A purification strategy for inositol 1,4,5-trisphosphate 3-kinase from rat liver based upon heparin interaction chromatography.
Rat liver inositol 1,4,5-trisphosphate [Ins (1,4,5)P3] 3-kinase was purified in high yield by a three-step procedure reliant upon chromatography on heparin and calmodulin agarose. Purified enzyme was stable in the presence of the detergent 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulphonate (CHAPS) (0.1-0.5%) and the sulphydryl reducing reagent dithiothreitol (DTT). The purified enzyme was activated 2-3-fold by Ca2+ (1 microM) in the presence of calmodulin. Pyrophosphate and heparin were identified as inhibitors of the enzyme.


Correction to: Lack of netrin-4 alters vascular remodeling in the retina.
The article "Lack of netrin-4 alters vascular remodeling in the retina".


Rapid changes in organochlorine pesticides in sediments from the East China sea and their response to human-induced catchment changes.
Human-induced catchment changes have affected the sedimentary processes in marginal seas, which will impact the transport and burial processes of materials and inevitably impact marine biogeochemical cycles. Organochlorine pesticides (OCPs) and sediment characteristics in surface sediments from the East China Sea (ECS) at two time points (2006 and 2018) were compared to understand the response of OCPs to human-induced catchment changes. A significant coarsening trend occurred after the impoundment of the Three Gorges Dam (TGD), with the mean grain size increasing from 6.4 ± 1.2 Φ to 4.4 ± 2.1 Φ, suggesting that the sedimentary environment in the ECS changed drastically. OCP concentrations in the ECS evidently decreased after the impoundment of the TGD, with mean values decreasing from 2.55 ± 1.51 ng g-1 to 1.08 ± 0.84 ng g-1. The deposition flux of OCP also decreased from 2.65 ± 1.67 ng cm-2 yr-1 to 0.89 ± 0.60 ng cm-2 yr-1. The reduction in the riverine input might be the reason that caused variations in the OCP concentration and deposition flux. In addition, sediment coarsening is likely to be the another primary factor influencing the differences in the distribution and deposition flux of the OCPs in the ECS. Therefore, the distribution and burial of OCPs in the ECS have been changed drastically, which may broadly impact the marine environment and biogeochemical cycles.


High incidence of acute promyelocytic leukemia specifically induced by N-nitroso-N-methylurea (NMU) in Sprague-Dawley rats.
Carcinogenic agents such as N-methyl-N-nitrosourea can cause tumors. The aims of the present study were to evaluate and classify a subtype of AML (acute myeloid leukemia) that was induced by NMU. According to previous publications, NMU induces not only mammary cancer but also leukemia in Sprague-Dawley (S-D) rats. However, the subtype of leukemia involved in NMU-treated rats is unknown. We found that both organ weight and relative organ weights were significantly higher in NMU-exposed rats than in controls. Morphological changes of rat livers and spleens were assessed by histological evaluation (H&E staining), which found that these tissues were abnormal in appearance. Also, cytological examination of the blood showed immature white blood cells in a smear using Liu's and Papanicolaou stains, indicating that gross abnormalities and histopathological changes were pathologically observed. NMU leukemia incidence was 97.1%. In this study, immunohistochemical (IHC) analysis was valuable in classifying the leukemia of poorly differentiated blasts induced by NMU. Paraffin blocks were stained for MPO, CD3, CD15, CD20, and CD34 markers. The NMU-induced group was positive for MPO, but negative for CD3, CD15, CD20, and CD34. These CD markers suggest that they are useful in helping diagnose APL (M3) leukemia. The model of NMU-induced leukemogenesis in an S-D rat suggests a more definite way to classify APL. This APL will provide an important tool for chemical carcinogenesis and leukemia studies.


Hyperspectral Imaging for Viability Assessment of Human Liver Allografts During Normothermic Machine Perfusion.
Normothermic machine perfusion (NMP) is nowadays frequently utilized in liver transplantation. Despite commonly accepted viability assessment criteria, such as perfusate lactate and perfusate pH, there is a lack of predictive organ evaluation strategies to ensure graft viability. Hyperspectral imaging (HSI)-as an optical imaging modality increasingly applied in the biomedical field-might provide additional useful data regarding allograft viability and performance of liver grafts during NMP. Twenty-five deceased donor liver allografts were included in the study. During NMP, graft viability was assessed conventionally and by means of HSI. Images of liver parenchyma were acquired at 1, 2, and 4 h of NMP, and subsequently analyzed using a specialized HSI acquisition software to compute oxygen saturation, tissue hemoglobin index, near-infrared perfusion index, and tissue water index. To analyze the association between HSI parameters and perfusate lactate as well as perfusate pH, we performed simple linear regression analysis. Perfusate lactate at 1, 2, and 4 h NMP was 1.5 [0.3-8.1], 0.9 [0.3-2.8], and 0.9 [0.1-2.2] mmol/L. Perfusate pH at 1, 2, and 4 h NMP was 7.329 [7.013-7.510], 7.318 [7.081-7.472], and 7.265 [6.967-7.462], respectively. Oxygen saturation predicted perfusate lactate at 1 and 2 h NMP (R2 = 0.1577, P = 0.0493; R2 = 0.1831, P = 0.0329; respectively). Tissue hemoglobin index predicted perfusate lactate at 1, 2, and 4 h NMP (R2 = 0.1916, P = 0.0286; R2 = 0.2900, P = 0.0055; R2 = 0.2453, P = 0.0139; respectively). HSI may serve as a noninvasive tool for viability assessment during NMP. Further evaluation and validation of HSI parameters are warranted in larger sample sizes.


A patient-derived orthotopic xenograft (PDOX) nude-mouse model precisely identifies effective and ineffective therapies for recurrent leiomyosarcoma.
Leiomyosarcoma is a rare and recalcitrant disease. Doxorubicin (DOX) is usually considered first-line treatment for this disease, but frequently is ineffective. In order to individualize therapy for this and other cancers, we have developed the patient-derived orthotopic xenograft (PDOX) mouse model. In the present study, we implanted a recurrent leiomyosarcoma from a resected tumor from the patient's thigh into the femoral muscle of nude mice. The following drugs were tested on the leiomyosarcoma PDOX model: DOX, the combination of gemcitabine (GEM) and docetaxel (DOC), trabectedin (TRA), temozolomide (TEM), pazopanib (PAZ) and olaratumab (OLA). Of these agents GEM/DOC, TRA and TEM were highly effective in the leiomyosarcoma PDOX model, the other agents, including first-line therapy DOX, were ineffective. Thus the leiomyosarcoma PDOX model could precisely distinguish effective and ineffective drugs, demonstrating the potential of the PDOX model for leiomyosarcoma treatment.


Revisiting Freund's incomplete adjuvant for vaccines in the developing world.
The rightful emphasis on collaboration between the public and private sectors in solving the world's health problems, especially those of the poor in the developing world, relies on industry developing new technologies with the support of government and foundations. However, certain products, despite their potential to have a great impact on disease in the developing world, will not be developed by industry because they carry the risk of lawsuits owing to possible severe adverse reactions--risks that are not counterbalanced by potential profit of products that are of limited use in the developed world. Freund's incomplete adjuvant (FIA) is one such example that is better developed in the public sector. In this article, we present the evidence that has led to our interest in FIA, evidence of its potential benefit in vaccines against blood-stage malaria, and the way forward to make safe, effective and affordable vaccines for malaria and other serious diseases in the developing world.


The action of human C3 in soluble or cross-linked form with resting and activated murine B lymphocytes.
The third component of complement C3 has been implied in the stimulation of B lymphocytes to proliferation and maturation for Ig secretion. We have reinvestigated the extent of this activation with either activated or resting murine splenic lymphocytes in serum-substituted cultures. Human C3 was used in either soluble or cross-linked form. Soluble as well as Sepharose-bound or glutaraldehyde-cross-linked C3, over a range of concentrations, was inactive with resting splenic lymphocytes of (C57BL/6J X DBA/2)F1, C3H/HeJ and C57BL/6J nu/nu mice. However, lipopolysaccharide-activated spleen cells, enriched for B cell blasts, were stimulated by immobilized and cross-linked C3, while they did not respond to soluble C3. The extent of restimulation was comparable to that induced by lipopolysaccharide and resulted in both increased proliferation and maturation to Ig-secreting cells. The stimulation of the blast cells appears to be C3 specific, since it can be inhibited by free C3.


Videoscopic fluorescence diagnosis of peritoneal and thoracic metastases from human hepatoblastoma in nude rats.
Various medical disciplines are employing photodynamic diagnosis (PDD) when searching for malignancies. It is still unknown whether pediatric solid tumors such as hepatoblastoma are susceptible to this technique as well. Human hepatoblastoma cells were injected into the abdomen or right thoracic cavity of nude rats. Tumor growth was allowed for 7 weeks. Then, photosensitization was induced by peritoneal lavage with 5-aminolevulinic acid (ALA). Applying the Storz PDD system and one 4-mm scope, all animals were investigated by videoscopic white light diagnosis (WD) and PDD. Suspicious lesions were marked and analyzed by spectrometry and histology. Positive fluorescence was documented for every tumor seen by WD in the abdomen or right thoracic cavity. Spectrometry of lesions showed a 6.34-fold increased fluorescence intensity. Histology revealed hepatoblastoma in all specimens. Human hepatoblastoma can be detected by PDD in a rat model. Considering the clinical success of this method in other specialties, our findings indicate that further investigations to evaluate the benefit of PDD for children with hepatoblastoma should be performed.


In vitro transfection of human bladder cancer cells by acoustic energy.
The objective of this study was to examine and quantify the shock-wave-induced transfection of human bladder carcinoma cells. Cell suspensions were transfected with different concentrations of the pEGFP-N1 plasmid. Shock-waves were applied in a degassed water bath with different numbers of impulses at different energy levels. Additionally, the effects of different DNA concentrations, frequencies and the absence/presence of a liquid air border were examined. After shock-wave application, the transfection rate increased up to a maximum of 27.10% after 1000 impulses at an energy level of 0.5 mJ/mm2. In comparison negative control groups were transfected significantly below 1%. An increase in acoustic power and frequency and of DNA concentration and the presence of a liquid-air border resulted in an increasing transfection rate. The results demonstrate that naked plasmid DNA can easily and effectively be delivered to malignant urothelial cells in vitro upon exposure to lithotripter-generated shock-waves.


T cell receptor repertoire sequencing reveals chemotherapy-driven clonal expansion in colorectal liver metastases.
Colorectal liver metastasis (CLM) is a leading cause of colorectal cancer mortality, and the response to immune checkpoint inhibition (ICI) in microsatellite-stable CRC has been disappointing. Administration of cytotoxic chemotherapy may cause increased density of tumor-infiltrating T cells, which has been associated with improved response to ICI. This study aimed to quantify and characterize T-cell infiltration in CLM using T-cell receptor (TCR) repertoire sequencing. Eighty-five resected CLMs from patients included in the Oslo CoMet study were subjected to TCR repertoire sequencing. Thirty-five and 15 patients had received neoadjuvant chemotherapy (NACT) within a short or long interval, respectively, prior to resection, while 35 patients had not been exposed to NACT. T-cell fractions were calculated, repertoire clonality was analyzed based on Hill evenness curves, and TCR sequence convergence was assessed using network analysis. Increased T-cell fractions (10.6% vs. 6.3%) were detected in CLMs exposed to NACT within a short interval prior to resection, while modestly increased clonality was observed in NACT-exposed tumors independently of the timing of NACT administration and surgery. While private clones made up >90% of detected clones, network connectivity analysis revealed that public clones contributed the majority of TCR sequence convergence. TCR repertoire sequencing can be used to quantify T-cell infiltration and clonality in clinical samples. This study provides evidence to support chemotherapy-driven T-cell clonal expansion in CLM in a clinical context.


Sporotrichosis caused by Sporothrix brasiliensis in Argentina: Case report, molecular identification and in vitro susceptibility pattern to antifungal drugs.
Sporotrichosis is considered a neglected disease of humans and animals in many regions of the world and is the most frequent implantation mycosis in Latin America. To illustrate the zoonotic importance of the disease, describing a case involving a veterinarian and an infant that acquired the disease from a domestic cat and to describe, genotype and characterize these new isolates. Direct examination of tissue samples from the two patients and feline lesions revealed the presence of Sporothrix yeast-like organisms. Fungal cultures and molecular identification of the strains were performed. Since antifungal susceptibility data of animal-borne isolates are scarce, the in vitro susceptibility testing by a microdilution reference method was determined against azoles, amphotericin B and terbinafine. Fungal culture and sequence analysis of the ITS region of rDNA and calmodulin and β-tubulin genes confirmed the diagnosis and the causative agent as Sporothrix brasiliensis. In all cases, terbinafine was the most active drug, followed by posaconazole, itraconazole and voriconazole; the least active drugs were amphotericine B and fluconazole. Lack of clinical response in the veterinarian and in the infant to itraconazole and potassium iodide, respectively was observed. This study contributed to the molecular epidemiology of Sporothrix species in Argentina and the characterization of the in vitro susceptibility pattern of S. brasiliensis isolates recovered from a cat and two humans involved in this case of zoonotic sporotrichosis. Bearing in mind the "One Health" concept, the experience described in the present study highlights the need for future strategies for sporotrichosis treatment, control and prevention.


Determination of pH-dependent antioxidant activity of palm (Borassus flabellifer) polyphenol compounds by photoluminol and DPPH methods: a comparison of redox reaction sensitivity.
Palm juice (Borassus flabellifer) is one of the most common and cheap natural juices. Fermented palm juice contains various phytochemical compounds that exhibit antioxidant activity. In the present study, we examined the effects of pH on the production of phytochemicals and their antioxidant activity during the fermentation process. The concentration of total phenolics and flavonoid compounds of fermented palm juice and their antioxidant activity were investigated at various pH. The results showed that total phenolics concentration and antioxidant activity of palm wine and palm vinegar increase as pH increases: 3.5 < 4.5 < 5.5. Maximum flavonoid concentration was obtained at pH 6.5. Measurements of antioxidant activity by conventional DPPH method and Photochem antioxidant analyzer technique were highly correlated, with a corresponding R 2 value of 0.94.


Inhibition of natural killer cell-mediated cytotoxicity by ML-9, a selective inhibitor of myosin light chain kinase.
To investigate the role of microfilaments in natural killer (NK) cell-mediated cytotoxicity, general microfilament inhibitors, cytochalasins B,D and dihydrocytochalasin B, and a selective inhibitor of myosin light chain kinase (MLCK) which regulates microfilament contraction, i.e. 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-9) were examined in an NK assay system. ML-9 inhibited NK cell activity in a dose-dependent manner without affecting target cell binding, whereas cytochalasins suppressed the binding. The dextran suspension method revealed that ML-9 inhibits the programming for the lysis stage of the lytic process. In the single cell assay, the addition of ML-9 after target cell binding had occurred inhibited the lysis of bound target cells, whereas the addition of cytochalasins in a similar manner did not affect it. Thus, these results suggest the possibility that microfilament contraction is involved in the lytic mechanism of NK cell-mediated cytolysis. However, the mechanism whereby cytochalasins inhibit target cell binding remains unclear.


[Surgical treatment of bites].
Thorough and profound debridement for acute bite injuries while sparing nerves, vessels and tendons. Acute traumatic and late presented bite injuries. General contraindication for anesthesia or surgery. Extensive flabellate local anesthesia/general anesthesia, wound irrigation using 0.9% NaCl or antiseptic solutions, removal of avital tissues, wound debridement, wound edge excision, anew extensive irrigation, drainage if necessary, wound closure where applicable (except older or punctual deep injuries), bandage, elastic wrapping and immobilization. If necessary, plastic surgery with coverage of remaining defects. Immobilization with initially daily wound evaluation, removal of drainage/loop on postoperative day 2; if necessary, antibiotic therapy with amoxicillin and clavulanic acid in high-risk wounds (e.g., puncture wounds, joint or bone involvement, extensive soft tissue squeezing), suture removal on day 10-12 after surgery. Of 142 bite injuries that were treated and retrospectively evaluated, 46% were caused by dogs and 32% by cats. Patients were on average 44 years old; 55% of all dog bites affected women, but 67% of all cat bites. In 48% of the cases, general anesthesia was necessary. The postoperative infection rate was 6.3%.


Heterogeneity of microbubble accumulation: a novel approach to discriminate between well-differentiated hepatocellular carcinomas and regenerative nodules.
This prospective study aimed to elucidate the possibility of differentiating well-differentiated hepatocellular carcinoma (wHCC) from regenerative nodule (RN) on the basis of the heterogeneity of microbubble accumulation. Intensity analysis was conducted on early-phase and late-phase (60 s and 900 s post-injection; perflubutane microbubble) harmonic sonograms in 33 focal hepatic lesions (≤ 15 mm; 30 patients with chronic liver disease) that were histologically proven as wHCC or RN. Heterogeneity of enhancement, an average of standard deviation of late-phase enhancement in three different sections in the lesions with late-phase iso-enhancement, was examined with respect to the histologic findings. Heterogeneity of enhancement was higher in wHCC (28.7 ± 3.8) than RN (19.8 ± 2.1, p = 0.0213) in the 29 late-phase iso-enhancement lesions. The best cut-off value of the heterogeneity for the diagnosis of wHCC was 25.58, and the sensitivity and specificity were 77.8% and 100%, respectively. A novel parameter, heterogeneity of microbubble accumulation, facilitates differentiation between wHCC and RN showing a late-phase, iso-enhancement appearance.


The idiosyncratic aspects of the epilepsy of Fyodor Dostoevsky.
The goal of this article is to review the idiosyncratic aspects of the epilepsy of Fyodor Dostoevsky, one of the greatest writers of all time. The onset of his seizures is controversial, with some evidence pointing to his childhood and other reports that would place the onset in his teens or his twenties. His life in prison in Siberia and then in the Russian army is reviewed. His lifestyle included many factors that exacerbated his epilepsy, especially stress and sleep deprivation. His compulsion for gambling played an important role in producing great stress in his life, as he tried to reverse his poverty in the casinos. The most idiosyncratic aspect of his epilepsy was his so-called ecstatic aura. The etiology of his seizures was probably inherited as revealed by the seizures of his father and the status epilepticus and death of his young son. This great writer died from lung hemorrhages in 1891. Discussed in this review is that he did not likely have an aura of ecstasy; only a few such possible cases can be found in the world literature. For those few cases, evidence from electrical self-stimulation studies in animals and humans, investigating "pleasure centers," can be found to involve the limbic system, especially the septal nucleus. Data from the human amygdala provide evidence why almost all auras are, in fact, unpleasant and not pleasant. A review of recent data on the risks to offspring of epileptic fathers confirms that the etiology of Dostoevsky's epilepsy was probably inherited and that he probably had an idiopathic generalized epilepsy with minor involvement of the temporal lobe. A relationship is seen between his severe obsession with gambling and his epilepsy. Finally, Fyodor Dostoevsky is an excellent example of the "temporal lobe personality."


Molecular design, chemical synthesis, and evaluation of cytosine-carbohydrate hybrids for selective recognition of a single guanine bulged duplex DNA.
The designed cytosine-carbohydrate hybrid molecule selectively recognized and stabilized the bulged duplex DNA possessing the complementary bulged DNA base, guanine, while the nucleotide base itself did not exhibit any such ability. It was also found that the assistance of the carbohydrate to stabilize the interaction between the nucleotide base and the complementally bulge DNA base is very helpful for the selective recognition and stabilization of the single-bulged duplex DNA.


The iron-sulphur centres of soluble hydrogenase from Alcaligenes eutrophus.
The soluble hydrogenase (hydrogen:NAD+ oxidoreductase (EC 220.127.116.11) from Alcaligenes eutrophus has been purified to homogeneity by an improved procedure, which includes preparative electrophoresis as final step. The specific activity of 57 mumol H2 oxidized/min per mg protein was achieved and the yield of pure enzyme from 200 g cells (wet weight) was about 16 mg/purification. After removal of non-functional iron, analysis of iron and acid-labile sulphur yielded average values of 11.5 and 12.9 atoms/molecule of enzyme, respectively. p-Chloromercuribenzoate was a strong inhibitor of hydrogenase and apparently competed with NAD not with H2. Chelating agents, CO and O2 failed to inhibit enzyme activity. The oxidized hydrogenase showed an EPR spectrum with a small signal at g = 2.02. On reduction the appearance of a high temperature (50--77 K) signal at g = 2.04, 1.95 and a more complex low temperature (less than 30 K) spectrum at g = 2.04, 2.0, 1.95, 1.93, 1.86 was observed. The pronounced temperature dependence and characteristic lineshape of the signals obtained with hydrogenase in 80--85% dimethylsulphoxide demonstrated that iron-sulphur centres of both the [2Fe-2S] and [4Fe-4S] types are present in the enzyme. Quantitation of the EPR signals indicated the existence of two identical centres each of the [4Fe-4S] and of the [2Fe-2S] type. The midpoint redox potentials of the [4Fe-4S] and the [2Fe-2S] centres were determined to be -445 mV and -325 mV, respectively. Spin coupling between two centres, indicated by the split feature of the low temperature spectrum of the native hydrogenase around g = 1.95, 1.93, has been established by power saturation studies. On reduction of the [Fe-4S] centres, the electron spin relaxation rate of the [2Fe-2S] centres was considerably increased. Treatment of hydrogenase with CO caused no change in EPR spectra.


HIF-1-regulated expression of calreticulin promotes breast tumorigenesis and progression through Wnt/β-catenin pathway activation.
Calreticulin (CALR) is a multifunctional protein that participates in various cellular processes, which include calcium homeostasis, cell adhesion, protein folding, and cancer progression. However, the role of CALR in breast cancer (BC) is unclear. Here, we report that CALR is overexpressed in BC compared with normal tissue, and its expression is correlated with patient mortality and stemness indices. CALR expression was increased in mammosphere cultures, CD24-CD44+ cells, and aldehyde dehydrogenase-expressing cells, which are enriched for breast cancer stem cells (BCSCs). Additionally, CALR knockdown led to BCSC depletion, which impaired tumor initiation and metastasis and enhanced chemosensitivity in vivo. Chromatin immunoprecipitation and reporter assays revealed that hypoxia-inducible factor 1 (HIF-1) directly activated CALR transcription in hypoxic BC cells. CALR expression was correlated with Wnt/β-catenin pathway activation, and an activator of Wnt/β-catenin signaling abrogated the inhibitory effect of CALR knockdown on mammosphere formation. Taken together, our results demonstrate that CALR facilitates BC progression by promoting the BCSC phenotype through Wnt/β-catenin signaling in an HIF-1-dependent manner and suggest that CALR may represent a target for BC therapy.


What's Mom and Dad Got to Do With It? Factors Related Between Mothers', Fathers', and Young Children's Weight Bias.
Our aim was to examine the role of parents in the transmission of weight bias to young children. Specifically, we assessed mothers' and fathers' weight bias and beliefs about the controllability of weight, and fear of fat in relation to their children's weight bias. Eighty-three mothers, 57 fathers, and their children (4- to 7-year-olds) participated. We failed to find any significant associations between children's weight bias, maternal responses, and most paternal responses. Only fathers' dislike of adults with overweight had daughters with more positive views of overweight figures. These results suggest that parents do not appear to contribute to the weight bias of preschoolers and their influence may only emerge in middle childhood. The present study also suggests that more work on the psychometric properties of weight bias scales and tasks to measure weight bias in children is vital to accurately evaluate interventions to decrease weight bias.


A novel CoMoO4 enwrapped ZIF-8 nanocomposite with enhanced visible light photocatalytic activity.
A hybrid nano catalyst, CoMoO4 anchored zeolitic imidazolate framework-8 (ZIF-8) has been synthesized by simplest in-situ chemical method. The characterization results showed that the CoMoO4@ZIF-8 composites had a crystalline structure with a uniform distribution of the Cobalt molybdate particles on the ZIF-8 surface. The FTIR spectra revealed the presence of characteristic peaks for both ZIF-8 and CoMoO4, indicating the successful incorporation of the metal molybdate into the ZIF-8 framework. The SEM-EDS analysis showed that the CoMoO4 nanoparticles (NPs) have been evenly distributed on the ZIF-8 surface. In HRTEM, some rod-like CoMoO4 is observed on the surface of the ZIF-8 material, which is stacked in a disorderly manner and a porous channel structure is formed. The photocatalytic activity of the CoMoO4@ZIF-8 has been evaluated using the degradation of methylene blue (MB) and antibiotic Ciprofloxacin (CIP) under visible light. The optimal photocatalytic activity was achieved with the CoMoO4@ZIF-8 composite, which showed a degradation efficiency of 100% under visible light after 40 min of irradiation. In conclusion, the CoMoO4@ZIF-8 composites showed enhanced photocatalytic activity under visible light, and it exhibited the best performance compared with pure CoMoO4 and ZIF-8.


Dual-Ligand Strategy Employing Rigid 2,5-Thiophenedicarboxylate and 1,10-Phenanthroline as Coligands for Solvothermal Synthesis of Eight Lanthanide(III) Coordination Polymers: Structural Diversity, DFT Study, and Exploration of the Luminescent Tb(III) Coordination Polymer as an Efficient Chemical Sensor for Nitroaromatic Compounds.
Lanthanide coordination polymers (Ln-CPs) are potential chemosensors when fabricated to depict a detectable change in optical properties on interaction with target analytes. This work investigates the interaction of nitroaromatic compounds with Ln-CPs leading to induced changes in fluorescence emission intensity, a crucial strategy to develop a selective and sensitive system for the sensing of nitroaromatics. Approaching toward this objective, solvothermal reactions of 2,5-thiophenedicarboxylic (2,5-TDC) acid, 1,10-phenanthroline (1,10-Phen), and Ln(NO3)3·xH2O are carried out to assemble eight Ln(III) coordination polymers [Ln2(2,5-TDC)3(1,10-Phen)2(H2O)2] [Ln = Pr (1), Nd (2)], {[Tb(2,5-TDC)1.5(1,10-Phen)(H2O)]·DMF} (3), and [Ln(2,5-TDC)1.5(1,10-Phen)]·xH2O (Ln = Tb (4), Dy (5), Ho (6), Er (7), and Yb (8)); x = 0 for CP 4, 5, 6, and 8 and x = 1 for CP 7 with two different space groups and dimensions. The as-synthesized polymers 1-8 are characterized by powder X-ray crystallography, infrared spectroscopy, and thermogravimetric analysis. The structure-corroborated density functional theory (DFT) studies are done on the selected CPs to investigate the interactions between different structural motifs of the assembled CPs. The luminescence properties of CP 4 are explored in detail and are found to be highly sensitive for the detection of p-nitrotoluene as indicated by the most intensive fluorescence quenching with the lowest limit of detection (0.88 ppm) and high quenching constant (4.3 × 104 M-1). Other nitro compounds (viz., o-nitrobenzaldehyde, m-nitroaniline, picric acid, m-dinitrobenzene, p-nitrophenol, and p-nitroaniline) are also screened for potential sensing by CP 4.


Accuracy of Resting Metabolic Rate Prediction Equations in Athletes: A Systematic Review with Meta-analysis.
Resting metabolic rate (RMR) prediction equations are often used to calculate RMR in athletes; however, their accuracy and precision can vary greatly. The aim of this systematic review and meta-analysis was to determine which RMR prediction equations are (i) most accurate (average predicted values closest to measured values) and (ii) most precise (number of individuals within 10% of measured value). A systematic search of PubMed, CINAHL, SPORTDiscus, Embase, and Web of Science up to November 2021 was conducted. Randomised controlled trials, cross-sectional observational studies, case studies or any other study wherein RMR, measured by indirect calorimetry, was compared with RMR predicted via prediction equations in adult athletes were included. A narrative synthesis and random-effects meta-analysis (where possible) was conducted. To explore heterogeneity and factors influencing accuracy, subgroup analysis was conducted based on sex, body composition measurement method, athlete characteristics (athlete status, energy availability, body weight), and RMR measurement characteristics (adherence to best practice guidelines, test preparation and prior physical activity). Twenty-nine studies (mixed sports/disciplines n = 8, endurance n = 5, recreational exercisers n = 5, rugby n = 3, other n = 8), with a total of 1430 participants (822 F, 608 M) and 100 different RMR prediction equations were included. Eleven equations satisfied criteria for meta-analysis for accuracy. Effect sizes for accuracy ranged from 0.04 to - 1.49. Predicted RMR values did not differ significantly from measured values for five equations (Cunningham (1980), Harris-Benedict (1918), Cunningham (1991), De Lorenzo, Ten-Haaf), whereas all others significantly underestimated or overestimated RMR (p < 0.05) (Mifflin-St. Jeor, Owen, FAO/WHO/UNU, Nelson, Koehler). Of the five equations, large heterogeneity was observed for all (p < 0.05, I2 range: 80-93%) except the Ten-Haaf (p = 0.48, I2 = 0%). Significant differences between subgroups were observed for some but not all equations for sex, athlete status, fasting status prior to RMR testing, and RMR measurement methodology. Nine equations satisfied criteria for meta-analysis for precision. Of the nine equations, the Ten-Haaf was found to be the most precise, predicting 80.2% of participants to be within ± 10% of measured values with all others ranging from 40.7 to 63.7%. Many RMR prediction equations have been used in athletes, which can differ widely in accuracy and precision. While no single equation is guaranteed to be superior, the Ten-Haaf (age, weight, height) equation appears to be the most accurate and precise in most situations. Some equations are documented as consistently underperforming and should be avoided. Choosing a prediction equation based on a population of similar characteristics (physical characteristics, sex, sport, athlete status) is preferable. Caution is warranted when interpreting RMR ratio of measured to predicted values as a proxy of energy availability from a single measurement. CRD42020218212.


Refractory bradycardia during retrograde pyelography and spinal anesthesia.
Bradycardia commonly occurs during spinal anesthesia as a result of vagally mediated slowing of sinoatrial (SA) node firing. Peritoneal traction or urinary bladder distension, for example, may serve as a stimulus for SA node inhibition, particularly when thoracic levels of spinal anesthesia interrupt function of the sympathetic limb of the autonomic nervous system. Although atropine dependably reverses such heart rate slowing, we recently encountered, during spinal anesthesia for cystoscopy and retrograde pyelography, bradycardia that was unexpected and refractory to treatment with atropine.


Possible pulmonary Rhizopus oryzae infection in a previously healthy child after a near-drowning incident.
This article reports on a previously healthy 17-month-old boy who developed pulmonary mucormycosis after a near-drowning incident in a goose pond. The patient survived without neurological sequelae and recovered, under treatment with amphotericin B, from the rare and often invasive fungal infection with Rhizopus spp., usually occurring in immunodeficient patients.


Donors, authors, and owners: how is genomic citizen science addressing interests in research outputs?
Citizen science is increasingly prevalent in the biomedical sciences, including the field of human genomics. Genomic citizen science initiatives present new opportunities to engage individuals in scientific discovery, but they also are provoking new questions regarding who owns the outputs of the research, including intangible ideas and discoveries and tangible writings, tools, technologies, and products. The legal and ethical claims of participants to research outputs become stronger-and also more likely to conflict with those of institution-based researchers and other stakeholders-as participants become more involved, quantitatively and qualitatively, in the research process. It is not yet known, however, how genomic citizen science initiatives are managing the interests of their participants in accessing and controlling research outputs in practice. To help fill this gap, we conducted an in-depth review of relevant policies and practices of U.S.-based genomic citizen science initiatives. We queried the peer-reviewed literature and grey literature to identify 22 genomic citizen science initiatives that satisfied six inclusion criteria. A data collection form was used to capture initiative features, policies, and practices relevant to participants' access to and control over research outputs. This analysis revealed that the genomic citizen science landscape is diverse and includes many initiatives that do not have institutional affiliations. Two trends that are in apparent tension were identified: commercialization and operationalization of a philosophy of openness. While most initiatives supported participants' access to research outputs, including datasets and published findings, none supported participants' control over results via intellectual property, licensing, or commercialization rights. However, several initiatives disclaimed their own rights to profit from outputs. There are opportunities for citizen science initiatives to incorporate more features that support participants' access to and control over research outputs, consistent with their specific objectives, operations, and technical capabilities.


The problem is getting us to stop. What teens say about smoking cessation.
Low participation and high dropout in many teen cessation programs may be due to lack of fit between teens' needs and the way programs are delivered. Qualitative studies, designed to identify and understand preferences of intervention participants and barriers to participation, offer opportunities to customize programs and improve their reach and effectiveness. Two sets of focus groups with high school students were held in the Portland, OR, metropolitan area to elicit reactions to two smoking cessation programs and discuss motivations for and experiences with quitting. Thirty-three students (15 girls, 18 boys) participated in the first set of four focus groups; 40 students (21 girls, 19 boys) in the five focus groups for the second. Participants preferred programs that respect the challenges that teens face in quitting, and acknowledge their choice in making the decision to quit. Teens wanted nonjudgmental and confidential support from cessation counselors, and preferred counselors who are ex-smokers, give useful quit tips, and can provide support for quit attempts. Private, computer-based programs and personalized telephone services were options for delivering cessation information and support. Teen smokers can supply valuable information to improve youth cessation programs to fit teen lifestyles, respect the challenges teens face, and acknowledge their choice in making the decision to quit.


First-trimester Down syndrome screening in renal-transplanted pregnant women: a model for adjusting the false-positives rates.
This study aimed to develop a model to adjust the increased β-hCG levels observed in renal-transplanted women, leading to increased false-positive rates in Down syndrome screening. Detailed data from 11 renal-transplanted and a nested-cohort of 70 pregnant women, matched by age, parity and gestational age were retrieved from our hospital records. Patient's age, multiples of the median (MoM) values for freeβ-hCG, pregnancy-associated plasma protein-A, nuchal translucency, and creatinine concentration and clearance were noted. Freeβ-hCG levels were adjusted according to the deviation of serum creatinine concentration by means of three different methods (median, proportionality and regression). Subsequently, Down syndrome risk was estimated with the three resulting adjusted fβ-hCG values. After adjustment, the median β-hCG MoM decreased from 2.15 MoM to 1.00 MoM (median method), 1.61 MoM (proportionality method) or 1.16 MoM (regression method). The non-adjusted 27% false-positive rate dropped to 18% (median method) and 10% (proportionality or regression methods) after re-estimation of the Down syndrome risk. In controls, the observed median for β-hCG MoM was 1.12, and the false-positive rate was 5.7%. In first-trimester Down syndrome screening, fβ-hCG adjustment by the regression method appears to be the best to match with controls.


Transport of dissolved organic matters derived from biomass-pyrogenic smoke (SDOMs) and their effects on mobility of heavy metal ions in saturated porous media.
Biomass-pyrogenic smoke-derived dissolved organic matter (SDOMs) percolating into the underground environment profoundly impacts the transport and fate of environmental pollutants in groundwater systems. Herein, SDOMs were produced by pyrolyzing wheat straw at 300-900 °C to explore their transport properties and effects on Cu2+ mobility in quartz sand porous media. The results indicated that SDOMs exhibited high mobility in saturated sand. Meanwhile, the mobility of SDOMs was enhanced at a higher pyrolysis temperature due to the decrease in their molecular sizes and the declined H-bonding interactions between SDOM molecules and sand grains. Furthermore, the transport of SDOMs was elevated as pH values were raised from 5.0 to 9.0, which resulted from the strengthened electrostatic repulsion between SDOMs and quartz sand particles. More importantly, SDOMs could facilitate Cu2+ transport in the quartz sand, which stemmed from forming soluble Cu-SDOM complexes. Intriguingly, the promotional function of SDOMs for the mobility of Cu2+ was strongly dependent on the pyrolysis temperature. Generally, SDOMs generated at higher temperatures exhibited superior effects. The phenomenon was mainly due to the differences in the Cu-binding capacities of various SDOMs (e.g., cation-π attractive interactions). Our findings highlight that the high-mobility SDOM can considerably affect heavy metal ions' environmental fate and transport.


Tilt table exercise echocardiography assessment in the diagnosis of coronary artery disease.
To assess the diagnostic performance of per-exercise echocardiography using a recent tilt table to investigate for coronary artery disease with a significance threshold for stenosis > or =70%. 104 consecutive patients (93 men) referred for elective coronary angiography underwent tilt table exercise echocardiography in which second harmonic imaging was used systematically. Images were recorded and interpreted by the same operator. The investigation was contributory in 81 patients (target HR at least 85% of the age-predicted maximal HR or criterion for discontinuation). The most common reason for a non-contributory investigation (negative investigation but submaximal or uninterpretable investigation) was submaximal exercise (91%). The prevalence of significant coronary artery disease in the cohort of 81 contributory investigations was 38%. Sensitivity and specificity to detect significant lesions was 90% and 94% respectively. The positive and negative predictive values were 90% and 94% respectively. The three false negatives involved distal lesions. The three false positives occurred in patients with regional wall motion abnormalities in the context of various heart diseases (severe mitral incompetence, diabetic and hypertensive cardiomyopathy, left bundle branch block). Using a high performance echocardiography machine with second harmonic imaging per-exercise tilt table echocardiography offers excellent diagnostic performance to detect significant coronary artery disease under everyday clinical practice conditions.


Management of Cystoid Macular Edema After Vitrectomy for Proliferative Vitreoretinopathy.
To assess therapies for cystoid macular edema (CME) following pars plana vitrectomy for proliferative vitreoretinopathy (PVR). Retrospective analysis of 42 eyes developing CME after PVR surgery. Treatments included topical therapy, sub-Tenon's triamcinolone acetonide (STTA), intravitreal bevacizumab and combinations thereof. Best-corrected visual acuity (BCVA) as well as central subfield thickness (CST) were tracked. Mean Snellen BCVA improved from 20/598 to 20/297 (logMAR change -0.21; confidence interval [CI], -0.39 to -0.03; P = .03). Mean CST improved from 448 µm to 260 µm (CI, -248.70 to -126.06; P < 0.01). There was no difference in efficacy between treatment subgroups (analysis of variance, P = 0.16, 0.43), but STTA yielded statistically significant improvement in both categories (CI, -0.79 to -0.11; P = 0.01; and CI, -333.74 to 166.51; P < .01). Treatment of CME following PVR surgery is possible with a variety of different options. STTA appears to yield anatomical and visual improvement. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:436-443.].


Nosocomial infection in kidney transplant recipients: a retrospective analysis of a single-center experience.
Posttransplant bacterial infections are important because of their influence on patient and graft outcomes. Therefore, prevention of infection as well as prompt diagnosis and appropriate treatment are crucial. In this retrospective analysis, we reviewed all posttransplant bacterial infections occurring during the admission of kidney transplant patients from January 2000 to May 2004. Of our patients, 25% had at least one episode of infection. Patients with immunosuppression based on an mTOR inhibitor showed the highest rate of wound infections compared to those receiving a calcineurin inhibitor (odds ratio 5.6, P < .001). Patients with renal failure caused by a urologic disease revealed a increased risk of a urinary tract infections (odds ratio 5.9, P < .001). Although infection complications are an important cause of morbidity in renal transplantation, the extensive use of antibiotics should be avoided in favor of a strict policy for infection prevention and control.


Acute airway obstruction requiring nasotracheal intubation following hypoglossal neuromonitoring: a case report.
Intraoperative neurophysiological monitoring (IONM) is utilized for both the localization of critical structures and for real time detection and prevention of intraoperative neurological injury. Use of IONM to monitor the hypoglossal nerve is performed during neurosurgical, otolaryngological, and vascular procedures to improve surgical outcomes. There is a paucity of literature describing potential complications of IONM of the hypoglossal nerve, especially with respect to airway compromise. Here we present our findings regarding a case of acute airway obstruction following hypoglossal nerve monitoring. A 54-year-old male was admitted for left far-lateral craniotomy and microsurgical clipping of a left posterior inferior cerebellar artery (PICA) aneurysm. Following induction and intubation but prior to the procedure start, the patient was placed in the ¾ prone position with the left side up and his neck was flexed approximately 10 degrees. He then underwent placement of subdermal needle electrodes into the facial muscles, trapezius muscles, soft palate, and tongue for IONM. The procedure lasted 523 minutes and was completed without complication. However, approximately one hour after emergence from general anesthesia, the patient experienced progressive difficulty breathing secondary to severe lingual swelling. He required emergent placement of a nasotracheal tube guided by a fiberoptic bronchoscope. He remained intubated for 3 days and was treated with dexamethasone, after which the swelling resolved, and the patient was successfully extubated. Acute lingual edema is a potentially life-threatening phenomenon that can lead to rapid airway compromise. Generally, causes of acute lingual swelling include hemorrhage, edema, infarction, and infection. In the case described above, we suspect traumatic injury to the tongue's vascular supply caused a deep tissue hematoma leading to postoperative acute lingual swelling and airway obstruction. With the widespread use of IONM, it becomes essential for providers to be aware that perioperative airway compromise is a potentially life-threatening complication, especially with respect to monitoring of the hypoglossal nerve. Awake fiberoptic nasotracheal intubation can successfully be employed to establish an emergency airway in such situations.


The effect of voluntary fasting and dehydration on flicker-induced retinal vascular dilation in a healthy individual: a case report.
Dynamic retinal vessel analysis represents a well-established method for the assessment of vascular reactivity during both normal conditions and after various provocations. We present a case where the subject showed abnormal retinal vessel reactivity after fasting voluntarily for 20 hours. A healthy, 21-year-old man who fasted voluntarily for 20 hours exhibited abnormal retinal vascular reactivity (dilation and constriction) after flicker provocation as measured using the Dynamic Retinal Vessel Analyser (Imedos, Jena, Germany). The abnormal vascular reactivity induced by fasting was significant; abnormal levels of important nutrients due to fasting and dehydration could play a role through altering the concentration of vasoactive substances such as nitric oxide. This hypothesis needs further investigation.


Development of a MSFIA system for sequential determination of antimony, arsenic and selenium using hydride generation atomic fluorescence spectrometry.
This paper proposed a multisyringe flow injection analysis (MSFIA) system for antimony, arsenic and selenium determination in peanut samples by hydride generation atomic fluorescence spectrometry (HG-AFS). The optimization step of the hydride generation was performed using a two-level full factorial design involving the parameters: hydrochloric acid, sodium tetrahydroborate and potassium iodide concentrations. So, using the chemical conditions optimized, this method allows the determination of these elements employing the external calibration technique using aqueous standards with limits of detection and quantification of 0.04 and 0.14µgL(-1) for antimony, 0.04 and 0.14µgL(-1) for arsenic and 0.14 and 0.37µgL(-1) for selenium, respectively. Additionally, the effect of vanadium, chromium, cobalt, nickel, zinc, copper, iron and molybdenum on the generation of chemical vapour was also studied. The precision expressed as relative standard deviation varied from 1.2 to 3.6% for antimony, 1.8-3.9% for arsenic and 1.8-2% for selenium. The accuracy for arsenic and selenium was confirmed using the certified peach leaves reference material SRM 1547 produced by National Institute of Standard and Technology. The proposed method showed 45 injection throughput (h(-1)) using 1.6mL sample volume for each element, 0.8mL NaBH4 0.5% (w/v) containing NaOH 0.05% (w/v), 0.8mL HCl 5M and 0.4mL KI 14% (w/v) containing L-ascorbic acid 2.5% (w/v). The method was applied to the determination of antimony, arsenic and selenium in peanut samples, which were firstly lyophilized and afterward digested using microwave assisted radiation. Six samples were analyzed and the contents of the elements found were: 28.7-41.3µgkg(-1) for arsenic, 86.4-480.1µgkg(-1) for selenium and 32.6-52.4µgkg(-1) for antimony. Addition/recovery tests were also performed to confirm the method accuracy for the three elements.


Gas diffusion electrodes for H2O2 production and their applications for electrochemical degradation of organic pollutants in water: A review.
Nowadays, it is a great challenge to minimize the negative impact of hazardous organic compounds in the environment. Highly efficient hydrogen peroxide (H2O2) production through electrochemical methods with gas diffusion electrodes (GDEs) is greatly demand for degradation of organic pollutants that present in drinking water and industrial wastewater. The GDEs as cathodic electrocatalyst manifest more cost-effective, lower energy consumption and higher oxygen utilization efficiency for H2O2 production as compared to other carbonaceous cathodes due to its worthy chemical and physical characteristics. In recent years, the crucial research and practical application of GDE for degradation of organic pollutants have been well developed. In this review, we focus on the novel design, fundamental aspects, influence factors, and electrochemical properties of GDEs. Furthermore, we investigate the generation of H2O2 through electrocatalytic processes and degradation mechanisms of refractory organic pollutants on GDEs. We describe the advanced methodologies towards electrochemical kinetics, which include the enhancement of GDEs electrochemical catalytic activity and mass transfer process. More importantly, we also highlight the other technologies assisted electrochemical process with GDEs to enlarge the practical application for water treatment. In addition, the developmental prospective and the existing research challenges of GDE-based electrocatalytic materials for real applications in H2O2 production and wastewater treatment are forecasted. According to our best knowledge, only few review articles have discussed GDEs in detail for H2O2 production and their applications for degradation of organic pollutants in water.


Body Representations of Internal Pollution: The Risk Perception of the Circulation of Environmental Contaminants in Pregnant and Breastfeeding Women in Spain.
In this article, we analyze how pregnant and breastfeeding women perceive the inside of their bodies as well as their thoughts regarding the accumulation and elimination of chemical compounds present in food, and how these are then transmitted to the fetus. We explore different social perceptions of risk regarding the circulation of chemical compounds inside the body using qualitative research based on the technique of body mapping, comprised of women's drawings of their bodies in combination with comments on the drawings, food diaries and narratives from in-depth interviews. We examine how these 41 women (21 pregnant and 20 breastfeeding) perceive the body's internal mechanisms during the stages of pregnancy and breastfeeding, as well as the circulation of chemical contaminants within it. The body mapping technique allowed us to analyze participants' knowledge of internal pollution, a little-understood process in society. Thanks to these pregnant and breastfeeding women, who made an effort to represent and reflect on these new risks, this study shows that scientists and obstetricians need to collaborate with women in order to better understand and publicize the risks of internal pollution.


Growth in milk consumption and reductions in child stunting: Historical evidence from cross-country panel data.
Agricultural and food policies are increasingly being tasked with doing more to improve the nutritional status of low-income populations, especially reductions in child stunting. Which specific food sectors warrant additional policy attention is less clear, although a growing body of research argues that increased animal-sourced food consumption in general, and increased dairy consumption specifically, can significantly reduce the risks of stunting, as well as deficiencies in micronutrients and high quality protein. However, experimental research on dairy's impacts on child growth in developing countries is very limited, and non-experimental evidence is confined to cross-sectional surveys. In this study we adopt a more macro lens by using a cross-country panel to show that increases in milk consumption over time are associated with large reductions in child stunting even after controlling for important confounding factors. Countries with high rates of stunting should therefore consider nutrition-sensitive strategies to increase dairy consumption among young children through both supply- and demand-side interventions.


Microhabitat, water relations, and photosynthesis of a desert fern, Notholaena parryi.
Interrelationships between morphology, microhabitat, water relations, and photosynthesis of a xeric fern, Notholaena parryi D.C. Eat. (Pteridaceae), were examined in the western Colorado desert. In its typical microhabitat rock outcroppings protected N. parryi from direct sunlight and moderated the diurnal variations in air temperature. For example, frond temperature at noon in late winter was 15.3° C, which was 7.3° C cooler than an energy budget simulation predicting frond temperature at an exposed site. The lowest soil water potential leading to daytime stomatal opening was about-1.5 MPa (-15 bars). Rainfall runoff that was channeled to the periphery of the rocks caused Ψsoil near the fern roots to rise above-1.5 MPa even after light rainfalls, and it remained above-1.5 MPa longer after rainfall than in non-rocky sites.The water potential gradient along the stipe necessary to support the observed rates of transpiration was about-10 MPa m-1; such a large gradient reflected the small conducting area in the xylem. The water vapor conductance decreased as the frond temperature was raised, an effect that became proportionally greater as the soil dried out. The daytime water-use efficiency (mass CO2 fixed/mass water transpired) was 0.0058 for a spring day. Individual fronds reached 90% of light saturation for photosynthesis at only 100 μEinsteins m-2 s-1, a photosynthetically active radiation similar to that from the diffuse sunlight incident on the generally north-facing microhabitat of the fern. Below 50 μE m-2 s-1 the quantum requirement was 13 Einsteins absorbed/mole CO2 fixed. The ratio of chlorophyll to P700 was 552, indicating a fairly large photosynthetic unit that is characteristic of plants adapted to shaded habitats. The temperature optimum for net photosynthesis shifted from 13° C in midwinter (mean daily air temperature of 11° C) to 19° C in early fall (air temperature of 23° C).


The interaction of lanthanide and calcium salts with phospholipid bilayer vesicles: the validity of the nuclear magnetic resonance method for determination of vesicle bilayer phospholipid surface ratios.
Contrary to a recent report (B. Sears et al., Biochemistry 15 (1976) 1635), it has been determined that the ratio of the number of phospholipids on the inner and outer surfaces of phospholipid bilayer vesicles can be accurately determined by NMR paramagnetic ion shift reagent studies of vesicles. It is concluded that the metal interacts with all of the phospholipid on the exposed bilayer surface. A ratio of outer phospholipid to inner surface phospholipid of 2.1 +/- 0.1 is obtained regardless of the nucleus studied, position of the nucleus relative to the metal ion binding site, molar ratio of metal to phospholipid over three orders of magnitude, or location of the metal ion of the inside or outside of the vesicle. Additionally, P-31 NMR studies using LaC13 and CaC12 indicate that Ca2+ weakly interacts with egg PC vesicles and that the lanthanides are adequate substitutes for Ca2+ since neither metal is found to perturb measurably the average polar head group conformation.


The severity of systemic lupus erythematosus negatively correlates with the increasing number of CD4+CD25(high)FoxP3+ regulatory T cells during repeated plasmapheresis treatments of patients.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by increased pathologic autoantibody production. A decrease in the number of CD4+CD25(high)FoxP3+ regulatory T cells can play a key role in the loss of tolerance to self antigens. Our aim was to determine the absolute number of peripheral CD4+CD25(high)FoxP3+ T cells in 44 patients with SLE, furthermore, to measure the changes in the number of CD+CD25(high)FoxP3+ T cells in 5 patients with severe SLE treated with repeated plasmapheresis for 4-6 days in comparison to the changes in the activity of disease (SLEDAI). Percent of CD4+CD25(high)FoxP3+ T cells were measured by flow cytometry. The absolute number of peripheral CD4+CD25(high)FoxP3+ T cells was significantly decreased in the 44 patients with SLE compared to the healthy controls n = 32 (0.012 +/- 0.006 vs. 0.038 +/- 0.017 G/L, p < 0.05). In the 5 patients with severe SLE the repeated plasmapheresis treatments increased the peripheral number of CD4+CD25(high)FoxP3+ T cells. As the number of CD4+CD25(high)FoxP3+ T cells increased during the treatment, the activity of disease (the value of SLE activity index) decreased. In the peripheral blood of SLE patients not only the ratio was decreased (as it was published earlier) but also the absolute number of these regulatory T cells. The repeated plasmapheresis treatments of SLE patients induced a significant increase in the number of peripheral CD4+CD25(high)FoxP3+ T cells in parallel to the decrease in the values of SLEDAI (the activity of disease). This phenomenon is, among others, possibly due to the elimination of interpheron-alpha and lymphocytotoxic antibodies during plasmapheresis.


Correction: Adductor Canal Block Duration of Analgesia Successfully Prolonged With Perineural Dexmedetomidine and Dexamethasone in Addition to IPACK Block for Total Knee Arthroplasty.
[This corrects the article DOI: 10.7759/cureus.10566.].


Clinical and imaging characteristics, outcomes and prognostic factors of intraocular foreign bodies extracted by vitrectomy.
To investigate the clinical and computer tomography (CT) features and visual prognostic factors of pars plana vitrectomy (PPV) for management of retained posterior segment intraocular foreign body (IOFB). Medical records of 96 patients with IOFB removed by PPV between July 2017 and June 2021 were retrieved. The medical records, including demographic data, initial and final best corrected visual acuity (BCVA) using standard Snellen chart, characteristics of IOFB, CT findings, and surgical details, were reviewed. Outcome was evaluated according to the final BCVA and prognostic factors were obtained. The mean age was 42.31 ± 12.05 years (range 13-71 years) with 94 males (97.9%) and two females (2.1%). CT was sensitive of IOFB in 93.75% (90 eyes) and the locations were consistent with that found during PPV: 20 foreign bodies were located in vitreous, 6 near ciliary body, and 70 on or in retina. Mean diameter of IOFB removed by PPV is 3.52 mm ± 3.01 mm (range 1-22; median 3), and mean area is 6.29 ± 6.48 mm2 (range 0.5-40; median 3), which was statistically associated with the initial VA < 0.1 and endophthalmitis. Endophthalmitis was found in 24 (25.0%) eyes and large wound together with scleral entry site might be related to the endophthalmitis. Visual outcome < 0.1 was associated with relative afferent pupillary defect, initial VA < 0.1, and presence of endophthalmitis. Initial VA ≥ 0.1 was independent predictive factor for a better final BCVA. Relative afferent pupillary defect, initial BCVA < 0.1, and presence of endophthalmitis are poor visual prognostic factors.


Superhydrophilic polyethersulfone (PES) membranes with high scale inhibition properties obtained through bionic mineralization and RTIPS.
Reverse thermally induced separation (RTIPS) was used to obtain a separation membrane with a better internal structure for a higher water flux and a surface that could easily form a hydration layer. In comparison to the traditional modification method, this work focused on the aspect that the internal structure obtained by changing the membrane-making method provided easier adhesion conditions for the dopamine/TiO2 hybrid nanoparticles (DA/TiO2 HNPs) obtained by biomimetic mineralization. It provided a basis for exploring the variation in adhesion with the water bath temperature and the amount of titanium added through the study of turbidity point, SEM images, water contact angle, thermogravimetric test, EDX, AFM, XPS, FTIR and other test results. The SEM images proved that the membrane obtained through the RTIPS method had a porous surface and spongy internal structure, furthermore, additional polymers were adsorbed. Use of EDX demonstrated that biomimetic mineralization prevented the production of agglomerated titanium dioxide. XPS and FTIR spectra confirmed the introduction and immobilization of HNP aggregation. Moreover, a decrease in the surface roughness and water contact angle further suggested an improvement in the hydrophilicity of the modified membrane. The introduction of HNP at a higher water bath temperature helped increase the water flux up to ten times, moreover, the oil-water separation efficiency could still reach over 99.50%. Lastly, a cycle test of the modified membrane under the optimal conditions helped confirm that the membrane forming conditions at this time could provide a better environment for the formation of the hydrophilic layer, which was conducive to the recycling of the separation membrane. In summary, more fixed more hydrophilic particles could be obtained through the RTIPS method based on biomimetic mineralization to prevent the accumulation of titanium dioxide, thus helping improve permeability and anti-fouling of the membrane.


Telomeres in lung disease.
Telomeres are DNA-protein structures that cap the ends of chromosomes; telomerase is the enzyme that ensures their integrity. Telomere biology has recently been implicated in the pathogenesis of a variety of lung diseases, including idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease/emphysema, and lung cancer. This review highlights recent discoveries pertaining to the role of telomere biology in lung disease.


Intraoperative squash cytology of central nervous system lesions: a single center study of 326 cases.
Cytology has been shown to be of great value in intraoperative consultations of central nervous system (CNS) pathology. Intraoperative smear cytology provides a rapid and reliable intraoperative diagnosis and guidance to the neurosurgeon during surgical resection and lesion targeting. It also helps the surgeon to monitor and modify the approach at surgery. The current study was undertaken to assess the accuracy and utility of intraoperative consultations for cytomorphological diagnosis by smear technique and correlate with histopathological diagnosis. A retrospective study of 326 cases of CNS intraoperative consultations was performed. Smears were prepared from the biopsy samples sent in isotonic saline for immediate processing and stained by the Haematoxylin and Eosin method. The cytomorphological features were noted and correlated with final histopathological diagnosis. Concordance between the intraoperative diagnosis and the final diagnosis was seen in 83.7% of cases. We demonstrated >95% accuracy for glioblastomas and >89% accuracy for meningiomas and schwannomas. A reduction of diagnostic accuracy was seen in oligodendrogliomas (60%) and anaplastic oligodendrogliomas (57.2%). Smear technique is a fairly accurate, relatively safe, rapid, simple, easily reproducible, and cost effective tool to diagnose brain tumors. Smear cytology is of great value in intraoperative consultation of CNS pathology.


Retaining well-fixed cementless stem in the treatment of infected hip arthroplasty.
Two-stage reconstruction, reimplantation after removal of an infected prosthesis, has been considered to be the gold standard for treatment of infected hip arthroplasty. However, during the removal of a well-fixed femoral stem, the proximal femur can be damaged and a sequestrum can be formed, which might lead to chronic osteomyelitis and difficulty in reimplantation. We wanted to determine whether infection after hip arthroplasty can be treated without removal of a well-fixed stem. We treated 19 patients who had an infection after hip replacement, but a well-fixed cementless stem, with 2-stage reconstruction. At the first stage, we removed the acetabular cup, the liner and the head, but not the stem. We then implanted a cup of cement spacer. After control of infection, we reimplanted the acetabular component and head. 2 patients did not undergo second-stage reconstruction because they were satisfied with the pain relief and the activity that they had with the cement-spacer implantation. The remaining 17 patients underwent the second-stage of the reconstruction using cementless arthroplasty. At a mean follow-up time of 4 (2-8) years, 15 of the patients had no recurrence of infection, with satisfactory clinical and radiographic outcome. This second-stage reconstruction after retention of the stem could be an alternative treatment option for periprosthetic infection with a well-fixed stem.


The significance of nuclear diameter in the biologic behavior of thyroid carcinomas: a retrospective study of 127 cases.
The relationship between nuclear diameter and biologic behavior was studied in 127 cases of thyroid carcinoma. Using a sonic digitizer coupled to a minicomputer, nuclear diameters of 200 randomly selected cancer cells from each case (hematoxylineosin-stained paraffin sections) projected at X 400 magnification were traced and averaged. A total of 25,400 measurements were made. The nuclear diameters varied from 4.7 to 13.1 micron. By analysis of variance, the nuclear diameters were significantly different (p = 0.0007) among the four types of thyroid cancers, being largest in the undifferentiated cancers (8.7 +/- 0.8 micron) and smallest in the medullary cancers (6.6 +/- 0.1 micron). Nuclear diameter was also significantly correlated with degree of tumor differentiation (p = 0.002), maximal tumor diameter (p = 0.03), mitotic rate (p = 0.002), and 5-year survival (p less than 0.05) for all types of tumors. The correlation between nuclear diameter and disease stage was significant only for undifferentiated cancers (p = 0.04). No significant correlations were seen between nuclear diameter and duration of disease, sex, or age of the patient.


Anatomic considerations for retrograde fibular medullary screw insertion: a cadaveric study.
A retrograde fibular medullary screw may be utilized in certain fractures about the ankle. The purpose of this study is to investigate the anatomic considerations of a retrograde medullary screw inserted from a lateral starting point to nearby anatomic structures about the distal fibula. Ten fresh-frozen cadaveric lower extremities were utilized. A 1.6-mm Kirschner wire was inserted into the distal fibula from a far-lateral starting point. A 3.2-mm cannulated drill bit was then inserted over the Kirschner wire. After placement of the drill bit, dissection of the lateral ankle was undertaken. The proximity of nearby anatomic structures to the drill bit was measured using calipers. A 4.5-mm cortical screw was then inserted using fluoroscopic guidance. Measurements were then taken again to assess the relationship of the screw head to adjacent structures. Mean distance from drill bit to nearby structures is as follows: Peroneus longus tendon 4.56 mm, peroneus brevis tendon 6.62 mm, sural nerve 4.13 mm, superior peroneal retinaculum 7.52 mm, inferior peroneal retinaculum 6.61 mm, anterior talofibular ligament (ATFL) 6.1 mm, calcaneofibular ligament (CFL) 6.7 mm. Average distance from 4.5-mm screw head to nearby structures is as follows: peroneus longus tendon 6.79 mm, peroneus brevis tendon 6.73 mm, ATFL 4.16 mm, CFL 5.14 mm, lateral talar process 9.41 mm. Retrograde medullary fibular screw fixation may be safely carried out through a lateral start point. Anatomic structures about the lateral ankle are nearby but not immediately adjacent to the drill bit.


Progress in synthesis of sensory important trace components of essential oils and natural flavours.
In this paper the role of sensory important trace components will be discussed. A chemical classification of the components is given as well as a review of methods of synthesis of the following substances applied in industry: cis-3-hexen-1-ol, rose oxide, alpha and beta-damascenone and damascone, theaspirone, raspberry ketone, pyranones, furanones and related products, alkylmethoxypyrazines, sulphur containing flavour substances.


Peripheral and central alterations of pituitary adenylate cyclase activating polypeptide-like immunoreactivity in the rat in response to activation of the trigeminovascular system.
Pituitary adenylate cyclase activating polypeptide (PACAP) is present in the cranial arteries and trigeminal sensory neurons. We therefore examined the alterations in PACAP-like immunoreactivity (PACAP-LI) in a time-dependent manner in two rat models of trigeminovascular system (TS) activation. In one group chemical stimulation (CS) was performed with i.p. nitroglycerol (NTG), and in the other one the trigeminal ganglia (TRG) were subjected to electrical stimulation (ES). The two biologically active forms, PACAP-38 and PACAP-27, were determined by means of radioimmunoassay (RIA) and mass spectrometry (MS) in the plasma, the cerebrospinal fluid (CSF), the trigeminal nucleus caudalis (TNC), the spinal cord (SC) and the TRG. The tissue concentrations of PACAP-27 were 10 times lower than those of PACAP-38 in the TNC and SC, but about half in the TRG. PACAP-38, but not PACAP-27, was present in the plasma. Neither form could be identified in the CSF. PACAP-38-LI in the plasma, SC and TRG remained unchanged after CS, but it was increased significantly in the TNC 90 and 180 min after NTG injection. In response to ES of the TRG, the level of PACAP-38 in the plasma and the TNC was significantly elevated 90 and 180 min later, but not in the SC or the TRG. The alterations in the levels of PACAP-27 in the tissue homogenates in response to both forms of stimulation were identical to those of PACAP-38. The selective increases in both forms of PACAP in the TNC suggest its important role in the central sensitization involved in migraine-like headache.


X-ray nanodiffraction analysis of stress oscillations in a W thin film on through-silicon via.
Synchrotron X-ray nanodiffraction is used to analyse residual stress distributions in a 200 nm-thick W film deposited on the scalloped inner wall of a through-silicon via. The diffraction data are evaluated using a novel dedicated methodology which allows the quantification of axial and tangential stress components under the condition that radial stresses are negligible. The results reveal oscillatory axial stresses in the range of ∼445-885 MPa, with a distribution that correlates well with the scallop wavelength and morphology, as well as nearly constant tangential stresses of ∼800 MPa. The discrepancy with larger stress values obtained from a finite-element model, as well as from a blanket W film, is attributed to the morphology and microstructural nature of the W film in the via.


Small, Long Blood Half-Life Iodine Nanoparticle for Vascular and Tumor Imaging.
Standard clinical X-ray contrast agents are small iodine-containing molecules that are rapidly cleared by the kidneys and provide robust imaging for only a few seconds, thereby limiting more extensive vascular and tissue biodistribution imaging as well as optimal tumor uptake. They are also not generally useful for preclinical microCT imaging where longer scan times are required for high resolution image acquisition. We here describe a new iodine nanoparticle contrast agent that has a unique combination of properties: 20 nm hydrodynamic diameter, covalent PEG coating, 40 hour blood half-life, 50% liver clearance after six months, accumulation in tumors, and well-tolerated to at least 4 g iodine/kg body weight after intravenous administration in mice. These characteristics are unique among the other iodine nanoparticles that have been previously reported and provide extended-time high contrast vascular imaging and tumor loading. As such, it is useful for preclinical MicroCT animal studies. Potential human applications might include X-ray radiation dose enhancement for cancer therapy and vascular imaging for life-threatening situations where high levels of contrast are needed for extended periods of time.


Effect of the CER[NP]:CER[AP] a ratio on the structure of a stratum corneum model lipid matrix - a molecular dynamics study.
In some dermal diseases with evident skin dehydration and desquamation, the natural ratio of CER[NP]:CER[AP] is altered in the extracellular matrix of the stratum corneum by increasing the concentration of CER[AP]. The extracellular matrix of the stratum corneum is composed of several stacked lipid bilayers. Molecular dynamics simulations were used to investigate the molecular nanostructure of CER[NP], CER[AP], cholesterol and lignoceric acid models of the extracellular matrix of the stratum corneum with a nativelike CER[NP]:CER[AP] 2:1 ratio and a CER[NP]:CER[AP] ratio of 1:2. Despite the very minor chemical difference between CER[NP] and CER[AP], which is only a single OH group, it was possible to observe differences between the structural influence of the two ceramides. In the models with 1:2 ratio, the higher CER[AP] content leads to a larger inclination of the acyl chains and a smaller overlap in the lamellar midplane, with a small increase of the repeat distance compared to the model with higher CER[NP] concentration. Because CER[AP] forms more H-bonds than CER[NP], the total number of hydrogen bonds in the headgroup region is larger in the models with higher CER[AP] concentration, reducing the mobility of the lipids towards the centre of the bilayer and resulting in less overlap and increased tilt angles.


Outcome of second hematopoietic cell transplantation in Hurler syndrome.
Hurler syndrome (HS) is an autosomal recessive, inherited metabolic storage disorder due to deficiency of lysosomal alpha-L-iduronidase (IDU) enzyme activity. Untreated patients develop progressive mental retardation and multisystem morbidity with a median life expectancy of 5 years. Allogeneic hematopoietic cell transplantation (HCT) can achieve stabilization and even improvement of intellect, with long-term survival. However, children with HS have an increased incidence of graft failure, usually with concomitant autologous marrow reconstitution. Between 1983 and 2000, 71 Hurler children underwent HCT at the University of Minnesota. Of these 71, 19 (27%) experienced graft failure. We report HCT outcomes in all 11 Hurler patients receiving a second HCT at the University of Minnesota. Median age at second HCT was 25 months (range, 16 to 45 months); median time from first HCT was 8 months (range, 4 to 18.5 months). The conditioning regimen consisted of cyclophosphamide/TBI/ATG (n = 8) or busulfan/cyclophosphamide/ATG (n = 3). The source of bone marrow was an unrelated donor in six, matched sibling in four, and mismatched related in one. Five of the 11 grafts were T cell depleted prior to infusion. Overall, 10 of 11 patients showed donor-derived engraftment, of whom three developed grade 3 to 4 acute GVHD. Five of 11 patients are surviving a median of 25 months (range, 2 months to 12 years) with an overall actuarial survival of 50% (95% CI, 27% to 93%) at 4 years. All five show sustained donor engraftment with normalization of IDU activity levels. Three of five evaluable patients demonstrated stabilization of neuropsychological function after second HCT. Currently, allogeneic donor-derived hematopoiesis provides the only chance for long-term survival and improved quality of life in Hurler patients. While graft failure in Hurler patients requires further investigation, a timely second HCT can be well-tolerated and beneficial.


Viral agents associated with infantile gastroenteritis in Nigeria: relative prevalence of adenovirus serotypes 40 and 41, astrovirus, and rotavirus serotypes 1 to 4.
Sixty-six stool specimens from infants with diarrhoea in Nigeria were examined for the presence of viral pathogens. Rotaviruses were found in 25.8% of specimens and astroviruses in 1.5%. Serotypes were determined for 47.1% of the rotavirus positive specimens, all of which were serotype 1. RNA analysis revealed no unusual electrophoretic profiles. No enteric adenoviruses were detected. In contrast, in a parallel study conducted in the UK, rotaviruses (including serotypes 1, 2 and 4) accounted for 21.9% of infections, adenovirus serotypes 40 and 41 13.6%, and astroviruses 4.5%.


Dihydroartemisinin and its anticancer activity against endometrial carcinoma and cervical cancer: involvement of apoptosis, autophagy and transferrin receptor.
Dihydroartemisinin (DHA) is a first-line antimalarial drug with relatively low toxicity. DHA has been speculated to possess a broad-spectrum antitumour effect. However, the potential value of DHA for the treatment of endometrial carcinoma or cervical cancer is unclear. We used human endometrial cancer cells and cervical cancer cells to assess whether DHA alone or when combined with cisplatin would induce cell death. We aimed to elucidate the role of autophagy in DHA-induced cytotoxicity in both endometrial and cervical cancer cells, and explore the impact of DHA treatment on cell proliferation, apoptosis and autophagy. DHA alone or in combination with cisplatin induced cell death in a dose- and time-dependent manner. Caspase-3 mRNA and cleaved caspase-3 protein levels were markedly elevated following DHA treatment either in the presence or absence of cisplatin, suggesting a role of apoptosis in DHA-induced cell death. DHA treatment activated the autophagic pathway, as evidenced by increased monodansylcadaverine-positive staining, elevated microtubule-associated protein 1 light chain 3 (LC3)-II/LC3-I ratio, and enhanced p62/sequestosome 1 degradation. Inhibition of autophagy by 3-methyladenine further enhanced the cytotoxicity of DHA towards tumour cells. mRNA levels of transferrin receptor (TfR) were suppressed upon DHA treatment and knockdown of TfR by RNA interference caused further DHA induction of cancer cell death. Our results suggest a clinical value for DHA in the treatment of endometrial carcinoma and cervical cancer. Our data revealed possible anticancer mechanisms of DHA that involve regulating apoptosis, autophagy pathway and levels of TfR.


Dual nuclease activity of a Cas2 protein in CRISPR-Cas subtype I-B of Leptospira interrogans.
Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130 carries a set of cas genes associated with CRISPR-Cas subtype I-B. Herein, we report for the first time active transcription of a set of cas genes (cas1 to cas8) of L. interrogans where cas4, cas1, cas2 and cas6, cas3, cas8, cas7, cas5 are clustered together in two independent operons. As an initial step toward comprehensive understanding of CRISPR-Cas system in spirochete, the biochemical study of one of the core Leptospira Cas2 proteins (Lep_Cas2) showed nuclease activity on both DNA and RNA in a nonspecific manner. Additionally, unlike other known Cas2 proteins, Lep_Cas2 showed metal-independent RNase activity and preferential activity on RNA over DNA. These results provide insight for understanding Cas2 diversity existing in the prokaryotic adaptive immune system.


Substituted 2-oxiranecarboxylic acids: a new group of candidate hypoglycaemic drugs.
Drugs to treat diabetes that can be taken orally have long been sought, although the successful management of insulin-dependent diabetes mellitus by simple chemotherapy may be an unachievable goal. The only drugs currently used for the treatment of non-insulin-dependent diabetes have limited effectiveness. In this article Peter Selby and Stanley Sherratt describe the development of a new group of candidate hypoglycaemic drugs, esters of substituted 2-oxiranecarboxylic acids, which merit full clinical evaluation. These drugs are hydrolysed to the free acids which are then converted to their coenzyme A esters in cells. The CoA esters inactivate carnitine palmitoyltransferase I in the outer mitochondrial membrane, thus preventing the excessive oxidation of long-chain fatty acids that occurs in diabetes. This causes a secondary decrease in hepatic gluconeogenesis and an increase in peripheral glucose utilization leading to improved glucose tolerance.


Mannose-binding lectin haplotypes influence Brucella abortus infection in the water buffalo (Bubalus bubalis).
A case-control study established that the haplotype pair HYA/HYA at the MBL (mannose binding lectin) locus of water buffalo is associated with resistance to Brucella abortus infection (P < 10(-7)) and the haplotype pairs LYD/LYD with susceptibility to the same pathogen (P < 10(-7)). The subjects included in the present study were tested twice-at a 1-month interval-for the presence of anti-B. abortus antibodies in the serum by agglutination, complement fixation and flow cytometry. Cases (335 subjects) included animals consistently positive to all these tests; controls (335 subjects) comprised animals exposed yet negative by the same tests. The serum from genetically resistant subjects displayed in vitro significantly higher antibacterial activity compared to the serum from genetically susceptible subjects, lending biological significance to the results from the association study. Inhibition of the antibacterial activity following heat treatment of the serum, addition of specific MBL inhibitors (EDTA, mannose, N-acetyl-D: -glucosamine) or anti-human MBL antiserum provide convincing evidence that the antibacterial activity present in the serum results from the interaction between MBL and B. abortus. A replication study (comprising 100 cases and 100 controls) confirmed the results from the original study.


Influence of CYP3A5 genetic variation on everolimus maintenance dosing after cardiac transplantation.
Everolimus (ERL) has become an alternative to calcineurin inhibitors (CNIs) due to its renal-sparing properties, especially in heart transplant (HTx) recipients with kidney dysfunction. However, ERL dosing is challenging due to its narrow therapeutic window combined with high interindividual pharmacokinetic variability. Our aim was to evaluate the effect of clinical and genetic factors on ERL dosing in a pilot cohort of 37 HTx recipients. Variants in CYP3A5, CYP3A4, CYP2C8, POR, NR1I2, and ABCB1 were genotyped, and clinical data were retrieved from patient charts. While ERL trough concentration (C0 ) was within the targeted range for most patients, over 30-fold variability in the dose-adjusted ERL C0 was observed. Regression analysis revealed a significant effect of the non-functional CYP3A5*3 variant on the dose-adjusted ERL C0 (p = 0.031). ERL dose requirement was 0.02 mg/kg/d higher in patients with CYP3A5*1/*3 genotype compared to patients with CYP3A5*3/*3 to reach the targeted C0 (p = 0.041). ERL therapy substantially improved estimated glomerular filtration rate (28.6 ± 6.6 mL/min/1.73 m(2)) in patients with baseline kidney dysfunction. Everolimus pharmacokinetics in HTx recipients is highly variable. Our preliminary data on patients on a CNI-free therapy regimen suggest that CYP3A5 genetic variation may contribute to this variability.


Influence of certain herbicides and a forest fertilizer on the nitrogen fixation by the lichen Peltigera praetextata.
Effects of herbicides (Garlone 3A, MCPA, 2,4-D and Krenite) and nitrogen fertilizer (NH4NO3), commonly used in Swedish forestry, on nitrogen fixation (C2H2-reduction) by Peltigera praetextata (Sommerf.) Zopf. (field and laboratory) and its phycobiont Nostoc sp. (laboratory) were studied. The alga was affected by the herbicides 2,4-D and Krenite and the fertilizer, with a decrease in nitrogenase activity. Nitrogen fixation by the lichen was not affected by herbicides but treatment with NH4NO3 led to depression of nitrogenase activity and serious disturbance of the symbiosis, the latter effect due to the fertilizer's lethal effects on the mycobiont (electron microscopy).


Mitosis counting in seminoma: an exercise of questionable significance.
Two pathologists reviewed and classified 45 cases of testicular seminoma, evaluating each case for multiple histologic variables, including mitotic rate. In addition to recording the mitotic count for each of thirty 0.1963-mm2 high-power fields, the investigators recorded the distribution of mitotic counts in many non-spermatocytic seminomas. Statistically significant differences for mitotic rate in the nonspermatocytic tumors were noted between the observers; one observer found a mean mitotic rate of 1.815/high-power field for 43 such tumors, whereas the other noted a mean mitotic rate of 1.388/high-power field (p = 0.001). These differences led to disagreement on the classification of 3 tumors. Of the 4 cases considered to be high-mitotic-rate seminomas by one or both observers, all patients had presented with stage I disease. Three of the patients were followed up for 23, 55, and 56 months, and all were free of disease; the fourth was lost to follow-up. The patient with the highest mitotic rate was free of disease at 55 months of follow-up. On the basis of our findings we question the value of the designation high-mitotic-rate seminoma. Analysis of the distribution of mitotic counts within the tumors revealed them to be Poisson distributed. With these data and other empirically derived data, it was possible to estimate the probability of misclassification of seminoma based on mitotic rate, the diagnostic mitotic rate threshold, and the number of fields counted for mitoses. Similar analysis might be valuable for other tumors, particularly those of smooth muscle origin, in which mitotic rate is of diagnostic or prognostic value.


Species composition and ecological structure of ground beetles (Coleoptera, Carabidae) communities as biological indicators of the agro-environmental sustainability.
Intensification of crop cultivation can have detrimental environmental consequences that however can be prevented by monitoring of the specific biological indicators sensitive to changes in the ambient environment. In this study the impact of crop type (spring wheat and corn) and cultivation intensity on the community of ground beetles (Coleoptera: Carabidae) in the forest-steppe of Western Siberia was investigated. A total of 39 species from 15 genera were collected. Ground beetles' community was characterized by a high evenness of species distribution across the agroecosystems. The average Jaccard's similarity index for species presence/absence was 65%, and for abundance it was 54%. The significant difference in the distribution of predatory and mixophytophages ground beetles in wheat crops (U test, P < 0.05) can be justified by the constant suppression of the weed component and the use of insecticides that lead to the dominance of the predators. Fauna of wheat crops was more diverse than that in corn (Margalef index, U test, P < 0.05). No significant differences in biological diversity indexes, except for the Simpson dominance index (U test, P < 0.05, wheat), were found in ground beetle communities in crops at different levels of intensification. A certain differentiation of predatory species was caused by the selective occurrence of the litter-soil species, especially abundant in the row-crop. The specificity of the ground beetle community of corn crops may have been caused by repeated inter-row tillage, which influenced the increase in porosity and topsoil relief and contributed to the creation of favorable microclimatic conditions. In general, the applied level of agrotechnological intensification had no significant effect on the species composition and ecological structure of beetle communities in agrolandscapes. The use of bioindicators made it possible to assess the environmental sustainability of the agricultural environment and also creates the prerequisites for the development of ecologically directed correction of agrotechnological operations in agroecosystem management.


Difference in Efficacy and Safety of Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy Containing 4-1BB and CD28 Co-Stimulatory Domains for B-Cell Acute Lymphoblastic Leukemia.
This study quantified the differences in the efficacy and safety of different stimulation domains of anti-CD19 chimeric antigen receptor (CAR) T therapy for B-cell acute lymphoblastic leukemia (B-ALL). Clinical trials related to anti-CD19 CAR T-cell therapy for B-ALL were searched in public databases from database inception to 13 November 2021. The differences in overall survival (OS) and progression-free survival (PFS) of B-ALL patients treated with anti-CAR T-cell therapy containing 4-1BB and CD28 co-stimulatory domains were compared by establishing a parametric survival function. The overall remission rate (ORR), the proportion of people with minimal residual disease (MRD)-negative complete remission (CR), the incidence of cytokine release syndrome (CRS), and the neurotoxicity across different co-stimulatory domains was assessed using a random-effects model. The correlation between the ORR, MRD-negative CR, PFS, and OS was tested. The results showed that the median OS of anti-CAR T-cell treatment containing 4-1BB and CD28 co-stimulatory domains was 15.0 months (95% CI: 11.0-20.0) and 8.5 months (95% CI: 5.0-14.0), and the median PFS was 7.0 months (95% CI: 4.0-11.5) and 3.0 months (95% CI: 1.5-7.0), respectively. Anti-CD19 CAR T-cells in the 4-1BB co-stimulatory domain showed superior benefits in patients who achieved ORR. The incidence of neurotoxicity was significantly higher in the CD28 co-stimulatory domain of anti-CD19 CAR T-cells than in the 4-1BB co-stimulatory domain. In addition, the ORR and MRD-negative CR were strongly correlated with OS and PFS, and PFS and OS were strongly correlated. The 4-1BB co-stimulatory domain suggested a better benefit-risk ratio than the CD28 co-stimulatory domain in B-ALL.


Improvement of biomass properties by pretreatment with ionic liquids for bioconversion process.
Cassava pulp residue and rice straw were used as a precursor for pretreatment with ionic liquids to study the effects of pretreatment conditions on product yield and properties. Cassava pulp residue is a potential biomass in the bioconversion process due to it requiring mild pretreatment conditions while providing a high sugar conversion. The maximum sugar conversion and lignin extraction are attained from pretreatment of biomasses with particle size of <38 μm and ionic liquid of 1-Ethyl-3-methylimidazolium acetate at 120°C for 24h. The effectiveness of ionic liquid for biomass pretreatment process follows the sequence: 1-Ethyl-3-methylimidazolium acetate>1-Ethyl-3-methylimidazolium diethyl phosphate>1,3-Dimethylimidazolium methyl sulfate. The increase of pretreatment temperature from 25 to 120°C and decrease of biomass particle size renders higher sugar conversion, lignin extraction and lower crystallinity index. However, pretreatment at temperatures higher than 120°C shows a sharp decline of regenerated biomass yield, sugar conversion and lignin extraction and giving higher crystallinity index at pretreatment temperature of 180°C.


Well-Defined, Molecular Bismuth Compounds: Catalysts in Photochemically Induced Radical Dehydrocoupling Reactions.
A series of diorgano(bismuth)chalcogenides, [Bi(di-aryl)EPh], has been synthesised and fully characterised (E=S, Se, Te). These molecular bismuth complexes have been exploited in homogeneous photochemically-induced radical catalysis, using the coupling of silanes with TEMPO as a model reaction (TEMPO=(tetramethyl-piperidin-1-yl)-oxyl). Their catalytic properties are complementary or superior to those of known catalysts for these coupling reactions. Catalytically competent intermediates of the reaction have been identified. Applied analytical techniques include NMR, UV/Vis, and EPR spectroscopy, mass spectrometry, single-crystal X-ray diffraction analysis, and (TD)-DFT calculations.


A familial predisposition in bronchial hyperresponsiveness among patients with allergic rhinitis.
Nonasthmatic subjects with allergic rhinitis often have bronchial hyperresponsiveness (BHR). The mechanisms responsible for BHR in asthma include genetic predisposition and airway inflammation, but the causes of BHR in allergic rhinitis are poorly understood. The aim of this study was to investigate whether there is a familial predisposition in allergic rhinitis-associated BHR. One hundred fifteen children with allergic rhinitis (probands) and their family members underwent methacholine bronchial challenge and skin prick tests with airborne allergens. The probands were divided into 2 groups: BHR(+) (methacholine PC20 <18 mg/mL determined by the dosimeter method; n = 42) and BHR(-) (n = 73). The overall prevalence of BHR was higher in family members of BHR(+) probands than in those of BHR(-) probands (23.3% [27 of 116] vs 10.5% [21 of 200], P <.01). In mothers, this difference was marked (21.4% vs 8.2%, P <.05); a similar trend was observed in fathers (16.7% vs 6.8%) and siblings (34.4% vs 18.5%), although the differences did not reach significance (.05 < P <.1). The bronchial responsiveness index (BR index), a continuous variable derived from the results of methacholine challenge, was significantly higher among family members of the BHR(+) group than those of the BHR(-) group. Furthermore, even when only family members without BHR were considered, the BR index was significantly higher among those (n = 89) of the BHR(+) group than those (n = 179) of the BHR(-) group. There was no difference in atopic status as assessed by the prevalence of atopy (or atopy index) between family members of the BHR(+) group and the BHR(-) group. Our results indicated that there is a significant familial predisposition for BHR among patients with allergic rhinitis. Further studies are needed to elucidate whether genetic factors play a role in allergic rhinitis-associated BHR.


Cytokinin and Metabolites Affect Rhizome Growth and Development in Kentucky Bluegrass (Poa pratensis).
Rhizome growth and development is regulated by phytohormone. However, endogenous phytohormones affect rhizome initiation, and sustained growth in perennial grass species remains elusive. In this study, we investigated the morphological characteristics and the content of indole-3-acetic acid (IAA), zeatin (ZT), gibberellic acid (GA3), and abscisic acid (ABA) in the rhizomes of two different Kentucky bluegrass. Using ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS), we performed metabolite analysis of two different rhizomes. In our study, the multi-rhizome Kentucky bluegrass material 'Yuzhong' had an average of 1113 rhizomes, while the few-rhizome material 'Anding' had an average of 347 rhizomes. The diameter of rhizome and length of rhizome internode in 'Yuzhong' were 1.68-fold and 1.33-fold higher than that of the 'Anding', respectively. The rhizome dry weight of 'Yuzhong' was 75.06 g, while the 'Anding' was 20.79 g. 'Yuzhong' had a higher ZT content (5.50 μg·g-1), which is 2.4-fold that of 'Anding' (2.27 μg·g-1). In contrast, the IAA, ABA, and GA3 content of rhizome were markedly higher in 'Anding' than 'Yuzhong'. Correlation analysis revealed significant correlations between ZT and ZT/ABA with the number of rhizomes, diameter of rhizome, and length of rhizome internode, whereas IAA, ABA, GA3, and IAA/ZT were opposite. In the metabolic profiles, we identified 163 differentially expressed metabolites (DEMs) (60 upregulated and 103 downregulated) in positive ion mode and 75 DEMs (36 upregulated and 39 downregulated) in negative ion mode. Histidine metabolism and ABC transporters pathways were the most significantly enriched in the positive and negative ion mode, respectively, both of which are involved in the synthesis and transport of cytokinin. These results indicate that cytokinin is crucial for rhizome development and promotes rhizome germination and growth of Kentucky bluegrass.