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The kidney tubules constitute two-thirds of the cells of the kidney and account for the majority of the organ’s metabolic energy expenditure. Acute tubular injury (ATI) is observed across various types of kidney diseases and may significantly contribute to progression to kidney failure. Non-invasive biomarkers of ATI may allow for early detection and drug development. Using the SomaScan proteomics platform on 434 patients with biopsy-confirmed kidney disease, we here identify plasma biomarkers associated with ATI severity. We employ regional transcriptomics and proteomics, single-cell RNA sequencing, and pathway analysis to explore biomarker protein and gene expression and enriched biological pathways. Additionally, we examine ATI biomarker associations with acute kidney injury (AKI) in the Kidney Precision Medicine Project (KPMP) (n = 44), the Atherosclerosis Risk in Communities (ARIC) study (n = 4610), and the COVID-19 Host Response and Clinical Outcomes (CHROME) study (n = 268). Our findings indicate 156 plasma proteins significantly linked to ATI with osteopontin, macrophage mannose receptor 1, and tenascin C showing the strongest associations. Pathway analysis highlight immune regulation and organelle stress responses in ATI pathogenesis.Acute tubular injury (ATI) significantly contributes to many kidney diseases. Here, the authors identify several immune response and cellular stress plasma proteins linked to ATI severity and acute kidney injury, which may aid in non-invasive ATI assessment. [ABSTRACT FROM AUTHOR]

Recently we reported about the consumption of red wines from grapes, having several health properties. There are different types of wines that originated from grapes and other fruits. In the present study fruit wines from persimmon, kiwifruit and pomegranate were investigated and compared for their antioxidant ability, using cupric ion reducing antioxidant capacity (CUPRAC) and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays. To the fruit wines were applied the same methods of investigation as to the traditional ones made from grapes. The results showed the highest antioxidant activity of pomegranate, followed by kiwifruit and persimmon wines. Fourier transform infrared (FTIR) spectroscopy was used in order to correlate these results. The interaction of wine bioactive compounds with the main serum proteins in the human metabolism, such as human serum albumin (HSA), globulin (GL), and fibrinogen (FB), showed that pomegranate wine possesses higher quenching properties than kiwifruit and persimmon wines. All determined fluorescence indices have a direct correlation with the bioactivity of polyphenols and not with the content of alcohol. We hypothesize that the results of the interaction of main human serum proteins with bioactive compounds of wines can be additional predictors of their health properties. The used analytical methods for quality of fruit wines can be applied to a wide range of fruits and vegetables. [ABSTRACT FROM AUTHOR]

People with diabetes feature a life-risking susceptibility to respiratory viral infection, including influenza and SARS-CoV-2 (ref. 1), whose mechanism remains unknown. In acquired and genetic mouse models of diabetes, induced with an acute pulmonary viral infection, we demonstrate that hyperglycaemia leads to impaired costimulatory molecule expression, antigen transport and T cell priming in distinct lung dendritic cell (DC) subsets, driving a defective antiviral adaptive immune response, delayed viral clearance and enhanced mortality. Mechanistically, hyperglycaemia induces an altered metabolic DC circuitry characterized by increased glucose-to-acetyl-CoA shunting and downstream histone acetylation, leading to global chromatin alterations. These, in turn, drive impaired expression of key DC effectors including central antigen presentation-related genes. Either glucose-lowering treatment or pharmacological modulation of histone acetylation rescues DC function and antiviral immunity. Collectively, we highlight a hyperglycaemia-driven metabolic-immune axis orchestrating DC dysfunction during pulmonary viral infection and identify metabolic checkpoints that may be therapeutically exploited in mitigating exacerbated disease in infected diabetics.Hyperglycaemia leads to impaired costimulatory molecule expression, antigen transport and T cell priming in distinct lung dendritic cell subsets, driving a defective antiviral adaptive immune response, delayed viral clearance and enhanced mortality. [ABSTRACT FROM AUTHOR]

We propose that autonomy is a crucial aspect of consumer choice. We offer a definition that situates autonomy among related constructs in philosophy and psychology, contrast actual with perceived autonomy in consumer contexts, examine the resilience of perceived autonomy, and sketch out an agenda for research into the role of perceived autonomy in an evolving marketplace increasingly characterized by automation. [ABSTRACT FROM AUTHOR]

Background: Photobiomodulation (PBM) has shown efficacy in preventing and treating cancer therapy-induced mucositis and dermatitis. However, there is contradictory information regarding the effect of PBM on (pre)malignant cells, which has led to questions regarding the safety of this technique. We address this issue using an orthotopic mouse model (Cal-33) with human squamous cell carcinoma of the oral cavity.Methods: Mice with actively growing orthotopic Cal-33 head and neck carcinoma tumors were divided into 4 groups: control, PBM only, radiation therapy (RT) only, and PBM + RT. We performed three experiments: (1) PBM at 660 nm, 18.4 J/cm2, and 5 RT × 4 Gy doses delivered daily; (2) PBM at 660 nm, 18.4 J/cm2, and 1 × 15 Gy RT; and (3) PBM at 660 nm + 850 nm, 45 mW/cm2, 3.4 J/cm2, and 1 × 15 Gy RT. Mice were weighed daily and tumor volumes were evaluated by IVIS. Survival time was also evaluated.Results: Animals treated with RT survived significantly longer and had significantly smaller tumor volume when compared with the control and PBM-only treatment groups. No significant differences were noted between the RT alone and PBM + RT groups in any of the experiments.Conclusion: Our results suggest that PBM at the utilized parameters does not provide protection to the tumor from the killing effects of RT. [ABSTRACT FROM AUTHOR]

Bioactivities of persimmon and kiwifruit were studied and compared in connection with their characteristics towards human health. Based on the results of our recently published research, two fruits growing in South Korea persimmon 'Fuyu' and kiwifruit 'Hayward' were investigated and compared. Spectroscopic, fluorescence and FTIR measurements and radical scavenging reactions were used to compare the qualities of persimmon and kiwifruit. The results of above methods showed that total polyphenol and tannin substances, vitamin C and values of antioxidant capacities were higher in kiwifruit than in persimmon. Phenolics were also characterized by specific IR bands and MS spectra. Antioxidant capacities of polyphenols extracted from the studied fruits correlated with the binding abilities during their interaction with serum albumin, one of the most important proteins in human metabolism. As a result of a complex reaction between the proteins and polyphenols, the fluorescence intensity of proteins decreased and such interaction can be a model in distribution of drugs. Relationship between the most active compounds and their influence on the quality of fruits was established, based on the relatively high bioactivity and quenching properties. In conclusion, kiwifruit and persimmon according to the obtained results contain high amounts of antioxidants and can be widely consumed as fresh, processed and functional foods. [ABSTRACT FROM AUTHOR]

Objective: To update the clinical practice guidelines for the management of oral mucositis (OM) that were developed by the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). This part focuses on honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents.Methods: A systematic review was conducted by the Mucositis Study Group of MASCC/ISOO. The body of evidence for each intervention, in each clinical setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, one of the following guidelines were determined: Recommendation, Suggestion, No Guideline Possible.Results: A total of 78 papers were identified within the scope of this section, of which 49 were included in this review and merged with nine publications that were reported in the previous guidelines update. A new Suggestion was made for honey (combined topical and systemic delivery) for the prevention of OM in head and neck cancer patients receiving radiotherapy with or without chemotherapy. A new Suggestion clarified that chewing gum is not effective for the prevention of OM in pediatric patients with hematological or solid cancer treated with chemotherapy. No guideline was possible for other interventions.Conclusions: Numerous natural products and herbal remedies were studied for the management of OM. Of the agents reviewed in this systematic review, a guideline in favor was made for honey (combined topical and systemic), while a guideline against was made for chewing gum. Additional research is warranted to clarify the potential of other interventions. [ABSTRACT FROM AUTHOR]

Purpose: To present the findings of combined oral assessment and gustometry testing of a series of head and neck and hematologic malignancies in patients with self-reported taste change after cytotoxic therapies.Methods: Patients with acute myeloid leukemia (AML), multiple myeloma (MM), and head and neck cancer (HNC) were evaluated for taste function. Chemical gustometry was conducted assessing chemosensory qualities that included sweet, sour, salty, bitter, umami, and spicy. NCI Common Terminology Criteria for Adverse Events (CTCAE) 4.0 and the Scale of Subjective Total Taste Acuity (STTA) were used to describe taste symptoms. Saliva flow rates were measured to determine the presence of hyposalivation. Patients were provided treatment trials for taste dysfunction, including zinc supplements, or medications that included clonazepam, megestrol acetate, and the cannabinoid dronabinol.Results: According to STTA, hematology cases reported the incidence of grades 2 and 3 taste disturbances as 60% and 40%, respectively. For HNC patients, the incidence of grades 2 and 3 was 44% each. Gustometry tests confirmed dysgeusia in all patients evaluated. In the hematology group, 80% of patients exhibited a decrease in sweet taste perception, and no patients correctly identified umami taste. In the HNC group, most patients could not identify salt taste, 66% of patients reported "no sensation" with spicy taste, bitter taste was reduced in some, and increased or altered in others, while only one patient could identify umami taste. In the hematologic and HNC patient groups, 80% and 66% reported grade 2 dry mouth, respectively, according to CTCAE 4.0. After treatment for taste dysfunction, 71% of all patients in the present study reported improvements in taste function.Conclusions: Persisting dysgeusia in cancer survivors may be assessed by patient report and taste testing. The taste most affected in our patients was umami. Treatment trials with current interventions for dysgeusia appeared effective and should be considered in cancer survivors. Understanding taste and flavor function during and following cancer treatment is important in developing rational prospective preventive and interventional strategies. [ABSTRACT FROM AUTHOR]

Purpose: To update the clinical practice guidelines for the use of natural and miscellaneous agents for the prevention and/or treatment of oral mucositis (OM).Methods: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer / International Society of Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, the following guidelines were determined: Recommendation, Suggestion, and No Guideline Possible.Results: A total of 78 papers were identified within the scope of this section, out of which 29 were included in this part, and were analyzed with 27 previously reviewed studies. A new Suggestion was made for oral glutamine for the prevention of OM in head and neck (H&N) cancer patients receiving radiotherapy with concomitant chemotherapy. The previous Recommendation against the use of parenteral glutamine for the prevention of OM in hematopoietic stem cell transplantation (HSCT) patients was re-established. A previous Suggestion for zinc to prevent OM in H&N cancer patients treated with radiotherapy or chemo-radiotherapy was reversed to No Guideline Possible. No guideline was possible for other interventions.Conclusions: Of the vitamins, minerals, and nutritional supplements studied for the management of OM, the evidence supports a Recommendation against parenteral glutamine in HSCT patients and a Suggestion in favor of oral glutamine in H&N cancer patients for the management of OM. [ABSTRACT FROM AUTHOR]

The effects of drought stress in autumn-growing Chinese cabbage cultivar on bioactive compounds, total antioxidant and binding properties to human serum albumin (HSA) were studied. Seedlings of 42 days growing Chinese cabbage Brassica rapa L. ssp. pekinensis cv. Bulam Plus (BRARP) were transplanted and maintained into pots during 3 weeks with soil water of the drought-treated (D-T) and control (C) plants at 10% and 30%, respectively. Polyphenols and the values of antioxidant capacities by three radical scavenging assays (CUPRAC, FRAP, ABTS) were determined in methanol extracts of the samples. MS spectra of phenolic extracts were compared in samples treated at different periods of time. The total polyphenols and their activities were slightly lower in drought-treated Chinese cabbage than in corresponding controls. The influence of polyphenols, total antioxidant and binding activities in D-T plants accumulation at drought stress in Chinese cabbage BRARP was reduced. Our study provides valuable information that Chinese cabbage BRARP can be consumed throughout the year in South Korea and other countries. [ABSTRACT FROM AUTHOR]

In the recent reports, there are contradictory conclusions about the nutritional and health properties of organic and conventionally growing vegetables. We hypothesized that organic cultivation system results in higher quality of asparagus ( Asparagus officinalis L.) because of organic manure and effective organisms. Therefore, new analytical methods were applied in order to find the differences in bioactive compounds between the plants growing under various cultivation systems. Total antioxidant capacities (TAC) of the conventional and organic greenhouse and conventional open-field farming of asparagus spears were determined by 2,2-azino-bis (3-ethyl-benzothiazoline-6-sulfonic acid) diammonium salt (ABTS), 1,1-diphenyl-2-picryl-hydrazyl (DPPH), and ferric-reducing antioxidant power (FRAP) assays, and UHPLC-PDA-MS was used for identification of some phenolic acids and flavonoids. Total phenolic compounds (TPC), total flavonoids, rutin, vitamin C, chlorophylls, carotenoids, and the values of TAC, determined in organic growing asparagus spears, were higher than in conventional, but not always significant. The applied for the first time FTIR spectroscopy as an estimation of the differences between the investigated samples showed more prominent bands in the region of polyphenols in organic asparagus spears than in conventional and provides a rapid and precise alternative to other methods. The binding properties of extracted polyphenols to HSA determined by 3D-fluorescence were relatively higher in organic asparagus spears than in other samples. Correlation between the amounts of total polyphenols and flavonoids and their quenching properties showed a linear relationship. All proposed analytical methods can be applied to a variety of studied plants. [ABSTRACT FROM AUTHOR]

The differential diagnosis for clear cell neoplasms of the sinonasal tract is wide but critical to understand. In this paper, we describe a case of renal cell-like adenocarcinoma (SNRCLA) presenting as a paranasal sinus mass with clear cell morphology. The relevant literature is reviewed and the workup for clear cell neoplasms described. SNRCLA is a rarely encountered low grade glandular malignancy of the paranasal sinuses. Despite its morphologic mimicry of renal cell carcinoma, SNRCLA demonstrates a seromucinous phenotype and is associated with a favorable prognosis and low recurrence rates after surgical resection. [ABSTRACT FROM AUTHOR]

Introduction: Children with recurrent urinary tract infections (rUTI) often show no identifiable cause of their infections. Neutrophil gelatinase-associated lipocalin (NGAL) is known to be upregulated within the uroepithelium and kidney of patients with UTI and exhibits a localized bacteriostatic effect through iron chelation. We hypothesize that some patients with rUTI without an identifiable cause of their recurrent infections have locally deficient NGAL production. We therefore explored whether a lack of NGAL production may be a factor in the pathogenesis of rUTI. Materials and methods: Patients seen in the urology clinic for rUTI who were <21 years of age were enrolled. Patients were excluded if they had UTI at the time of enrollment, evidence of renal disease, decreased renal function, known anatomic abnormality of the genitourinary tract, or other reasons that predispose to UTI, such as neurogenic bladder, the need for intermittent catheterization, or unrepaired posterior urethral valves. Control patients were healthy children enrolled from the emergency department with no history of UTI or renal dysfunction, normal urinalysis at the time of enrollment, and presenting no diagnosis associated with increased NGAL levels, such as acute kidney injury or infection. NGAL was measured by immunoblot. Results: Fifteen cases and controls were enrolled. Median urinary NGAL levels were significantly decreased in rUTI patients compared with controls [15 (14-29) ng/ml vs 30 (27-61) ng/ml; p = 0.002)] Although comparatively diminished, measurable NGAL levels were present in all patients with rUTI. Conclusions: Urinary NGAL is significantly decreased in patients with compared with patients without rUTI. These data suggest that some patients with rUTI may be predisposed to UTI because of a relative local deficiency in urinary NGAL production. [ABSTRACT FROM AUTHOR]

Summary: Associations between bone mineral density and aortic valvular, aortic annular, and mitral annular calcification were investigated in a cross-sectional analysis of a population-based cohort of 1497 older adults. Although there was no association between continuous bone mineral density and outcomes, a significant association between osteoporosis and aortic valvular calcification in men was found. Introduction: The process of cardiac calcification bears a resemblance to skeletal bone metabolism and its regulation. Experimental studies suggest that bone mineral density (BMD) and valvular calcification may be reciprocally related, but epidemiologic data are sparse. Methods: We tested the hypothesis that BMD of the total hip and femoral neck measured by dual-energy X-ray absorptiometry (DXA) is inversely associated with prevalence of three echocardiographic measures of cardiac calcification in a cross-sectional analysis of 1497 older adults from the Cardiovascular Health Study. The adjusted association of BMD with aortic valve calcification (AVC), aortic annular calcification (AAC), and mitral annular calcification (MAC) was assessed with relative risk (RR) regression. Results: Mean (SD) age was 76.2 (4.8) years; 58% were women. Cardiac calcification was highly prevalent in women and men: AVC, 59.5 and 71.0%; AAC 45.1 and 46.7%; MAC 42.8 and 39.5%, respectively. After limited and full adjustment for potential confounders, no statistically significant associations were detected between continuous BMD at either site and the three measures of calcification. Assessment of WHO BMD categories revealed a significant association between osteoporosis at the total hip and AVC in men (adjusted RR compared with normal BMD = 1.24 (1.01-1.53)). In graded sensitivity analyses, there were apparent inverse associations between femoral neck BMD and AVC with stenosis in men, and femoral neck BMD and moderate/severe MAC in women, but these were not significant. Conclusion: These findings support further investigation of the sex-specific relationships between low BMD and cardiac calcification, and whether processes linking the two could be targeted for therapeutic ends. [ABSTRACT FROM AUTHOR]

The effects of bioactivity, binding properties, anti-obesity and antioxidant enzyme activities in different fractions from the roots of Codonopsis lanceolata [ C. lanceolata (CL)] in comparison with Nelumbo nucifera Gaertn. [ N. nucifera Gaertn (NN)] were evaluated in vitro. The rate of cell survival progressively decreased in a dose-dependent manner. Butyl alcohol fraction of CL exhibited a pronounced cytotoxic effect (75.73 %) comparable to that of hexane (79.82 %), following by methylene chloride (84.02 %), ethyl acetate (87.62 %) and water fractions (86.30 %) at the same concentration at 200 μg/mL on 3T3-L1 cells. Confluent 3T3-L1 cells were treated with 50 µg/mL of CL and NN extracts and then stained with Oil Red O solution. Inhibitory degree of lipid accumulation against these extracts showed a significant level compared with the control sample. Both lipid accumulation and adipocyte differentiation showed relatively high effects in methyl chloride fraction. Comparative results of cytotoxicity and inhibitory degree of lipid accumulation were obtained with extracts of N. nucifera Gaertn. roots. The root extract of C. lanceolata had the significantly highest SOD enzyme activity of 84.5 % in ethyl acetate fraction and the lowest in water (57.9 %). Similar correlations were found for CAT, APX and POD activities as the highest in ethyl acetate partition layer compared with the other fractions. The binding properties were determined by interaction of polyphenols extracts of CL and NN with human serum albumin. Overall results of properties of these two plants suggest that the roots of C. lanceolata and N. nucifera Gaertn. may assist in the potential biological activity on anti-obesity, cytotoxic, antioxidant and binding capacities as a part of functional food. Graphical Abstract: CL, NN, Codonopsis lanceolata, Nelumbo nucifera Gaertn. I, II, Effects of solvent fractions on lipid accumulation in 3T3-L1 cells of CL, NN. Con, control; MC, methylene chloride fraction; III, IV, 3D-fluorescence spectra and corresponding contour maps (III, IV) of polyphenols of CL and NN in interaction with human serum albumin. [ABSTRACT FROM AUTHOR]

Bone has recently emerged as a pleiotropic endocrine organ that secretes at least two hormones, FGF23 and osteocalcin, which regulate kidney function and glucose homeostasis, respectively. These findings have raised the question of whether other bone-derived hormones exist and what their potential functions are. Here we identify, through molecular and genetic analyses in mice, lipocalin 2 (LCN2) as an osteoblast-enriched, secreted protein. Loss- and gain-of-function experiments in mice demonstrate that osteoblast-derived LCN2 maintains glucose homeostasis by inducing insulin secretion and improves glucose tolerance and insulin sensitivity. In addition, osteoblast-derived LCN2 inhibits food intake. LCN2 crosses the blood-brain barrier, binds to the melanocortin 4 receptor (MC4R) in the paraventricular and ventromedial neurons of the hypothalamus and activates an MC4R-dependent anorexigenic (appetite-suppressing) pathway. These results identify LCN2 as a bone-derived hormone with metabolic regulatory effects, which suppresses appetite in a MC4R-dependent manner, and show that the control of appetite is an endocrine function of bone. [ABSTRACT FROM AUTHOR]

Aim: Patients treated with allogeneic hematopoietic stem cell transplantation (HSCT) may experience oral complications associated with chronic graft-versus-host disease (cGVHD). These complications may significantly affect quality of life, even many years post-HSCT. Current treatment options for oral cGVHD are limited and often include steroid or other immunomodulatory medications, which may not adequately control the oral condition. A non-immunosuppressive intervention for symptomatic relief in oral cGVHD would thus be a welcome addition to the treatment paradigm.Materials and Methods: We report seven cases of oral cGVHD that were treated with photobiomodulation therapy (PBM), previously known as low-level laser therapy (LLLT). Patients underwent at least two PBM treatments per week in addition to local treatment with steroids, and if on systemic therapies, these were either unchanged or dosage was reduced during the period of PBM therapy. Follow-up data is presented for 4 weeks of treatment.Results: Oral pain, sensitivity, and dry mouth improved in most patients. These findings suggest PBM therapy may represent an additional approach for management of oral cGVHD, and suggest that controlled studies should be conducted to confirm the efficacy and safety of PBM therapy in oral cGVHD and to determine optimal PBM therapy protocols. [ABSTRACT FROM AUTHOR]

Purpose: We present the findings of a structured systematic review of the literature assessing orofacial pain induced by malignant disease and/or its therapy (excluding mucositis). This evaluation of the literature published after the 1989 NIH Development Consensus conference on the oral complications of cancer therapies is an effort to assess the prevalence of pain, quality of life and economic impact, and management strategies for cancer therapy-induced orofacial pain.Methods: A systematic medical literature search was conducted with assistance from a research librarian in MEDLINE/PubMed and EMBASE databases for articles published between January 1, 1990 and December 31, 2008. Each study was independently assessed by two reviewers with expertise in the field of oral oncology.Results: Thirty-nine studies assessed pain in the head and neck region. The measure was commonly embedded in quality of life studies. Most of these studies described pain in head and neck cancer (HNC) patients, which therefore became the focus of the report. Pain is common in patients with HNC and is reported by approximately half of patients prior to cancer therapy, 81% during therapy, 70% at the end of therapy, and by 36% at 6 months after treatment. Pain is experienced beyond the 6-month period by approximately one third of patients and is typically more severe than pre-treatment cancer-induced pain.Conclusions: This systematic review identified the presence of pain before cancer therapy, likely attributable to the cancer; an increase in pain during therapy and the common persistence of pain following cancer treatment. Continuing research should use validated tools to prospectively assess orofacial pain, its causes and pathophysiology, and its effect on quality of life and economic impact. Clinical trials of pain management in this setting are also warranted. [ABSTRACT FROM AUTHOR]

Purpose: This systematic review aims to examine the prevalence of bisphosphonate osteonecrosis (BON) in the cancer population, prevention and treatment protocols, and quality of life issues.Methods: A search of MEDLINE/PubMed and EMBASE form October 2003 to December 31, 2008 was conducted with the objective of identifying publications that contained original data regarding BON.Results: A total of 28 publications fulfilled inclusion criteria, but only 22 were used for prevalence analysis. No randomized controlled clinical trials, meta-analysis, or quality of life papers were found that contained information regarding either prevalence or treatment protocols for the management of BON. The overall weighted prevalence of BON included a sample of 39,124 patients with a mean weighted prevalence of 6.1%. The weighted prevalence was 13.3% for studies with documented follow-up with a sample size of 927 individuals. The weighted prevalence in studies with undocumented follow-up was 0.7% in a sample of 8,829 chart reviews. Epidemiological studies evaluated a total of 29,368 individual records, and the weighted BON prevalence was 1.2%.Conclusions: High-quality studies are needed to accurately characterize the prevalence of BON, and to determine effective treatment protocols. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to assess late effects of cytotoxic therapy with hematopoietic stem cell transplantation (HCT) on dental development in survivors of childhood cancer.Materials and Methods: Forty children who underwent allogeneic HCT for a variety of hematological malignancies were evaluated at a minimum of 2 years after transplantation. We obtained information on oral symptoms, exposed panoramic radiographs (PRG), and performed an oral examination. PRGs were scored for agenesis and root and/or crown abnormalities. The root-crown ratio was calculated, and dental age was assessed using Demirjian' s method.Main Results: The studied group showed a significantly higher prevalence of tooth agenesis compared to normative data for first and second premolars in both the maxilla and mandible, as well as the second molars in the mandible (all p values <0.001). Children who were <3 years old at the time of cancer treatment had significantly more missing teeth than older children, F(2,37) = 7.58, p < 0.002. Root-crown ratios were lower in the study sample than those from normative data. In addition, the mean dental age was higher (as a result of earlier apical root closure) than the mean chronological age, t(28) = 2.47, p < 0.020.Conclusions: Nearly all children examined had dental development disturbances, including agenesis, short roots, and arrested root development. An oral/dental evaluation and preventative oral supportive care regimens should be part of programs monitoring late effects in long-term survivors of childhood cancer. [ABSTRACT FROM AUTHOR]

Purpose: Low-level laser therapy (LLLT) efficacy for the prevention of cancer treatment-induced oral mucositis (OM) has been amply described. However, potential protection of malignant cells remains a legitimate concern for clinicians. We tested LLLT-induced protection from ionizing radiation killing in both malignant and normal cells.Methods: We treated six groups each of normal human lymphoblasts (TK6) and human leukemia cells (HL60) with He-Ne LLLT (632.8 nm, 35 mW, CW, 1 cm(2), 35 mW/cm(2) for 3-343 s, 0.1-12 J/cm(2)) prior to exposure to ionizing radiation (IR). Cells were then incubated and counted daily to determine their survival. Optimization of IR dose and incubation time was established prior to testing the effect of LLLT.Results: Growth curves for both cell lines showed significant declines after exposure to 50-200 cGy IR when compared to controls. Pre-radiation exposure to LLLT (4.0 J/cm(2)) followed by 1-h incubation blocked this decline in TK6 but not in HL60 cells. The latter cells were sensitized to the killing effects of IR in a dose-dependent manner.Conclusion: This study shows that pre-IR LLLT treatment results in a differential response of normal vs. malignant cells, suggesting that LLLT does not confer protection and may even sensitize cancer cells to IR killing. [ABSTRACT FROM AUTHOR]

Purpose: There is a large body of evidence supporting the efficacy of low level laser therapy (LLLT), more recently termed photobiomodulation (PBM), for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved, may expand the applications for PBM in the management of other complications associated with HNC treatment. This article (part 1) describes PBM mechanisms of action, dosimetry, and safety aspects and, in doing so, provides a basis for a companion paper (part 2) which describes the potential breadth of potential applications of PBM in the management of side-effects of (chemo)radiation therapy in patients being treated for HNC and proposes PBM parameters.Methods: This study is a narrative non-systematic review.Results: We review PBM mechanisms of action and dosimetric considerations. Virtually, all conditions modulated by PBM (e.g., ulceration, inflammation, lymphedema, pain, fibrosis, neurological and muscular injury) are thought to be involved in the pathogenesis of (chemo)radiation therapy-induced complications in patients treated for HNC. The impact of PBM on tumor behavior and tumor response to treatment has been insufficiently studied. In vitro studies assessing the effect of PBM on tumor cells report conflicting results, perhaps attributable to inconsistencies of PBM power and dose. Nonetheless, the biological bases for the broad clinical activities ascribed to PBM have also been noted to be similar to those activities and pathways associated with negative tumor behaviors and impeded response to treatment. While there are no anecdotal descriptions of poor tumor outcomes in patients treated with PBM, confirming its neutrality with respect to cancer responsiveness is a critical priority.Conclusion: Based on its therapeutic effects, PBM may have utility in a broad range of oral, oropharyngeal, facial, and neck complications of HNC treatment. Although evidence suggests that PBM using LLLT is safe in HNC patients, more research is imperative and vigilance remains warranted to detect any potential adverse effects of PBM on cancer treatment outcomes and survival. [ABSTRACT FROM AUTHOR]

Purpose: There is a large body of evidence supporting the efficacy of low-level laser therapy (LLLT), more recently termed photobiomodulation (PBM) for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved and dosimetric parameters may lead to the management of a broader range of complications associated with HNC treatment. This could enhance patient adherence to cancer therapy, and improve quality of life and treatment outcomes. The mechanisms of action, dosimetric, and safety considerations for PBM have been reviewed in part 1. Part 2 discusses the head and neck treatment side effects for which PBM may prove to be effective. In addition, PBM parameters for each of these complications are suggested and future research directions are discussed.Methods: Narrative review and presentation of PBM parameters are based on current evidence and expert opinion.Results: PBM may have potential applications in the management of a broad range of side effects of (chemo)radiation therapy (CRT) in patients being treated for HNC. For OM management, optimal PBM parameters identified were as follows: wavelength, typically between 633 and 685 nm or 780-830 nm; energy density, laser or light-emitting diode (LED) output between 10 and 150 mW; dose, 2-3 J (J/cm(2)), and no more than 6 J/cm(2) on the tissue surface treated; treatment schedule, two to three times a week up to daily; emission type, pulsed (<100 Hz); and route of delivery, intraorally and/or transcutaneously. To facilitate further studies, we propose potentially effective PBM parameters for prophylactic and therapeutic use in supportive care for dermatitis, dysphagia, dry mouth, dysgeusia, trismus, necrosis, lymphedema, and voice/speech alterations.Conclusion: PBM may have a role in supportive care for a broad range of complications associated with the treatment of HNC with CRT. The suggested PBM irradiation and dosimetric parameters, which are potentially effective for these complications, are intended to provide guidance for well-designed future studies. It is imperative that such studies include elucidating the effects of PBM on oncology treatment outcomes. [ABSTRACT FROM AUTHOR]

This commentary attempts to clarify the setting of photobiomodulation (BPM) therapy in the management of oral mucositis. The suggested dose range balances efficacy data with our current understanding about PBM safety. The literature about the molecular basis of photobiomodulation and its controversial relationship to malignant transformation is briefly presented. [ABSTRACT FROM AUTHOR]

Purpose: Sirolimus (rapamycin) is a mammalian target of rapamycin pathway blocker. The efficacy of sirolimus is currently studied for its antiproliferative properties in various malignancies and particularly in squamous cell carcinoma and other oral disorders. Topical application at the oral cavity can augment sirolimus availability at the site of action by increasing sirolimus levels in saliva and hence efficacy, along with improved safety (low levels in the blood to avoid side effects) and compliance. Our purpose was to evaluate the release profile and safety of a topical sirolimus sustained-release varnish drug delivery system. Subjects and methods: Sirolimus sustained-release varnish drug delivery system containing a total of 0.5 mg of the drug was applied to nine healthy male volunteers. Saliva and blood levels were determined utilizing mass spectrometry and chemiluminescent microparticle immunoassay, respectively. The prolonged release profile and safety were evaluated for the oral topical delivery system. Results: After the application of the drug delivery system, a sustained-release profile was observed in the oral cavity. We have measured moderate sirolimus levels for up to 12 h. The safety was confirmed, and systemic sirolimus blood levels were negligible. Conclusions: After an application of sirolimus sustained-release varnish drug delivery system, prolonged drug levels can be achieved in the saliva. The oral topical sirolimus concentrations were potentially therapeutic along with minimal systemic exposure. These results broaden the potential clinical use of sustained-release oral topical rapalogs. [ABSTRACT FROM AUTHOR]

Background: Lipocalin 2 (LCN2 or neutrophil gelatinase-associated lipocalin) is a secretory protein discovered from neutrophils, which accumulates in the blood and urine during acute kidney injury (AKI) and in the blood by bacterial infection. Little is known about the tissue source and molecular forms of this protein under normal and pathophysiologic conditions. Methods: By sandwich ELISA, serum and urinary LCN2 levels were measured in 36 patients with hematologic malignancies who transiently became neutropenic by stem cell transplantation (SCT). To evaluate contribution of neutrophil-derived LCN2 in the physiologic blood LCN2 concentrations, we examined CCAAT/enhancer-binding protein ε (C/EBPε) knockout mice, which lack mature neutrophils. Results: In patients without AKI and bacterial infection, at 1 week after SCT, the median blood neutrophil counts became zero and serum LCN2 levels were decreased by 76 ± 6 % ( p < 0.01), but urinary LCN2 levels were not altered. During neutropenic conditions, bacterial infection caused only a modest rise of serum LCN2 but AKI produced a marked rise of serum and urinary LCN2 levels. Serum LCN2 concentrations in C/EBPε knockout mice were reduced by 66 ± 11 % compared to wild-type mice ( p < 0.05). Blood LCN2 existed predominantly in high molecular weight forms (>100 kDa), while urinary LCN2 was mainly in low molecular weight forms. Conclusion: Our findings suggest that neutrophils are the major source of circulating LCN2 in normal and infected conditions, whereas blood and urinary LCN2 mainly derive from the kidney during AKI, and that the molecular forms and regulation of blood and urinary LCN2 are clearly distinct. [ABSTRACT FROM AUTHOR]

An unusual presentation of a case of myeloblastoma (granulocystic sarcoma, chloroma) as demonstrated by computed tomography (CT) and selective angiography is reported. Our patient, who presented with acute hydrocephalus due to a large posterior fossa myeloblastoma, had no evidence of systemic disease in either peripheral blood smear, bone marrow aspiration, lumbar puncture or further metastatic workup. While no evidence for generalized disease was seen, systemic chemotherapy may help to prevent overt systemic leukemia. [ABSTRACT FROM AUTHOR]

Purpose: The identification of experienced and knowledgeable dental specialists to provide appropriate oral care for cancer patients, as well as the integration of this care within general oncology management, may be a challenge. This paper discusses the general and additional requirements for dental care providers to support the cancer patient and provide prevention and/or treatment for oral complications of cancer therapy. Methods: We performed a literature review of specific issues regarding the oral cavity and adjacent structures in the cancer patient, including detection and early diagnosis of oral malignancy. We incorporated the systemic effects of cancer and its therapy that affect oral disease and treatment. We present a summary of how to seek expert dental care for cancer patients and for referral from the dental and medical community. Results: Due to the complexity conferred by the disease and its treatment, cancer patients require educated, experienced dentists for treatment and/or prevention of oral-related morbidity. Correct diagnosis and evidence-based prophylactic and therapeutic oral care can significantly improve patient quality of life and reduce morbidity and healthcare costs. Conclusions: The knowledge and expertise of dental professionals regarding prevention/treatment of complications and secondary malignant lesions in cancer patients are critical. Integration of oral care with the oncology care and in survivors requires effective communication between dental and medical providers beginning ideally at diagnosis. These clinicians may be identified at the cancer center, nearby hospital dental programs, and, less commonly, in the community. [ABSTRACT FROM AUTHOR]

A Correction to this paper has been published: https://doi.org/10.1007/s00520-021-06141-9 [ABSTRACT FROM AUTHOR]

Accumulated evidence indicates that the interconversion of iron between ferric (Fe 3+) and ferrous (Fe 2+) can be realized through interaction with reactive oxygen species in the Fenton and Haber–Weiss reactions and thereby physiologically effects redox cycling. The imbalance of iron and ROS may eventually cause tissue damage such as renal proximal tubule injury and necrosis. Many approaches were exploited to ameliorate the oxidative stress caused by the imbalance. (−)-Epigallocatechin-3-gallate, the most active and most abundant catechin in tea, was found to be involved in the protection of a spectrum of renal injuries caused by oxidative stress. Most of studies suggested that EGCG works as an antioxidant. In this paper, Multivariate analysis of the LC–MS data of tea extracts and binding assays showed that the tea polyphenol EGCG can form stable complex with iron through the protein Ngal, a biomarker of acute kidney injury. UV–Vis and Luminescence spectrum methods showed that Ngal can inhibit the chemical reactivity of iron and EGCG through forming an Ngal–EGCG–iron complex. In thinking of the interaction of iron and ROS, we proposed that EGCG may work as both antioxidant and Ngal binding siderphore in protection of kidney from injuries. [ABSTRACT FROM AUTHOR]

Background: Reports of osteonecrosis of the jaw (ONJ) have associated this lesion to treatment with bisphosphonates (BPs) and dental procedures. In this study, we investigated the association of specific dental diagnoses and procedures with ONJ among patients with past BP use. Methods: Dentists from three practice-based research networks provided ONJ cases and controls (1:3). Data gathered from patients and dental offices with two respective standard questionnaires included demographic, medical, pharmaceutical, and dental information. Diagnoses and procedures up to 3 years prior to ONJ (prior to interview for controls) were analyzed within risk strata, defined by BP use and cancer status, using interaction terms within conditional logistic regression models. Results: We enrolled 191 ONJ cases and 573 controls from 119 dental offices. Among participants who had used only oral BP, extraction was the only dental risk factor for ONJ (odds ratio (OR) = 12, p = 0.01). Suppuration was also more prevalent in cases (18 %) than in controls (9 %), but not statistically significant (OR = 9, p = 0.06). Among participants who had not used either oral or IV BP (a majority of whom received radiation therapy to the head and neck), suppuration was the only dental risk factor for ONJ (prevalence = 34 % for cases and 8 % for controls; OR = 7, p = 0.01). The prevalence of extractions in this group was also higher, but not statistically significant (44 vs 10 %; OR = 3). Limited power precludes definitive findings among participants exposed to IV BP. Conclusions: Among patients taking oral BP, extraction was the only dental procedure associated with subsequent ONJ development Clinical relevance: Results of this study suggest that routine dental procedures are not associated with development of ONJ in patients exposed to BPs. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to review the available literature and define clinical practice guidelines for the use of natural agents for the prevention and treatment of oral mucositis. Methods: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology. The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, and no guideline possible. Results: A total of 49 papers across 15 interventions were examined. A new suggestion was developed in favor of systemic zinc supplements administered orally in the prevention of oral mucositis in oral cancer patients receiving radiation therapy or chemoradiation (Level III evidence). A recommendation was made against the use of intravenous glutamine for the prevention of oral mucositis in patients receiving high-dose chemotherapy prior to hematopoietic stem cell transplant (Level II evidence). No guideline was possible for any other agent, due to inadequate and/or conflicting evidence. Conclusions: Of the various natural agents reviewed here, the available evidence supported a guideline only for two agents: a suggestion in favor of zinc and a recommendation against glutamine, in the treatment settings listed above. Well-designed studies of other natural agents are warranted. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this systematic review was to analyze the available literature and define clinical practice guidelines for the use of the following agents for the prevention and treatment of oral mucositis (OM): allopurinol, midline mucosa-sparing radiation blocks, payayor, pentoxifylline, timing of radiation therapy (RT) (morning versus late afternoon), pilocarpine, bethanechol, chewing gum, propantheline, and tetrachlorodecaoxide. Methods: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, no guideline possible. Results: A total of 32 papers across 10 interventions were examined. New suggestions were developed against the use of systemic pilocarpine administered orally for prevention of OM during RT in head and neck cancer patients and in patients receiving high-dose chemotherapy, with or without total body irradiation, prior to hematopoietic stem cell transplantation. A suggestion was also made against the use of systemic pentoxifylline administered orally for the prevention of OM in patients undergoing bone marrow transplantation. No guideline was possible for any other agent reviewed due to inadequate and/or conflicting evidence. Conclusions: None of the agents reviewed was determined to be effective for the prevention or treatment of OM. Two agents, pilocarpine and pentoxifylline, were determined to be ineffective, in the populations listed above. Additional well-designed research is needed on other interventions. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the antioxidant and binding effects of gooseberry, a less-studied berry, and to compare with blueberry and cranberry in the model of interaction with human serum albumin (HSA). The relationship between the scavenging properties of dietary polyphenols of the selected berries and their affinities for HSA were investigated by fluorescence analysis. In order to perform the extraction and identification of the antioxidants present in the samples, different types of extraction solvents were used, such as water, ethyl acetate, and diethyl ether. The polyphenols, tannins, anthocyanins and ascorbic acid contents, and the total antioxidant capacities (TACs) of the berry extracts were assessed by using ESI-MS, FTIR, and radical scavenging assays. The contents of bioactive compounds and the levels of TACs in water extracts differed significantly and were the highest in water extracts in comparison with other extracts in all the investigated berries ( P < 0.05). Gooseberry water extracts contained: polyphenols (mg GAE/g DW)-5.37 ± 0.6, tannins (mg CE/g DW)-0.71 ± 0.2, anthocyanins (mg CGE/g DW)-12.0 ± 1.2, ascorbic acid (mg AA/g DW)-5.15 ± 0.5, and TACs (μMTE/g DW) by ABTS and FRAP assays were 15.53 ± 1.6 and 6.51 ± 0.7, respectively. In conclusion, the bioactivity of gooseberry was lower than blueberries and cranberries. The antioxidant and binding properties of gooseberries in comparison with widely consumed blueberries and cranberries can be used as a new source for food supplementation. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to examine feasibility of testing and frequency of abnormal plasma glucose among dental patients in The Dental Practice-Based Research Network. Methods: Eligible dental patients were ≥19 years old and had at least one American Diabetes Association-defined risk factor for diabetes mellitus or an existing diagnosis of diabetes or pre-diabetes. Random (fasting not required) plasma glucose was measured in standardized fashion using a commercial glucometer. Readings <70 or >300 mg/dl triggered re-testing. Patients with glucose ≥126 mg/dl were referred for medical follow-up. Results: Of 498 subjects in 28 dental practices, 491 (98 %) consented and 418 (85.1 %) qualified for testing. Fifty-one patients (12.2 %) had diabetes; 24 (5.7 %) had pre-diabetes. Glucose ranged from 50 to 465 mg/dl. One hundred twenty-nine subjects (31 %) had readings outside the normal range; of these, 28 (6.7 %) had readings <80 mg/dl and 101 (24.2 %) had readings ≥126 mg/dl; in nine patients (seven with diabetes), glucose was >200 mg/dl. Conclusions: A significant proportion of patients tested had abnormal blood glucose. Routine glucose testing in dental practice of populations at risk or diagnosed with diabetes may be beneficial and community dental practices hold promise as settings for diabetes and pre-diabetes screening and monitoring. Clinical relevance: Results suggest that implementation of glucose measurement in dental practice may provide important clinical and health information for both patients and practitioners. [ABSTRACT FROM AUTHOR]

Background: Kidney failure predicts mortality in patients with cirrhosis. Identification of kidney failure etiology and recognition of those at the highest mortality risk remains a challenge. Aims: We hypothesized that urinary neutrophil gelatinase-associated lipocalin (uNGAL) predicts mortality and identifies hepatorenal syndrome (HRS) in patients with cirrhosis. Methods: Prospectively enrolled patients with cirrhosis were investigated by uNGAL immunoblot upon hospital admission. Kidney failure type was determined blinded to NGAL measurements. Results: One hundred eighteen patients were enrolled. Fifty-two (44 %) patients had normal kidney function, 14 (12 %) stable chronic kidney disease, 17 (14 %) prerenal azotemia, 20 (17 %) HRS, and 15 (13 %) intrinsic acute kidney injury (iAKI). Patients with HRS had uNGAL levels intermediate between prerenal azotemia [median (IQR) 105 (27.5-387.5) vs. 20 (15-45) ng/mL, p = 0.004] and iAKI [325 (100-700), p < 0.001]. Fifteen (13 %) patients died. In unadjusted analysis, uNGAL predicted inpatient mortality (OR 2.00, 95 % CI 1.36-2.94) and mortality or liver transplantation (OR 2.01, 95 % CI 1.42-2.85). In multiple regression models, uNGAL > 110 ng/mL (OR 6.05, 95 % CI 1.35-27.2) and HRS (OR 6.71, 95 % CI 1.76-25.5) independently predicted mortality, adjusting for age and serum creatinine >1.5 mg/dL. Conclusions: uNGAL strongly predicts short-term inpatient mortality in both unadjusted and adjusted models. Patients with HRS may have uNGAL levels intermediate between those with prerenal azotemia and iAKI. Further studies are needed to determine if uNGAL can improve discrimination of HRS from other types of acute kidney injury and predict short- and long-term cirrhosis outcomes. [ABSTRACT FROM AUTHOR]

Seeds and leaves of indigo ( Polygonum tinctorium Ait.) plant were investigated and compared with another medicinal plant named prolipid for their properties such as chemical composition, antioxidant, and anticancer effects by Fourier transform infrared, three-dimensional fluorescence spectroscopy, and electrospray ionization-MS in negative mode. It was found that polyphenols, flavonoids, and flavanols were significantly higher in prolipid ( P < 0.05), following by indigo mature leaves, immature leaves, and seeds. Methanol extract of mature indigo leaves in comparison with the ethyl acetate extract showed higher inhibition of proliferation. The interaction between polyphenol extracts of indigo mature leaves and BSA showed that indigo has a strong ability, as other widely used medicinal plants, to quench the intrinsic fluorescence of BSA by forming complexes. In conclusion, indigo mature leaves were compared with prolipid. High content of bioactive compounds, antioxidant, fluorescence, and antiproliferative properties of indigo justifies the use of this plant as a medicinal plant and a new source of antioxidants. [ABSTRACT FROM AUTHOR]

Many proteins have been proposed to act as surrogate markers of organ damage, yet for many candidates the essential biomarker characteristics that link the protein to the injured organ have not yet been described. We generated an Ngal reporter mouse by inserting a double-fusion reporter gene encoding luciferase-2 and mCherry (Luc2-mC) into the Ngal (Lcn2) locus. The Ngal-Luc2-mC reporter accurately recapitulated the endogenous message and illuminated injuries in vivo in real time. In the kidney, Ngal-Luc2-mC imaging showed a sensitive, rapid, dose-dependent, reversible, and organ- and cell-specific relationship with tubular stress, which correlated with the level of urinary Ngal (uNgal). Unexpectedly, specific cells of the distal nephron were the source of uNgal. Cells isolated from Ngal-Luc2-mC mice also revealed both the onset and the resolution of the injury, and the actions of NF-κB inhibitors and antibiotics during infection. Thus, imaging of Ngal-Luc2-mC mice and cells identified injurious and reparative agents that affect kidney damage. [ABSTRACT FROM AUTHOR]

Background Accurate grading of dermatologic adverse events (AE) due to epidermal growth factor receptor (EGFR) inhibitors (EGFRIs) is necessary for drug toxicity determinations, interagent comparisons, and supportive care trials. The most widely used severity grading scale, the National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE v4.0), was not designed specifically for this class of agents and may result in underreporting and poor grading of distinctive adverse events. We believe a class-specific grading scale is needed to help standardize assessment and improve reporting of EGFRI-associated dermatologic AEs. Methods The Multinational Association of Supportive Care in Cancer (MASCC) Skin Toxicity Study Group conducted an international multidisciplinary meeting that included 20 clinicians and researchers from academic centers and government agencies. Experts from different disciplines presented current information specific to EGFRI-induced dermatologic toxicities: grading scale development, pharmacovigilance safety reporting, health-related quality of life, patient reporting, and pharmacology. Group discussions, literature reviews, and professional expertise established the theoretical foundation for the proposed grading scale. Results A new grading system is proposed for the most common events associated with EGFRI-induced dermatologic AEs: papulopustular reaction or acneiform rash, nail changes, erythema, pruritus, xerosis, hair changes, telangiectasias, hyperpigmentation, mucositis, flushing, radiation dermatitis, hyposalivation, and taste changes. The proposed scale maintains consistency with the grading principles and language of the existing CTCAE version 4.0 and MedDRA terminology and includes relevant patient-reported health-related quality of life factors. Conclusions A grading scale specific to EGFR inhibitor dermatologic AEs is presented for formal integration into future versions of CTCAE and for validation in clinical trial settings. The study group designed this scale to detect and report EGFRI-related toxicities with greater sensitivity, specificity, and range than the scales currently used. This scale should serve as a foundation for efforts to perform objective interdrug comparisons and assessments of supportive care treatment strategiesmore effectively than with current methods. [ABSTRACT FROM AUTHOR]

Glial cell line–derived neurotrophic factor signaling through the Ret receptor tyrosine kinase is crucial for ureteric bud branching morphogenesis during kidney development, yet few of the downstream genes are known. Here we show that the ETS transcription factors Etv4 and Etv5 are positively regulated by Ret signaling in the ureteric bud tips. Mice lacking both Etv4 alleles and one Etv5 allele show either renal agenesis or severe hypodysplasia, whereas kidney development fails completely in double homozygotes. We identified several genes whose expression in the ureteric bud depends on Etv4 and Etv5, including Cxcr4, Myb, Met and Mmp14. Thus, Etv4 and Etv5 are key components of a gene network downstream of Ret that promotes and controls renal branching morphogenesis. [ABSTRACT FROM AUTHOR]

Very few biomarkers exist for monitoring chronic kidney disease (CKD). We have recently shown that serum neutrophil gelatinase-associated lipocalin (NGAL) represents a novel biomarker for early identification of acute kidney injury. In this study, we hypothesized that serum NGAL may also represent a biomarker for the quantitation of CKD. Forty-five children with CKD stages 2–4 were prospectively recruited for measurement of serum NGAL, serum cystatin C, glomerular filtration rate (GFR) by Ioversol clearance, and estimated GFR (eGFR) by Schwartz formula. Serum NGAL significantly correlated with cystatin C ( r=0.74, P<0.000). Both NGAL and cystatin C significantly correlated with measured GFR ( r=0.62, P<0.000; and r=0.71, P<0.000, respectively) as well as with eGFR ( r=0.66, P<0.000 and r=0.59, P<0.000, respectively). At GFR levels of ≥30 ml/min per 1.73 m2, serum NGAL, cystatin C, and eGFR were all significantly correlated with measured GFR. However, in subjects with lower GFRs (<30 ml/min per 1.73 m2), serum NGAL levels correlated best with measured GFR ( r=0.62), followed by cystatin C ( r=0.41). We conclude that (a) both serum NGAL and cystatin C may prove useful in the quantitation of CKD, and (b) by correlation analysis, NGAL outperforms cystatin C and eGFR at lower levels of measured GFR. [ABSTRACT FROM AUTHOR]

Acute kidney injury secondary to ischemia–reperfusion in renal allografts often results in delayed graft function. We tested the hypothesis that expression of neutrophil gelatinase-associated lipocalin (NGAL) is an early marker of acute kidney injury following transplantation. Sections from paraffin-embedded protocol biopsy specimens obtained at approximately one hour of reperfusion after transplantation of 13 cadaveric (CAD) and 12 living-related (LRD) renal allografts were examined by immunohistochemistry for expression of NGAL. The staining intensity was correlated with cold ischemia time, peak post-operative serum creatinine, and dialysis requirement. There were no differences between the LRD and CAD groups in age, gender or preoperative serum creatinine. Using a scoring system of 0 (no staining) to 3 (most intense staining), NGAL expression was significantly increased in CAD specimens (2.3±0.8 versus 0.8±0.7 in LRD, p<0.001). There was a strong correlation between NGAL staining intensity and cold ischemia time ( R=0.87, p<0.001). Importantly, NGAL staining in these early CAD biopsies was strongly correlated with peak postoperative serum creatinine, which occurred days later ( R=0.86, p<0.001). Four patients developed delayed graft function requiring dialysis during the first week posttransplantation; all of these patients displayed the most intense NGAL staining in their first protocol biopsies. We conclude that NGAL staining intensity in early protocol biopsies represents a novel predictive biomarker of acute kidney injury following transplantation. [ABSTRACT FROM AUTHOR]

Objective: To report five patients on hemodialysis via an indwelling central venous catheter who developed a thrombus located exclusively on the right atrial wall opposing the emptying site of the superior vena cava and to determine the possible cause of this location.Design: Transthoracic echocardiography was performed in four of the patients as work-up for suspected endocarditis or pulmonary embolism and in one patient for syncope evaluation. The right atrial clots were confirmed in all the patients by transesophageal echocardiography.Design and Setting: General intensive care unit of a university hospital, tertiary referral center.Patients: Five patients with end-stage chronic renal failure on hemodialysis via subclavian or internal jugular vein catheter.Interventions: Three of these patients underwent surgical thrombectomy, and two others were medically treated.Measurements and Results: The clots were 2-4 cm in length and three of them were infected. Two of the three surgically treated patients and one of the two medically treated patients died. All the patients had the catheter tip in the right atrium, in two of them the bent catheter rubbed the atrial endocardium, and in all the cases the clot was located on the atrial free wall facing the superior vena cava emptying.Conclusions: We postulate that the mechanism of thrombus formation at this location is related to friction of the catheter on the atrial endocardium, and therefore positioning the distal segment of the central venous catheters in the right atrium should be avoided. [ABSTRACT FROM AUTHOR]

Presents research that finds defective acidification in cystic fibrosis cells of the `trans'-Golgi/`trans'-Golgi network, and of prelysosomes and of endosomes as a result of diminished C1-conductance. Sialylation of proteins and lipids is reducedand ligand traffic altered.

Children suffering from chronic physical illness are considered to be at increased risk for behavioural problems. There is also evidence that their siblings are at risk for behavioural problems. This study investigated parent-reported behavioural problems in chronically ill children and their siblings. There were significant positive correlations between the behaviour problem scores of the ill children and the scores of their siblings. Siblings older than the ill child had significantly higher behaviour problem scores of an internalizing nature than did the younger siblings. Sibling behaviour problem scores were similar to those of a comparison group of normal children and significantly different from those of a comparison group of psychiatrically referred children. Siblings of chronically ill children showed no greater likelihood of receiving scores in the clinical range of behaviour problems than children in the general population. Implications of the findings and suggestions for future research are discussed. [ABSTRACT FROM AUTHOR]

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The present study examined the expectancies of success, evaluations of performance, and achievement-related attributions that high school students made about verbal and spatial tasks that typically show sex differences. Although no sex differences were found in task performance, boys expected to do better than girls on both the spatial and verbal tasks. After completing the task, the girls continued to evaluate their performance more negatively than did boys on the spatial tasks. On spatial tasks girls also attributed to themselves less ability and saw the tasks as being more difficult than did boys. The results suggest that there are generalized, rather than task-specific, sex differences in achievement expectancies, evaluations, and attributions. These findings are discussed in terms of their implications for sex-related differences in cognitive functioning and subsequent achievement behaviors. [ABSTRACT FROM AUTHOR]

Background: In recent years attempts have been made to treat hydatid liver cysts laparoscopically. The purpose of this study was to evaluate different aspects of this approach and to examine whether a reasonable model could be developed. Methods: Three different subjects were analyzed. In the first, physical aspects related to transmembrane pressures were analyzed to demonstrate that evacuation of the cyst under pneumoperitoneum does not carry increased risk of spillage, and may even offer an advantage when the proper technique is used. In the second subject, an isolated liver model of a goat was used to study several techniques for evacuating hydatid cysts without spillage. This was tested qualitatively by demonstrating scolices in the fluid medium around the isolated liver after surgical manipulations. In the third subject, the implication of the technique was evaluated in human patients. Results: According to basic physical assumptions, the following conclusions were reached: (1) The increase in intracystic pressure is equal to or less than the increase in intraperitoneal pressure after pneumoperitoneum. (2) Aspiration of parasitic cysts by laparoscopic needle through a large cannula under ``vacuum'' or by sealing the cannula and adhering it to the liver by cyanoacrylate or fibrin glue was found to be very safe. Simple needle aspiration failed to prevent spillage. (3) A new transparent cannula 18 mm in diameter with a beveled tip was designed that enables good accessibility to liver cysts and safe evacuation even of huge and complex cysts. Conclusions: The novel technique to manage hydatid liver cysts, described in the study, is feasible, sensible, and safe. The isolated goat liver containing hydatid cysts can be used as a reliable animal model to test new techniques in the future. [ABSTRACT FROM AUTHOR]

The present study compared the pattern of service utilization over a 1-year period, of 349 newly referred adult patients to the four community mental health clinics in Jerusalem. Treatment in these clinics is provided free of charge and there are no limits on length of treatment. Irrespective of patient diagnosis and clinic setting, the percentage of patients remaining in contact with the clinics declined sharply during the first 3 months, and after 6 months stabilized to around 25-40%. However, among patients with nonmajor psychiatric disorders, inter-clinic variation in compliance with treatment was observed. In clinics with a long-term psychotherapeutic orientation, a larger proportion of patients was referred to other services following intake, and a larger proportion of patients dropped out of treatment. In these clinics, more patients were placed on waiting lists before beginning treatment, and the drop-out rate among these patients was significantly higher than that of patients in treatment. The implications of these results for treatment policy in public services are discussed. [ABSTRACT FROM AUTHOR]