Tumor microenvironment(TME) and single-source dual-energy CT(ssDECT) on assessment of inconformity between RECIST1.1 and pathological remission in neoadjuvant immunotherapy of NSCLC.

BACKGROUND: The inconformity (IC) between pathological and imaging remissions after neoadjuvant immunotherapy in patients with NSCLC can affect the evaluation of curative effect of neoadjuvant therapy and the decision regarding the chance of surgery. MATERIALS AND METHODS: Patients who achieved disease control(CR/PR/SD) after neoadjuvant chemoimmunotherapy from a clinical trial (NCT04326153) and after neoadjuvant chemotherapy during the same period were enrolled in this study. All patients underwent radical resection and systematic mediastinal lymphadenectomy after neoadjuvant treatments. The pathological remission, immunohistochemistry (CD4, CD8, CD20, CD56, FoxP3, CD68, CD163, CD11b tumor-infiltrating lymphocytes, or macrophages), and single-source dual-energy computed tomography (ssDECT) scans were assessed. The IC between imaging remission by CT and pathological remission was investigated. The underlying cause of IC, the correlation between IC and DFS, and prognostic biomarkers were explored. RESULTS: After neoadjuvant immunotherapy, enhanced immune killing and reduced immunosuppressive performance were observed. 70 % of neoadjuvant chemoimmunotherapy patients were in high/medium IC level. Massive necrosis and repair around and inside the cancer nest were the main pathological changes observed 30-45 days post-treatment with PD1/PD-L1 antibody and were the main causes of IC between the pathology and imaging responses after neoadjuvant immunotherapy. High IC and preoperative CD8 expression (H score ≥ 3) indicate a high pathological response rate and prolonged DFS. Iodine material density ssDECT images showed that the iodine content in the lesion causes hyperattenuation in post-neoadjuvant lesion in PCR patient. CONCLUSIONS: Compared to chemotherapy and targeted therapy, the efficacy of neoadjuvant immunotherapy was underestimated based on the RECIST criteria due to the unique antitumor therapeutic mechanism. Preoperative CD8+ expression and ssDECT predict this IC and evaluate the residual tumor cells. This is of great significance for screening immune beneficiaries and making more accurate judgments about the timing of surgery.

Low intake of iodized salt and iodine containing supplements among pregnant women with apparently insufficient iodine status - time to change policy?

BACKGROUND: Iodine is an essential nutrient for human health throughout the life cycle, especially during early stages of intrauterine life and infancy, to ensure adequate neurocognitive development. The growing global reliance on desalinated iodine-diluted water raises the specter of increased iodine deficiency in several regions. The case of Israel may be instructive for exploring the link between iodine status and habitual iodine intake in the setting of extensive national reliance on desalinated water. The aim of this study was to explore the relationship between iodine intake, including iodized salt and iodine-containing supplements intake, and iodine status among pregnant women residing in a sub-district of Israel that is highly reliant on desalinated iodine-diluted water. METHODS: A total of 134 consecutive pregnant women were recruited on a voluntary basis from the obstetrics department of the Barzilai University Medical Center during 2018. Blood was drawn from participants to determine levels of serum thyrotropin (TSH), thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb) and thyroglobulin (Tg). An iodine food frequency questionnaire (sIFFQ) was used to assess iodine intake from food, IS and ICS. A questionnaire was used to collect data on demographic and health characteristics. RESULTS: A total of 105 pregnant women without known or reported thyroid disease were included in the study. Elevated Tg values (≥ 13 µg/L), were found among 67% of participants, indicating insufficient iodine status. The estimated iodine intake (median, mean ± SD 189, 187 ± 106 µg/d by sIFFQ) was lower than the levels recommended by the World Health Organization and the Institute of Medicine (250 vs. 220 µg/day respectively). The prevalence of iodized salt intake and iodine containing supplement intake were 4 and 52% (respectively). Values of Tg > 13 µg/L were inversely associated with compliance with World Health Organization and Institute of Medicine recommendations. CONCLUSIONS: While the Israeli Ministry of Health has recommended the intake of iodized salt and iodine containing supplements, this is apparently insufficient for achieving optimal iodine status among Israeli pregnant women. The evidence of highly prevalent probable iodine deficiency in a sample of pregnant women suggests an urgent need for a national policy of iodized salt regulation, as well as guidelines to promote iodine containing supplements and adherence to them by caregivers. In addition, studies similar to this one should be undertaken in additional countries reliant on desalinated iodine-diluted water to further assess the impact of desalinization on maternal iodine status.

[A Noval Method for Producing Antibacterial Wound Dressing by Using Fused Deposition Molding with Post-3D-printed Process].

Using three-dimensional printing to produce antibacterial wound dressing is a new topic that will change the production style of wound dressing industry. Combining with post-3D-printed process, a desktop fused deposition molding equipment can be used to produce wound dressing containing polyvinyl alcohol, alginate and chitosan. The wound dressing produced by FDM has good aspects of absorbency, moisture vapour transmission rate and mechanical property. After loaded with antibacterial agent iodine and silver nano particle, the antibacterial activity rate increases to 99% and it is suitable to use as antibacterial wound dressing. This method affects the production of wound dressing to a more cost-effective way, and provides a possible individualized treatment for patient in the future.

DNA double strand break (DSB) induction and cell survival in iodine-enhanced computed tomography (CT).

A multi-scale Monte Carlo model is proposed to assess the dosimetric and biological impact of iodine-based contrast agents commonly used in computed tomography. As presented, the model integrates the general purpose MCNP6 code system for larger-scale radiation transport and dose assessment with the Monte Carlo damage simulation to determine the sub-cellular characteristics and spatial distribution of initial DNA damage. The repair-misrepair-fixation model is then used to relate DNA double strand break (DSB) induction to reproductive cell death. Comparisons of measured and modeled changes in reproductive cell survival for ultrasoft characteristic k-shell x-rays (0.25-4.55 keV) up to orthovoltage (200-500 kVp) x-rays indicate that the relative biological effectiveness (RBE) for DSB induction is within a few percent of the RBE for cell survival. Because of the very short range of secondary electrons produced by low energy x-ray interactions with contrast agents, the concentration and subcellular distribution of iodine within and near cellular targets have a significant impact on the estimated absorbed dose and number of DSB produced in the cell nucleus. For some plausible models of the cell-level distribution of contrast agent, the model predicts an increase in RBE-weighted dose (RWD) for the endpoint of DSB induction of 1.22-1.40 for a 5-10 mg ml-1 iodine concentration in blood compared to an RWD increase of 1.07 ± 0.19 from a recent clinical trial. The modeled RWD of 2.58 ± 0.03 is also in good agreement with the measured RWD of 2.3 ± 0.5 for an iodine concentration of 50 mg ml-1 relative to no iodine. The good agreement between modeled and measured DSB and cell survival estimates provides some confidence that the presented model can be used to accurately assess biological dose for other concentrations of the same or different contrast agents.

Research needs for assessing iodine intake, iodine status, and the effects of maternal iodine supplementation.

The Office of Dietary Supplements of the NIH convened 3 workshops on iodine nutrition in Rockville, Maryland, in 2014. The purpose of the current article is to summarize and briefly discuss a list of research and resource needs developed with the input of workshop participants. This list is composed of the basic, clinical, translational, and population studies required for characterizing the benefits and risks of iodine supplementation, along with related data, analyses, evaluations, methods development, and supporting activities. Ancillary studies designed to use the participant, biological sample, and data resources of ongoing and completed studies (including those not originally concerned with iodine) may provide an efficient, cost-effective means to address some of these research and resource needs. In the United States, the foremost question is whether neurobehavioral development in the offspring of mildly to moderately iodine-deficient women is improved by maternal iodine supplementation during pregnancy. It is important to identify the benefits and risks of iodine supplementation in all population subgroups so that supplementation can be targeted, if necessary, to avoid increasing the risk of thyroid dysfunction and related adverse health effects in those with high iodine intakes. Ultimately, there will be a need for well-designed trials and other studies to assess the impact of maternal supplementation on neurodevelopmental outcomes in the offspring. However, 2 basic information gaps loom ahead of such a study: the development of robust, valid, and convenient biomarkers of individual iodine status and the identification of infant and toddler neurobehavioral development endpoints that are sensitive to mild maternal iodine deficiency during pregnancy and its reversal by supplementation.

[Assessment of the efficiency of prevention of iodine deficiency among the children's population of the city of Mezhdurechensk of the Kemerovo region].

In the article there are presented results of a study of indices of ioduria in preschool kids and school children of the city of Mezhdurechensk (south of the Kemerovo region). 411 children aged of 3-17 years participated in the study. The median of ioduria on preschooler kids was 97,0 pg/l, and the proportion of urine samples with iodine levels less than 50 pg/l - 1,0%. The median of ioduria in school children is 98,0 pg/l, the percentage of urine samples with iodine levels less than 50 pg/l accounts for 1,3%. On average, on the population of children there was established that the percentage of urine samples with iodine levels from 50-100 pg/l (mild deficiency) was detected in 53,5% of children. Comparative analysis of indices of the level of ioduria according to data obtained in 2008 and 2014 in a group of school children showed that the measures taken to prevent diseases caused by iodine deficiency (the use of iodized salt in the diet of children and adolescents from organized groups on a regular basis) have given positive results.

[Assessment of the using effectiveness of iodine containing additives in development of meat products for child nutrition].

The effectiveness of iodine containing additives on the basis of whey protein and milk protein casein compared to iodized salt in the composition of meat minced semi-finished products for child nutrition was examined in the experiment on laboratory animals. Four variants of the semi-finished products were investigated: 1 - control; 2 - enriched with iodine containing milk protein casein; 3 - enriched with iodine containing whey proteins; 4 - enriched with iodized salt. The semi-finished products were enriched at the level of 15% of the daily norm of iodine requirement for children at the age of 7-12 years. Iodine content in 100 g of product was 20 µkg. Rats (initial body weight 140±20 g, n=80) were divided into five groups (control, intact and three experimental groups). Groups 1 and 5 included the animals fed with a standard vivarium diet throughout the experiment. The rats from groups 2-4 were fed with the iodine enriched diet: group 2 received diet containing semi-finished products No. 2; group 3 sample No. 3 and group 4 - sample No. 4. The first stage of the experiment was aimed at accumulation of iodine in tissues and organs of animals consumed the tested iodine containing additives in the composition of semi-finished products. The second stage of the experiment consisted in simulation of the mercazolilum-induced (50 mg/kg b.w.) hypothyroidism (iodine deficiency) and detection of preventive effects of iodine containing meat semi-finished products in a model of experimental hypothyroidism in rats. The data obtained upon the end of the experiment suggest that the highest effect for correction of iodine deficiency was achieved when using the culinary products enriched with iodine containing whey proteins (sample No. 3): the level of thyroxine (T4) was restored by 98.7% in the animals from group 3 compared to the indices of the intact group, Т3 by 100%, TSH - by 89.3%. This effect was confirmed by the hematological and biochemical blood indexes, as well as the dynamics of their weight change: the level of white blood cells was significantly lower by 28%, granulocytes by 44%, monocytes by 42% compared to control rats; the weight gain of the animals of the 3 group was 20.3%, closer to that of intact animals - 26.4%, while in the control group it was 2.6 %.

Comparative study of disinfectants for use in low-cost gravity driven household water purifiers.

Point-of-use (POU) gravity-driven household water purifiers have been proven to be a simple, low-cost and effective intervention for reducing the impact of waterborne diseases in developing countries. The goal of this study was to compare commonly used water disinfectants for their feasibility of adoption in low-cost POU water purifiers. The potency of each candidate disinfectant was evaluated by conducting a batch disinfection study for estimating the concentration of disinfectant needed to inactivate a given concentration of the bacterial strain Escherichia coli ATCC 11229. Based on the concentration of disinfectant required, the size, weight and cost of a model purifier employing that disinfectant were estimated. Model purifiers based on different disinfectants were compared and disinfectants which resulted in the most safe, compact and inexpensive purifiers were identified. Purifiers based on bromine, tincture iodine, calcium hypochlorite and sodium dichloroisocyanurate were found to be most efficient, cost effective and compact with replacement parts costing US$3.60-6.00 for every 3,000 L of water purified and are thus expected to present the most attractive value proposition to end users.

A Monte Carlo (MC) based individual calibration method for in vivo x-ray fluorescence analysis (XRF).

X-ray fluorescence analysis (XRF) is a non-invasive method that can be used for in vivo determination of thyroid iodine content. System calibrations with phantoms resembling the neck may give misleading results in the cases when the measurement situation largely differs from the calibration situation. In such cases, Monte Carlo (MC) simulations offer a possibility of improving the calibration by better accounting for individual features of the measured subjects. This study investigates the prospects of implementing MC simulations in a calibration procedure applicable to in vivo XRF measurements. Simulations were performed with Penelope 2005 to examine a procedure where a parameter, independent of the iodine concentration, was used to get an estimate of the expected detector signal if the thyroid had been measured outside the neck. An attempt to increase the simulation speed and reduce the variance by exclusion of electrons and by implementation of interaction forcing was conducted. Special attention was given to the geometry features: analysed volume, source-sample-detector distances, thyroid lobe size and position in the neck. Implementation of interaction forcing and exclusion of electrons had no obvious adverse effect on the quotients while the simulation time involved in an individual calibration was low enough to be clinically feasible.

[Application of Monte Carlo sampling method in iodized salt monitoring].

OBJECTIVE: To explore a sampling method which could reflect iodine deficiency disorders (IDD) status at provincial level and discover risk areas with non-iodized salt problem. METHOD: Baseline data of Iodized salt from Gansu and Fujian provinces were analyzed with Monte Carlo method both at county and prefecture levels respectively. True positive rate and false positive rate were also calculated. RESULTS: With data from 7 - 8 villages or 4 - 5 townships counties at risk could be discovered. The true positive rate was around 80% and false positive rate was around 20%. At prefecture level, when randomly selecting and checking 3 counties, the samples would satisfy the discovery of all the risk areas with non-iodized salt problem. CONCLUSIONS: We suggested that the sampling method of iodized salt investigation in national IDD surveillance as follows: to randomly choose 3 counties at each prefecture, 4 townships at each county, 2 villages at each township and 10 salt samples by household survey. The coverage rate of iodized salt in a province could be calculated by post-weighted method with population number.

Anomalous Rayleigh scatter in dilute media.

Anomalous Rayleigh scatter is examined for dilute concentrations of the biomedically relevant element iodine in aqueous media including measurements with monochromatic synchrotron radiation in the vicinity of the iodine K-edge. The measurements agree with anomalous scatter-factor corrections to the form-factor approximation which has been shown to have good agreement with higher precision S-matrix calculations for small angle scatter over a wide range of energies but has not been adequately tested at the edge. Monte Carlo modelling, including the modelling of polarized Compton and Rayleigh scattered x-rays, is used to determine the relative contributions of the scatter and fluorescent components at the detector as well as the modelling of self-absorption and relative dose in the determination of detection limits. A Rayleigh scatter minimum of 28 barns/sr was observed at an energy 10 +/- 5 eV below the K-edge of iodine at a position predicted from an evaluation of the dispersion integral that includes bound-bound resonance contributions. Minimum detectable concentrations for observation of the anomalous Rayleigh scatter feature at an exposure of 10 mSv, predicted for iodine and iron, are 1 mg ml(-1) and 10 mg ml(-1), respectively. Upper limits to detection of the feature imposed by degradation of the signal by self-absorption are 0.021 g cm(-2) and 0.0029 g cm(-2) radiation lengths, respectively.

Comparison of four antiseptic preparations for skin in the prevention of contamination of percutaneously drawn blood cultures: a randomized trial.

A number of skin antiseptics have been used to prevent the contamination of blood cultures, but the comparative efficacies of these agents have not been extensively evaluated. We therefore sought to compare the efficacy of four skin antiseptics in preventing blood culture contamination in a randomized, crossover, investigator-blinded study conducted in an emergency department and the inpatient wards of a university hospital. The patient group included all patients from whom blood samples were obtained percutaneously for culture. Skin antisepsis was performed with 10% povidone-iodine, 70% isopropyl alcohol, tincture of iodine, or povidone-iodine with 70% ethyl alcohol (i.e., Persist). The blood culture contamination rate associated with each antiseptic was then determined. A total of 333 (2.62%) of 12,692 blood cultures were contaminated during the study period compared to 413 (3.21%) of 12,859 blood cultures obtained during the previous 12-month period (relative risk = 0.82; 95% confidence interval, 0.71 to 0.94; P = 0.006). During the study, the contamination rates were determined to be 2.93% with povidone-iodine, 2.58% with tincture of iodine, 2.50% with isopropyl alcohol, and 2.46% with Persist (P = 0.62). We detected no significant differences in the blood culture contamination rates among these four antiseptics, although there was some evidence suggesting greater efficacy among the alcohol-containing antiseptics. Among the evaluated antiseptics, isopropyl alcohol may be the optimal antiseptic for use prior to obtaining blood for culture, given its convenience, low cost, and tolerability.

[Method of quantitative assessment of antimicrobial effects of iodine-containing preparations]. / Metod kolichestvennoi otsenki antimikrobnogo deistviia iodsoderzhashchikh preparatov.

Iodine-containing preparations were studied by UV spectral analysis. Water-soluble composition of 1,3-diethylbenzimidasolium triiodide is inactivated in the presence of meat-peptone broth. Dissolving of these preparations in a mixture of acetone and stearic acid does not change the physicochemical properties or impair the antibacterial effect. A high antibacterial effect of 12 iodine-containing compounds has been demonstrated: 15-min exposure suppressed the growth of bacteria at the minimal concentration of 0.1-1.0 microgram/ml.

The devastating consequence of iodine deficiency.

Endemic cretinism is the most striking consequence of iodine deficiency. Although cretinism is a serious condition, it usually involves only about 5% of the population even in serious endemic areas. There is a spectrum between cretinism and normality, many are able to perform simple work and look apparently normal, but it is difficult for them to perform skilled labor. Studies in China using the IQ distribution curve revealed that every person in an endemic area lost about 10-15 IQ points, so that the socio-economic development of the community was severely affected.

Test for postischaemic hyperaemia: a means of clinical assessment of microcirculatory reactivity in tissues of patients with liability to seasonal ischaemic noxae.

The postischaemic hyperaemia test has been employed to study 30 cases, with a tendency to seasonal exacerbation, 5 at bronchial and 25 at articular level. It was found that in these cases with a tendency to seasonal peaks as many as 73% show an excessive postischaemic hyperaemia even in the phase of clinical normality. This excess regresses (strongly in 33% of the cases, very well in 47%, and moderately in 20%) after the administration of non-steroid anti-inflammatory drugs. By using physiocrenological treatments with waters of high iodine content (baths and aerosol-type inhalations) it is possible to obtain in over 60% of the cases (after an initial increase, a so-called thermal crisis) a definite attenuation of the postischaemic hyperaemia. The study points out the clinical usefulness of the test in sorting out the cases in which drugs might induce an iatrogenic block of the physiological hyperaemia due to work.

A comparison of methods for collecting clean-catch urine specimens in a clinic population of obstetric patients.

A descriptive study comparing the use of the gram-positive skin cleansers Zephiran and hexachlorophene to Prepodyne, a gram-negative cleanser, was performed upon 1, 469 specimens from patients attending the prenatal clinic of a large university hospital. The period prevalence rate of symptomatic and asymptomatic bacteriuria in 1, 350 patients was 11.5 per cent. Group teaching compared to individualized teaching of the patients to collect their own aliquots did not appear to have a measurable effect upon the levels of bacteriuria. Significant differences were found at p equals 0.05 between all the serially sampled groups using the different cleansers. No significant difference was found between the two groups using only hexachlorophene when compared for differences between patient-collected and nurse-collected specimens; nevertheless, the patient-collected specimens had greater proportions of low bacterial counts than those collected by the nurses. This study indicates that carefully instructed patients in large clinic populations are more efficient than the nurses when they collect their own midstream specimens, using an adequate cleansing agent. An analysis of the rates disclosed that Zephiran cleansing had high contamination levels, whereas Prepodyne significantly reduced contamination of the specimens. However, the possible reduction of the rate of 10-5 specimens to 9.1 per cent in the group using Prepodyne did not rule out the possibility of reduced specificity, and the hazard of false-negative results occuring with the use of gram-negative skin cleansers requires further study.