Analysis of cellular and cell free mitochondrial DNA content and reactive oxygen species levels in maternal blood during normal pregnancy: a pilot study.
Alterations in mitochondrial signatures such as mitochondrial DNA (mtDNA) content in maternal blood have been linked to pregnancy-related complications. However, changes in maternal mtDNA content, their distribution and associated signaling during normal pregnancies are not clear; which could suggest their physiological role in maternal adaptation to pregnancy related changes and a reference threshold. to assess the distribution of mtDNA in peripheral blood and their association with circulatory ROS levels across different trimesters of healthy pregnancy. In this pilot cross sectional study, blood samples of normal pregnant women from each trimester (total = 60) and age-matched non-pregnant (NP) women as control group (n = 20) were analyzed for a) the relative distribution of mtDNA content in cellular and cell free (plasma) fractions using relative quantitative polymerase chain reaction (qPCR) and b) the levels of circulating reactive oxygen species (ROS) by measurement of plasma H2O2. The results were compared between pregnant and NP groups and within trimesters for significant differences, and were also analyzed for their correlation between groups using statistical methods. While, we observed a significant decline in cellular mtDNA; plasma mtDNA was significant increased across all trimesters compared to NP. However, from comparisons within trimesters; only cellular mtDNA content in 3rd trimester was significantly reduced compared to 1st trimester, and plasma mtDNA did not differ significantly among different trimesters. A significantly higher level of plasma H2O2 was also observed during 3rd trimester compared to NP and to 1st trimester. Correlation analysis showed that, while cellular mtDNA content was negatively correlated to plasma mtDNA and to plasma H2O2 levels; plasma mtDNA was positively correlated with plasma H2O2 content. This study suggested that normal pregnancy is associated with an opposing trend of reduced cellular mtDNA with increased circulatory mtDNA and H2O2 levels, which may contribute to maternal adaptation, required during different stages of pregnancy. Estimation of mtDNA distribution and ROS level in maternal blood could show mitochondrial functionality during normal pregnancy, and could be exploited to identify their prognostic/ diagnostic potential in pregnancy complications.


Enhancement of the enantioselectivity of carboxylesterase A by structure-based mutagenesis.
Previously studied Bacillus subtilis carboxylesterases (CesA and CesB) have potential for the kinetic resolution of racemic esters of 1,2-O-isopropylideneglycerol (IPG). CesA exhibits high activity but low enantioselectivity towards IPG-butyrate and IPG-caprylate, while the more enantioselective CesB does not process IPG-butyrate and exhibits several-fold lower activity than CesA towards IPG-caprylate. A sequence and structure comparison allowed us to identify active site residues that may cause the difference in (enantio)selectivities of CesA and CesB towards these IPG esters. This structure-based approach led to the identification of two active site residues in CesA (F166 and F182), as promising candidates for mutagenesis in order to enhance its enantioselectivity. Mutagenesis of positions 166 and 182 in CesA yielded novel variants with enhanced enantioselectivity and without significant loss of catalytic activity. For IPG-butyrate, a CesA double mutant F166V/F182C (ER=13) was generated showing a ∼13-fold increased enantioselectivity as compared to wild-type CesA (E=1). For IPG-caprylate, we designed a CesA double mutant F166V/F182Y (ER=9) displaying a ∼5-fold increased enantioselectivity as compared to the wild-type enzyme (ER=2). These findings, combined with the results of molecular docking experiments, demonstrate the importance of residues at positions 166 and 182 for the enantioselectivity of CesA, and may contribute to the development of efficient biocatalysts.


Phenotypic Profiling and Molecular Mechanisms in Hyperparathyroidism-jaw Tumor Syndrome.
Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a heritable form of primary hyperparathyroidism caused by germline inactivating mutations in CDC73 encoding parafibromin and is associated with an increased risk of parathyroid cancer. There is little evidence to guide the management of patients with the disease. (1) Characterize the natural history of HPT-JT, (2) correlate genotype and histology of parathyroid tumors with parafibromin immunostaining, (3) understand molecular changes downstream to CDC73 loss. Retrospective study of patients with HPT-JT syndrome (genetically confirmed or affected first-degree relatives). Independent review of uterine tumor from 2 patients and staining for parafibromin on parathyroid tumors from 19 patients (13 adenomas, 6 carcinomas) was performed. RNA-sequencing was performed in 21 parathyroid samples (8 HPT-JT-related adenomas, 6 HPT-JT-related carcinomas, and 7 sporadic carcinomas with wild-type CDC73). We identified 68 patients from 29 kindreds with HPT-JT with median age at last follow-up of 39 [interquartile range, 29-53] years. A total of 55/68 (81%) developed primary hyperparathyroidism; 17/55 (31%) had parathyroid carcinoma. Twelve of 32 (38%) females developed uterine tumors. Of the 11 patients who had surgical resection for uterine tumors, 12/24 (50%) tumors were rare mixed epithelial mesenchymal polypoid lesions. Four of 68 patients (6%) developed solid kidney tumors; 3/4 had a CDC73 variant at p.M1 residue. Parafibromin staining of parathyroid tumors did not correlate with tumor histology or genotype. RNA-sequencing showed a significant association of HPT-JT-related parathyroid tumors with transmembrane receptor protein tyrosine kinase signaling pathway, mesodermal commitment pathway, and cell-cell adhesion. Multiple, recurrent atypical adenomyomatous uterine polyps appear to be enriched in women with HPT-JT and appear characteristic of the disease. Patients with CDC73 variants at p.M1 residue appear predisposed to kidney tumors. NCT04969926.


Bat-associated histoplasmosis can be transmitted at entrances of bat caves and not only inside the caves.
Our observation of histoplasmosis cases augments the current knowledge on transmission by bats. In the presented cases, the only contact happened in the proximity of a bat cave but not inside the cave. We wish to communicate and stress that even outside of caves, bats may disperse the organism.


Evaluation of immune markers in asymptomatic AIDS patients receiving fish oil supplementation.
The effects of oral fish oil (FO) supplementation (8 g/day, capsules) on nutritional status and selected immune markers (CD4/CD8 ratio, IL-1beta, erythrocyte MDA release, dehydroepiandrosterone sulfate [DHEA-S]) were studied in a homogeneous group of asymptomatic HIV-infected patients during 6 weeks. All subjects were classified clinically as A2 according to the CDC revised criteria (mean CD4 count 290 +/-123 cells/mm(3)) and were receiving zidovudine retroviral treatment. The calculated mean energy intake was 3437 +/- 372 Kcal/d, composed of 14% protein, 38% lipids and 48% carbohydrates, and was not modified during the study. The anthropometric parameters, and hematological and plasma biochemistry data showed non-significant changes after FO supplementation. Mean malonyldialdehyde (MDA) release before treatment was: unstimulated 71.5 +/- 37 and stimulated 350.9 +/- 79.8 nmol/g Hb. After FO supplementation (T(6)) MDA release showed unstimulated values of 96.1 +/- 62, and a significant increase after stimulation of 614.1 106.4 nmol/g Hb, which was, however, within the normal range. In the patient's samples, IL-1beta levels in the unstimulated blood culture showed a statistical increase with respect to the normal range before (T(0)) and after (T(6)) FO supplementation with a slight decrease after (mean 49.8 vs 40.9 pg/ml). The stimulated IL-1beta levels after treatment showed a statistically significant decrease that was maintained within the normal range (T(0): 797.7 vs T(6): 535.6 pg/ml). Taken collectively, these results suggest a tendency toward improvement in immune function.


Molecular evaluation of thrombosis using X-ray phase contrast imaging with microbubbles targeted to P-selectin in mice.
X-ray phase contrast imaging (PCI) provides excellent image contrast by utilizing the phase shift. The introduction of microbubbles into tissues can cause a phase shift to make microbubbles visibly identified on PCI. In this study, we assessed the feasibility of targeted microbubble-based PCI for the detection of thrombosis. The absorption and phase contrast images of P-selectin-targeted microbubbles (MBP) were obtained and compared in vitro. MBP, control IgG-targeted microbubbles (MBC), and unbound microbubbles (MBU) were tested for binding specificity on thrombi expressing P-selectin. MBP were used as molecular PCI probes to evaluate P-selectin expression in a mouse model of arteriovenous shunt thrombosis that was created using PE tubes in the bypass outside of the mouse body. PCI clearly showed the microbubbles not viewable via absorption contrast imaging (ACI). In vitro attachment of MBP (91.60 ± 11.63) to thrombi was significantly higher than attachment of MBC (17.80 ± 4.02, P < 0.001) or MBU (9.80 ± 2.59, P < 0.001). In the mouse model of arteriovenous shunt thrombosis, the binding affinity of MBP (15.50 ± 6.25) was significantly greater than that of MBC (0.50 ± 0.84, P < 0.001) or MBU (0.33 ± 0.52, P < 0.001). Our results indicate that molecular PCI may be considered as a novel and promising imaging modality for the investigation of thrombosis. • Small thrombi are rarely detected by conventional radiography. • Phase contrast imaging (PCI) provides higher contrast and spatial resolution than conventional radiography. • P-selectin targeted microbubbles detected by PCI may suggest early thrombosis.


There are two forms of androgen binding protein in human testes. Comparison of their protomeric variants with serum testosterone-estradiol binding globulin.
To determine how the androgen binding protein in human testes (hABP) is related to the serum protein, testosterone-estradiol binding globulin (hTeBG), both proteins were isolated and compared. The hABP in extracts of human testes was composed of two molecular species based on concanavalin A (ConA)-Sepharose chromatography. Form I hABP did not interact with ConA while Form II hABP bound to ConA and eluted with alpha-methylmannoside. Form I and Form II hABP from five batches of testes were then purified approximately 30,500- and 30,000-fold to apparent homogeneity by high-performance liquid chromatography and compared with hTeBG isolated from human pregnancy serum. Fractionation of both forms of hABP and hTeBG by polyacrylamide gel electrophoresis in the absence of sodium dodecyl sulfate suggested that the native forms of these proteins were indistinguishable. However, analysis of the purified proteins on sodium dodecyl sulfate-containing polyacrylamide gels indicated that all three were dimers and that each was composed of monomers of at least two sizes which were not present in equimolar concentrations. Two distinctive monomers or protomers of each protein were designated as heavy (H) and light (L) according to their electrophoretic mobilities on sodium dodecyl sulfate-polyacrylamide gels. The H and L protomers of Form I hABP showed apparent molecular weights of 55,000 and 52,000, respectively, in all preparations and were usually present in a 4:5 ratio (H:L). The two components of Form II hABP had apparent molecular weights of 53,000 and 48,000, respectively, and existed in a ratio of approximately 20:1. These two components could not be distinguished in some preparations where Form II hABP migrated as a broad band rather than as distinct protomers. By contrast, hTeBG, which was similar to Form II hABP with respect to ConA binding, always exhibited discrete H and L protomers in a 10:1 ratio. Photolysis of these highly purified proteins with delta 6-[3H]testosterone resulted in specific covalent labeling of their binding sites, confirming that the products identified by silver staining and immunoblotting were indeed steroid binding proteins. The H and L protomers of Form I hABP and hTeBG were separated and examined by peptide mapping using Staphylococcus aureus protease V8 and chymotrypsin. The comparison of the respective fragmentation patterns of protomers indicated that Form I hABP and hTeBG contained distinctive peptides.(ABSTRACT TRUNCATED AT 400 WORDS)


Online colloidal particle monitoring for controlled coagulation pretreatment to lower microfiltration membrane fouling at a potable water reuse facility.
Fouling of microfiltration (MF)) membranes during water/wastewater treatment is predominantly caused by colloidal particles (size <1 µm) in the feed water. Until recently no online technology was available to directly measure the occurrence of colloidal particles in these waters. This study evaluated the viability of a novel online light scattering technology (Nanoparticle Tracking Analysis) to continuously monitor colloidal particles in the membrane feed water (a secondary-treated wastewater) for targeted removal by injecting coagulant at a dosage proportional to the measured concentration of colloidal particles. A diurnal variation was observed in the colloidal particle concentration in the feed water with the lowest concentration occurring at approximately 6 am and the highest concentration occurring after mid-day. The peak colloidal particle concentrations were 4 to 6 times higher than the lowest concentrations measured on the same day. Bench-scale studies were performed to develop a relationship between colloidal particle concentration and the optimum coagulant dosage required for their removal. Subsequently, a pilot-scale study was performed using two MF pilot units operated in parallel, one receiving targeted coagulant dosing and the other with no coagulant dosing, to demonstrate the effectiveness of targeted coagulant dosing in preventing membrane fouling. The pilot unit that received targeted coagulant dose experienced only 4 to 20% of the transmembrane pressure increase of the increase experienced by the pilot unit that received no coagulant. Evaluation of fouling resistance indicated that targeted coagulation improved flux by predominantly lowering the irreversible fouling. The filtrate water quality measured by colloidal particle concentration, chemical oxygen demand (COD), and turbidity were very similar for the two pilot units. This suggests that although the efficiency of particle and organic materials removal does not change with coagulant addition, the particles filtered by the membrane in the control unit contributed to membrane irreversible fouling, while in the coagulant-treated unit, the coagulated colloidal particles were removed away from the membrane into the backwash stream during the frequent backwash/air scour procedures.


Immunological detection and definition of minimal residual neuroblastoma disease in bone marrow samples obtained during or after therapy.
Immunological staining by the alkaline phosphatase/anti-alkaline phosphatase (APAAP) technique has been used to recognize low levels of neuroblastoma cells in bone marrow mononuclear cells. Immunological phenotyping with 11 well characterized monoclonal antibodies was performed on 16 children with neuroblastoma and BM involvement during or after therapy. Neuroblasts were detected in 11 of 16 patients (0.1-5%), whereas BM biopsies on six of these patients were classified as normal. Aspirates, stained conventionally, were positive for pathological cells in three patients only. The comparison of the phenotype of the neuroblastoma cells at the time of diagnosis to the phenotype of the residual cells within one patient revealed differences. The phenotype of residual disease in different patients on the other hand showed a unique pattern. The above mentioned results lead to the conclusion that the immunological procedure is particularly suitable for the analysis of minimal residual neuroblastoma since the technique allows very minor cell populations to be identified in BM samples.


Survey of human enterovirus occurrence in fresh and marine surface waters on Long Island.
A variety of surface water systems, including a lake, a creek, and two marine embayments, were analyzed on a monthly basis for indigenous human enteroviruses and coliform bacteria. Findings are discussed in terms of the probable pollution sources to each system and their relationship to data from previous studies.


Oxidation-reduction reactions of copper-thiolate centres in Cu-thionein.
Cu-thionein from yeast was investigated by EPR spectroscopy to probe the oxidation state of copper, and the effects on it of oxidizing and reducing agents. At pH 0.2 the copper was released, but no EPR signal from Cu(II) was observed, unless air was present. Optical experiments did not detect any disulphide groups which might have been formed during anaerobic release of copper. The mercurial, p-hydroxymercuribenzoate caused the release of EPR-detectable copper only under aerobic conditions, and EDTA caused release of Cu(II) on heating. No reduction of the copper-thiolate units in Cu-thionein by ascorbate was detected. Potentiometric titrations with hexachloroiridate(IV) or hexacyanoferrate(III) produced several different Cu(II) EPR signals at various stages of oxidation. The former oxidizing agent required a lower oxidation-reduction potential (+350 mV) to oxidize the copper, than the latter (+410 mV) and neither titration was fully reversible. The EPR signal from Cu(II) oxidized by hexachloroiridate(IV) resembled that produced by p-hydroxy-mercuribenzoate in air, suggesting that the copper was released from its thiolate ligands. It is concluded that the EPR non-detectable copper in the native protein is Cu(I). Oxidation-reduction of the copper-thiolate clusters of Cu-thionein is proposed to be decisive for controlling storage and transport of cellular copper.


Cardiac channelopathy causing sudden death as revealed by molecular autopsy.
Mutations in cardiac ion channel genes have been identified to cause sudden unexplained deaths (SUD), and polymorphisms have also been suggested to be risk factors. Therefore, postmortem genetic testing has become an important tool in elucidating the cause of death. In a sudden death case, a LQT-3-associated mutation (Il768V) in the cardiac sodium channel gene SCN5A was detected beside the common polymorphism H558R which is known to mitigate the effect of mutations in the gene. Both sequence variations were heterozygous. Large number of intervening base pairs make it impossible to identify whether they were located in cis or trans. Functional consequences of both variants were characterized after expressing different cRNAs in Xenopus oocytes by voltage clamp measurements. Western blot analysis indicates that the cis configuration of both variants may lead to a null allele. Since the woman had received an injection of Ultracain®, the potential effect of this drug was tested. In a trans configuration of both variants, the mutant channel exhibited an increase susceptibility of at least 10% for blocking with the drug articaine. Another novel finding is that the midpoint of activation in the case of the mutant channel is leftward shifted of at least -10 mV. The results of the study suggest that postmortem molecular screening is an important tool to elucidate the cause of SUD and that the administration of a drug and a functional interaction between polymorphisms and ion channel mutations may trigger the risk for sudden death.


Psychiatric symptoms and pain in maxillofacial injury following motor vehicle accidents: A comparative study.
Post-traumatic stress disorders, depression, and pain are rarely discussed in the literature on maxillofacial injuries, and psychiatric symptoms and pain are not identified and managed in such patients. The aim of this study was to determine the symptoms of post-traumatic stress disorders, depression, and pain in people with maxillofacial injuries following motor vehicle accidents. In this cross-sectional study, people injured in motor vehicle accidents from March to September 2015 who were referred to a medical educational center in the northern part of Iran for treatment follow-up were sampled. The existing symptoms of post-traumatic stress disorder by PSS, depression by BDI-II, and pain by NRS were assessed. SPSS software version 21 was used for analysis. Maxillofacial injured patients had significant differences in terms of post-traumatic stress disorder (p = .006), depression (p = .001), pain (p = .001), and length of hospital stay (p = .002) than patients without maxillofacial injuries. Motor vehicle accident victims with maxillofacial injuries suffered significantly more from post-traumatic stress disorders and depression, pain and length of hospital stay than patients with other injuries.


Comparisons of Medical Cost Trajectories Between Non-Hispanic Black and Non-Hispanic White Patients With Newly Diagnosed Localized Prostate Cancer.
This study applied a recently developed statistical method to compare the mean cost trajectories between non-Hispanic White (NHW) and non-Hispanic Black (NHB) patients with localized prostate cancer conditioning on patients' survival. In this observational study, we modeled cost trajectories of NHW and NHB patients with localized prostate cancer for 3 survival durations: 24, 48, and 72 months. We also compared the cost trajectories between NHW and NHB, stratified by comorbidities scores. We find that the mean cost trajectories of NHB were significantly higher than the trajectories of NHW in the last 12 months before death, regardless of the survival duration and patients' baseline comorbidity scores. For patients with comorbidity score ≥2, mean cost trajectories within the first year of diagnosis for NHB were significantly higher than those for NHW, except for the subgroup of patients with comorbidity 2-3 and whose survival length was 72 months. Our results suggested that a higher proportion of NHB patients with high comorbidity scores are likely contribute to their higher end-of-life costs than those for NHW patients. To narrow the gap in healthcare-related financial burden between NHB and NHW patients with localized prostate cancer, policy makers need to explore different strategies to better manage comorbidities.


Ba3 (BO3 )(CO3 )F: The First Borate Carbonate Fluoride Synthesized by the High-Temperature Solution Method.
In contrast to the well-investigated halogen-containing borates and carbonates, very few halogen-containing borate carbonate compounds have been reported. Specifically, no example of borate carbonate fluoride has been synthesized successfully until now. Herein, the planar π-conjugated units [BO3 ]3- and [CO3 ]2- and the F- ions are introduced simultaneously into one crystal structure resulting in the first borate carbonate fluoride, Ba3 (BO3 )(CO3 )F, by the high-temperature solution method in the atmosphere. Its structure features a hexagonal channel formed by the [BO3 ]3- and [CO3 ]2- units with the [F3 Ba8 ]13+ trimers filled in the channel. Various characterizations including single crystal- and powder-XRD, EDX, IR, UV-vis-NIR, and TG-DSC, together with the first principles calculation have been carried out to verify the structure and fully understand the structure-property relationships.


Arthroscopic resection of humeroradial synovial plica for persistent lateral elbow pain.
To review the outcome of 121 patients who underwent arthroscopic resection of a humeroradial synovial plica for persistent lateral elbow pain. 92 men and 29 women aged 24 to 56 (mean, 38) years with chronic lateral elbow pain underwent arthroscopic resection of a humeroradial synovial plica using a motorised soft tissue shaver, followed by intensive physiotherapy. The modified elbow score and range of motion were assessed, as were wound healing, infection, soft tissue swelling or effusion, tenderness, ligamentous instability, and motor strength. No patient had any ligamentous instability. 80 patients were pain-free at 3 months; only 3 patients were taking pain medication at 6 months. All patients had full pronation and supination; the mean range of motion was 3º to 135º of flexion. The mean modified elbow score at 12 months was 93.2 (range, 72-100). The percentages of patients with excellent, good, fair, and poor score were 70%, 17%, 8%, and 5% at 3 months, 74%, 20%, 3%, and 3% at 6 months, and 76%, 18%, 3%, and 3% at 12 months, respectively. A humeroradial synovial plica is one of the causes of chronic lateral elbow pain. Arthroscopic resection of the synovial plica followed by intensive physiotherapy achieved good outcome.


Transcriptome analysis of rosette and folding leaves in Chinese cabbage using high-throughput RNA sequencing.
In this study, we report the first use of RNA-sequencing to gain insight into the wide range of transcriptional events that are associated with leafy head development in Chinese cabbage. We generated 53.5 million sequence reads (90 bp in length) from the rosette and heading leaves. The sequence reads were aligned to the recently sequenced Chiifu genome and were analyzed to measure the gene expression levels, to detect alternative splicing events and novel transcripts, to determine the expression of single nucleotide polymorphisms, and to refine the annotated gene structures. The analysis of the global gene expression pattern suggests two important concepts, which govern leafy head formation. Firstly, some stimuli, such as carbohydrate levels, light intensity and endogenous hormones might play a critical role in regulating the leafy head formation. Secondly, the regulation of transcription factors, protein kinases and calcium may also be involved in this developmental process.


Abnormal prenatal brain development in Chiari II malformation.
The Chiari II is a relatively common birth defect that is associated with open spinal abnormalities and is characterized by caudal migration of the posterior fossa contents through the foramen magnum. The pathophysiology of Chiari II is not entirely known, and the neurobiological substrate beyond posterior fossa findings remains unexplored. We aimed to identify brain regions altered in Chiari II fetuses between 17 and 26 GW. We used in vivo structural T2-weighted MRIs of 31 fetuses (6 controls and 25 cases with Chiari II). The results of our study indicated altered development of diencephalon and proliferative zones (ventricular and subventricular zones) in fetuses with a Chiari II malformation compared to controls. Specifically, fetuses with Chiari II showed significantly smaller volumes of the diencephalon and significantly larger volumes of lateral ventricles and proliferative zones. We conclude that regional brain development should be taken into consideration when evaluating prenatal brain development in fetuses with Chiari II.


Generational changes in height and body mass differences between British Asians and the general population in Glasgow.
A weighted total of 630 pupils aged 14-15 in Glasgow schools, about evenly divided between pupils of South Asian and non-Asian (overwhelmingly British) background, were measured for height and weight and compared with previous results for a similar Glasgow sample aged 30-40. Among 14-15-year-olds, British Asians were not so short compared with non-Asians as among 30-40-year-olds, especially females. Among 30-40-year-old Glasgow Asians only 7% were born in the UK, while among 14-15-year-old Glasgow Asians 86% were so born, indicating that they are the children of migrants. Generational differences in these comparisons cannot be due to positive selection of the migrant generation for height, and are attributed to improved environment, including nutrition and public health measures. This suggests the possibility of corresponding improvements in coronary and diabetic risk.


Outcomes of HLA-B27-positive and HLA-B27-negative acute anterior uveitis.
Outcomes of HLA-B27-positive and HLA-B27-negative acute anterior uveitis were assessed after a mean follow-up of nine years. Rheumatologic complications, in particular the presence and course of ankylosing spondylitis, were examined during the same period. A hospital-based prospective study of 119 patients with HLA-B27-positive and 35 patients with HLA-B27-negative acute anterior uveitis was performed. All patients underwent a complete ophthalmologic and rheumatologic examination, including sacroiliac x-rays, and were examined again nine years later. No statistically significant differences in ocular complications and visual outcome were found between both patient groups with acute anterior uveitis after nine years. Posterior synechiae were observed in one half of the affected eyes. Blindness was infrequent. Rheumatologic complications, including ankylosing spondylitis, originally seen in one half of the HLA-B27-positive patients, were observed in two thirds of the patients nine years later, compared to only two of 35 HLA-B27-negative patients. When ankylosing spondylitis was evident at first examination no clinically significant deterioration was observed nine years later. After nine years we observed an ocular outcome equal for both patient groups. A small percentage of affected eyes became blind. Rheumatologic complications occurred in 55 (72%) of 76 HLA-B27-positive males and in 24 (56%) of 43 HLA-B27-positive females with acute anterior uveitis. The rheumatologic complications had a good prognosis.


The transcription factor ERG recruits CCR4-NOT to control mRNA decay and mitotic progression.
Control of mRNA levels, a fundamental aspect in the regulation of gene expression, is achieved through a balance between mRNA synthesis and decay. E26-related gene (Erg) proteins are canonical transcription factors whose previously described functions are confined to the control of mRNA synthesis. Here, we report that ERG also regulates gene expression by affecting mRNA stability and identify the molecular mechanisms underlying this function in human cells. ERG is recruited to mRNAs via interaction with the RNA-binding protein RBPMS, and it promotes mRNA decay by binding CNOT2, a component of the CCR4-NOT deadenylation complex. Transcriptome-wide mRNA stability analysis revealed that ERG controls the degradation of a subset of mRNAs highly connected to Aurora signaling, whose decay during S phase is necessary for mitotic progression. Our data indicate that control of gene expression by mammalian transcription factors may follow a more complex scheme than previously anticipated, integrating mRNA synthesis and degradation.


Ligand and receptor dynamics contribute to the mechanism of graded PPARγ agonism.
Ligand binding to proteins is not a static process, but rather involves a number of complex dynamic transitions. A flexible ligand can change conformation upon binding its target. The conformation and dynamics of a protein can change to facilitate ligand binding. The conformation of the ligand, however, is generally presumed to have one primary binding mode, shifting the protein conformational ensemble from one state to another. We report solution nuclear magnetic resonance (NMR) studies that reveal peroxisome proliferator-activated receptor γ (PPARγ) modulators can sample multiple binding modes manifesting in multiple receptor conformations in slow conformational exchange. Our NMR, hydrogen/deuterium exchange and docking studies reveal that ligand-induced receptor stabilization and binding mode occupancy correlate with the graded agonist response of the ligand. Our results suggest that ligand and receptor dynamics affect the graded transcriptional output of PPARγ modulators.


A metafluid with multistable density and internal energy states.
Investigating and tailoring the thermodynamic properties of different fluids is crucial to many fields. For example, the efficiency, operation range, and environmental safety of applications in energy and refrigeration cycles are highly affected by the properties of the respective available fluids. Here, we suggest combining gas, liquid and multistable elastic capsules to create an artificial fluid with a multitude of stable states. We study, theoretically and experimentally, the suspension's internal energy, equilibrium pressure-density relations, and their stability for both adiabatic and isothermal processes. We show that the elastic multistability of the capsules endows the fluid with multistable thermodynamic properties, including the ability of capturing and storing energy at standard atmospheric conditions, not found in naturally available fluids.


Characterization of the novel KIR3DL3*116 allele identified in a Chinese Han individual.
The novel KIR3DL3*116 allele differs from the closest allele KIR3DL3*00902 by a single missense mutation.


A novel RNA digesting activity from commercial polynucleotide phosphorylase.
RNase A4 is a new RNase activity found as a contaminant in commercial polynucleotide phosphorylase. This enzyme has the ability of hydrolyzing the phosphodiester bond between pyrimidine-A in both loop and paired regions of RNA.


Anti-apoptotic effect of melatonin on preimplantation development of porcine parthenogenetic embryos.
In the present study, we investigated the effect of melatonin on the preimplantation development of porcine parthenogenetic and somatic cell nuclear transfer (SCNT) embryos. Parthenogenetic embryos were cultured in mNCSU-23 supplemented with various concentrations of melatonin for 7 days. The results revealed that 100 pM was the optimal concentration, which resulted in significantly increased cleavage and blastocyst formation rates. Additionally, 100 pM melatonin provided the highest increase in total cell number of blastocysts. Therefore, the subsequent experiments were performed with 100 pM melatonin. ROS level in 2-8 cell stage embryos in the presence or absence of melatonin was evaluated. Embryos cultured with melatonin showed significantly decreased ROS. Blastocysts cultured with melatonin for 7 days were analyzed by the TUNEL assay. It was observed that melatonin not only increased (P < 0.05) the total cell number but also decreased (P < 0.05) the rate of apoptotic nuclei. Blastocysts cultured with melatonin were assessed for the expression of apoptosis-related genes Bcl-xl and Bax, and of pluripotency marker gene Oct-4 by real-time quantitative PCR. Analysis of data showed that the expression of Bcl-xl was higher (1.7-fold) compared to the control while the expression of Bax was significantly decreased relative to the control (0.7-fold) (P < 0.05). Moreover, the expression of Oct-4 was 1.7-fold higher than the control. These results indicated that melatonin had beneficial effects on the development of porcine parthenogenetic embryos. Based on the findings of parthenogenetic embryos, we investigated the effect of melatonin on the development of porcine SCNT embryos. The results also demonstrated increased cleavage and blastocyst formation rates, and the total cell numbers in blastocysts were significantly higher when the embryos were cultured with melatonin. Therefore, these data suggested that melatonin may have important implications for improving porcine preimplantation SCNT embryo development.


Real-time presurgical resting-state fMRI in patients with brain tumors: Quality control and comparison with task-fMRI and intraoperative mapping.
Resting-state functional magnetic resonance imaging (rsfMRI) is a promising task-free functional imaging approach, which may complement or replace task-based fMRI (tfMRI) in patients who have difficulties performing required tasks. However, rsfMRI is highly sensitive to head movement and physiological noise, and validation relative to tfMRI and intraoperative electrocortical mapping is still necessary. In this study, we investigate (a) the feasibility of real-time rsfMRI for presurgical mapping of eloquent networks with monitoring of data quality in patients with brain tumors and (b) rsfMRI localization of eloquent cortex compared with tfMRI and intraoperative electrocortical stimulation (ECS) in retrospective analysis. Five brain tumor patients were studied with rsfMRI and tfMRI on a clinical 3T scanner using MultiBand(8)-echo planar imaging (EPI) with repetition time: 400 ms. Moving-averaged sliding-window correlation analysis with regression of motion parameters and signals from white matter and cerebrospinal fluid was used to map sensorimotor and language resting-state networks. Data quality monitoring enabled rapid optimization of scan protocols, early identification of task noncompliance, and head movement-related false-positive connectivity to determine scan continuation or repetition. Sensorimotor and language resting-state networks were identifiable within 1 min of scan time. The Euclidean distance between ECS and rsfMRI connectivity and task-activation in motor cortex, Broca's, and Wernicke's areas was 5-10 mm, with the exception of discordant rsfMRI and ECS localization of Wernicke's area in one patient due to possible cortical reorganization and/or altered neurovascular coupling. This study demonstrates the potential of real-time high-speed rsfMRI for presurgical mapping of eloquent cortex with real-time data quality control, and clinically acceptable concordance of rsfMRI with tfMRI and ECS localization.


A rapid extraction method for detecting aflatoxin producing isolates.
A rapid extraction method for screening aflatoxin producing potential ofAspergillus flavus group isolates is described. The method is performed using a moist wheat medium with ca. five infected grains extracted with 2 mL of chloroform, and using thin layer chromatography. This method was proved with 95A. flavus isolates from animal feeds.


Nutritional quality and consumer health perception of online delivery food in the context of China.
Today, the popularization of mobile internet technology has enabled the public's need for food convenience and diversity arising from modern fast-paced lifestyles to be met at a relatively low cost. The digital age of the restaurant industry has arrived. Online food delivery (OFD) is rapidly developing globally. However, the public's awareness of the nutritional quality of food through OFD and their knowledge of dietary nutrition remain to be investigated. In the context of China, this study attempts to evaluate the nutritional quality of best-selling OFD set meals (i.e., meal combos) based on the current official Chinese dietary guidelines 2022. It accomplishes this by collecting data on popular OFD restaurants among consumers in 115 Chinese universities from the restaurants' delivery addresses. Moreover, 20,430 valid questionnaires were collected online from undergraduates, graduate students, and other young groups aged 18-30 throughout China for descriptive analysis to investigate consumers' perceptions of the nutritional quality of food through OFD and its health impact. The results of the nutritional quality evaluation of the OFD set meals ranged widely from 15 to 85, with a mean of 36.57 out of a possible maximum score of 100; and 89.56% scored less than 50. The nutritional quality of OFD foods was thus generally low. The nutritional quality of foods was negatively correlated with their popularity among consumers. Young OFD consumers generally paid low attention to dietary nutrition knowledge and seldom paid attention to nutritional quality when choosing OFD foods while the nutritional quality of OFD foods was generally low. Respondents subjectively reported that long-term consumption of OFD food caused weight gain, increased blood lipids, and gastrointestinal discomfort. They thought that the reason might be excessive oil, salt, and sugar in the food, while ignoring the balance between different types of food.


Intoxication with sulindac, tiaramide hydrochloride and diclofenac sodium.
Overdosage intoxication of sulindac, tiaramide and diclofenac caused excitability of central nervous system, followed by unconsciousness. The case was treated with ordinary therapies and direct hemoperfusion (DHP). Serum concentrations of these drugs and their metabolites were correlated well with the clinical symptoms. DHP may be effective to eliminate these drugs and their metabolites.


Creation and Adoption of Large Language Models in Medicine.
There is increased interest in and potential benefits from using large language models (LLMs) in medicine. However, by simply wondering how the LLMs and the applications powered by them will reshape medicine instead of getting actively involved, the agency in shaping how these tools can be used in medicine is lost. Applications powered by LLMs are increasingly used to perform medical tasks without the underlying language model being trained on medical records and without verifying their purported benefit in performing those tasks. The creation and use of LLMs in medicine need to be actively shaped by provisioning relevant training data, specifying the desired benefits, and evaluating the benefits via testing in real-world deployments.


Associations of the skin, oral and gut microbiome with aging, frailty and infection risk reservoirs in older adults.
Older adults represent a vulnerable population with elevated risk for numerous morbidities. To explore the association of the microbiome with aging and age-related susceptibilities including frailty and infectious disease risk, we conducted a longitudinal study of the skin, oral, and gut microbiota in 47 community- or skilled nursing facility-dwelling older adults vs. younger adults. We found that microbiome changes were not associated with chronological age so much as frailty: we identified prominent changes in microbiome features associated with susceptibility to pathogen colonization and disease risk, including diversity, stability, heterogeneity, and biogeographic determinism, which were moreover associated with a loss of Cutibacterium (C.) acnes in the skin microbiome. Strikingly, the skin microbiota were also the primary reservoir for antimicrobial resistance, clinically important pathobionts, and nosocomial strains, suggesting a potential role particularly for the skin microbiome in disease risk and dissemination of multidrug resistant pathogens.


The assessment of the relationships between body posture indices and the Y-Balance Test results in the adolescents.
The purpose of this work was to assess the differences of the values of body posture indices, measured with the Moire's method, between girls and boys aged 13 and the relationships of these values with the results of the Y-Balance Test. The study involved a group of healthy volunteers attending junior high schools in Cracow. The group consisted of 20 girls and 35 boys. Basic somatic parameters were measured within this work: body height and weight. Body posture was assessed according to the general methodology of the Moire's technique and 14 body posture indices were obtained as a result: 6 in the sagittal plane, 1 in the axial plane and 7 in the coronal plane. Postural stability was assessed with the Y-Balance Test (YBT). The studied girls and boys had practically the same body posture - statistical differences were found only in 3 out of 14 assessed indices measured with the Moire's technique. Scoliosis was found in as many as 51% of the subjects, however, mean values of deviations from the C7-S1 line were not large. In the group of girls, the set of blades (below - above) was statistically significantly correlated with the global YBT result for the right inferior extremity, and in the group of boys - the set of the waist triangles (below - above) was statistically significantly correlated with the global YBT results for the right and left inferior extremities.


Portal Vein Stent Placement in Five Patients with Chronic Portal Vein Thrombosis Prior to Pancreatic Surgery.
Five patients with pancreatic tumors and chronic portal vein (PV) thrombosis underwent PV stent placement before surgery. The patients either had resectable tumors or locally advanced tumors with stable, partial, or complete response to neoadjuvant therapy. PV stent placement removed periportal collaterals in all cases, with no complications, in a mean time of 150 minutes. Patients received a daily dose of subcutaneous low-molecular-weight heparin until 12 hours before surgery, and low-molecular-weight heparin was resumed for 30 days after surgery. Surgery was performed 1 day to 3 months after PV stent placement, with no complications related to periportal collaterals.


A facile ultrasonic-assisted fabrication of nitrogen-doped carbon dots/BiOBr up-conversion nanocomposites for visible light photocatalytic enhancements.
A highly efficient novel photocatalyst consisting of nitrogen-carbon dots (N-CDs) and three-dimensional (3D) hierarchical BiOBr was synthesized via a simple ultrasonic-assisted method and used for the degradation of hazardous dyes. Deposition of N-CDs onto the surface of BiOBr was confirmed through structure and composition characterizations. The N-CDs/BiOBr composites exhibited superior activity for organic contaminant degradation under visible light and the 1 wt% N-CDs/BiOBr composite showed the highest degradation rate, indicating that N-CDs/BiOBr composites have great potential for application in mitigating hazardous contaminants. The N-CDs played an important role in improving the photocatalytic performance, owing to the enhancement of up-converted photoluminescence behavior as well as the efficient separation of photogenerated charge carriers originating from the intimately contacted interface. A possible photocatalytic mechanism was proposed based on the experimental results.


[Five-fraction radiotherapy for breast cancer].
Extreme hypofractionation in adjuvant breast radiotherapy currently generates a lot of interest. We propose here a synthesis of hypofractionation trials and present the DESTHE COL and DESTHE GR projects, encouraged by the French National Cancer Institute (INCa), which experiment care pathways in order to deploy effective strategies to de-escalate the therapeutics and to reduce sequelae after cancer treatment.


Intravenous cocaine infusions in humans: dose responsivity and correlations of cardiovascular vs. subjective effects.
Eight experienced IV cocaine users were intravenously administered 0, 10, 20, and 40 mg of cocaine hydrochloride on separate days in a pseudo-randomized ascending dose series, such that the 20 mg dose always preceded the 40 mg dose. They were subsequently administered 0, 20, and 40 mg of cocaine in a fully randomized presentation order. Cardiovascular effects of cocaine were significantly different from placebo for the 20 mg, but not the 10 mg dose, in contrast to subjective responses which differed from placebo for the 10 mg dose. Cardiovascular and subjective effects of cocaine did not differ between the 20 and 40 mg dose conditions for the pseudo-randomized trials, but did differ in the fully randomized trials. This lack of difference in responsivity between the 20 and 40 mg dose in the earlier trials may possibly have been due to contrast effects. Cardiovascular responses were not consistently correlated with subjective responses, either within a cocaine dose condition or across doses.


Periprosthetic pathologic fracture following tibial Echinoccocosis: A case report.
Hydatid disease in humans caused by the parasitic tapeworm Echinococcus granulosus has an osseous involvement of about 0.5%-2.5% of all cases in humans. The location of hydatid cysts in the tibia is seldom described in the medical literature, and its diagnosis and treatment is challenging. This paper presents a patient, with a long term, well tolerated, bilateral total knee arthroplasty (TKA), treated at our clinic, with a recent history of pain and oedema in her left upper leg. After achieving a, radiologically and histhopathologically, well documented, diagnosis of Echinoccocosis lesion in her left proximal tibia, a surgical intervention was planed, a wide resection of the cyst performed, and a specific anti-helmintic therapy was instituted. Four years later, she returns to our observation complaining of pain and unable to bear weight on her left knee, from which a pathologic fracture, adjacent to the tibial component, was diagnosed. After surgical debridement of the newly advanced hydatid cyst growth, the TKA was revised, and due to the tibial component failure and the femoral implant loosening, a semi-constrained total knee revision arthroplasty was executed. Functional outcome was excellent. Although challenges in treatment of musculoskeletal hydatid cysts (HC) lesions have been documented, data regarding the musculoskeletal HC lesions resembling tumor is scarce, and those resulting in a prosthetic failure have not been published. The authors intend to add data concerning the therapeutic approach to this entity.


The correlation between size of renal cell carcinoma and its histopathological characteristics: a single center study of 1867 renal cell carcinoma cases.
What's known on the subject? and What does the study add? We had known from former studies of RCC that the risks of high grade tumours increased with tumour size and probability of localized tumour decreased with tumour size increasing. Our study had provided large and detailed data about pathologic features of RCC. We also examined the exactly changing of probabilities of different subtypes with diameter increasing and evaluated the effects of hemorrhage, necrosis and cystic degeneration on pathologic subtypes. • To investigate the correlation between tumour size and histopathological characteristics of renal cell carcinoma (RCC). • A total of 1867 patients who underwent surgical operation between January 2002 and March 2010 due to RCC were included. According to 1997 WHO recommendation about Fuhrman nuclear grading of RCC which criteria we used, tumours were stratified by the largest pathologic diameter into 5 groups, the discrepancy of tumour grade between different groups and whether tumour size could predict histological subtype were analyzed. • The largest diameter (mean ± sd) of G1, G2, and G3 tumours were 3.27 ± 1.46 cm,4.87 ± 2.23 cm, and 7.39 ± 3.11 cm, respectively. The percentage of extracapsular extension tumours in 2 cm or less, 2.1 and 4.0 cm, 4.1 to 7 cm, 7.1 to 10 cm, and more than 10 cm group were 0.5%, 4.3%, 19.8%, 57.9%, and 91.9%, respectively. The distribution of G1 tumours shows a decreasing trend with the diameter becoming larger, while the G3 tumours shows an opposite trend (P < 0.05). Logistic regression analysis predicted that the odds of papillary, chromophobe, and other types vs clear cell decreased with increase in tumour size. If the tumour was complicated with hemorrhage or necrosis, the chance of being chromophobe was higher, while the probability of being papillary and chromophobe decreased when a tumour with cystic degeneration. • There was a significant correlation between tumour size and tumour grade and stage; Larger tumours were prone to have higher grade and stage, and the probability of being clear cell carcinoma grew higher as the tumour size increased.


Involvement of different neuronal components in the induction of cortical plasticity with associative stimulation.
Paired associative stimulation (PAS), with stimulus interval of 21.5 or 25 ms, using transcranial magnetic stimulation in the posterior-anterior (PA) current direction, produces a long-term-potentiation-like effect. Stimulation with PA directed current generates both early and late indirect (I)-waves while that in anterior-posterior (AP) current predominantly elicits late I-waves. Short interval intracortical inhibition (SICI) inhibits late I-waves but not early I-waves. To investigate how cortical inhibition modulates the effects of PAS. PAS at stimulus interval of 21.5 ms conditioned by SICI (SICI-PAS) was compared to PAS alone with both PA and AP directed currents. PAS with both current directions increased cortical excitability. SICI-PAS increased cortical excitability in the PA but not the AP current direction. Both early and late I-waves circuits can mediate cortical PAS plasticity under different conditions. Plasticity induction with the late but not the early I-wave circuits is blocked by SICI.


Development of low-cost metal oxide pH electrodes based on the polymeric precursor method.
In this work, the polymeric precursor method was used to prepare low-cost solid-state sensors for pH determination based on iridium oxide as the main pH sensitive material. The iridium content was reduced with addition of TiO(2), forming the binary system IrO(x)-TiO(2), whose electroanalytical properties were evaluated in comparison with a commercial glass pH electrode. The minimum iridium content which gave suitable results was 30mol%, and the electrode presented Nernstian and fast response in the pH range from 1 to 13, with no hysteresis effect observed. Besides, the electrode showed high selectivity in the presence of alkali ions as Li(+), Na(+) or K(+). The amount of iridium in the prepared electrodes was very small (<0.1mg), supporting the efficiency of this method on the simple preparation of functional low-cost pH electrodes.


Stroke in Latin America.
Stroke is one of the leading causes of mortality in Latin America, with variable incidence and prevalence throughout the continent reflecting regional socioeconomic differences. In Latin America, uncontrolled hypertension is one of the major causes of stroke, but other modifiable risk factors also play a role, such as heavy alcohol consumption and smoking. Intracerebral hemorrhage and lacunar stroke are more frequent in Latin America than in North America and Europe. There are multiple causes of stroke that are endemic to Latin America, including neurocysticercosis, Chagas' disease, sickle cell anemia, malaria, hemorrhagic fever, and snake bites.


Displaying of acetylcholinesterase mutants on surface of yeast for ultra-trace fluorescence detection of organophosphate pesticides with gold nanoclusters.
Acetylcholinesterase (AChE) has been widely applied on the enzyme inhibition-based detection of organophosphate pesticides (OPs). To improve the sensitivity of fluorometric OPs assay, great efforts were made to change the fluorometric probes or analytical strategies rather than improve the sensitivity of AChE towards OPs. In this work, AChE wild-type (WT) and mutants (E69Y and E69Y/F330L) from Drosophila were successfully displayed on the surface of yeast through a-agglutinin-mediated microbial surface display system. The location of AChE on yeast surface was confirmed by immunofluorescence analysis. Further, a fluorescence OPs detection method was developed by combining yeast surface-displayed AChE mutants and protein-directed electronegative fluorescent gold nanoclusters (Au NCs). Yeast surface-displayed AChE can catalyze the hydrolysis of acetylthiocholine to produce thiocholine. The electropositive thiocholine can not only bind with AuNCs by Au-S bond but also absorb Au NCs by the electrostatic interaction, leading to the aggregation of AuNCs and corresponding fluorescence quenching. When AChE was incubated with paraoxon, a typical model of OPs, the activity of AChE was inhibited and the thiocholine-induced aggregation of AuNCs was reduced. The fluorescence assay based on Au NCs and yest-AChE-E69Y/F330L exhibited the ultra-sensitivity for ultra-trace OPs and 2-6 orders of magnitude lower detection limit (3.3 × 10-14 M) than those of AChE-WT-based method and other reported methods. In addition, the proposed method showed excellent reliability for the real samples assay. This work would provide an alternative strategy for the improvement of bio-analysis at its source.


Declining incidence of hepatitis C related hepatocellular carcinoma in the era of interferon-free therapies: A population-based cohort study.
The impact of interferon (IFN)-free therapies on the epidemiology of hepatitis C virus (HCV) related hepatocellular carcinoma (HCC) is not well understood at a population level. Our goal was to bridge this evidence gap. This study included all patients in Scotland with chronic HCV and a diagnosis of cirrhosis during 1999-2019. Incident cases of HCC, episodes of curative HCC therapy, and HCC-related deaths were identified through linkage to nationwide registries. Three time periods were examined: 1999-2010 (pegylated interferon-ribavirin [PIR]); 2011-2013 (First-generation DAA); and 2014-2019 (IFN-free era). We used regression modelling to determine time trends for (i) number diagnosed and living with HCV cirrhosis, (ii) HCC cumulative incidence, (iii) HCC curative treatment uptake and (iv) post-HCC mortality. 3347 cirrhosis patients were identified of which 381 (11.4%) developed HCC. After HCC diagnosis, 140 (36.7%) received curative HCC treatment and there were 202 deaths from HCC. The average annual number of patients diagnosed and living with HCV cirrhosis was approximately seven times higher in the IFN-free versus the PIR era, whereas the number of incident HCCs was four times higher. However, the cumulative incidence of HCC was significantly lower in the IFN-free versus PIR era (sdHR: 0.65; 95%CI:0.47-0.88; P = .006). Among HCC patients, diagnosis in the IFN-free era was not associated with improved uptake of curative treatment (aOR:1.18; 95%CI:0.69-2.01; P = .54), or reduced post-HCC mortality (sdHR: 0.74; 95%CI:0.53-1.05; P = .09). The cumulative incidence of HCC is declining in HCV cirrhosis patients, but uptake of curative HCC therapy and post-HCC survival remains suboptimal.


The "Healthcare Workers' Wellbeing [Benessere Operatori]" Project: A Longitudinal Evaluation of Psychological Responses of Italian Healthcare Workers during the COVID-19 Pandemic.
COVID-19 forced healthcare workers to work in unprecedented and critical circumstances, exacerbating already-problematic and stressful working conditions. The "Healthcare workers' wellbeing (Benessere Operatori)" project aimed at identifying psychological and personal factors, influencing individuals' responses to the COVID-19 pandemic. 291 healthcare workers took part in the project by answering an online questionnaire twice (after the first wave of COVID-19 and during the second wave) and completing questions on socio-demographic and work-related information, the Depression Anxiety Stress Scale-21, the Insomnia Severity Index, the Impact of Event Scale-Revised, the State-Trait Anger Expression Inventory-2, the Maslach Burnout Inventory, the Multidimensional Scale of Perceived Social Support, and the Brief Cope. Higher levels of worry, worse working conditions, a previous history of psychiatric illness, being a nurse, older age, and avoidant and emotion-focused coping strategies seem to be risk factors for healthcare workers' mental health. High levels of perceived social support, the attendance of emergency training, and problem-focused coping strategies play a protective role. An innovative, and more flexible, data mining statistical approach (i.e., a regression trees approach for repeated measures data) allowed us to identify risk factors and derive classification rules that could be helpful to implement targeted interventions for healthcare workers.


[Use of blood and its derivatives by the emergency surgeon].
In spite of the fact that the initial injury has to be treated as quickly as possible, in many emergency pathologies, the priority in early resuscitation periods is to provide an adequate blood flow, tissue perfusion and oxygenation. In multiple injuries, treatment starts before diagnosis because diagnostic examinations cannot begin until the patient's condition has become more stable.


Sleeve gastrectomy suppresses hepatic de novo cholesterogenesis and improves hepatic cholesterol accumulation in obese rats with type 2 diabetes mellitus.
Cholesterol metabolic disturbance increases the risk of various acquired diseases and affects public health. An apparent correlation between hypercholesterolemia and type 2 diabetes mellitus (T2DM) was confirmed recently. Bariatric surgery can induce durable and sufficient loss of body weight and T2DM remission. A previous study illustrated a cholesterol-lowering effect of sleeve gastrectomy (SG), but the intrinsic mechanism is still elusive. The present study aimed to investigate the effects of SG on hypercholesterolemia and hepatic cholesterol accumulation in a T2DM rat model. Obese rats with T2DM were randomly subjected to sham operation, sham operation combined with food restriction, or SG. Body weight, food intake, blood glucose, body composition, and cholesterol level were measured at the indicated time points. Subsequently, hepatic cholesterol content and both protein and transcriptional levels of sterol regulatory element-binding protein 2, 3-hydroxy-3-methylglutaryl-coenzyme A reductase, and low-density lipoprotein receptor were measured at 2 and 4 wk postoperatively. SG rapidly reduced blood glucose independent of loss of body weight and food restriction. Rats that underwent SG exhibited lower total cholesterol and free cholesterol in both serum and liver. The cholesterol-lowering effect was independent of loss of body weight and food restriction at just 2 wk postoperatively. Protein and mRNA expression of sterol regulatory element-binding protein 2, 3-hydroxy-3-methylglutaryl-coenzyme A reductase, and low-density lipoprotein receptor were inhibited at 2 wk postoperatively and recovered by 4 wk after SG. SG alleviated hypercholesterolemia and hepatic cholesterol accumulation partially by inhibiting hepatic de novo cholesterogenesis.


Role of the carboxyl terminal di-leucine in phosphorylation and internalization of C5a receptor.
The carboxyl tail of G protein-coupled receptors contains motifs that regulate receptor interactions with intracellular partners. Activation of the human neutrophil complement fragment C5a receptor (C5aR) is terminated by phosphorylation of the carboxyl tail followed by receptor internalization. In this study, we demonstrated that bulky hydrophobic residues in the membrane-proximal region of the C5aR carboxyl tail play an important role in proper structure and function of the receptor: Substitution of leucine 319 with alanine (L319A) resulted in receptor retention in the endoplasmic reticulum, whereas a L318A substitution allowed receptor transport to the cell surface, but showed slow internalization upon activation, presumably due to a defect in phosphorylation by both PKC and GRK. Normal agonist-induced activation of ERK1/2 and intracellular calcium release suggested that the L318A mutation did not affect receptor signaling. Binding of GRK2 and PKCbetaII to intracellular loop 3 of C5aR in vitro indicated that mutagenesis of L318 did not affect kinase binding. Limited proteolysis with trypsin revealed a conformational difference between wild type and mutant receptor. Our studies support a model in which the L318/L319 stabilizes an amphipathic helix (Q305-R320) in the membrane-proximal region of C5aR.


Bioturbation by cyprinid fish affecting the food availability for predatory water mites.
Field observations suggested that benthivorous fish, causing bioturbation, are able to effect the food availability for predacious water mites feeding on bottom dwelling chironomid larvae. This hypothesis was tested in the laboratory. In an undisturbed situation the predation rate exercised by the water mites on the tube dwelling chironomid Cladotanytarsus mancus was very low. However, when the sediment was disturbed, the predation rate increased substantially. The relevance of this for the field situation is discussed.


Hepatitis Outreach Network: a practical strategy for hepatitis screening with linkage to care in foreign-born communities.
Many foreign-born persons in the US are at high risk of chronic hepatitis B (HBV) and C (HCV) infections, yet are not aware of their infection, and lack healthcare coverage or linkage to care. A unique partnership, the Hepatitis Outreach Network, combines the expertise and resources of the Mount Sinai School of Medicine, the NYC Department of Health and Mental Hygiene, and community-based organizations, to provide education, screening and link to care in communities with high prevalence of chronic viral hepatitis. Comprehensive HBV and HCV screening identifies infected patients, who then receive further evaluation from either local or Mount Sinai physicians, combined with patient-navigators who organize follow-up visits. Of 1603 persons screened, 76 had HBV and 75 had HCV. Importantly, screening for HCV based on traditional risk factors would have missed 67% of those who tested positive. Of the 76 persons with HCV infection, 49 (64%) received a medical evaluation (26 with local providers and 23 at Mount Sinai). Of the 49 HCV-infected persons evaluated, treatment was recommended in 11 and begun in 8 (73%). Of the 76 persons with HBV infection, 43 (57%) received a medical evaluation (31 with local providers and 12 at Mount Sinai). Of the 43 HBV-infected persons evaluated, treatment was recommended and begun in 5 (100%). Hepatitis Outreach Network has successfully established novel proof of concept for identifying HBV and HCV infections in foreign-born persons through use of several unique elements that effectively link them to care.


Dramatic radiotherapy response of a giant T4 cutaneous squamous cell carcinoma of the scalp with extensive bone destruction: a case report.
Patients with large cutaneous squamous cell carcinoma of the scalp are a treatment challenge. We report a case of dramatic radiotherapy response of a patient with a giant cutaneous squamous cell carcinoma of the scalp with extensive skull destruction and suspected infiltration of the dura mater and superior sagittal sinus. This case is the first report of this kind in the literature that shows that large bone defects can heal with the resolution of tumor and inflammation by secondary intention without surgical reconstruction. We want to put an end to concerns about radiocurability of tumors with extensive bone involvement, and show sustained complete response after definitive radiotherapy and programmed cell death protein-1 inhibiting antibody therapy. A 74-year-old White man presented with a 7.2 × 6.8 × 5.5 cm painless tumor on the right parietal region of the scalp. Medical imaging revealed widespread destruction of the skull and suspected infiltration of the dura mater and superior sagittal sinus. Biopsies showed cutaneous squamous cell carcinoma (cT4a cN0 cM0, stage IVA). The patient was treated with a total dose of 60 Gy, at 2 Gy per daily fraction with volumetric modulated arc therapy using 6 megavoltage photons. The biologically effective dose (alpha/beta 10 Gy) was 72 Gy. The tumor response correlated with dose received. The patient had a massive tumor necrosis secondary to tumor shrinkage after 18 fractions (36 Gy, biologically effective dose 43.2 Gy). Leakage of cerebrospinal fluid did not occur. Radiotherapy did not hamper the patient's quality of life. The patient had a clear regression of the initial tumor on the final day of radiotherapy. The bone defect healed by secondary intention without surgical interventions. The patient achieved a complete response with a good cosmetic result after 82 days follow-up. He started a programmed cell death protein-1 inhibiting antibody therapy with cemiplimab 2 months after radiotherapy, and is now at 10 months follow-up without evidence of recurrence. Definitive radiotherapy is a safe and highly effective therapy for giant tumors of the scalp with extensive bone destruction. We report a sustained complete response with a good cosmetic result after secondary wound healing.


Heavy metals, parasitologic and oxidative stress biomarker investigations in Heterotis niloticus from Lekki Lagoon, Lagos, Nigeria.
Heavy metal toxicity in aquatic life as a result of human activities poses a grave health threat to water quality, aquatic and human life. Parasites may serve as indicators of heavy metal pollution. This research investigated the health status of the fish Heterotis niloticus viz-a-viz quality of the water and sediments in Lekki lagoon, parasitic infection, presence of heavy metals and oxidative stress response in the liver and intestine of the fish. Parasites recovered were also analyzed for the extent of bioaccumulation of heavy metals. The metals in water, sediments, parasites, and fish were analyzed using Atomic Absorption Spectrometry. Heavy metal concentrations in the surface water were generally below regulatory limits of World Health Organization. Sediment had high levels of aluminium (124.78 mg/kg) and iron (327.41 mg/kg); other heavy metals were below regulatory limits. Tenuisentis niloticus, an acanthocephalan, was the only parasite recovered. Seventy (70) out of 100 fish sampled were infected with the parasite. T. niloticus bioaccumulated Cd, Ni, and Pb between 65 to 100 times more than the liver and 12 to 200 times more than the intestine. Other metals bioaccumulated from the host tissues by the parasite had the magnitude between 1 to 12 times as the liver and 1 to 30 times as the intestine. There were significant differences in the activities of antioxidant enzymes between the parasitized and non-parasitized fishes. Fish tissues also showed histological alterations, ranging from mild infiltration of inflammatory cells to moderate inflammation and haemorrhagic lesions. Human activities that introduce stressors into the lagoon should be controlled.


Effect of food on kinetics of 8-methoxsalen.
Kinetics of 8-methoxsalen were studied in 5 healthy subjects under fasting and nonfasting conditions. The plasma concentration-time data could be fitted to a zero order absorption one-compartment model. The area under the curve (AUC) values were higher (p less than 0.05) under nonfasting compared to fasting conditions, indicating higher relative bioavailability of the drug in the presence of food. No significant differences were observed in the lag-time for the start of the absorption, the apparent zero-order absorption rate constant, or the elimination rate constant. It is suggested that the drug should be taken in a standardized way in relation to food during the ultraviolet (UV) light treatment.


Subunits of fatty acid synthetase complexes. Enzymatic activities and properties of the half-molecular weight nonidentical subunits of pigeon liver fatty acid synthetase.
The separation of the half-molecular weight, nonidentical subunits (I and II) of the pigeon liver fatty acid synthetase complex has been achieved on a large (20 mg) scale by affinity chromatography on Sepharose epsilon-aminocaproyl pantetheine. This separation requires a careful control of temperature, ionic strength, pH, and column flow rate for success. The yield of subunit II is further improved by transacetylation (with acetyl-CoA) of the dissociated fatty acid synthetase prior to affinity chromatography. The separated subunit I (reductase) contains the 4'-phosphopantetheine (A2) acyl binding site, two NADPH binding sites, and beta-ketoacyl and crotonyl thioester reductases. Subunit II (transacylase) contains the B1 (hydroxyl or loading) and B2 (cysteine) acyl binding sites, and acetyl- and malonyl-CoA: pantetheine transacylases. When subunit I is mixed in equimolar quantities with subunit II, an additional NADPH binding site is found even though subunit II alone shows no NADPH binding. Both subunits contain activities for the partial reactions, beta-hydroxybutyryl thioester dehydrase (crotonase) and palmityl-CoA deacylase. Subunit I has 8 sulfhydryl groups per mol whereas subunit II has 60. Reconstitution of fatty acid synthetase activity to 75% of the control level is achieved on reassociation of subunits I and II.


The effect of concussion history on cognitive-motor integration in elite hockey players.
To observe the effects of concussion history on cognitive-motor integration in elite-level athletes. The study included 102 National Hockey League draft prospects (n = 51 concussion history [CH]; n = 51 no history [NC]). Participants completed two computer-based visuomotor tasks, one involved 'standard' visuomotor mapping and one involved 'nonstandard' mapping in which vision and action were decoupled. We observed a significant effect of group on reaction time (CH slower) and accuracy (CH worse), but a group by condition interaction only for reaction time (p < 0.05). There were no other deficits found. We discussed these findings in comparison to our previous work with non-elite athletes. Previously concussed elite-level athletes may have lingering neurological deficits that are not detected using standard clinical assessments.


Genotoxicity and subchronic toxicity studies of supercritical carbon dioxide and acetone extracts of rosemary.
Toxicology studies conducted with oil-soluble rosemary extracts to support authorization as a food additive (antioxidant) in the EU include an Ames test using a supercritical carbon dioxide extract (D74), a full 90-day study using D74 and an acetone extract (F62), and an investigative 90-day study with a 28-day recovery period (using D74 only). D74 was non-mutagenic in the Ames test. In the full 90-day study, where rats (20/sex/group) were either provided control diet or diets containing D74 (300, 600, or 2400 mg/kg) or F62 (3800 mg/kg), liver enlargement and hepatocellular hypertrophy were observed. To determine a mode of action and assess the reversibility of the hepatic effects, an investigative 90-day study was conducted using female rats (10/group receiving control diet or diet containing 2400 mg/kg D74). Liver enlargement was fully reversible after 28 days and microsomal enzyme analysis revealed reversible induction of cytochrome P450 enzymes (CYP2A1, CYP2A2, CYP2C11, CYP2E1, and CYP4A), demonstrating that the hepatic effects were adaptive and of no toxicological concern. Therefore, the highest dietary concentrations were established as the NOAELs. The investigative 90-day study NOAEL (providing 64 mg/kg bw/day carnosol and carnosic acid [the primary antioxidant components]) was used to establish a temporary ADI for rosemary extracts.


Mitral valve replacement with a porcine heterograft in an infant.
Mitral valve replacement for congenital mitral stenosis has been performed infrequently in infants. In all but two previously reported infants, the valve has been replaced with a mechanical prosthesis. The case history of an infant is reported in whom emergency mitral valve replacement was successfully performed with a porcine heterograft excised from a tubular prosthesis. This approach is an acceptable alternative when a valve of appropriate size is unavailable.


Levels of health literacy among people living with HIV in outpatient care: a cross-sectional study from Denmark.
Low health literacy (HL) among people living with HIV (PLWHIV) encounter more disease related complications, more difficulty understanding health-related information and low adherence. Considering that, the HL levels among PLWHIV needs to be further investigated. The objective of this study was to investigate the levels of HL and patient involvement among PLWHIV in an outpatient clinic in Denmark. A second objective was to examine differences in HL levels across socio-demographic characteristics. In 2019, a population of 682 PLWHIV from a Danish outpatient hospital clinic were enrolled in cross-sectional study. Patients who had a digital postbox received an electronic questionnaire including following domains; health literacy, patient involvement, and socio-demographic status. Health literacy was measured using the Health Literacy Questionnaire (HLQ) through scores on three subscales: social support for health (HLQ4), engaging with healthcare providers (HLQ6), and understanding health information (HLQ9). An unpaired t-test was used to investigate mean differences in the HLQ scores across socio-demographic variables. A total of 338 (55%) patients responded to the questionnaire. The included participants demonstrated high levels of HLQ4 (mean = 4.2) and HLQ6 (mean = 4.2), but lower for HLQ9 (mean = 2.9). In total 70-80% reported being involved in decisions about their health. We found a positive association between high level of HL (HLQ9) and living with a partner and higher levels of HL (HLQ4, HLQ6, and HLQ9) and employment. PLWHIV in a Danish out-patient care population were found to have high levels of HL despite differences in demographic characteristics. Further research is needed to examine the levels of HL among non-responders to develop HL approaches and strategies to meet the needs of individuals with different HL skills.


Low levels of residual oil fly ash (ROFA) impair innate immune response against environmental mycobacteria infection in vitro.
Epidemiological studies have shown that pollution derived from industrial and vehicular transportation provokes adverse health effects causing broad spectrum of ambient respiratory diseases. Therefore, air pollution should be taken into account when microbial diseases are evaluated. Environmental mycobacteria (EM) are opportunist pathogens in a variety of immunocompromised patients eliciting significant impact on human morbidity and mortality. The aim of this study was to evaluate the in vitro effects of residual oil fly ash (ROFA) on the alveolar macrophages (AMs) response to opportunistic bacteria. AMs from young Wistar rats were obtained by bronchoalveolar lavage and co-cultured with Mycobacterium phlei (MOI 10). We exposed AM cultures to ROFA to characterize the effect of low ROFA concentrations (0, 2.5, and 5μg/ml) and evaluated the response of pre-exposed AM against the bacilli. Low ROFA concentrations induced superoxide anion and nitrites production (p<0.001). Pre-exposure to ROFA (2.5 and 5μg/ml) caused a significant reduction on TNFα (p<0.001) and superoxide anion (p<0.001) production but, did not modify the nitrite production when AM were co-cultured with M. phlei. In addition, ROFA significantly diminished AM killing ability in culture (p<0.001). Hence, our results indicate that pre-exposure to low levels of ROFA modifies the innate pulmonary defence mechanisms against environmental mycobacteria.


Congruence of vascular network remodeling and neuronal dispersion in the hippocampus of reelin-deficient mice.
In the hippocampus, neurons and fiber projections are strictly organized in layers and supplied with oxygen via a vascular network that also develops layer-specific characteristics in wild-type mice, as shown in the present study for the first time in a quantitative manner. By contrast, in the reeler mutant, well known for its neuronal migration defects due to the lack of the extracellular matrix protein reelin, emerging layer-specific characteristics of the vascular pattern were found to be remodeled during development of the dentate gyrus. Remarkably, in the first postnatal week, when a granule cell layer was still discernable in the reeler dentate gyrus, also the reeler vascular pattern resembled wild type. Thus, at postnatal day 6, unbranched microvessels traversed the granule cell layer and bifurcated when reaching the subgranular zone. Only after the first postnatal week vascular network remodeling in the reeler dentate gyrus became apparent, when the proportion of dispersed granule cells increased. Hence, vessel bifurcation frequency decreased in the maturing reeler dentate gyrus, but increased in wild type, resulting in significant differences (approx. 100%; p < 0.01) between adult wild type and reeler. Moreover, layer-specific vessel bifurcation frequencies disappeared in the maturing reeler dentate gyrus. Finally, a wild type-like vascular pattern was also found in the dentate gyrus of mice deficient for the reelin receptor very low density lipoprotein receptor (VLDLR), precluding a requirement of VLDLR for normal vascular pattern formation in the dentate gyrus. In sum, our findings show that vascular network remodeling in the reeler dentate gyrus is closely linked to the progression of granule cell dispersion.


Studies on the mechanism of oxidative phosphorylation. Flow-force relationships in mitochondrial energy-linked reactions.
The relationship between the steady-state level of membrane potential (delta psi) and the rates of energy production and consumption has been studied in mitochondria and submitochondrial particles. The energy-linked reactions investigated were oxidative phosphorylation (with NADH, succinate, and beta-hydroxybutyrate as respiratory substrates) and nucleoside triphosphate-driven transhydrogenation from NADH to NADP and uphill electron transfer from succinate to NAD. Results have shown the following. 1) Attenuation of the rates of the energy-producing reactions results in a parallel change in the rates of the energy-consuming reactions with little or no change in the magnitude of steady-state delta psi. 2) At low rates of energy production and consumption, steady-state delta psi decreases. However, this is due largely to the energy leak of the system which lowers static-head delta psi when the rate of energy production is slow. 3) When the rate of energy production and static-head delta psi are held constant, and the rate of energy consumption is diminished by partial inhibition or the use of suboptimal conditions (e.g. subsaturating substrate concentrations), then even a small decrease in the rate of energy consumption results in an upward adjustment of the level of steady-state delta psi. The lower the rate of energy input, the greater the upward adjustment of steady-state delta psi upon suppression of the rate of energy consumption. 4) The above results have been discussed with regard to the role of bulk-phase delta mu H+ or delta psi in the mitochondrial energy transfer reactions.


Tissue polarity: PCP inheritance ensured by selective mitotic endocytosis.
Recent findings report the selective internalization of core planar cell polarity components during mitosis followed by cell-non-autonomous polarized recycling. This novel mechanistic model explains how tissue polarity is inherited in daughter cells of proliferative tissue.


Enhanced transscleral lontophoretic transport with ion-exchange membrane.
Transscleral iontophoresis has been recently re-examined for drug delivery to the back of the eye. In conventional iontophoresis, due to the relatively high electromobility of the endogenous competing ions (counterions) relative to that of the drug ion in the tissue barrier, the efficiency of iontophoretic drug delivery is generally low. The objective of the present study was to examine ion-exchange membrane-enhanced transscleral iontophoretic transport in which the ion-exchange membrane in series with the sclera can hinder the transport of the competing counterions and selectively allow the transport of the permeant across the sclera. The physical properties of the Ionac ion-exchange membrane and excised rabbit sclera were determined in equilibrium uptake experiments and in passive and iontophoretic transport experiments with salicylate, tetraethylammonium, urea, and mannitol. Transscleral experiments with the ion-exchange membrane were conducted with salicylate and excised rabbit sclera in vitro. The contribution of electroosmosis to electrotransport during transscleral iontophoresis was assessed with urea and mannitol. The ion-exchange membrane is highly positively charged and has a small effective pore size. The sclera is relatively porous with a large effective pore size and low pore tortuosity. The sclera is also net negatively charged but this does not significantly affect the transport of small ions. A three-fold steady-state transscleral flux enhancement of salicylate was observed in ion-exchange membrane-enhanced iontophoresis over conventional transscleral iontophoresis without the membrane. Such enhancement was relatively independent of the applied electric current density and the thickness of the studied ion-exchange membrane assembly. Although the ion-exchange membrane altered transscleral electroosmosis, the contribution of electroosmosis to electrotransport was not significant. The present study has demonstrated the potential of ion-exchange membranes for enhancing iontophoretic transport and drug delivery.


Near complete loss of retinal ganglion cells in the math5/brn3b double knockout elicits severe reductions of other cell types during retinal development.
Retinal ganglion cells (RGCs) are the first cell type to differentiate during retinal histogenesis. It has been postulated that specified RGCs subsequently influence the number and fate of the remaining progenitors to produce the rest of the retinal cell types. However, several genetic knockout models have argued against this developmental role for RGCs. Although it is known that RGCs secrete cellular factors implicated in cell proliferation, survival, and differentiation, until now, limited publications have shown that reductions in the RGC number cause significant changes in these processes. In this study, we observed that Math5 and Brn3b double null mice exhibited over a 99% reduction in the number of RGCs during development. This severe reduction of RGCs is accompanied by a drastic loss in the number of all other retinal cell types that was never seen before. Unlike Brn3b null or Math5 null animals, mice null for both alleles lack an optic nerve and have severe retinal dysfunction. Results of this study support the hypothesis that RGCs play a pivotal role in the late phase of mammalian retina development.


A rare presentation of systemic salmonellosis.
We are reporting an unusual case of disseminated Salmonella enteritidis D, phage group E2 infection in an 18-year-old male, which was resistant to massive antibiotic treatment. Rare complications such as pylephlebitis, mediastinal adenopathy, osteomyelitis with pathological clavicular fracture, osteitis and spondylitis were observed. We found an immunological defect that no doubt contributed to this severe illness.


Dual mobility cups in revision total hip arthroplasty.
The purpose of our study was to evaluate the dislocation and aseptic loosening rates of a dual mobility construct in revision total hip arthroplasty (THA). Three hundred thirty-four revision THAs performed between 2006 and 2011, using a dual mobility cup, were included in this retrospective study. The indications for revision were aseptic loosening (70%), infection (21%) and recurrent instability (9%). The minimum follow-up was five years (mean 7 ± 2 years, maximum 10 years). At the latest follow-up, 11 episodes of dislocation occurred, seven of which were recurrent (1.3% for aseptic loosening, 2.8% for infection and 3.4% for recurrent dislocation). Ten cases of aseptic loosening occurred; in seven of them, a cemented cup into a reinforcement ring had been used (OR = 14, p = 0.0001). This study provided evidence of the advantages of dual mobility cups in all revision THA indications.


Acid phosphatases of the mosquito Culex tarsalis coquillett.
1. Spectrophotometric and isoelectric focusing (IEF) electrophoretic characterization of the acid phosphatases (ACP) of the mosquito, Culex tarsalis, are presented. 2. ACP hydrolysis of P-nitrophenylphosphate (Pnp) was optimal at 37 degrees C, pH 5.25 in the presence of 15 mM MgCl2 and 0.1% (w/v) polyvinylpyrollidone (PVP). Vmax and Km values varied significantly between the various mosquito strains examined. 3. Several divalent cations (i.e. Mn2+, Ca2+, Ba2+ and Co2+), either the chloride or sulphate salts, were stimulatory for ACP. Both Cu2+ and Fe2+ (15 mM) were inhibitory. 4. Slight inhibition (i.e. 10%) of ACP activity was observed with dithiothreitol (100 mM) and 50% inhibition by cysteine (100 mM). 5. ACP activity was cyclic during the 15-day post-adult emergence period of the study. No significant differences were noted between the ACP specific activities of males and females nor between geographic strains. 6. IEF electrophoresis revealed three alpha-naphthyl phosphate hydrolytic ACP isozymes within the pH 4.5-5.5 range (i.e. ACP4.8, ACP5.3 and ACP5.5). 7. IEF ACP isozymes were stimulated by PVP, Mg2+, Zn2+ and inhibited by cysteine, EDTA (except ACP5.3) and NaFl. 8. IEF detection of ACP with Pnp revealed an ACP isozyme (ACP4.3) distinct from those ACP isozymes capable of alpha-naphthyl phosphate hydrolysis.


Harmonic Scalpel Versus Coblation Tonsillectomy A Comparative Study.
Tonsillectomy is an age old procedure in ENT practice. Though traditional dissection method is gold standard, we surgeons are trying different techniques like electrocautery, coblation, harmonic scalpel (HS) mainly to improve surgical convenience, to decrease operative time, post operative pain, intra and post operative bleeding and fast return to normal life. In this particular study we are comparing coblation and HS as surgical tool in tonsillectomy. It is a prospective double-blind randomized controlled trial where information was compared between two groups of coblation and HS tonsillectomy. A total number of 128 patients were compared over operation time, intra-operative blood loss, postoperative pain, time needed to regain the normal diet and activity and postoperative haemorrhage. We found statistically significant differences in operation time (p < 0.001) and intra operative blood loss (p < 0.001). Secondary haemorrhage rate was far better in HS (1.5%) group compared to coblation (7.8%). Whereas postoperative pain, time needed to go back to the normal diet and activity were better in HS group but the difference is not significant. This study revealed a significantly less operative time and intra-operative and post operative blood loss in harmonic scalpel tonsillectomy in comparison with coblation method. These findings addressed HS tonsillectomy as an advanced method.


Increased calpain expression following experimental cerebral venous thrombosis in rats.
Calpains are intracellular proteases that are activated by increased intracellular calcium with proteolytic activity mainly against the cytoskeleton. We tested the expression of calpains and their substrates in an animal model of experimental cerebral venous thrombosis. Cerebral venous thrombosis was induced in seven male rats by rostral and caudal ligation of the superior sagittal sinus and injection of a thrombogenic cephalin suspension. Each animal survived 3 h of thrombosis. Using a polyclonal antibody against the 80 kD subunit of micro-calpain, immunohistochemistry of the region of interest (venous infarction) showed a loss of microtubule-associated protein-2. The micro-calpain-positive cells in the region of interest and normal tissue were measured using a video-imaging microscopy unit with magnification power of 400x. A cell was considered calpain positive when the nucleus and the periplasma were stained by the micro-calpain antibody. The mean infarct size was 13.4+/-3.7% of one whole coronal section. A total of 57+/-14% of the cells were found to be calpain positive in the region of interest, whereas 5+/-2% of all cellular elements in unaffected tissue were calpain positive (p<0.001). In conclusion, cerebral venous thrombosis causes an increase in calpain expression in affected tissue which is manifested by a loss of microtubule-associated protein-2. This increase might mediate secondary neuronal injury.


circ_0004140 promotes LUAD tumor progression and immune resistance through circ_0004140/miR-1184/CCL22 axis.
Lung adenocarcinoma (LUAD) is a highly prevalent cancer with high mortality. Immune resistance and tumor metastasis are the pivotal factors for the promotion of LUAD. CircRNAs have been revealed a crucial pre-clinical diagnostic and therapeutic potentials in LUAD. Herein, we identify a novel circRNA (circ_0004140), derived from the oncogene YAP1, which is up-regulated in LUAD. The high expression of circ_0004140 is correlated with poor prognosis and CTL cells dysfunction in LUAD patients. Knockdown of circ_0004140 regulated LUAD cells proliferation, migration, and apoptosis. Mechanistically, circ_0004140 served as a sponge of miR-1184 targeting C-C motif chemokine ligand 22(CCL22). Overexpression of CCL22 reversed the inhibitory effect induced by si-circ_0004140 on cells proliferation and migration. Moreover, we also revealed that elevated circ_ooo4140 was related to cytotoxic lymphocyte exhaustion, and a combination therapy of C-021 (CCL22/CCR4 axis inhibitor) and anti-PD-1 attenuated LUAD promotion and immune resistance. In conclusion, circ_0004140 may drive resistance to anti-PD-1 immunotherapy, providing a novel potential therapeutic target for LUAD treatment.


Training in Safe Opioid Prescribing and Treatment of Opioid Use Disorder in Internal Medicine Residencies: a National Survey of Program Directors.
Training future clinicians in safe opioid prescribing (SOP) and treatment of opioid use disorder (OUD) is critical to address the opioid epidemic. The Accreditation Council on Graduate Medical Education requires all programs to provide instruction and experience in pain management and will mandate addiction medicine clinical experiences for internal medicine trainees. Assess residents' training in SOP and treatment of OUD and identify training barriers. Cross-sectional nationally representative survey was emailed in 2019. Four hundred twenty-two Association of Program Directors in Internal Medicine members in US internal medicine residency programs. Program opportunities and challenges to developing or implementing training in SOP, treatment of OUD, and buprenorphine waiver training, and perceived curricular effectiveness. The response rate was 69.4% (293/422). Most programs required didactics in SOP (94.2%) and treatment of OUD (71.7%). Few programs required clinical experiences including addiction medicine clinics (28/240, 11.7%), inpatient consult services (11/240, 4.6%), or offsite treatment rotations (8/240, 3.3%). Lack of trained faculty limited developing or implementing curricula (61.5%). Few respondents reported that their program was "very effective" in teaching SOP (80/285, 28.1%) or treatment of OUD (43/282, 15.3%). Some programs offered buprenorphine waiver training to residents (83/286, 29.0%) and faculty (94/286, 32.9%) with few mandating training (11.7% (28/240) and 5.4% (13/240) respectively). Only 60 of 19,466 (0.3%) residents completed buprenorphine waiver training. Primary care programs/tracks were more likely to offer waiver training to residents (odds ratio [OR], 3.07; 95% CI, 1.68-5.60; P < 0.001) and faculty (OR, 1.08; 95% CI, 1.01-3.22; P = 0.05). In this nationally representative survey, few internal medicine residency programs provided clinical training in SOP and treatment of OUD, and training was not viewed as very effective. Lack of effective training may have adverse implications for patients, clinicians, and society.


Effects of synthesis inhibition and nervous activity on concentrations of neuronal substance P.
1. When dorsal root ganglia were incubated in vitro with a range of concentrations of anisomycin, incorporation of [ 3H ]lysine into protein and synthesis of substance P(SP) were inhibited to a similar extent confirming that SP is synthesised by a conventional ribosomal mechanism. 2. Doses of anisomycin sufficient to inhibit protein synthesis in mouse CNS in vivo by greater than 95% did not cause a significant fall in the SP content of any of five brain areas, spinal cord, dorsal root ganglia or cornea over an 8 h period. 3. Electrical stimulation of the hind limbs however, produced a 25% fall in the SP content of the dorsal spinal cord of these animals. 4. These findings suggest that the turnover-time of neuronal SP is much longer than that of non-peptide neurotransmitters.


The basis function regression in pharmaceutical analysis. Theory and example of application.
The BFR (Basis Function Regression) is an interesting alternative to common techniques (such as PCR or PLS) in chemometrics. It is based on projecting the spectral information onto some number of equally spaced spline bases, than obtaining integrals of resulted curves. Existing references show that in certain cases it can reduce almost twice the RMSEP values. As this technique is not so popular in chemometrics nor applied in pharmaceutical analysis, it is desirable to present its theoretical considerations and implementation (with example MATLAB/Octave code). As an illustrative example we present the chemometric model for content recognition of a tablet (12 possible compounds in binary or ternary combinations) from the UV spectrum of its methanolic extract. The BFR technique gave lowest prediction error and the estimators obtained have more meritorical meaning than in case of PCR, PLS and other techniques used for comparison. In our opinion this technique should be considered in any chemometric approach as it often shows better performance.


Ginkgo biloba extract alleviates fatty liver hemorrhagic syndrome in laying hens via reshaping gut microbiota.
Ginkgo biloba extract (GBE) is evidenced to be effective in the prevention and alleviation of metabolic disorders, including obesity, diabetes and fatty liver disease. However, the role of GBE in alleviating fatty liver hemorrhagic syndrome (FLHS) in laying hens and the underlying mechanisms remain to be elucidated. Here, we investigated the effects of GBE on relieving FLHS with an emphasis on the modulatory role of GBE in chicken gut microbiota. The results showed that GBE treatment ameliorated biochemical blood indicators in high-fat diet (HFD)-induced FLHS laying hen model by decreasing the levels of TG, TC, ALT and ALP. The lipid accumulation and pathological score of liver were also relieved after GBE treatment. Moreover, GBE treatment enhanced the antioxidant activity of liver and serum by increasing GSH, SOD, T-AOC, GSH-PX and reducing MDA, and downregulated the expression of genes related to lipid synthesis (FAS, LXRα, GPAT1, PPARγ and ChREBP1) and inflammatory cytokines (TNF-α, IL-6, TLR4 and NF-κB) in the liver. Microbial profiling analysis revealed that GBE treatment reshaped the HFD-perturbed gut microbiota, particularly elevated the abundance of Megasphaera in the cecum. Meanwhile, targeted metabolomic analysis of SCFAs revealed that GBE treatment significantly promoted the production of total SCFAs, acetate and propionate, which were positively correlated with the GBE-enriched gut microbiota. Finally, we confirmed that the GBE-altered gut microbiota was sufficient to alleviate FLHS by fecal microbiota transplantation (FMT). We provided evidence that GBE alleviated FLHS in HFD-induced laying hens through reshaping the composition of gut microbiota. Our findings shed light on mechanism underlying the anti-FLHS efficacy of GBE and lay foundations for future use of GBE as additive to prevent and control FLHS in laying hen industry.


Steven D. Johnson.
Interview with Steve Johnson, who works on plant-pollinator interactions at the University of KwaZulu-Natal in South Africa.