How to Decide Oxygen Therapy in Childhood Carbon Monoxide Poisoning?
Carbon monoxide poisoning is an important cause of morbidity and mortality all over the world. In our study, it was aimed to determine the clinical and laboratory parameters that may be effective in deciding the need for hyperbaric oxygen therapy in the management of cases. From January 2012 to the end of December 2019, 83 patients who applied to a university hospital pediatric emergency department in İstanbul with the diagnosis of carbon monoxide poisoning were included. Demographic characteristics, carbon monoxide source, exposure duration, treatment approach, physical examination findings, Glasgow Coma Score, laboratory results, electrocardiogram, cranial imaging, and chest x-ray were evaluated from the records. The median age of the patients was 56 (37.0-100.0) months and 48 (57.8%) of them were male. The median time of exposure to carbon monoxide was 5.0 (0.5-3.0) hours in those who received hyperbaric oxygen therapy and was significantly higher than those who received normobaric oxygen therapy (P < .001). Myocardial ischemia, chest pain, pulmonary edema, and renal failure were not detected in any of the cases. The median lactate level was detected as 1.5 (1.0-2.15) mmol/L in those who received normobaric oxygen therapy and 3.7 (3.17-4.62) mmol/L in those who received hyperbaric oxygen therapy, and the difference between them was statistically significant (P < .001). A guideline containing precise clinical and laboratory parameters for hyperbaric oxygen therapy in children has not been developed yet. In our study, carbon monoxide exposure duration, carboxyhemoglobin levels, neurological symptoms, and lactate levels were found to be guiding parameters in determining the need for hyperbaric oxygen therapy.


CARD9 Forms an Alternative CBM Complex in Richter Syndrome.
Richter syndrome (RS) is defined as the transformation of chronic lymphocytic leukemia (CLL) into an aggressive lymphoma, mostly diffuse large B-cell lymphoma (DLBCL). Despite intensive therapy, patients with RS have an unfavorable clinical outcome. The detailed pathobiology of Richter transformation still needs to be elucidated. Here, we report high mRNA and protein levels of CARD9 in the RS cell line U-RT1. Co-immunoprecipitation revealed the assembly of a CBM complex using CARD9 instead of CARD11. CARD9 is known to be an activator of NF-кB signaling in myeloid cells. U-RT1 Western blot analyses showed phosphorylation of IκB as well as IKK, indicating a constitutively active canonical NF-кB pathway. This was further supported by the significant reduction in cell viability and CYLD cleavage products after CARD9 siRNA knockdown. We also showed immunostaining for CARD9 in 53% of cases analyzed in a series of RS tissue specimens, whereas other lymphomas rarely show CARD9 expression. This is the first report on ectopic expression and function of CARD9 in an aggressive B-cell lymphoma. Our findings suggest that CARD9 may contribute to the pathogenesis of RS.


Defibrotide Inhibits Antiphospholipid Antibody-Mediated Neutrophil Extracellular Trap Formation and Venous Thrombosis.
Defibrotide is a heterogenous mixture of polyanionic oligonucleotides currently approved for treatment of transplant-associated venoocclusive disease. While defibrotide has a known role in limiting endothelial cell activation, some studies have also demonstrated anti-leukocyte properties. In a recent study, we found that neutrophil extracellular traps (NETs) play a role in the thrombotic complications of antiphospholipid syndrome (APS). In the present study, we investigated the hypothesis that defibrotide might act to mitigate APS-relevant NET formation in vitro and in mouse models. We used in vitro assays and a mouse model to determine the mechanisms by which defibrotide inhibits NET formation and venous thrombosis in APS. At doses ranging from 1 to 10 μg/ml, defibrotide significantly suppressed NET formation from control neutrophils stimulated with IgG isolated from patients with APS. Defibrotide increased levels of intracellular cyclic AMP in neutrophils, and its suppressive effects on NET formation were mitigated by blocking adenosine A2A receptor or by inhibiting the cyclic AMP-dependent kinase protein kinase A. Defibrotide at doses ranging from 15 to 150 mg/kg/day inhibited NET formation and venous thrombosis in a model of antiphospholipid antibody-accelerated thrombosis-an effect that was reduced in adenosine A2A receptor-knockout mice. This study is the first to demonstrate mechanisms by which defibrotide counteracts neutrophil-mediated thrombotic inflammation inherent to APS.


Gender identity in a group of retarded children.
The Michigan Gender Identity Test (MGIT) was administered to 52 retarded and 36 normal children to assess the acquisition of gender identity. This instrument required the ability to sort and categorize photographs of boys and girls wearing conventional clothing and with conventional hair-styles. As part of the test, each child was expected to recognize a self-photo and to be able to categorize it as a boy or a girl. In general, a significant correlation was found between MGIT performance and mental age for the retarded children. The performance of the normal children correlated significantly with both chronological age and mental age.


In Memory of the Virologist Jianguo Wu, 1957-2022.
It is with deep sorrow that we mourn the passing of the virologist Professor Jianguo Wu [...].


Processing glycosidases of Saccharomyces cerevisiae.
The properties of the N-glycan processing glycosidases located in the endoplasmic reticulum of Saccharomyces cerevisiae are described. alpha-Glucosidase I encoded by CWH41 cleaves the terminal alpha1, 2-linked glucose and alpha-glucosidase II encoded by ROT2 removes the two alpha1,3-linked glucose residues from the Glc3Man9GlcNAc2 oligosaccharide precursor while the alpha1,2-mannosidase encoded by MNS1 removes one specific mannose to form a single isomer of Man8GlcNAc2. Although trimming by these glycosidases is not essential for the formation of N-glycan outer chains, recent studies on mutants lacking these enzymes indicate that alpha-glucosidases I and II play an indirect role in cell wall beta1,6-glucan formation and that the alpha1,2-mannosidase is involved in endoplasmic reticulum quality control. Detailed structure-function studies of recombinant yeast alpha1,2-mannosidase are described that serve as a model for other members of this enzyme family that has been conserved through eukaryotic evolution.


Retraction Note to: Lupeol induces apoptosis and inhibits invasion in gallbladder carcinoma GBC-SD cells by suppression of EGFR/MMP-9 signaling pathway.
[This retracts the article DOI: 10.1007/s10616-014-9763-7.].


A simple, rapid, reliable reverse haemolytic plaque assay and positive quality control test for routine use.
A simple, rapid, reliable protein A reverse haemolytic plaque assay is described. Monolayers of protein A-coupled sheep red blood cells, in liquid medium, are formed in shallow 15 mm diameter chambers of the type commercially available for leucocyte migration inhibition assays. No agarose is necessary and the chambers are quick and easy to use, economical of reagents, and of a constant size and volume. Results compare favourably with those obtained using Cunningham chambers. The assay is ideal for clinical studies in which large numbers of samples are assayed daily. A positive quality control test for the protein A reverse hemolytic plaque assays is described. Spleen cells are stimulated with pokeweed mitogen to give high numbers of secreting cells. The cells are harvested on day 6 of culture and stored in aliquots at -70 degrees C. When thawed and tested in the protein A assay, these secreting cells form a sensitive and reproducible monitor of the day-to-day performance of the assay. Variation between operators and between batches of reagents may also be checked if desired, with little additional time, effort or expense.


Solubility of airborne radioactive fuel particles from the Chernobyl reactor and implication to dose.
Airborne particles of nuclear fuel from the Chernobyl reactor that had been collected on air filters and stored, were characterised using in vitro dissolution tests to assess effective doses after their inhalation. As solvent, the Gamble biological fluid was used to simulate lung fluid. The solubility of the measured radionuclides decreased in the order (137)Cs>(90)Sr>>(241)Am>or=(239+240)Pu in the simulated lung fluid. The dissolution rate constant of e.g. (239+249)Pu ranged from 0.72 to 5.4 x 10(-6) g x cm(-2) d(-1) and decreased (for all nuclides) with increasing particle size as predicted from theoretical considerations. Considering the inhalation dose, decreasing dose with size and increasing doses with lower solubility may partly counterbalance each other for (137)Cs and (90)Sr. On the other hand, for (239)Pu and (241)Am larger particles and associated lower solubility both change the resulting dose in the same direction towards lower values. The comparison of the experimentally determined dose coefficients with ICRP values indicates that nuclear fuel particles closely resemble type M material characteristics for (137)Cs and (90)Sr and type S material characteristics for (239)Pu and (241)Am.


Interaction of penicillin with HLA-A and -B antigens.
When lymphocytes of healthy donors were incubated with penicillin and washed before HLA typing, the cytotoxic reactivity of some typing sera with their corresponding antigen was blocked. When the penicillin was added to the cytotoxicity assay at different times, competition between penicillin and alloantiserum for binding on or near the same epitope on the HLA molecule could be observed. On the basis of the inhibition experiments, HLA antigens can be divided into three groups: 1. Antibody reactivity blocked by penicillin (Bw35) 2. Antibody reactivity not blocked by penicillin (B14) 3. Antibody reactivity blocked by penicillin in some donors but not in others (A2). This third group may provide an opportunity to determine structural differences among, until now, serologically indistinguishable HLA molecules. By adding penicillin to a multispecific serum, containing both antibodies that can and cannot be blocked, a monospecific typing serum can be obtained. The differential effect of penicillin on the HLA antigens was not restricted to complement-dependent cytotoxicity on lymphocytes. Similar results were obtained when the HLA antisera were tested with indirect immunofluorescence on platelets or in absorption experiments.


The Mutation Profile of Calreticulin in Patients with Myeloproliferative Neoplasms and Acute Leukemia.
Calreticulin (CALR) plays important roles in cell proliferation, apoptosis, and immune responses. CALR mutations were described recently in Janus kinase 2 gene (JAK2)-negative or MPL-negative primary myelofibrosis (PMF) and essential thrombocythemia (ET) patients. CALR trails JAK2 as the second most mutated gene in myeloproliferative neoplasms (MPNs). However, little is known about CALR mutation in Chinese patients with leukemia. In the present study, a cohort of 305 Chinese patients with hematopoietic neoplasms was screened for CALR mutations, with the aim of uncovering the frequency of CALR mutations in leukemia and MPNs. Polymerase chain reaction and direct sequencing were performed to analyze mutations of CALR in 305 patients with hematopoietic malignancies, including 135 acute myeloid leukemia patients, 57 acute lymphoblastic leukemia patients, and 113 MPN patients. CALR mutations were found in 10.6% (12 of 113) of samples from patients with MPNs. CALR mutations were determined in 11.3% (6 of 53), 21.7% (5 of 23), and 9.1% (1/11) of patients with ET, PMF, and unclassifiable MPN, respectively. We showed that MPN patients carrying CALR mutations presented with higher platelet counts and lower hemoglobin levels compared to those with mutated JAK2. However, all of the leukemia patients had negative results for CALR mutations.


Pharmacokinetics in Non-Insulin-Dependent Diabetics of the Aldose Reductase Inhibitor, Zopolrestat.
The pharmacokinetics of zopolrestat have been examined in non-insulin-dependent diabetic patients after oral administration of a single dose of 1000 mg zopolrestat. T(max) ranged from 2 to 4 h with a mean C(max) of 100 &mgr;g ml(minus sign1). Mean plasma half-life of zopolrestat was 26.9 h. The same patients were also administered oral doses of 1000 mg day(minus sign1) for 10 consecutive days. Mean T(max) was 4.3 h and mean C(max) was 208 &mgr;g ml(minus sign1). Plasma accumulation, the ratio of AUC((0--24)) for the last dose to AUC((0--24)) for the first dose, was 2.67. Apparent oral clearance was 5.71 ml min(minus sign1) and apparent volume of distribution was 12.9 L. The mean urinary excretion of unchanged drug over the 24-h period following the last dose was 36% of the dose while another 7% of the dose appeared in the urine as an acylglucuronide of zopolrestat. Renal clearance of zopolrestat was 1.82 ml min(minus sign1). Binding of zopolrestat to plasma proteins exceeded 99% and was concentration dependent.


Cyclosporin A inhibits apical secretory K+ channels in rabbit cortical collecting tubule principal cells.
We used the cell-attached patch clamp configuration to examine the effect of basolateral cyclosporin A (CsA) exposure on low conductance K+ channels found in the principal cell apical membrane of rabbit cortical collecting tubule (CCT) primary cultures. Baseline K+ channel activity, measured as mean NPo (number of channels x open probability), was 2.7 +/- 1.1 (N = 29). NPo fell by 69% (0.84 +/- 0.32; N = 32) in cultures pretreated with 500 ng/ml CsA for 30 minutes prior to patching. Chelation of intracellular [Ca2+]i (10 mM BAPTA/AM; N = 8) or removal of extracellular Ca2+ (N = 9), but not prevention of [Ca2+]i store release (10 microM TMB-8; N = 7), abolished CsA-induced inhibition. This suggested that CsA effects were mediated by an initial rise in [Ca2+]i via Ca2+ influx. Either 25 nM AVP (N = 10) or 0.25 microM thapsigargin (N = 8) (causing IP3-dependent and -independent release of [Ca2+]i stores, respectively) augmented, while 25 pM (N = 6) or 250 pM AVP (N = 8) reversed CSA-induced channel inhibition. Apical membrane protein kinase C (PKC) activation with 0.1 microM phorbol ester, PMA (N = 8) or 10 microM synthetic diacylglycerol, OAG (N = 7), mimicked (mean NPo = 0.99 +/- 0.40) the inhibitory effect of CsA. Apical PKC inhibition by prolonged apical exposure to PMA (N = 10) or 100 microM D-sphingosine (N = 6) blocked CsA's effect. Cyclic AMP increasing maneuvers, 10 microM forskolin (N = 5) or 0.5 mM db-cAMP (N = 8), stimulated basal K+ channel activity in the absence of CsA. (1) basolateral exposure to CsA inhibits the activity of apical membrane 13 pS channels responsible for physiologic K+ secretion in rabbit CCT principal cells. (2) The inhibition is mediated by changes in intracellular Ca2+ and activation of apical PKC. (3) Pharmacologic AVP (nM) augments CsA-induced inhibition by releasing intracellular Ca2+ stores; more physiologic AVP (pM) attenuates channel inhibition, probably through cAMP generation. (4) Inhibition of apical secretory K+ channels by CsA likely contributes to decreased kaliuresis and clinical hyperkalemia observed in patients on CsA therapy.


Stat1 negatively regulates angiogenesis, tumorigenicity and metastasis of tumor cells.
Stat1 is deficient or inactive in many types of human tumors whereas some tumors have activated Stat1. Whether Stat1 affects tumor growth and metastasis is unclear. In the present study, we used Stat1 knockout tumor cells to determine (1) whether Stat1 can regulate angiogenesis, growth, and metastasis of tumor cells; and (2) whether Stat1 is required for the inhibitory effect of IFN-beta on the expression of angiogenic factor bFGF. Highly tumorigenic and metastatic RAD-105 tumor cells derived from a fibrosarcoma of a Stat1 knockout mouse were reconstituted with a Stat1 expression vector. The reconstitution of Stat1 suppressed the tumorigenicity and metastasis of RAD-105 cells in nude mice which correlated with a decreased microvessel density and decreased expression of proangiogenic molecules bFGF, MMP-2, and MMP-9 in vivo. Moreover, noncytotoxic concentrations of IFN-beta significantly inhibited the in vitro expression of bFGF in the Stat1-reconstituted cells but not in the Stat1-deficient cells, which was consistent with decreased bFGF expression of Stat1-reconstituted tumors in vivo. Therefore, Stat1 is essential for IFN-mediated inhibition of bFGF production, suggesting that tumor-intrinsic Stat1 is an important mediator for antiangiogenic signals, such as IFN. Collectively, these data demonstrate that Stat1 expressed by tumor cells is a negative regulator of tumor angiogenesis and, hence, tumor growth and metastasis.


Migraine in children.
Migraine is a hereditary disorder afflicting 5 per cent of school-age children. Symptoms are protean and may not include headache. Migraine should be suspected when transitory neurologic disturbances are present that clear completely. A positive family history is the best clue to diagnosis.


Characteristics of bacterial colonization and urinary tract infection after indwelling of double-J ureteral stent.
To investigate the natural history of bacterial colonization on the stent and in the urine after different periods of indwelling ureteral stent placement. A total of 57 double-J stents from 52 patients (21 men and 31 women, mean age 52 years, range 20 to 79) were examined. In all patients, short-term (2 to 3 days) antimicrobial therapy was administered at the time of stenting. Regular urinalysis and urine culture were performed until the stent was removed. The stents were removed by aseptic manipulation, and the proximal and distal tip segments of the stents were obtained. Three culture specimens were acquired from each stent segment (inner surface washing suspension, outer surface washing suspension, and from the stent tip itself). Bacterial colonies were found in 44% (25 of 57) of the stents. Of the multiple pathogens identified, Enterococcus species (6 of 25) was the most common, followed by Escherichia coli (5 of 25). After short-term antibiotic prophylaxis, the bacteria did not colonize within the first 2 weeks of stent placement. However, the colonization rate increased as the duration of the stent placement lengthened. Colonization of the stent was followed by colonization of the urine. The results of our study demonstrated that bacterial colonization at the stent began 2 weeks after indwelling stent placement and that stent colonization preceded urine colonization. The rate of colonization increased with longer periods of stenting.


Impact of fibrinogen levels and modified Glasgow prognostic score on survival of stage III/N2 non-small cell lung cancer patients treated with neoadjuvant therapy and radical resection.
The prognostic value of pretreatment and preoperative fibrinogen plasma levels and the modified Glasgow prognostic score (mGPS) in stage III/N2 non-small cell lung cancer (NSCLC) patients who receive neoadjuvant treatment followed by radical surgery is yet unclear. Fibrinogen levels and mGPS of 84 patients with initial stage III/N2 NSCLC, who received neoadjuvant therapy followed by complete surgical resection from 2002 to 2014 were retrospectively analyzed and correlated with clinical parameters and overall survival (OS). Data were analyzed using log-rank and Cox regression analysis adjusted for clinical and pathological factors. Median serum fibrinogen level after neoadjuvant treatment was 439 mg/dL (IQR 158 mg/dL). Elevated fibrinogen levels (> 400 mg/dL) after neoadjuvant treatment were significantly associated with poorer OS (28.2 months vs. 60.9 months, HR 0.562, p = 0.048). Importantly, a decrease in fibrinogen levels after neoadjuvant treatment (n = 34) was found to be an independent predictor for favorable OS in multivariate analysis (HR 0.994, p = 0.025). Out of 80 patients, 55, 19 and 6 patients had a mGPS of 0, 1 and 2, respectively. Moreover, elevated mGPS after neoadjuvant treatment (mGPS 1-2) showed a non-significant trend for poorer OS compared to mGPS 0 (28.2 vs. 46.5 months, HR 0.587, p = 0.066). Elevated fibrinogen levels after neoadjuvant therapy prior to surgery in stage III/N2 NSCLC patients are associated with significant disadvantage for OS. A decrease in fibrinogen levels after neoadjuvant therapy was found to be a predictor for superior OS in this retrospective patient cohort.


An overview of methodological considerations regarding adaptive stopping, arm dropping, and randomization in clinical trials.
Adaptive features may increase flexibility and efficiency of clinical trials, and improve participants' chances of being allocated to better interventions. Our objective is to provide thorough guidance on key methodological considerations for adaptive clinical trials. We provide an overview of key methodological considerations for clinical trials employing adaptive stopping, adaptive arm dropping, and response-adaptive randomization. We cover pros and cons of different decisions and provide guidance on using simulation to compare different adaptive trial designs. We focus on Bayesian multi-arm adaptive trials, although the same general considerations apply to frequentist adaptive trials. We provide guidance on 1) interventions and possible common control, 2) outcome selection, follow-up duration and model choice, 3) timing of adaptive analyses, 4) decision rules for adaptive stopping and arm dropping, 5) randomization strategies, 6) performance metrics, their prioritization, and arm selection strategies, and 7) simulations, assessment of performance under different scenarios, and reporting. Finally, we provide an example using a newly developed R simulation engine that may be used to evaluate and compare different adaptive trial designs. This overview may help trialists design better and more transparent adaptive clinical trials and to adequately compare them before initiation.


Granulocytosis induced in vivo by a mouse marrow stromal cell line, BMA1, which produces colony stimulating factor.
Nude mice were inoculated with BMA1 cells. These are cells which produce granulocyte-macrophage colony stimulating factor (GM-CSF); They are derived from mouse bone marrow stromal cells transfected with adenovirus 5 DNA. Progressive neutrophilia developed as the tumor grew, but disappeared quickly after local tumor excision. Media conditioned with tumor cells had GM-CSF but neither erythropoietin nor burst-promoting activity. In all the tumors which developed, focal areas of bone formation were found among fibrosarcomatous tissues.


[Long-term evolution of achalasia of the lower esophageal sphincter and intestinal paraneoplasic pseudo-obstruction revealing small cell lung carcinoma].
We report a case of a small cell carcinoma of the lung revealed by chronic intestinal pseudo-obstruction associated with achalasia of the lower esophageal sphincter. Tumoral remission was achieved for more than 21 months after chemoradiotherapy but this did not prevent the paraneoplasic syndrome from persisting and medical treatment was not successful in treating the intestinal pseudo-obstruction or the dysphagia, which was not improved by esophageal dilation.


Three families of automated text analysis.
Since the beginning of this millennium, data in the form of human-generated text in a machine-readable format has become increasingly available to social scientists, presenting a unique window into social life. However, harnessing vast quantities of this highly unstructured data in a systematic way presents a unique combination of analytical and methodological challenges. Luckily, our understanding of how to overcome these challenges has also developed greatly over this same period. In this article, I present a novel typology of the methods social scientists have used to analyze text data at scale in the interest of testing and developing social theory. I describe three "families" of methods: analyses of (1) term frequency, (2) document structure, and (3) semantic similarity. For each family of methods, I discuss their logical and statistical foundations, analytical strengths and weaknesses, as well as prominent variants and applications.


Anticoagulant and antiheparin activities of a pentosan polysulphate.
Pentosan polysulphate (PPS, Hemoclar, MW 6,700) was observed to have a low affinity for ATIII-Sepharose eluting at 0.3M NaCl. Tested in vitro it had, as previously reported, a low potency as an anticoagulant, about 10 times less than heparin on a weight for weight basis. Only the KCCT was affected by low concentrations of PPS unlike heparin by which both thrombin time and KCCT were affected. Upon injection of PPS subcutaneously (50mg) the heparin activity measured by chromogenic anti factor Xa and by KCCT was in the ratio of 2:1. When injected intravenously (40mg) into 3 healthy volunteers a significant prolongation of a modified prothrombin time was observed in 2 subjects. When PPS was added to heparin containing plasma it was observed to completely inhibit heparin at low concentrations (2:1 on a weight to weight basis) when measured in the thrombin and prothrombin time but not in the KCCT. The antiheparin effect of PPS was also observed in a purified system in obviating the heparin potentiation of the rate of inhibition of thrombin by antithrombin III. Observations showed that at higher concentrations of PPS it acted by directly inhibiting thrombin without the intervention of antithrombin III but also to potentiate the rate of fibrin monomer polymerization.


Intensity-modulated radiation therapy for pediatric medulloblastoma: early report on the reduction of ototoxicity.
The combination of cisplatin chemotherapy and radiation therapy for the treatment of medulloblastoma has been shown to cause significant ototoxicity, impairing a child's cognitive function and quality of life. Our purpose is to determine whether the new conformal technique of intensity-modulated radiation therapy (IMRT) can achieve lower rates of hearing loss by decreasing the radiation dose delivered to the cochlea and eighth cranial nerve (auditory apparatus). Twenty-six pediatric patients treated for medulloblastoma were retrospectively divided into two groups that received either conventional radiotherapy (Conventional-RT Group) or IMRT (IMRT Group). One hundred thirteen pure-tone audiograms were evaluated retrospectively, and hearing function was graded on a scale of 0 to 4 according to the Pediatric Oncology Group's toxicity criteria. Statistical analysis comparing the rates of ototoxicity was performed using Fisher's exact test with two-tailed analysis. When compared to conventional radiotherapy, IMRT delivered 68% of the radiation dose to the auditory apparatus (mean dose: 36.7 vs. 54.2 Gy). Audiometric evaluation showed that mean decibel hearing thresholds of the IMRT Group were lower at every frequency compared to those of the Conventional-RT Group, despite having higher cumulative doses of cisplatin. The overall incidence of ototoxicity was lower in the IMRT Group. Thirteen percent of the IMRT Group had Grade 3 or 4 hearing loss, compared to 64% of the Conventional-RT Group (p < 0.014). The conformal technique of IMRT delivered much lower doses of radiation to the auditory apparatus, while still delivering full doses to the desired target volume. Our findings suggest that, despite higher doses of cisplatin, and despite radiotherapy before cisplatin therapy, treatment with IMRT can achieve a lower rate of hearing loss.


Mode division multiplexing using an orbital angular momentum mode sorter and MIMO-DSP over a graded-index few-mode optical fibre.
Mode division multiplexing (MDM)- using a multimode optical fiber's N spatial modes as data channels to transmit N independent data streams - has received interest as it can potentially increase optical fiber data transmission capacity N-times with respect to single mode optical fibers. Two challenges of MDM are (1) designing mode (de)multiplexers with high mode selectivity (2) designing mode (de)multiplexers without cascaded beam splitting's 1/N insertion loss. One spatial mode basis that has received interest is that of orbital angular momentum (OAM) modes. In this paper, using a device referred to as an OAM mode sorter, we show that OAM modes can be (de)multiplexed over a multimode optical fiber with higher than -15 dB mode selectivity and without cascaded beam splitting's 1/N insertion loss. As a proof of concept, the OAM modes of the LP11 mode group (OAM-1,0 and OAM+1,0), each carrying 20-Gbit/s polarization division multiplexed and quadrature phase shift keyed data streams, are transmitted 5km over a graded-index, few-mode optical fibre. Channel crosstalk is mitigated using 4 × 4 multiple-input-multiple-output digital-signal-processing with <1.5 dB power penalties at a bit-error-rate of 2 × 10(-3).


Isoflurane requirements during combined general/epidural anesthesia for major abdominal surgery.
We evaluated the effects of bupivacaine on the requirements for thiopental and isoflurane during combined general/epidural anesthesia. Sixty patients scheduled for colon resection were randomly distributed into six groups that received, before the induction of anesthesia, an epidural (T9-10) bolus (8 mL) followed by an infusion (8 mL/h) of saline (Groups 1 and 4), bupivacaine 0.0625% plus fentanyl 2 microg/mL (Groups 2 and 5), or bupivacaine 0.125% plus fentanyl 2 microg/mL (Groups 3 and 6). We evaluated the amount of thiopental needed to abolish the eyelid reflex and the percentage of isoflurane required to maintain the bispectral index (BIS) between 50 and 60 (Groups 1-3) or the mean arterial blood pressure (MAP) within 20% of basal values (Groups 4-6). All groups required similar doses of thiopental (5 mg/kg); the time of evaluation, but not epidural treatment, had a significant effect (P < 0.0001) on BIS and MAP. After tracheal intubation, MAP and BIS increased by 18% and 49%, respectively (P < 0.05). In the bupivacaine groups, isoflurane requirements similarly decreased by 35% (P < 0.03). For BIS and MAP, the epidural treatment (P < 0.02) and type of evaluation (P < 0.03) had a significant effect; MAP was lower (P < 0.05) with 0.125% bupivacaine. We conclude that epidural bupivacaine does not alter the thiopental dose, but it decreases isoflurane requirements by 35%. This study demonstrates that both doses of bupivacaine and fentanyl induce similar isoflurane-sparing effects. However, patients receiving 0.125% bupivacaine showed lower values of MAP when compared with controls, and thus bupivacaine 0.0625% should be favored during combined anesthesia. In patients undergoing colon resection under combined anesthesia, isoflurane requirements were assessed by changes in blood pressure or bispectral index. Epidural bupivacaine at concentrations of 0.125% or 0.0625% (each with 2 mg/mL of fentanyl) induced the same sparing of isoflurane (35%). The smaller dose produced less hypotension and should be favored.


Maternal exposure to cetylpyridinium chloride impairs oogenesis by causing mitochondria disorder in neonates.
Cetylpyridinium Chloride (CPC) is a common disinfectant with potential mitochondrial toxicity. However, the effects of CPC on female reproduction remains unclear. In the present study, pregnant mice were exposed to environmentally relevant doses of CPC for 3 days, the effects were evaluated in the female offspring. Maternal exposure to CPC caused loss of oocytes in neonatal ovaries. TEM analysis of neonatal ovaries showed CPC caused aberrant mitochondrial morphology including vacuolated and disorganized structure, reduced functional cristae. In addition, CPC decreased mitochondrial membrane potential in neonatal oocytes. Seahorse analysis showed that CPC hampered mitochondrial reserve, manifested as reduced spare respiratory capacity. Furthermore, CPC damaged mitochondrial function and impaired developmental competence of MII oocytes, suggesting a persisting impact into adulthood. In summary, this is the first known demonstration that maternal exposure to CPC caused mitochondrial disorders in neonatal ovaries and had long-term effects on fertility of the female offspring.


Concentrations of heavy metal and radioactivity in surface water and sediment of Hazar Lake (Elaziğ, Turkey).
Concentration of heavy metals and natural gross radioactivity were measured in the surface water and sediment of Hazar Lake (Elaziğ, Turkey). Eight sampling sites were pre-defined in different locations of the lake. A preliminary study on heavy metals (Zn, Fe, Mn, Ni, Cu, Cr, Co and Pb), major elements (Na, K, Ca, Mg) concentrations and natural radioactivity related to 226Ra, gross-alpha and gross-beta radiations in the surface water and deep sediments were determined. The obtained results showed that, in general, the heavy metals (Zn, Fe, Mn, Ni, Cu and Pb) and major elements (Na, K, Ca, Mg) concentrations in water did not exceed WHO (World Health Organization, 1999), EC (Europe Community, 1998), EPA (Environment Protection Agency, 2002) and TSE-266 (Turkish Standard, 1997) guidelines. Generally, heavy metals and major elements concentration of the sediments were found decrease in sequence of Fe>Mg>Ca>Mn>Zn>Ni>Cr>Cu>Co>Pb. The results of this study indicated that a general absence of serious pollution in the Hazar Lake. The results obtained from the radioactivity determination indicate that the surface water radioactivity concentration of 226Ra, gross-alpha and gross-beta were ranging from 0.52+/-0.02 to 2.02+/-0.06 Bq/l and from 0.65+/-0.03 to 2.52+/-0.07 Bq/l and from 0.01+/-0.01 to 0.14+/-0.01 Bq/l, respectively. Deep sediment radioactivity concentrations of 226Ra is ranging from 0.07+/-0.03 to 0.32+/-0.07 Bq/g.


Visualization of individual axons in excised lamprey spinal cord by magnetic resonance microscopy.
The direct visualization of axons within their native tissue environment by magnetic resonance (MR) microscopy is presented for the first time in the excised larval sea lamprey spinal cord. A home-built transverse radio frequency coil of 1.5 mm diameter was used in conjunction with a commercial 400 MHz MR microscopy system, implementing both 2-D and 3-D imaging pulse sequences. Images having nominal voxel sizes of 9x9x500 and 9x9x125 microm(3), respectively, in the lamprey spinal cord were obtained, resolving individual Mauthner and Müller axons. Furthermore, architectural changes associated with axonal degeneration were visualized in the spinal cord of one animal, excised 8 weeks after hemisection of the cord. Although the lamprey previously has not been the subject of MR microscopy investigations, these results demonstrate the method's potential for imaging this axon system, which is an important model of spinal cord injury and regeneration.


Extracellular Vesicles and the Propagation of Yeast Prions.
Infectious proteins or prions are self-replicating transmissible aggregates responsible for heritable traits in yeasts and amyloid diseases in mammals. Extensive investigations into the many prions discovered in the yeast Saccharomyces cerevisiae, and most importantly the [PSI+] prion, shaped our understanding of the cellular mechanisms involved in amyloidosis. [PSI+] arises from the assembly of the translation terminator Sup35p into insoluble fibrillar aggregates leading to nonsense suppression phenotypes. We recently found that infectious Sup35p particles traffic via extracellular (EV) and periplasmic (PV) vesicles in a growth phase and glucose-dependent manner. In this chapter, I will summarize these findings and explain how they fit in current models of yeast prions transmission.


Core-shell structured Z-scheme Ag2S/AgIO3 composites for photocatalytic organic pollutants degradation.
Constructing direct Z-scheme system is a promising strategy to boost the photocatalytic performance for pollution waters restoration, but it is of great challenge because of the requirement of appropriately staggered energy band alignment and intimate interfacial interaction between semiconductors. Herein, a class of core-shell structured Ag2S-AgIO3 Z-scheme heterostructure photocatalysts are designed and developed. Ag2S is generated by the in-situ ion exchange reaction and anchored on the surface of AgIO3, so the intimate interface between AgIO3 and Ag2S is realized. Integration of AgIO3 and Ag2S extends the ultraviolet absorption of AgIO3 to Vis-NIR region, and also promote the charge separation and migration efficiency, contributing to the enhanced photocatalysis activity for composite catalysts. The optimal Ag2S-AgIO4-4 catalyst exhibits a MO photo-degradation rate constant of 0.298 h-1, which reaches 5.77 and 11.4-folds higher than that of AgIO3 (0.044 h-1) and Ag2S (0.024 h-1). The as-obtained composite catalyst exhibits universally photocatalytic activity in disintegrating diverse industrial pollutants and pharmaceuticals. Particularly, driven by natural sunlight, the Ag2S-AgIO4-4 can effectively decompose MO. A plausible Z-scheme photocatalytic mechanism and reaction pathways of MO degradation over composite catalyst are systemically investigated and proposed.


On the evolution of blue proteins.
Amino acid sequences of 8 plastocyanins, 8 azurins, stellacyanin, two regions in human ceruloplasmin (ferroxidase)--all of which proteins are known to bind a blue (type 1) copper--and subunit II of bovine mitochondrial cytochrome c oxidase were compared by statistical methods to assess similarities and derive possible evolutionary relationships. It is suggested that all of the examined proteins are monophyletic. The two ceruloplasmin partial sequences clearly demonstrate that this protein has undergone a duplication. A calculated most parcimonious phylogenetic tree shows the divergence of the azurin and plastocyanin ancestor to be the earliest event. Stellacyanin and later the blue oxidase (ceruloplasmin) evolved from the plastocyanin branch, which the cytochrome c oxidase subunit evolved from the azurin ancestor.


Human iPSC-derived fallopian tube organoids with BRCA1 mutation recapitulate early-stage carcinogenesis.
Germline pathogenic mutations in BReast CAncer (BRCA1) genes are thought to drive normal fallopian tube epithelial (FTE) cell transformation to high-grade serous ovarian cancer. No human models capture the sequence of events for disease initiation and progression. Here, we generate induced pluripotent stem cells (iPSCs) from healthy individuals and young ovarian cancer patients with germline pathogenic BRCA1 mutations (BRCA1mut). Following differentiation into FTE organoids, BRCA1mut lines exhibit cellular abnormalities consistent with neoplastic transformation compared to controls. BRCA1mut organoids show an increased production of cancer-specific proteins and survival following transplantation into mice. Organoids from women with the most aggressive ovarian cancer show the greatest pathology, indicating the potential value to predict clinical severity prior to disease onset. These human FTE organoids from BRCA1mut carriers provide a faithful physiological in vitro model of FTE lesion generation and early carcinogenesis. This platform can be used for personalized mechanistic and drug screening studies.


Assessment of occupational exposure to 4,4'-methylenedianiline by the analysis of urine and blood samples.
Seven workers at a work site where methylenedianiline (MDA) was used as a curing agent for an epoxy resin were studied during 4 workdays and one weekend. Internal exposure was monitored by analysis of 4,4'-MDA in hydrolysed urine and blood. After acidic hydrolysis, MDA was extracted, derivatised by use of pentafluoropropionic anhydride, and determined by gas chromatography and mass spectrometry, with negative ion chemical ionization. There was wide variation of MDA concentrations in hydrolysed blood between the workers (range 10-60 nmol/l). Also, the urinary excretion rate varied considerably both between and within the individual workers (0-90 mumol/h). The urinary excretion displayed some variation in relation to exposed periods. The urinary levels were linearly related to the concentrations in blood (rs = 0.93, P = 0.02). The present results show the value of excretion of MDA in hydrolysed urine and concentrations in blood as means for the biological monitoring of MDA exposure. In this case, the exposure was probably mainly dermal, in spite of extensive protection measures.


Characterization of pokeweed antiviral protein binding to mRNA cap analogs: competition with nucleotides and enhancement by translation initiation factor iso4G.
Pokeweed antiviral protein (PAP) is a type I ribosomal inactivating protein (RIP). PAP binds to and depurinates the sarcin/ricin loop (SRL) of ribosomal RNA resulting in the cessation of protein synthesis. PAP has also been shown to bind to mRNA cap analogs and depurinate mRNA downstream of the cap structure. The biological role of cap binding and its possible role in PAP activity are not known. Here we show the first direct quantitative evidence for PAP binding to the cap analog m(7)GTP. We report a binding affinity of 43.3+/-0.1 nM at 25 degrees C as determined by fluorescence quenching experiments. This is similar to the values reported for wheat cap-binding proteins eIFiso4E and eIFiso4F. van't Hoff analysis of m(7)GTP-PAP equilibrium reveals a binding reaction that is enthalpy driven and entropy favored with TDeltaS degrees contributing 15% to the overall value of DeltaG degrees . This is in contrast to the wheat cap-binding proteins which are enthalpically driven in the DeltaG degrees for binding. Competition experiments indicate that ATP and GTP compete for the cap-binding site on PAP with slightly different affinities. Fluorescence studies of PAP-eIFiso4G binding reveal a protein-protein interaction with a K(d) of 108.4+/-0.3 nM. eIFiso4G was shown to enhance the interaction of PAP with m(7)GTP cap analog by 2.4-fold. These results suggest the involvement of PAP-translation initiation factor complexes in RNA selection and depurination.


Use of wearable technology for performance assessment: a validation study.
The prevalence of osteoarthritis is increasing globally but current compliance with rehabilitation remains poor. This study explores whether wearable sensors can be used to provide objective measures of performance with a view to using them as motivators to aid compliance to osteoarthritis rehabilitation. More specifically, the use of a novel attachable wearable sensor integrated into clothing and inertial measurement units located in two different positions, at the waist and thigh pocket, was investigated. Fourteen healthy volunteers were asked to complete exercises adapted from a knee osteoarthritis rehabilitation programme whilst wearing the three sensors including five times sit-to-stand test, treadmill walking at slow, preferred and fast speeds. The performances of the three sensors were validated against a motion capture system and an instrumented treadmill. The systems showed a high correlation (r(2) > 0.7) and agreement (mean difference range: -0.02-0.03 m, 0.005-0.68 s) with gold standards. The novel attachable wearable sensor was able to monitor exercise tasks as well as the inertial measurement units (ICC > 0.95). Results also suggested that a functional placement (e.g., situated in a pocket) is a valid position for performance monitoring. This study shows the potential use of wearable technologies for assessing subject performance during exercise and suggests functional solutions to enhance acceptance.


Six-year experience of detection and investigation of possible Middle East Respiratory Syndrome coronavirus cases, England, 2012-2018.
Surveillance for Middle East Respiratory Syndrome (MERS) has been undertaken in the UK since September 2012. This study describes the surveillance outcomes in England from 2012 to 2018. This was a descriptive study using surveillance data. Local health protection teams in England report possible MERS cases to the National Infection Service with clinical and laboratory data. A total of 1301 possible MERS cases were identified in the study period. Five cases were laboratory-confirmed MERS. The majority of cases had travelled to Saudi Arabia (56.7%) and United Arab Emirates (25.9%). Fifty-four percent of cases were men and 43.7% were women. The majority of cases (65.1%) were aged 45 years or older. The number of tests increased in the period after Hajj each year. Laboratory-confirmed alternative diagnoses were available for 513 (39.4%) cases; influenza was the most common virus detected (n = 255, 52.4%). Our study highlights the importance of differential diagnosis of influenza and other respiratory pathogens and early influenza antiviral treatment.


Association of Hoover's Sign with Maximal Expiratory-to-Inspiratory Pressure Ratio in Patients with COPD.
In chronic obstructive pulmonary disease (COPD) some patients develop paradoxical inspiratory rib motion, which is termed Hoover's sign. Our objective was to determine whether Hoover's sign is associated with a difference in the maximal expiratory pressure (MEP), the maximal inspiratory pressure (MIP), the MEP/MIP ratio, and other features on pulmonary function tests (PFTs). This observational prospective single-center cohort study enrolled patients with an established diagnosis of COPD with Global initiative for chronic Obstructive Lung Disease (GOLD) stage 3 (severe) and 4 (very severe) based on PFTs. Respiratory pressure measurements were also collected. Patients were examined for the presence or absence of Hoover's sign on physical examination by 2 internal medicine resident physicians trained in examining for Hoover's sign by a pulmonologist. A total of 71 patients were examined for the presence of Hoover's sign. Hoover's sign was present in 49.3% of patients. Observer agreement (k statistic) was 0.8 for Hoover's sign. Median MEP/MIP was significantly greater in patients with Hoover's sign than those without Hoover's sign (1.88 versus 1.16, p<0.001). Patients with Hoover's sign also had a significantly lower MIP (39.0 versus 58.0, p<0.001) and higher residual volume (RV) to total lung capacity (TLC) ratio indicating a higher degree of air trapping (65 versus 59.5, p<0.014). The presence of Hoover's sign in patients with COPD is associated with a higher MEP/MIP ratio. This suggests respiratory pressure measurements can predict diaphragm dysfunction in patients with GOLD stage 3 and 4 COPD. Patients with Hoover's sign were also found to have a lower MIP and more air trapping.


Higher prevalence of vitamin D deficiency in mothers of rachitic than nonrachitic children.
Vitamin D deficiency [serum 25-hydroxyvitamin D <25 nmol/L (<10 ng/mL)] was identified in 92% of rachitic Arab children and 97% of their mothers compared with 22% of nonrachitic children and 52% of their mothers. There was a positive correlation between maternal and child vitamin D levels. We conclude that mothers of rachitic children should be investigated and treated for vitamin D deficiency.


Optimal tracers for parallel labeling experiments and 13C metabolic flux analysis: A new precision and synergy scoring system.
13C-Metabolic flux analysis (13C-MFA) is a widely used approach in metabolic engineering for quantifying intracellular metabolic fluxes. The precision of fluxes determined by 13C-MFA depends largely on the choice of isotopic tracers and the specific set of labeling measurements. A recent advance in the field is the use of parallel labeling experiments for improved flux precision and accuracy. However, as of today, no systemic methods exist for identifying optimal tracers for parallel labeling experiments. In this contribution, we have addressed this problem by introducing a new scoring system and evaluating thousands of different isotopic tracer schemes. Based on this extensive analysis we have identified optimal tracers for 13C-MFA. The best single tracers were doubly 13C-labeled glucose tracers, including [1,6-13C]glucose, [5,6-13C]glucose and [1,2-13C]glucose, which consistently produced the highest flux precision independent of the metabolic flux map (here, 100 random flux maps were evaluated). Moreover, we demonstrate that pure glucose tracers perform better overall than mixtures of glucose tracers. For parallel labeling experiments the optimal isotopic tracers were [1,6-13C]glucose and [1,2-13C]glucose. Combined analysis of [1,6-13C]glucose and [1,2-13C]glucose labeling data improved the flux precision score by nearly 20-fold compared to widely use tracer mixture 80% [1-13C]glucose +20% [U-13C]glucose.


siRNA-mediated silencing of CD44 delivered by Jet Pei enhanced Doxorubicin chemo sensitivity and altered miRNA expression in human breast cancer cell line (MDA-MB468).
CD44, as a superficial cellular glycoprotein, is an essential factor in cell-cell and cell-matrix interaction. The CD44 expression level has been substantially up-regulated in breast cancer, and this upregulation facilitates tumor proliferation and angiogenesis. This study aims to evaluate the combination therapy of Jet Pei/CD44-specific-siRNA/doxorubicin in breast cancer MDA-MB468 cell line. The MTT assay, wound healing test, colony formation assay, DAPI staining, and flow cytometry were performed to investigate the tumoral cell viability, migration, clonogenesis, and apoptosis progression. The quantitative real-time PCR (qRT-PCR) was performed to demonstrate the CD44 expression level. Finally, the effect of CD44 silencing on the expression of VEGF, CXCR4, MMP9, and MiR-142-3p was measured. The combination of CD44-specific-siRNA with doxorubicin decreased tumoral metastasis, proliferation, invasion, and migration, and increased apoptosis in MDA-MB468 cells. In conclusions, CD44 can serve as a therapeutic target in breast cancer. Moreover, the combination therapy of CD44-specific-siRNA with doxorubicin can be a promising treatment for patients with breast cancer.


Recombinant Listeria monocytogenes expressing an immunodominant peptide fails to protect after intravaginal challenge with herpes simplex virus-2.
Recombinant Listeria monocytogenes expressing a type-common herpes simplex virus (HSV) gB-peptide was shown previously to protect against footpad inoculation with HSV-1. We tested this construct for protection against vaginal challenge with HSV-2. Primed mice demonstrated strong recall responses, had modest reductions in HSV-2 DNA in vaginal mucosa, but were not protected from disease.


Reduced and Delayed Cerebrovascular Reactivity in Patients with Parkinson's Disease.
Cerebrovascular dysfunction in Parkinson's disease (PD) is heterogeneous and may contribute to disease pathophysiology or progression. There is a need to understand the mechanisms by which cerebrovascular dysfunction is altered in participants with PD. The objective of this study is to test the hypothesis that participants with PD exhibit a significant reduction in the ability of the cerebral vessels to dilate in response to vasoactive challenges relative to healthy controls (HC). The current study uses a vasodilatory challenge while participants undergo functional magnetic resonance imaging to quantify the amplitude and delay of cerebrovascular reactivity in participants with PD relative to age and sex-matched HC. An analysis of covariance was used to evaluate differences in cerebrovascular reactivity amplitude and latency between PD participants and HC. A significant main effect of group was observed for whole-brain cerebrovascular reactivity amplitude (F(1, 28) = 4.38, p = 0.046, Hedge's g = 0.73) and latency (F(1, 28) = 16.35, p < 0.001, Hedge's g = 1.42). Participants with PD exhibited reduced whole-brain amplitude and increased latencies in cerebrovascular reactivity relative to HC. The evaluation of regional effects indicates that the largest effects were observed in the cuneus, precuneus, and parietal regions. PD participants exhibited reduced and delayed cerebrovascular reactivity. This dysfunction may play an important role in chronic hypoxia, neuroinflammation, and protein aggregation, mechanisms that could lead to disease progression. Cerebrovascular reactivity may serve as an important biomarker and target for future interventions. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Clinical asthma phenotypes in the real world: opportunities and challenges.
Asthma is a common, chronic and heterogeneous syndrome, affecting people of all ages, all races and both sexes. It may range from mild disease with barely noticeable symptoms, to very severe disease with constant symptoms that greatly hinder the life of the patient. Guidelines issued by various medical societies provide guidance on how to diagnose and manage asthmatic patients. It is now increasingly recognised that asthma management must be individualised, tailored not only to the severity of the disease but to the phenotypic characteristics of each patient. The aim of asthma treatment is control of asthma and the prevention of risk of exacerbations and fixed airflow limitation. Asthma control can be easily assessed clinically through simple screening tools such as the use of validated questionnaires and spirometry. The use of inflammatory biomarkers can be an alternative approach that, however, requires more time and resources. Asthma treatment involves the use of controllers, mainly inhaled corticosteroids and long-acting β2-agonists, and relievers, mainly rapid-acting β2-agonists. Controller medications reduce airway inflammation, lead to better symptom control and reduce the risk of future exacerbations. Reliever (rescue) medications alleviate symptoms and prevent exercise-induced bronchoconstriction. Treatment must be based on a "stepwise approach" in order to achieve good control of symptoms and to minimise future risks of exacerbations. That is, less treatment for mild disease, more treatment for severe, uncontrolled disease. Once good asthma control has been achieved and maintained, treatment should be stepped down. In severe asthmatics, phenotypic characterisation becomes more clinically useful and add-on treatment such as anti-immunoglobulin E monoclonal antibodies may be required. Despite our better understanding of asthma, there are still patients who will not respond to treatment and remain symptomatic. Dissemination of guidelines and national plans allowing early diagnosis of asthma as well as access to specialised primary and secondary care for asthmatic patients, personalised treatment and continuity of care may lead to excellence in care and controlled asthma for the majority of patients. Education of the patient in asthma is also very important, as in every chronic disease, as the patients live with the disease every day while they visit a healthcare professional a few times a year. Future planning for new treatments should focus on the needs of such severe asthma patients.


Ferrokinetics and erythropoiesis in man: an evaluation of ferrokinetic measurements.
The plasma iron clearance half-time and plasma iron turnover have usually been interpreted as measures of total erythroid activity and the red-cell utilization of 59Fe has been equated with effective red-cell production. Erythrocyte iron turnover has sometimes been calculated as the product of plasma iron turnover and percentage utilization. We have assessed these measurements as estimates of erythroid activity by comparing them with total marrow iron turnover and red-cell iron turnover determined by the method of Ricketts et al (1975) in 10 normal subjects and 51 patients with an uncomplicated haematological disorder. The results show that the plasma iron clearance half-time does not reflect erythroid activity and that plasma iron turnover can be particularly misleading in patients with reduced marrow activity. Red-cell utilization and erythrocyte iron turnover give a distorted reflection of effective erythropoiesis except in patients with erythroid hypoplasia. Marrow iron turnover and red-cell iron turnover provide more realistic and generally applicable assessments of the degree and effectiveness of erythroid activity.


[So-called "celery-carrot-mugwort-spice syndrome." RAST results with new spice discs].
RAST investigations on the sera of 27 patients suffering from celery allergy showed specific IgE to mugwort and birch in 15 cases; sensitization to mugwort or birch alone only occurred in 5 and 7 cases, respectively. Positive RAST results were also obtained with several spices. We found a relationship between spice and celery allergy.


Glutamate release inhibitors: a critical assessment of their action mechanism.
A number of important experimental data do not support the widespread hypothesis that Na(+)-channels block is cerebroprotective, essentially because it reduces presynaptic glutamate release: (i) the inhibition of exocytosis by these compounds is not specific to glutamate; (ii) aspartate efflux produced by various stimuli was also reduced, but aspartate cannot be released by exocytosis because it is not concentrated within presynaptic vesicles; and (iii) glutamate accumulated extracellularly during ischaemic or traumatic insult to the CNS is mainly of cytosolic origin. As an alternative, we propose that use-dependent Na(+)-channel blockers enhance the resistance of nerve cells to insults, primarily by decreasing their energy demand, and that reduced efflux of glutamate and other compounds is a consequence of attenuated cellular stress.


A First Step for the Molecular Characterization of Neurological Involvement of Behçet Syndrome: an Italian Pivotal Study.
Behçet syndrome (BS) is a vasculitis characterized by several clinical manifestations including the rare neurological involvement (neuro-BS, NBS). The aim of our pivotal study was to investigate the mutational status of several inflammation-related genes in a cohort of Italian patients with and without the neurological involvement (20 NBS vs 40 no-NBS patients). The preliminary in silico single nucleotide polymorphism (SNP) selection and primer design were performed by NCBI Primer-Blast tool. Genomic DNA was isolated and amplified using PCR. PCR amplicons were sequenced and bioinformatically analysed. Twelve tagSNPs were selected and genotyped: ERAP1 rs30187, rs17482078, and rs27044; IL10 rs1800872 and rs1518111, IL12A rs17810546, IL23R rs17375018, IL23R-IL12RB2 rs924080, STAT4 rs7572482, CCR1 rs7616215, KLRC4 rs2617170, and UBAC2 rs3825427. ERAP1 and IL23R SNPs showed statistically significant higher frequencies in NBS group than no-NBS. ERAP1 rs30187 AA was more common in no-NBS patients (20.0% NBS vs 47.5% no-NBS; p < 0.05), while rs17482078 GA frequency was higher in NBS patients (55.0% NBS vs 22.5% no-NBS; p < 0.05, OR: 4.21). IL23R rs17375018 GG was more frequent in NBS group (65.0% NBS vs 40.0% no-NBS; p < 0.05), according to a previous finding. No other statistically significant differences were found. In conclusion, ERAP1 and IL23R SNPs were found associated with neurological involvement of BS. Additional and larger analyses were required to verify our preliminary findings.


Pharmacokinetics and safety of tiotropium+olodaterol 5 μg/5 μg fixed-dose combination in Chinese patients with COPD.
Chronic obstructive pulmonary disease (COPD) is one of the major causes of morbidity and mortality worldwide and in China. For patients with more severe symptoms, initial treatment with long acting β2-agonists and long-acting muscarinic antagonists combination therapy is recommended. Tiotropium + olodaterol fixed-dose combination (Tio + Olo FDC) is an aqueous solution of tiotropium bromide and olodaterol delivered by the RESPIMAT® Soft Mist™ inhaler for patients with moderate to very severe COPD. This single site, open-label, phase Ib clinical study assessed the pharmacokinetic (PK) and safety profiles of once-daily Tio + Olo FDC (5 μg/5 μg) after single dose and at steady state in Chinese patients with moderate to severe COPD over 3 weeks. The PK and safety profiles of Japanese and Caucasian populations from 2 independent COPD studies were provided for comparison. A total of 12 Chinese patients received Tio + Olo FDC. After multiple inhaled administration of Tio + Olo FDC, tiotropium and olodaterol were rapidly absorbed and reached peak plasma concentration at about 5 and 25 min, respectively. The accumulation ratios after multiple administrations were 1.3 and 1.6 for tiotropium and olodaterol in Chinese patients. Tio + Olo FDC was well-tolerated; all AEs were mild. Tio + Olo FDC (5 μg/5 μg) was rapidly absorbed and had a good safety profile in Chinese patients with COPD.


An unsubstituted C2 hydrogen of adenine is critical and sufficient at the -11 position of a promoter to signal base pair deformation.
The conserved A:T base pair at the -11 position of the promoters in Escherichia coli is very sensitive to substitutions. In vitro transcription with the galP1 promoter having a natural or unnatural base in either strand at position -11 showed that only a purine base with no side group at C2 in the nontemplate strand is transcriptionally potent; neither a purine with an amino group at C2 nor a pyrimidine support transcription. The amino group at C6 in the omnipresent adenine at -11 does not play any role in promoting transcription. The nature of the base, complementary or noncomplementary, at -11 in the template strand also does not influence transcription. We propose that the adenine, by becoming extrahelical, interacts with an amino acid(s) of the 2.3-2.4 region of sigma for which an unsubstituted C2 hydrogen is critical.


The immediate psychological effects of Coronavirus Disease 2019 on medical and non-medical students in China.
To investigate the immediate psychological effects of Coronavirus Disease 2019 (COVID-19) on medical and non-medical students. An online survey of 805 medical students and 1900 non-medical students was conducted from Feb 4, 2020 to Feb 7, 2020, in China. The questionnaire measured the subjective estimated severity of COVID-19, the impact of the outbreak, and the levels of anxiety and depression of both medical and non-medical students. Medical students estimated COVID-19 to be more serious and disastrous than non-medical students, while they scored lower than non-medical students on the Impact of Event Scale-Revised (IES-R), and less severe anxiety and depression than non-medical students. The students experienced greater impact from the outbreak and a higher rate of anxiety and depression with increased time focusing on the outbreak. The difference in psychological effects between medical and non-medical students was further enlarged when focusing time was prolonged. The immediate psychological effects of COVID-19 on medical and non-medical students exhibit different characteristics. The outcome of this study provides implication that providing accurate and transparent information about the epidemic and appropriate COVID-19-based knowledge in accessible ways will contribute to the public's mental health during the outbreak.


Induction of suppressors of cytokine signaling (SOCS) in the retina during experimental autoimmune uveitis (EAU): potential neuroprotective role of SOCS proteins.
Suppressors of cytokine signaling (SOCS) are implicated in immunopathogenic mechanisms of autoimmune diseases. We show here that SOCS expression in retina is temporarily correlated with progression of experimental autoimmune uveitis (EAU), an organ-specific autoimmune disease that serves as model of human uveitis. Peak of EAU correlates with highest SOCS genes expression while disease resolution coincides with their down-regulation. Surprisingly, SOCS5 is constitutively expressed in retina. SOCS5 expression increases significantly during EAU and remains elevated even after disease resolution. Our data suggest that cytokine-inducible SOCS members may be involved in negative regulation of inflammatory cytokines activities during EAU, while constitutively expressed SOCS5 may have neuroprotective functions.


A fulminant case of Guillain-Barré syndrome: topographic and fibre size related analysis of demyelinating changes.
In a necropsy case of early fulminant Guillain-Barré syndrome, demyelinating changes were observed throughout the peripheral nervous system, most conspicuous in the spinal nerve roots. The central/peripheral nervous system transition regions and most proximal zones of the roots escaped damage. In some root areas there were widespread early changes in myelin sheaths in the absence of significant infiltrates of inflammatory cells. In the fibre size analytical study, small myelinated fibres were preferentially involved.


Usefulness of daptomycin lock therapy in children with catheter-related bacteremia after failed vancomycin lock therapy.
Catheter-related bacteremia (CRB) is a significant cause of morbidity, resource expenditure and prolonged hospital stays in patients with long-term catheters, whose numbers have increased considerably in recent years. Antibiotic lock therapy reaches high concentrations in the catheter, allowing good penetration into the biofilm, being vancomycin the most commonly used one in gram-positive infections. Several authors have recently reported the superior in vitro efficacy of daptomycin compared with vancomycin, especially for eradicating biofilms. Although there is some data on the use of daptomycin for antibiotic lock in animal models and adults, there are no data on its use in children. A descriptive study was conducted in a tertiary hospital, including patients younger than 16 years in whom daptomycin lock therapy was employed between 2018 and 2022. We report three pediatric patients in whom CRB was confirmed on admission by paired blood cultures positive for CoNS sensitive to vancomycin, daptomycin and linezolid. All patients started vancomycin lock therapy and systemic antibiotic therapy with proven sensitivity for the isolated bacteria, without achieving negative blood cultures. Due to the persistence of positive cultures, vancomycin lock therapy was replaced by daptomycin, and blood cultures turned negative, with no relapses or need for catheter removal. The use of daptomycin lock therapy could be considered in children with CoNS catheter infection, especially when other antibiotic lock therapy had failed.


Dependence of induction of osteocalcin gene expression on the presence of wild-type p53 in a murine osteosarcoma cell line.
The p53 gene undergoes rearrangement in a high percentage of osteosarcomas, resulting in loss of its expression. A p53-null murine osteosarcoma cell line F6 was transfected with either a wild-type or a mutant p53 gene. Stably transfected cell lines were obtained, and their differentiation capabilities were compared in vitro with the parental cell line. Alkaline phosphatase and osteocalcin expression were measured as early and late differentiation markers, respectively. Induction of alkaline phosphatase expression was not affected by the presence of either p53 gene, whereas osteocalcin expression was seen in cells containing the wild-type p53 gene but not in the parental p53-null or mutant-expressing cell lines. That the induction of osteocalcin was intrinsically dependent on the presence of wild-type p53 was also indicated by the use of a temperature-sensitive Val 135 p53 mutant at 32 degrees C; predominant expression of p53 in the wild-type conformation resulted in osteocalcin expression. While the wild-type p53 gene could suppress tumor formation in vivo, the tumors expressing the mutant p53 gene grew two to three times as large as the tumors that did not express p53. Therefore, the absence of end-point differentiation in bone due to p53 rearrangements may contribute to the maintenance of the tumorigenic phenotype in osteosarcomas.


Bilateral metachronous germinoma of the basal ganglia occurring long after total removal of a mature pineal teratoma: case report.
We report the extremely rare occurrence of a second germ cell tumor at a different site and with different histological types long after total removal of a mature pineal teratoma. A 10-year-old boy who presented with headache and vomiting was admitted to our hospital. Neuroradiological studies revealed a tumor in the pineal region. The tumor was totally removed. Histologically, the tumor proved to be a mature teratoma. The patient's postoperative course was uneventful. The patient received no adjuvant therapy and was followed in the outpatient clinic. Three years later, he was readmitted with transient left upper limb weakness and vomiting. Neuroradiological studies showed a tumor in the bilateral basal ganglia. The second tumor, which was located in the right basal ganglion, was partially removed for biopsy. Histologically, the tumor proved to be a germinoma. The patient received three cycles of combination chemotherapy consisting of carboplatin and etoposide with radiotherapy. After the second course of chemotherapy, magnetic resonance imaging studies revealed no evidence of the tumor. The second tumor was considered to be a de novo metachronous neoplasm rather than a recurrence of the original mature teratoma. We think that if primordial germ cell groups exist along the midline of the brain, more than two primordial germ cell groups could give rise to metachronous neoplasms at different sites and with different histological types.


Kinetics of circulating cytotoxic T lymphocyte precursors that have a high avidity for donor antigens: correlation with the rejection status of the human cardiac allograft.
Studies on graft infiltrating cells demonstrated that accumulation of cytotoxic T lymphocytes (CTL) with high avidity for donor antigens (Ag) coincided with acute cardiac rejection. In the present study, we analyse whether such high-avidity CTL are present within the peripheral blood of cardiac transplant recipients and whether their kinetics correspond with the rejection status of the allograft. Using limiting dilution analysis (LDA), donor-specific CTL were enumerated in serial blood samples of seven patients. From each patient, 7-11 samples were obtained during the first year after transplantation and up to three samples were obtained at a later date. Enumerated donor-specific CTL were divided into CTL with high or low avidity for donor Ag, depending on their sensitivity to CD8-blocking. In contrast to the situation in the graft, the donor-specific CTL present within the peripheral blood were CTL precursors (pCTL) and not fully mature CTL (cCTL). The number of donor-specific pCTL among peripheral blood cells fluctuated irrespective of the rejection grade of the allograft, indicating that the frequency of circulating donor-specific CTL does not reflect the immunological status of the allograft. During acute cardiac rejection, 66% (median) of the circulating donor-specific pCTL had a high avidity for donor Ag. This percentage significantly exceeded pre- and postrejection values obtained during the first year post-transplantation (median, 39% and 37%, respectively). The disparity in avidity increased even further more than 1 year after transplantation, when stable engraftment was achieved. Among donor-specific pCTL in peripheral blood, those with a high avidity were absent (median, 0%). Hence the avidity of circulating donor-specific CTL might inform us about the immune status of the cardiac allograft.


Probenecid-Boosted Tenofovir: A Physiologically-Based Pharmacokinetic Model-Informed Strategy for On-Demand HIV Preexposure Prophylaxis.
Multiple doses of tenofovir disoproxil fumarate (TDF) together with emtricitabine is effective for HIV preexposure prophylaxis (PrEP). TDF is converted to tenofovir (TFV) in circulation, which is subsequently cleared via tubular secretion by organic ion transporters (OATs; OAT1 and OAT3). Using in vitro kinetic parameters for TFV and the OAT1 and OAT3 inhibitor probenecid, a bottom-up physiologically-based pharmacokinetic model was successfully developed for the first time that accurately describes the probenecid-TFV interaction. This model predicted an increase in TFV plasma exposure by 60%, which was within 15% of the observed clinical pharmacokinetic data, and a threefold decrease in renal cells exposure following coadministration of a 600 mg TDF dose with 2 g probenecid. When compared with multiple-dose regimens, a single-dose probenecid-boosted TDF regimen may be effective for HIV PrEP and improve adherence and safety by minimizing TFV-induced nephrotoxicity by reducing TFV accumulation in renal cells.


Thoracoscopic removal of an intrathoracic Kirschner wire. Case report.
We report the clinical case of a clinical case of a 50-year-old woman who had a very rare complication related to the insertion of Kirschner wires for fixation of a left humerus fracture. Sixteen years after the placement of the Kirschner wires, a routine chest X-ray revealed that one of the Kirschner wires had migrated through the pleural cavity. Chest computed tomographic scans confirmed the presence of a metallic wire inside the left lung parenchyma, adjacent to the superior pulmonary artery. This particular case was managed through a video-assisted thoracoscopic approach, and the wire was easily removed from the pleural cavity, thereby avoiding the need of a thoracotomy.


Physicochemical, Stress Degradation Evaluation and Pharmacokinetic Study of AZGH102, a New Synthesized COX2 Inhibitors after I.V. and Oral Administration in Male and Female Rats.
Coxibs such as celecoxib, rofecoxib, and valdecoxib are introduced as selective COX-2 inhibitors to the market. It has been reported that inhibition of COX-2 beside traditional effects of NSAIDs, reduces the risk of colorectal, breast and lung cancers and also slow the progress of Alzheimer's disease. Zarghi et al. reported 8-benzoyl-2-(4-(methylsulfonyl)phenyl)quinoline-4-carboxylic acid (AZGH 102) as a novel compound with similar IC50 to celecoxib besides improved selectivity index (COX-1/COX-2 inhibitory potency) in comparison with celecoxib. In this study, the physicochemical properties of AZGH 102 such as solubility, log P, and stability were evaluated and the pharmacokinetic characteristics of this compound following intravenous (10 mg/Kg), and oral administration (20 mg/Kg), to male and female Wistar rats were investigated. As the data demonstrated, the AZGH 102 classified as lipophil compound and had suitable stability. This derivative absorbs and distributes faster in female than in male. The AUC 0-∞, absolute bioavailability, Cl and Vd were different in both sexes. According to the obtained data, the AZGH 102 has a sex dependent pharmacokinetic in Wistar rats.


A Chilean Experience of Telestroke in a COVID-19 Pandemic Year.
Telemedicine for stroke patients' care (telestroke [TS]) has grown notably in recent decades and may offer advantages during health crisis. Hospital admissions related to stroke have decreased globally during the COVID-19 pandemic, but scarce information is available regarding the effect of COVID-19 in TS. Using a population-based TS registry, we investigated the impact of the first year of the COVID-19 pandemic throughout our TS network in Santiago, Chile. Stroke codes evaluated after the onset of COVID-19 restrictions in Chile (defined as March 15, 2020) were compared with those evaluated in 2019. We analyzed differences between number of stroke codes, thrombolysis rate, stroke severity, and time from the stroke onset to hospital admission. We observed that the number of stroke codes and the number of patients undergoing reperfusion therapy did not change significantly (p = 0.669 and 0.415, respectively). No differences were found with respect to the median time from the stroke onset to admission (p = 0.581) or in National Institutes of Health Stroke Scale (NIHSS) scores (p = 0.055). The decision-making-to-needle time was significantly shorter in the COVID-19 period (median 5 min [IQR 3-8], p < 0.016), but no significant changes were found at the other times. This study demonstrates the potential of adapting TS to extreme situations such as the COVID-19 pandemic, as well as the importance of establishing networks that facilitate patient access to quality treatments.


Bilateral paramedian thalamic infarct in the presence of an unpaired thalamic perforating artery.
Bilateral paramedian thalamic infarction is rare. The suggested mechanism is occlusion of a central unpaired thalamic perforating artery--an anatomic variant. In the few existing reports of this condition, the diagnosis was based on computed tomography (CT) or magnetic resonance imaging (MRI) findings alone. Other causes of thalamic lesions were not ruled out, and there was no angiographic demonstration of the presumed variant artery. We present a case of a 48-year-old man with a bilateral thalamic infarction seen on CT and MRI. Initial neurological examination revealed lethargy, severe combined motor and sensory aphasia, and a mild upward gaze limitation. The patient had no focal motor deficits. After 24 hours, the patient was more alert and his speech became more fluent, but Korsakoff-type amnesia with poor attention span became apparent. The patient improved slowly over 6 months of rehabilitation. Bilateral thalamic lesions can be caused by several conditions. Among those are thiamine deficiency, cerebral lupus, toxoplasmosis, cysticercosis, cerebral syphilitic gumma, and even tumors and fungal infections. All these were ruled out in our case. Superselective digital subtraction angiography (DSA) demonstrated a single unpaired thalamic perforator. To our knowledge, this is the first time this anatomical variant has been demonstrated in vivo in association with bilateral thalamic infarction.


An accessible method to standardize polyethylene microsphere (<100 μm) concentrations for zooplankton ingestion experiments.
The ubiquity of microplastics has caused alarm as to the impact of these materials on aquatic life, leading to experimental studies to understand these effects. In zooplankton bioassays, microspheres (Ms) are often used as a proxy to represent aquatic microplastic contamination due to their homogeneity and small sizes (<100 μm). The present study proposes an accessible protocol that does not require highly specialized equipment for the creation of Ms stock solutions and environmentally realistic experimental concentrations and describes some common issues. Adult females of the calanoid copepod Centropages furcatus underwent treatments of two Ms sizes at experimental concentrations of 10 Ms/mL. They consumed on average 0.9 ± 2.6 Ms/mL of 45-53 μm Ms, and 2.4 ± 1.1 Ms/mL of 38-45 μm Ms. The results are not directly comparable with other studies due to the wide variety of methods used but successfully demonstrate the reproducibility of the proposed protocol.


Concerted Creativity: Emergence in the Socio-(Im)Material and Intangible Practice of Making Music.
The purpose of this article is to explore how the basic conception of 'emergence' informs the study of creativity as a socio-material practice. Initially, the article explicates how creative processes, products and performances involve not only tangible, but also intangible and social elements. Secondly, the theoretical conception of creativity as socio-material and the general philosophical notion of emergence are introduced. Inspired by the idea that a 'whole' is other than the sum of its 'parts' and by examples primarily from the world of music, the article argues that the relationship between subject and object - the main analytical focus of studies on creativity as a socio-material practice - is fundamentally embedded in an emergent process. The article concludes by highlighting how emergence theory acknowledges the performance or product as an intangible material for creative processes of musicians, and that studies of the socio-materiality of creative practices clearly involving tangible, intangible and social elements must refer to the emergent process through which the creative product or performance evolves meaning. The theoretical framework suggested is relevant for researchers interested in exploring how materials, social settings and physical environments are involved in creative processes.


[Renal obstruction during pregnancy. Internal drainage using the JJ ureteral probe].
The advantage of using JJ ureteral stent during pregnancy in case of ureteral obstruction is shown two clinical observations. We use ultrasonography to control the site of this catheter during the operation and for the follow-up of the patients.


Small incision lenticule extraction (SMILE) history, fundamentals of a new refractive surgery technique and clinical outcomes.
This review summarizes the current status of the small incision lenticule extraction (SMILE) procedure. Following the early work by Sekundo et al. and Shah et al., SMILE has become increasingly popular. The accuracy of the creation of the lenticule with the VisuMax femtosecond laser (Carl Zeiss Meditec) has been verified using very high-frequency (VHF) digital ultrasound and optical coherence tomography (OCT). Visual and refractive outcomes have been shown to be similar to those achieved with laser in situ keratomileusis (LASIK), notably in a large population reported by Hjortdal, Vestergaard et al. Safety in terms of the change in corrected distance visual acuity (CDVA) has also been shown to be similar to LASIK. It was expected that there would be less postoperative dry eye after SMILE compared to LASIK because the anterior stroma is disturbed only by the small incision, meaning that the anterior corneal nerves should be less affected. A number of studies have demonstrated a lower reduction and faster recovery of corneal sensation after SMILE than LASIK. Some studies have also used confocal microscopy to demonstrate a lower decrease in subbasal nerve fiber density after SMILE than LASIK. The potential biomechanical advantages of SMILE have been modeled by Reinstein et al. based on the non-linearity of tensile strength through the stroma. Studies have reported a similar change in Ocular Response Analyzer (Reichert) parameters after SMILE and LASIK, however, these have previously been shown to be unreliable as a representation of corneal biomechanics. Retreatment options after SMILE are discussed. Tissue addition applications of the SMILE procedure are also discussed including the potential for cryo-preservation of the lenticule for later reimplantation (Mohamed-Noriega, Angunawela, Lim et al.), and a new procedure referred to as endokeratophakia in which a myopic SMILE lenticule is implanted into a hyperopic patient (Pradhan et al.). Finally, studies reporting microdistortions in Bowman's layer and corneal wound healing responses are also described.


A blood-brain barrier overview on structure, function, impairment, and biomarkers of integrity.
The blood-brain barrier is playing a critical role in controlling the influx and efflux of biological substances essential for the brain's metabolic activity as well as neuronal function. Thus, the functional and structural integrity of the BBB is pivotal to maintain the homeostasis of the brain microenvironment. The different cells and structures contributing to developing this barrier are summarized along with the different functions that BBB plays at the brain-blood interface. We also explained the role of shear stress in maintaining BBB integrity. Furthermore, we elaborated on the clinical aspects that correlate between BBB disruption and different neurological and pathological conditions. Finally, we discussed several biomarkers that can help to assess the BBB permeability and integrity in-vitro or in-vivo and briefly explain their advantages and disadvantages.


Interictal estimation of intracranial seizure onset in temporal lobe epilepsy.
To evaluate the lateralizing and localizing values of interictal focal slow activity (IFSA), single pulse electrical stimulation (SPES) and (18)FDG PET, in order to estimate their potential to complement ictal intracranial recordings and reduce prolonged monitoring in patients with temporal lobe epilepsy. The study includes 30 consecutive patients with bilateral temporal subdural electrodes and focal seizure onset. IFSA, SPES and (18)FDG PET when available, were visually assessed and their combined lateralization was based on the majority of the individual lateralizing tests. In the 18 patients who had all three tests, lateralization was congruent with seizure onset areas in 15 (83%). When lateralized (15 patients), (18)FDG PET was always congruent with intracranial seizure onset. In all 12 patients without (18)FDG PET, lateralization combining IFSA and SPES was congruent with seizure onset, including two with bilateral independent seizure onset on subdural monitoring. 22 out of the 23 patients who had surgery enjoyed favorable outcome (Engel I or II). Intracranial IFSA and SPES can reliably predict the side and site (mesial versus lateral temporal) of seizure onset when they lateralize to the same side. (18)FDG PET can be useful in planning electrode implantation. During intracranial recordings, IFSA and SPES have the potential to reduce telemetry time, risks and costs.


Postpneumonic empyema in childhood: selecting appropriate therapy.
In order to identify appropriate treatment options for postpneumonic empyema, we reviewed the medical records and, when possible, obtained long-term follow-up chest radiographs and pulmonary function tests on children treated for empyema during the past 11 years. Fifty-one patients were treated in various ways, with antibiotics alone (N = 10), or in combination with tube thoracostomy (N = 23) or decortication (N = 18). Despite administration of appropriate antibiotics and establishment of pleural drainage, many children required prolonged hospitalization and eventual decortication. Based on this review, a scoring system was developed allowing early classification by severity of pleural disease. Factors found to be predictors of severe pleural disease include (1) low pleural fluid pH or (2) glucose; (3) presence of moderate or severe scoliosis or (4) pleural peel or parenchymal entrapment by chest radiography; and (5) infection due to anaerobes, gram-negative organisms, or mycoplasma. Complete opacification of a hemithorax on chest radiography and a pleural peel to thoracic ratio greater than 40% were also associated with severe pleural disease. In patients with mild disease (N = 7), response to antibiotics alone, rapid resolution of fever, and shorter hospital stays were observed. In patients with more severe infections (moderate = 22, severe = 22), decortication accomplished earlier defervescence, radiographic improvement, and hospital discharge than simple tube thoracostomy. No deaths or morbidity were associated with decortication, which could often be accomplished through a minithoracotomy. Follow-up chest radiographs and pulmonary fuction tests showed a prompt return to normal after decortication. This experience indicates utility of a pleural disease severity scoring system in selection of treatment options for children with postpneumonic empyema.(ABSTRACT TRUNCATED AT 250 WORDS)


Microwave synthesized complex concentrated alloy coatings: Plausible solution to cavitation induced erosion-corrosion.
Surface phenomenon such as cavitation erosion-corrosion limits the working life and durability of the fluid machines through significantly altering the efficiency. Surface modification is an apparent and economical route for improving the sustainability of these components. Recently developed complex concentrated alloys (CCAs) or high entropy alloys (HEAs) possess exceptional properties owing to high configurational entropy. We developed CCA coatings on the stainless steel using a facial and effective microwave processing technique. The effect of Al molar fraction in AlxCoCrFeNi (x = 0.1-3) CCAs on ultrasonic cavitation erosion-corrosion was investigated in 3.5% NaCl solution. For comparison, cavitation erosion and electrochemical corrosion behavior of the pre- and post-tested samples was also performed. Detailed microstructure and mechanical characterization of the developed coatings were also preformed using different analytical techniques. The equimolar CCA coating showed apical degradation resistance under both pure erosion and erosion-corrosion conditions. The observed behavior is attributed to high strain hardening, optimal hardness, fracture toughness, and utmost stability of the passive layer. The phenomenal conjugation of these properties was associated with highest configurational entropy for equimolar composition resulting in sluggish diffusion, and severe lattice straining. Compared to pits, striations and cracks characterizing the morphology of the degraded stainless steel, the equimolar and Al0.1CoCrFeNi CCAs showed TTS (tearing topograph surface) as the dominant failure mode characterized by presence of microplastic deformation. The degradation of the Al3CoCrFeNi CCA occurred mainly through brittle failure mode. The difference in failure mechanism is related to the mechanical properties and underlying microstructure.


Hospitalization Patterns for Inpatient Pediatric Surgery and Procedures in California: 2000-2016.
We report hospitalization patterns from 2000 to 2016 for young children (ages 0-5 years old) in California who underwent 1 of the 20 most common inpatient procedures that required general anesthesia and evaluate the estimated probability of treatment at a tertiary care children's hospital (CH) by year. We hypothesized that children ≤5 years old increasingly undergo care at tertiary care CHs for common inpatient surgeries or other procedures that require general anesthesia. Data from the California Office of Statewide Health Planning and Development dataset were used to determine procedure, patient age, year of procedure, and hospital name. Hospitals were designated as either tertiary care CHs, children's units within general hospitals (CUGHs), or general hospitals (GHs) based on the California Children's Services Provider List. A tertiary care CH was defined using the California Children's Services definition as a referral hospital that provides comprehensive, multidisciplinary, regionalized pediatric care to children from birth up to 21 years of age with a full range of medical and surgical care for severely ill children. We report the unadjusted percentage of patients treated at each hospital type and, after controlling for patient covariates and comorbidities, the estimated probability of undergoing care at a tertiary care CH from 2000 to 2016. There were 172,318 treatment episodes from 2000 to 2016. The estimated probability of undergoing care at a tertiary care CH increased from 63.4% (95% confidence interval [CI], 62.4%-64.4%) in 2000 to 78.3% (95% CI, 77.3%-79.4%) in 2016. Children ≤5 years old undergoing common inpatient procedures that require general anesthesia increasingly receive care at tertiary care CHs in California.


Soluble c-kit proteins and antireceptor monoclonal antibodies confine the binding site of the stem cell factor.
The binding of the stem cell factor (SCF) to the c-kit-encoded receptor tyrosine kinase stimulates a variety of biochemical responses that culminate in cellular proliferation, migration, or survival. The extracellular domain of p145kit consists of five immunoglobulin-like domains. To confine the ligand binding site to this portion of the receptor we generated a panel of murine monoclonal antibodies (mAbs) to the Kit protein and identified two mAbs that efficiently displaced receptor-bound SCF and also inhibited proliferation of SCF-dependent human megakaryocytes. To map the epitopes of these mAbs we constructed and expressed soluble portions of the extracellular domain of Kit, which included either the two amino-terminal Ig-like domains (denoted Kit 1-2), three Ig-like domains (Kit 1-2-3), or the entire extracellular portion (Kit-X). All three recombinant proteins were recognized by the ligand inhibitory mAbs, suggesting that the SCF binding site resides in the amino-terminal half of the ecto-domain. Consistent with this conclusion, all of the soluble proteins inhibited SCF binding to Kit-expressing cells, and they also underwent specific covalent cross-linking to the radiolabeled ligand. However, whereas Kit 1-2-3 and Kit-X displayed comparable ligand affinities, deletion of the third Ig-like domain, in Kit 1-2, involved significant reduction in SCF binding. Hence, the binding site of SCF probably includes Ig-like domains 1 and 2, but structural determinants distal to this portion may also participate in ligand recognition.


Using video presentation to recruit healthcare workers during COVID-19 pandemic.
During COVID-19 pandemic, the recruitment of new personnel was necessary to guarantee an adequate healthcare level to all patients affected by SARS-CoV-2 virus. In order to deal with the sanitary emergency, unusual selection procedures have been adopted inside the public health system by searching for new healthcare personnel. The recruitment of new candidates with a short self-introduction was very effective and permitted to select 65 nurses.


Optimized electrostatic surfaces parallel increased thermostability: a structural bioinformatic analysis.
It has been known for some time that thermophilic proteins generally have increased numbers of non-covalent interactions (salt bridges, hydrogen bonds, etc.) compared with their mesophilic orthologs. Recently, anecdotal structural comparisons suggest that non-specific acid-base ion pairs on the protein surface can be an evolutionary efficient mechanism to increase thermostability. In this comprehensive structural analysis, we confirm this to be the case. Comparison of 127 orthologous mesophilic- thermophilic protein groups indicates a clear preference for stabilizing acid-base pairs on the surface of thermophilic proteins. Compared with positions in the core, stabilizing surface mutations are less likely to disrupt the tertiary structure, and thus more likely to be evolutionarily selected. Therefore, we believe that our results, in addition to being theoretically interesting, will facilitate identification of charge-altering mutations likely to increase the stability of a particular protein structure.


Stimulation of human peripheral lymphocytes via CD3 and soluble antigen abrogates specific antibody production by reducing memory B cell numbers.
Human B cells are polyclonally activated in vitro by T cells stimulated with immobilized anti-CD3 monoclonal antibodies. We have analysed the effect of CD3 ligation on the production of antigen-specific antibodies, using peripheral blood lymphocytes from tetanus toxoid vaccinated blood donors. High levels of antigen-specific antibodies were obtained after stimulation with anti-CD3 antibodies for 7 days. Addition of soluble recall antigen did not affect the total amount of Ig produced, but dramatically decreased the antigen-specific response. The addition of IL-2, IL-4, and anti-CD40 or anti-CD28 antibodies or the removal of antigen did not restore the B cell response. Analysis using limiting dilution of B cells showed that the frequency of antigen-specific memory B cells decreased significantly in cultures stimulated with antigen. The antigen-specific B cell response could be completely restored only if the soluble antigen was cross-linked on the surface of the B cells. These results suggested that peripheral memory B cells were eliminated or anergized in the presence of soluble antigen.


Presumed primary immune-mediated thrombocytopenia in four cats.
Feline primary immune-mediated thrombocytopenia (pIMT) is a rare hematological disorder. Platelet-bound antibody assays for cats have variable specificity and sensitivity and are not widely available. Diagnosis of pIMT is made on the basis of exclusion of other identifiable causes of thrombocytopenia and the response to immunosuppressive therapy. This report describes four cats with severe thrombocytopenia and no detectable underlying disease. One cat was euthanased because of pulmonary hemorrhage, while the other cats had frequent relapses, two of these cats developed diabetes mellitus due to long-term corticosteroid therapy. In these cats IMT had a chronic course and responded poorly to therapy with prednisolone. Alternative immunomodulatory drugs may be considered in the treatment of feline IMT.


Cholinergic neurons in the rat nodose ganglia.
Presence of acetylcholine (ACh) in the vagal afferent fibres of the rat was investigated. In the nodose ganglion, which contains the cell bodies of this sensitive contingent, a choline acetyltransferase (ChAT) activity, a choline (Ch) uptake and an endogenous content of acetylcholine were detected. These data were confirmed by ChAT immunohistological visualization.