Insulin-Related Lipohypertrophy: Lipogenic Action or Tissue Trauma?

Lipohypertrophy has been suggested as an outcome of lipogenic action of insulin and/or injection-related tissue trauma. In a cross-sectional study, we evaluated the predictors of lipohypertrophy in 372 type 1 diabetes patients (mean age 17.1 years) receiving subcutaneous insulin with pen and/or syringes for ≥3 months. On examining injection sites with inspection and palpation technique, 62.1% patients demonstrated lipohypertrophy. Univariate analysis showed that gender, BMI, HbA1c, injection device, rotation, injection area, needle length, insulin regimen, and total daily dose of insulin were associated with lipohypertrophy (p < 0.05). Notably, the mean needle reuse was comparable in patients with or without lipohypertrophy (8.1 vs. 7.2, p = 0.534). In multivariate logistic regression, gender, HbA1c, TDD, injection devices, and needle length lost its significance. Further, injections over smaller area (≤8.5 × 5.5 cm) and non-rotation of sites were found to be strongest independent predictor of lipohypertrophy (p < 0.0005 for both) with increased odds of 23.2 (95% CI 9.1–59.2) and 6.3 (95% CI 3.4–11.9) times, respectively. Being underweight was also a significant independent predictor (odds ratio [OR] 13.0 [95% CI 2.2–75.2], p = 0.004). Compared to rapid plus long-acting analogs, regular insulin plus long-acting analogs and conventional premixed insulin users had 3.2 (95% CI 1.5–6.8, p = 0.003) and 4.6 (95% CI 1.4–15.7, p = 0.014) fold higher risk of lipohypertrophy (mean injection frequency 4.01 vs. 4.01 vs. 2.09, respectively). Sub-group analysis showed that lipohypertrophy was 79% less likely in patients with multiple daily injections (≥4) than twice-daily regimen (OR 0.21, p < 0.0005). Moreover, lipohypertrophy was reduced to half with bolus doses of rapid-acting insulin analogs than regular insulin (p = 0.003), even though mean injection frequency was comparable (4.01 vs. 3.93, p = 0.229). This difference was statistically insignificant for basal doses with NPH or long-acting analogs (p = 0.069). Therefore, injection area, rotation, BMI, and insulin regimen are the best predictors of lipohypertrophy and together could correctly identify lipohypertrophy status in 84.4% patients with excellent discrimination capability (AUC = 0.906, p < 0.0005). In conclusion, findings of our study suggest that delivering rapidly absorbed insulin analogs over large injection area along with greater split of total daily doses reduce insulin-induced lipogenesis and outplay tissue trauma added through frequent injections and needle reuse

Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic

Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality. Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children <18 years who were newly diagnosed with or undergoing active treatment for acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, retinoblastoma, Wilms tumour, glioma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, medulloblastoma and neuroblastoma. Of 2327 cases, 2118 patients were included in the study. The primary outcome measure was all-cause mortality at 30 days, 90 days and 12 months. Results All-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3-11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); p<0.001), lower middle income (OR 3.32 (95% CI 1.96 to 5.61); p<0.001) and upper middle income (OR 3.49 (95% CI 2.02 to 6.03); p<0.001) country status and chemotherapy (OR 0.55 (95% CI 0.36 to 0.86); p=0.008) and immunotherapy (OR 0.27 (95% CI 0.08 to 0.91); p=0.035) within 30 days from MDT plan. Multivariable analysis revealed laboratory-confirmed SARS-CoV-2 infection (OR 5.33 (95% CI 1.19 to 23.84); p=0.029) was associated with 30-day mortality. Conclusions Children with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer

Psychopathological Organizations and Attachment Styles in Patients with Fear of Flying: A Case Study

Objectives The scope of the study is to identify the leading “organization of meaning” in patients affected by aviophobia and the related attachment style. Specifically we hypothesized that participants with fear of flying would predominantly display a phobic organization of meaning, associated with an anxious-ambivalent attachment style. Methods 150 adults, divided between an experimental group (FOF) and a control group (CON), completed three research instruments: two self-report questionnaires assessing attachment style (AAQ and ASQ) and the self-characterization, a qualitative constructivist tool. Results The insecure attachment style prevailed in aviophobics rather than control group. Socioeconomic and gender differences were found. The vocabulary used by the group with flying phobia featured a system of meaning referring to “freedom” family semantics. Conclusions Attachment style appears to be a necessary but insufficient condition for predicting fear of flying. A greater role in the disorder is played by the organization of patients’ personality, as argued by socio-constructionist and constructivist authors. Implication for clinical work and psychotherapy are discussed

Determination of Perfluorinated and Polyfluorinated Alkyl Substances (PFASs) in PM₁₀ Samples: Analytical Method, Seasonal Trends, and Implications for Urban Air Quality in the City of Terni (Central Italy)

A quantitative analytical method for PFAS determination in airborne particulate matter (PM) has been developed using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS), allowing for the determination of 33 compounds. The procedure was applied to ambient PM10 with limits of quantification for PFAS in the fg m−3 range. PM10 samples collected during a year-long campaign conducted in an urban site in Umbria (Central Italy) have been characterized for their PFAS content. Among the seven detected PFASs, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) were the most abundant compounds. Furthermore, this work allowed us to obtain the first seasonal trend of airborne PFASs in Central Italy. Seasonal trend analysis shows that PFAS concentration in the atmosphere peaks in summertime. A comparison with trends of other relevant primary and secondary air pollutants determined at the sampling site suggests a secondary nature of the observed PFAS, which are formed in the atmosphere directly from gaseous precursors and can contribute to worsen the urban air quality in summertime

Optimization of Ultrasound-Assisted Extraction of Chlorogenic Acid from Potato Sprout Waste and Enhancement of the In Vitro Total Antioxidant Capacity

Potato sprouts, an underutilized by-product of potato processing, could be exploited for the recovery of caffeoyl-quinic acids (CQAs), a family of polyphenols with well-recognized biological activities. In this work, the predominant compound of this class, 5-CQA, was extracted by Ultrasound-Assisted Extraction (UAE) under conditions optimized by an Experimental Design. The investigated variables solid/solvent ratio (1:10–1:50 g/mL), water content in ethanol (30–100% v/v) and UAE time (5–20 min) highlighted a critical influence of the last two factors on the extraction efficiency: extracts richer in 5-CQA were obtained with lower water content (30%) and time (5 min). The addition of ascorbic acid (1.7 mM) as anti-browning agent to the extraction solvent improved the extraction efficiency of 5-CQA compared to acetic and citric acids (3158.71 μg/mL, 1766.71 μg/mL, 1468.20 μg/mL, respectively). A parallel trend for the three acids and an increase in 5-CQA recovery was obtained with the use of freeze-dried sprouts (4980.05 μg/mL, 4795.62, 4211.25 μg/mL, respectively). Total antioxidant capacity (TAC) in vitro demonstrated UAE being a more valuable technique than conventional maceration. Furthermore, three-times-higher values of TPC (7.89 mg GAE/g) and TAC (FRAP: 24.01 mg TE/g; DPPH: 26.20 mg TE/g; ABTS 26.72 mg TE/g) were measured for the optimized extract compared to the initial one. An HPLC-DAD method was applied to monitor 5-CQA recovery, while an LC-HRMS/MS investigation allowed us to perform analyte identity confirmation along with detection of the glycoalkaloids α-solanine and α-chaconine. This evidence underlines the necessity to develop purification strategies in order to maximize the potential of potato sprout waste as a source of 5-CQA

LC-MS/MS assay for the simultaneous determination of tocopherols, polyunsaturated fatty acids and their metabolites in human plasma and serum

The role of vitamin E in both enzymatic and free radical-dependent metabolism of polyunsaturated fatty acids (PUFAs) has been well demonstrated. This study proposed a new LC-MS/MS method to quantify the main vitamin E forms, their metabolites and main PUFA species in human blood, since, at present, there are not procedures able to simultaneously determine these two classes of compounds. After the optimization of sample treatment and reverse-phase separation conditions, tandem mass spectrometry detection was evaluated experimenting both positive and negative electrospray ionisation modes. The procedure was also preliminarily adapted to assess five arachidonic acid-derived eicosanoids that could be under the influence of vitamin E function, such as LTB4 (leukotriene B4), 20-HETE (20-hydroxyeicosatetraenoic acid) and their ω-oxidation metabolites. After the validation study, the performance characteristics were confirmed analysing a certified reference material (SRM® 1950 - frozen human plasma by NIST). Finally, an application of the method in the analysis of lipid abnormalities of chronic kidney disease patients was shown

Multiple Heart-Cutting Two-Dimensional HPLC-UV Achiral–Chiral Analysis of Branched-Chain Amino Acids in Food Supplements under Environmentally Friendly Conditions

A multiple heart-cutting (mLC-LC) two-dimensional HPLC-UV achiral–chiral method for the direct analysis of branched-chain amino acids (BCAAs) in food supplements under environmentally friendly conditions was developed to cope with the very well-known limited chemoselectivity of chromatographic media for enantioselective analysis. Both achiral and chiral methods were developed in compliance with the main principles of green chromatography. The achiral analysis was performed isocratically with an optimized ion-pair reversed-phase (IP-RP) method based on a water/EtOH (95:5, v/v) mobile phase containing heptafluorobutyric acid (7 mM) as the IP agent. The achiral method was characterized by a very appreciable performance and was validated before the analysis of the real sample. High recovery values for all compounds (from 97% to 101%) were found in the interday evaluation. Additionally, low RSD% values in the long-term period were measured, in the range between 1.1% and 4.8%. Still, an LOQ value of 0.06 mg/mL was established for all compounds. The quantitative analysis of a commercial food supplement revealed that BCAAs were present in amounts very close to those declared by the producer. The enantioselective analysis was carried out through the application of the chiral ligand-exchange chromatography (CLEC) approach, using O-benzyl-(S)-serine ((S)-OBS, 0.5 mM) as the chiral selector and Cu(II) nitrate (0.25 mM) as the metal source in the eluent. Resolution and separation factor values up to 2.31 and 1.43, respectively, were obtained. The two chromatographic systems were connected through a six-port switching valve, and the developed two-dimensional mLC-LC method confirmed the absence of D-enantiomers of BCAAs in the food supplement, as reported in the manufacturer’s label