5.6%) were present. In hyperplastic goiters and in follicular carcinomas the patterns of gangliosides were similar to that of normal tissue except for GM3 which, in the last tissue, was higher (34%). In papillary carcinomas low levels of GM3 (11%) and GT1b (0.8%) with a high level of GD1b (12.6%) were found. In anaplastic carcinomas GM3 was very high (47%) whereas GD3 was low (18%). In these tumors also a high percentage (14.0%) of GD1a was found. In medullary carcinomas the lowest levels of GM3 (4%) with the highest level of GD3 (64%) were found. Although large differences of the gangliosides distribution were clearly encountered in the various pathological human thyroid, no correlation between lack of TSH response and some individual ganglioside could be made. No differences in the individual phospholipid in the various tissues studied were found.