Objectives: This study quantified the burden of hypoxic respiratory failure (HRF)/persistent pulmonary hypertension of newborn (PPHN) in preterm and term/near-term infants (T/NTs) by examining health care resource utilization (HRU) and charges in the United States.

Methods: Preterms and T/NTs (≤34 and >34 weeks of gestation, respectively) having HRF/PPHN, with/without meconium aspiration in inpatient setting from January 1, 2011-October 31, 2015 were identified from the Vizient database (first hospitalization=index hospitalization). Comorbidities, treatments, HRU, and charges during index hospitalization were evaluated among preterms and T/NTs with HRF/PPHN. Logistic regression was performed to evaluate mortality-related factors.

Results: This retrospective study included 504 preterms and 414 T/NTs with HRF/PPHN. Preterms were more likely to have respiratory distress syndrome, neonatal jaundice, and anemia of prematurity than T/NTs. Preterms had significantly longer inpatient stays (54.1 vs 29.0 days), time in a neonatal intensive care unit (34.1 vs 17.5 days), time on ventilation (4.7 vs 2.2 days), and higher total hospitalization charges ($613 350 vs $422 558) (all P<0.001). Similar rates were observed for use of antibiotics (96.2% vs 95.4%), sildenafil (9.5% vs 8.2%), or inhaled nitric oxide (93.8% vs 94.2%). Preterms had a significantly higher likelihood of mortality than T/NTs (odds ratio: 3.6, 95% confidence interval: 2.3-5.0).

Conclusions: The findings of more severe comorbidities, higher HRU, hospitalization charges, and mortality in preterms than in T/NTs underscore the significant clinical and economic burden of HRF/PPHN among infants. The results show significant unmet medical need; further research is warranted to determine new treatments and real-world evidence for improved patient outcomes.

Keywords: health care costs; hypertension; infant; meconium aspiration syndrome; newborn; nitric oxide; pulmonary.

A computerized pharmacy service is ideal for long-term care and a fairly stable resident census at the 812-bed Jewish Home and Hospital for Aged (JHHA). The skilled nursing facility (SNF) now uses pharmacy-generated medication administration records (MARs), drug stop-order lists, and formulary listings. The health-related facility (HRF) self-medicated residents receive individual counseling during pharmacy computer-mediated medication refill appointments. Improvements in clinical services have involved antibiotic and drug use review through selected drug category, computerized drug profiles, and drug regimen review. Administrative and financial benefits have been realized through cost reports and budget reduction, and streamlined internal pharmacy operations. Although most software packages are designed for retail use, pharmacy personnel at JHHA have successfully implemented and tailor designed the AIMS system to the needs of long-term care pharmacy.

An investigation of the effects of apodization on a holographic demultiplexer that is based on a photopolymer grating is presented. Uniform and Gaussian apodized gratings are fabricated in a DuPont HRF-150-38 photopolymer. From the theoretical and experimental results, the spectral response of the apodized grating has a larger main lobe but lower sidelobes than those in the uniform-grating case. A 42-channel demultiplexer that is based on the Gaussian apodized grating with an 0.4-nm channel spacing is demonstrated. A cross-talk level of -30 dB and an interchannel uniformity of 1.5 dB are archived in the wavelength range of approximately 1550 nm.

The production of histamine releasing factor (HRF) by mononuclear cells (MNC) from intrinsic asthmatic patients has previously been reported. In this study, we investigated the effect of preincubation of lymphocytes with autogenic killed bacteria upon the production of HRF. Bacteria were isolated from the sputum, and nasopharyngeal swab obtained from patients and control subjects. MNC from intrinsic asthmatics and healthy controls were preincubated with killed bacteria for 4 h, then washed and cultured for 18 h. HRF activity of the cell-free supernatants was assayed in the histamine release test using basophils from normal subjects. We found that MNC from the patients spontaneously produce significant amounts of HRF. Preincubation of the cells with autogenic bacterial antigens enhanced HRF production in 12 of 25 patients and only in one of 15 control subjects. No specific bacterial strain was identified as having the sole stimulatory property for HRF production; rather, individual susceptibility predisposes to the ability to produce HRF in response to some common bacteria. When MNC from healthy subjects were preincubated with bacterial antigens isolated from the patients, no enhancement in HRF production was observed. We concluded that MNC from some intrinsic asthmatics are specifically sensitized to certain bacterial antigens and release HRF upon contact with these antigens.

The supernatant of mitogen- or antigen-stimulated mononuclear cell cultures is known to contain a large number of biologically active molecules. In the present study, we have stimulated human mononuclear cells and rat spleen cells with Con A or antigen (PPD) respectively to produce lymphokines, such as histamine releasing factor (HRF), which is capable of causing histamine release from rat mast cells and human basophils. Histamine was measured fluorimetrically by Shore et al. This assay is sensitive and reproducible: replicates varied by less than 15% in triplicate samples.

We have recently described a specific antagonist of histamine-releasing factors that inhibits histamine release from basophils and mast cells. This histamine release inhibitory factor (HRIF) is produced by PBMC upon stimulation with histamine as well as mitogens such as Con A. The objective of this study was to investigate the cellular origin of HRIF produced by PBMC. Monocytes, T cells, and B cells were isolated to 96 to 99% purity by a combination of plastic adherence, E rosetting, and negative selection with mAb (OKM1, OKT11, OKB7, OKT4, and OKT8) and C. Purified subpopulations were cultured with histamine or Con A and then the processed supernatants were assayed for the inhibition of HRF-induced histamine release from basophils. The results of this study suggest that the highest amount of HRIF is synthesized by B cells followed by T cells and monocytes. The B cell origin of HRIF was confirmed by abolishing the activity after incubation of the cells with OKB7 mAb and C. Both CD4- and CD8- T cells are capable of producing HRIF. In mixing experiments, the synthesis of HRIF by two different subpopulations has been less than additive. T + B cells produced most of the HRIF activity. Monocytes tended to suppress the synthesis of HRIF by B cells. The synthesis of HRIF by so many cell types suggests that a fine balance between HRIF and HRF may regulate the mediator release from basophils and mast cells.

BACKGROUND

Histamine releasing factors (HRF) are members of the beta chemokine family of cytokines and have been characterized using recombinant proteins. Mononuclear cell and/or platelet supernatants have been shown to contain HRF and the initial void peak obtained using Mono Q anion exchange chromatography possesses such activity, as do two later peaks eluted from the column.

OBJECTIVE

We wished to further characterize the activity present in the void peak and determine which of the chemokines present are responsible for the activity measured.

METHODS

We fractionated the void peak obtained from Mono Q chromatography on Mono S. The elution profile of individual chemokines was determined and the fractions were assayed for histamine releasing capability. We used monospecific antisera to inhibit the activity and quantitate the contribution of each protein.

RESULTS

The fractions contained MCP-1/MCAF, CTAPIII/NAP-2, IL8, and a small quantity of RANTES. About 90-95% of the total histamine containing capability was attributable to MCP-1/MCAF. There was a small contribution by CTAPIII/NAP-2, and RANTES, and no activity associated with IL8.

CONCLUSIONS

MCP-1/MCAF is the critical HRF present in the initial void peak obtained by anion exchange chromatography of supernatants derived from human mononuclear cells and platelets. The alpha chemokine CTAPIII/NAP-2 has relatively weak activity and IL8 has none although they are prominent in this fraction and overlap with MCP-1/MCAF. RANTES makes a minor contribution but most of it is eluted in a later peak.

Guinea pig spleen cells, thymocytes, and blood mononuclear cells have been shown to produce a histamine releasing factor (HRF) spontaneously or after stimulation with PHA or specific antigens. In this study we have shown that antigenic stimulation of spleen cells obtained from animals immunized with high doses of antigen suppresses the spontaneous HRF production. Likewise, stimulation with Con A of spleen cells also inhibits the spontaneous HRF production. When the supernatants from Con A- and antigen-stimulated cultures were added to fresh thymocyte cultures, a significant inhibition of HRF production was observed. These supernatants also inhibited HRF-induced histamine release from mast cells. We have identified an inhibitor of HRF synthesis (IHS) and also a histamine release inhibitory factor (HRIF) by gel chromatography. Virtually all mitogen- and antigen-stimulated culture supernatants elaborated the activities of HRF, IHS, and HRIF in various quantities depending on the dose of antigen and the kind of adjuvant used for immunization. IHS has a MW of 22K-35K and 10K. This cytokine also inhibits DNA synthesis by thymocytes. HRIF has a MW of 15K-20K and 10K. It inhibits both HRF- and antigen-induced histamine release from lung mast cells. These results suggest that lymphocytes produce a variety of factors which function to regulate histamine release from mast cells.

Histamine release induced by the lymphokine-histamine releasing factor (HRF), like IgE-mediated release is a two step event--the Ca2+-independent activation step in which HRF primes the cells for histamine release and the Ca2+-dependent histamine release. The stimulus produced by the activation step decays relatively slowly and exponentially with a half-time of 38 min. By the 'receptor desensitization' approach, HRF appears to possess specific receptors on basophils as demonstrated by its ability to desensitize the cells to itself for subsequent histamine release. Cross desensitization experiments further suggested that a close relationship might exist between any such receptors and cell-bound IgE molecules, since desensitization of cells to anti-IgE also resulted in their desensitization to HRF as well; though the reverse was not the case. Nevertheless, any such relationship does not involve binding and cross linking of cell-bound IgE molecules by HRF. The putative HRF receptors may be distinct from those proposed for macrophage migration inhibitory factor (MIF) and leucocyte migration inhibitory factor (LIF) since, unlike the latter lymphokines whose interactions with their target cells show specificity for certain simple sugars, HRF's interaction with basophils show no such specificity to any of the simple sugars tested.

The in vitro production of histamine releasing factor (HRF) by lymphoid cells of rats, both normal and infected with Nippostrongylus brasiliensis, has been studied. Spleen cells and thymocytes were cultured either alone or in the presence of mitogen (PHA, 10 and 50 micrograms/ml) and the dialysed cell-free supernatants were tested for histamine releasing activity on rat peritoneal and pleural mast cell in vitro. We found that spleen cells and thymocytes of normal rats stimulated with PHA in 24 h cultures generated a factor which released histamine and 5-hydroxytryptamine from mast cells, and this ability was potentiated following N. brasiliensis infection of rats - lymphoid cells donors. Pleural mast cells were more sensitive to the action of HRF than peritoneal cells. Rat HRF had an apparent m.w. of 50,000 to 70,000 daltons as determined by gel chromatography and was a heat stable protein inducing histamine release from homologous mast cells in a very rapid (complete in 1-2 min at 37 degrees C), dose and temperature dependent secretory process.

We report reliability-test results of transmission-type holographic optical elements (HOE's) made with the DuPont photopolymer HRF-600. The reliability tests performed include 6000 cycles of liquid-to-liquid thermal-shock cycling (-55 degrees C-125 degrees C), 2200 cycles of air-to-air thermal cycling (-55 degrees C-125 degrees C), 1500 h of humidity testing (85 degrees C and a relative humidity of 85%), and 675 h of burn-in testing at 125 degrees C. A total of 210 holograms was tested, with 532 data points collected for diffraction-efficiency measurements. The results show that the average efficiency change after these tests is in the range of -4% to 0% and the standard deviation is only ~10%.

Objective: To analyze the histopathological features and histopathological risk factors (HRF) of tumor recurrence after vitrectomy in patients with retinoblastoma (RB). Methods: Retrospective case series. Twenty-nine patients (29 eyes) who underwent enucleation from April 2014 to April 2019 at the Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University due to tumor recurrence after vitrectomy in the other hospitals were enrolled and archived. The pathological sections of the other hospitals were read by the pathologists of the department and the pathological report was written. Histopathological features and HRF were analyzed in this group of patients. The HRF used in this study was defined as tumor invasion of the optic nerve, the choroid (the largest diameter ≥ 3 mm and mostly reaching the inner sclera), the sclera, the anterior segment of the eye, and tumor passing through the scleral and growing outside the eyeball. Results: Of the 29 patients with RB recurrence after vitrectomy, 18 (62.1%) were male and 11 (37.9%) were female. The age was 1-10 years with a median age of 3 years. Among 29 eyes, the tumor invaded the ciliary body in 19 eyes (65.5%), the iris in 14 eyes (48.3%), the anterior chamber in 10 eyes (34.5%), and the anterior chamber angle in 7 eyes (24.1%). Of the 29 eyes, 27 eyes (93.1%) had HRF. The most common HRF was invading the anterior segment of the eye(77.8%, 21/27). Conclusions: In patients with recurrence after vitrectomy for RB, the most common tumor invasion site in histopathology is the anterior segment of the eye, particularly the ciliary body. More than 90% of the patients have HRF. Vitrectomy for RB treatment requires a rigorous surgical indication assessment. (Chin J Ophthalmol, 2019, 55: 854-859).

Proteins from TCTP/HRF family were identified as venom toxins of spiders from different genus. We have found a TCTP toxin in the venom gland of Loxosceles intermedia, a venomous spider very common in South Brazil. TCTP from L. intermedia, named LiTCTP, was cloned, produced in a heterologous prokaryotic system, and the recombinant toxin was biochemically characterized. Our results point that LiTCTP is involved in the inflammatory events of Loxocelism, the clinical signs triggered after Loxosceles sp. bite, which include intense inflammatory reaction at the bite site followed by local necrosis. TCTP toxins were also identified in spiders from different genus. There are very few articles about TCTP toxins in other venomous animals in the literature, although a NCBI database search on the protein sequences reveals TCTP on snake's venom glands transcriptomic and genomic studies. Studies on TCTP as a venom toxin are very few and its biological role as a venom component in prey capture is still unknown.

In order to identify genes associated with distinct stages of mammary carcinoma we have investigated the transcriptional profile of normal mammary gland epithelial cells, cell lines derived from primary tumors, from bone marrow micrometastases and from ascites fluid. mRNA's for ribosomal protein L41 and URIM (Up-Regulated In Metastasis) were consistently increased in all cells derived from metastatic lesions. mRNA for human secreted frizzled-related protein (hsFRP) was found to be dramatically down-regulated in all mammary tumor cells compared to non-transformed mammary gland epithelial cells. mRNA for Human Hypoxia Related Factor--2 (HRF-2) and a transcript including the human mitochondrial control region were significantly overexpressed in the cell lines derived from primary tumors and ascites fluid. A new gene, referred to as PKW, was only expressed in one of the primary tumor cell lines, the one derived from a medullary carcinoma. The small and the large transcript which are derived by differential splicing encode potential proteins comprising 95 aa and 130 aa, sharing 88 aa at the N-terminus. The IEP's suggest a nuclear localization of the proteins. Surprisingly mRNA for the new gene was detected only in the salivary gland, but not in other adult human tissues and a restricted panel of embryonic tissues. The same holds true for a panel of human tumor cell lines and cell lines derived from ductal mammary carcinoma. RT-PCR revealed expression of PKW in 4 out of 11 breast carcinomas.

OBJECTIVE

Study the feasibility and planning robustness of a novel biological dose painting approach prescribing biological effect instead of dose.

METHODS

Prescribed'effect maps' were generated using models relating FMISO-PET tracer uptake to hypoxia reduction factors (HRF). HRFs decrease the LQ-model radio response parameters a and β and therefore the delivered biological effect. The model is driven by four parameters (m, K, p50, Imax), whose values have been determined through a comprehensive literature search. A planning study on ten previously treated patients with oropharyngeal cancer was conducted. Dose-painted plans were generated with the KonRad inverse planning system (DKFZ, Heidelberg). Simulated FMISO-PET images were generated by defining clinically relevant hypoxic sub-volumes within the GTV. Tracer uptake values were derived from various PET imaging studies for head and neck cancer. Each treatment plan was developed in four steps: 1) Simulate hypoxia tracer distribution in GTV. 2) Prescribe biological effect. 3) Optimize dose-painted plan under the same normal tissue constraints of the nominal clinical plan. 4) Conduct robustness analysis by evaluation of the dose-painted plan for 27 parameters combinations of K, m, p50 (mean ± 1SD).

RESULTS

The predicted biological effect of clinical plans under normoxic conditions overestimates the delivered effect due to decreased radio-sensitivity in hypoxic tumours. Biological dose painting compensates for hypoxia by delivering a higher dose to hypoxic sub-volumes while still maintaining all critical structure dose limits. Model parameter uncertainties clearly affect robustness. The high uncertainty on p50 (pO2 for which tracer concentration is half of maximum uptake) was found to cause the largest variations in the delivered biological effect.

CONCLUSIONS

Clinically acceptable dose-painted plans can be generated without sacrificing the normal tissue constraints. Planning robustness suffers from the high uncertainty on the p50 value. Improved methods to determine the model parameters would be desirable. Financial support provided by Ryerson University, Toronto, Ontario, Canada.

OBJECTIVE

The recommended intervals between surveillance colonoscopies are based on the most recent examination findings. However, whether the two previous colonoscopies affect second surveillance colonoscopic findings is not established. The aim of this study is to estimate the risk of obtaining high-risk findings (HRF) on the next surveillance colonoscopy using the results of two previous colonoscopies, and to estimate the appropriate time interval for the next surveillance colonoscopy.

METHODS

Among subjects who underwent screening colonoscopy during January 2002-December 2009, patients who underwent second surveillance colonoscopy before June 2012 were enrolled. "No adenoma" was defined as a hyperplastic polyp or no polyp, "low-risk findings (LRF)" as one or two small (< 1 cm) tubular adenomas, and "HRF" as advanced adenoma, cancer, or any sized multiple (≥ 3) adenomas.

RESULTS

Among enrolled 852 subjects, 65 (7.6%) had HRF at second surveillance colonoscopy. Multivariate analysis showed that HRF on second surveillance colonoscopy were associated with male and HRF on screening colonoscopy (all, P < 0.01). In subjects with LRF on first surveillance colonoscopy, HRF on the screening colonoscopy significantly affected the detection of HRF on second surveillance colonoscopy (P < 0.01). Patients with HRF on screening colonoscopy and LRF on the first surveillance colonoscopy had no different risk of HRF on second surveillance colonoscopy from those with HRF on first surveillance colonoscopy (P>> 0.05).

CONCLUSIONS

The HRF on second surveillance are significantly associated with previous two colonoscopic results. In patients with LRF on first surveillance, screening colonoscopic findings should be considered to determine the optimal surveillance interval.

To explore the titer of glucose-6-phosphate isomerase (GPI) for early diagnosis of the outpatient with rheumatoid arthritis (RA) in real life, and to analyze its relationship with disease activity.

In the study, 1 051 patients with arthritis were collected in the group who had joints tender and swelling, and 90 cases of healthy people as a control group. ELISA method was used to detect the serum level of GPI, and according to clinical features and laboratory test, all the patients including 525 RA patients, the other patients including osteoarthritis (OA), 134 cases of seronegative spine joint disease (SpA), 104 cases of systemic lupus erythematosus (SLE), 31 cases of primary Sjogren syndrome (pSS), 24 cases of gout arthritis (GA), 22 cases of other connective tissue diseases (including polymyalgia rheumatica, dermatomyositis, systemic sclerosis, adult Still disease) and 46 cases of other diseases (including 165 cases of osteoporosis, avascular necrosis of the femoral head, traumatic osteomyelitis, bone and joint disease, juvenile rheumatoid arthritis, tumor). The diagnostic values of GPI were assessed, and the differences between the GPI positive and negative groups of the RA patients in clinical characteristics, disease activity, severity and inflammatory index analyzed.

The positive rate of serum GPI in the patients with RA was 55.4%, contrasting to other autoimmune diseases (14.3%) and healthy controls (7.78%)(P<0.001). Compared with the OA and SpA patients, the RA group was increased more significantly, and the difference was statistically significant (P<0.001). The diagnostic value of GPI alone for RA was 0.39 mg/L, the sensitivity was 54.2%, and specificity was 87.3%. The positive rate of GPI in RF negative patients was 36.1%; the positive rate of GPI in anti-CCP antibody negative patients was 34.2%; the positive rate of GPI in RF and anti-CCP antibody negative patients was 24.1%. The level of GPI had positive correlation (P<0.05) with ESR, RF, anti-CCP antibody and HRF-IgG.

GPI is sensitive in the patients with RA; GPI positive is important in the diagnosis of RA with anti-CCP antibody and/or RF negative patients. The titer of GPI is related with disease activity of RA.

Thermal oxidation of VOC is extremely energy intensive, and necessitates high efficiency heat recovery from the exhaust heat. In this paper, two independent parameters heat recovery factor (HRF) and equipment cost factor (ECF) are introduced. HRF and ECF can be used to evaluate separately the merits of energy efficiency and cost effectiveness of VOC oxidation systems. Another parameter equipment cost against heat recovery (ECHR) which is a function of HRF and ECF is introduced to evaluate the merit of different systems for the thermal oxidation of VOC. Respective cost models were derived for recuperative thermal oxidizer (TO) and regenerative thermal oxidizer (RTO). Application examples are presented to show the use and the importance of these parameters. An application examples show that TO has a lower ECF while RTO has a higher HRF. However when analyzed using ECHR, RTO would be of advantage economically in longer periods of use. The analytical models presented can be applied in similar environmental protection systems.

OBJECTIVE

To study the evidence-based therapy of inhaled nitric oxide (iNO) for hypoxic respiratory failure (HRF) in term and near-term infants by analyzing the literature systematically.

METHODS

The literature related to the treatment of HRF with iNO was retrieved from the following: PubMed, EMBASE, OVID, Springer and Chinese Journals Full-Text Database (CNKI). The relevant literature on randomized controlled trials (RCTs) that met the criteria was statistically analyzed by the software of Review Manager 4.2, as recommended by Cochrane Collaboration.

RESULTS

A total of 162 articles were retrieved. Fifteen met the criteria and were selected for Meta analysis (4 single center and 11 multicenter randomized trials). Meta analysis showed that 30-60 minutes iNO therapy decreased the oxygenation index (P<0.05), increased PaO2 significantly, and reduced need of extracorporeal membrane oxygenation(ECMO) (P<0.05). However, for the neonates with HRF caused by congenital diaphragmatic hernia, iNO therapy did not result in a significant reduction in the oxygenation index and death rate. There was no significant difference in the occurrence of neurodevelopmental sequelae between the iNO and control groups.

CONCLUSIONS

The currently published evidence from RCTs supports the use of iNO in term and near-term infants with HRF but except for the HRF infants caused by diaphragmatic hernia. The effect of iNO therapy on long-term neurodevelopment needs to be further studied.

OBJECTIVE

This study compared macular capillary leucocyte velocity values measured with a psychophysical blue-field entoptic simulation (BFS) technique and confocal scanning laser Doppler flowmetry.

METHODS

A cross-sectional study was performed where macular capillary leucocyte velocity was measured by BFS using an Oculix BFS-2000 V2.1 psychophysical system and by confocal scanning laser Doppler flowmetry using Heidelberg retinal flowmetry (HRF) in 35 type 1 diabetes women during the second trimester.

RESULTS

The macular leucocyte velocities measured with BFS correlated significantly with the 50th percentile (r = 0.345, p = 0.042, n = 35, Spearman's non-parametric correlation), the 75th percentile (r = 0.432, p = 0.009) and the 90th percentile (r = 0.373, p = 0.027) of HRF flow values during the second trimester. However, there was no correlation between BFS velocity and the 25th percentile of HRF measurements.

CONCLUSIONS

Blue-field simulation is known to be an experimental technique that provides a quantitative measure of flow in the perifoveal capillary network. By contrast, HRF imaging reflects quantitative, multispectral, objective and non-invasive measurements in a two-dimensional projection of a three-dimensional retinal capillary bed. Our study showed that BFS velocity was correlated with HRF values in a group of women with diabetes during pregnancy. The positive correlation between BFS and HRF values suggests that the psychophysical BFS and scanning laser-based HRF measure similar functions in the retina.