Long-term Intake Research Articles

1376-P: Dietary Sodium Intake and Risk of Incident Type 2 Diabetes

Background: Type 2 Diabetes (T2D) and hypertension often coexist and share many common risk factors. High dietary sodium intake is a well-established risk factor for hypertension, whereas few studies have assessed the relation between dietary sodium intake and type 2 diabetes (T2D). In this study, we aimed to evaluate the association between the frequency of adding salt to foods, a surrogate marker for evaluating the long-term sodium intake, and incident T2D risk. Methods: A total of 402,982 participants from UK biobank, who were free of diabetes, chronic kidney disease, cancer, or cardiovascular disease at baseline, and had completed information on adding salt were analyzed in this study. Cox proportional hazards models were used to estimate the association between the frequency of adding salt to foods and incident T2D. Results: During a median of 11.8 years of follow-up, 13,120 incident T2D were documented. Compared with participants who Never/Rarely added salt to foods, the adjusted Hazard Ratios (95% confidence interval) were 1.13 (1.08, 1.17), 1.20 (1.14, 1.26), and 1.39 (1.30, 1.49) across the groups of Sometimes, Usually, and Always, respectively (P-trend<0.001). We did not find significant interactions between the frequency of adding salt to foods and baseline hypertension status and other covariates on the risk of incident T2D. The observed positive association was partly mediated by body mass index (BMI), waist to hip ratio, and C-reactive protein, with a significant mediation effect of 32.9%, 36.6% and 7.0%, respectively. The significant mediation effect of BMI was largely driven by the body fat mass rather than the body fat-free mass. Conclusions: Our findings for the first time indicate that higher frequency of adding salt to foods, a surrogate marker for a person’s long-term salt taste preference and intake, is associated with a higher T2D risk. Disclosure X.Wang: None. H.Ma: None. R.Tang: None. Q.Xue: None. X.Li: None. Y.Heianza: None. L.Qi: None.

Development of dish-based population-specific food frequency questionnaire for dietary assessments in Afghanistan

Purpose: Dietary intake assessment has an essential role in chronic disease studies and general public health outcomes. To measure dietary intakes in epidemiologic studies, various dietary assessment methods are used. Among them, food frequency questionnaires (FFQs) can provide useful measures of dietary intake. This study aimed to report the development of a population-specific dish-based food frequency questionnaire (DFQ) to assess long-term usual dietary intakes in Afghanistan. Design/Methodology/Approach: We considered the Willet format and followed these steps; listing commonly consumed Afghani foods, determining food groups, defining portion sizes, and determining the frequency response options for each food item. We prepared a comprehensive list of foods and dishes commonly used in Afghanistan. We categorized dishes and food items in the questionnaire into eight major groups. Portion sizes for food items and mixed dishes were defined based on the most commonly consumed and understandable portion sizes for each item among the Afghan general population. The frequency response options for each food item were defined separately in a row against the food list. Findings: We developed a new population-specific DFQ in Afghanistan containing 103 food items or dishes, which can be used as an instrument for the assessment of long-term dietary intakes as well as diet-disease associations in Afghanistan. Originality/Value: This is the first ever-developed dietary assessment tool in Afghanistan.

Distribution, determination method, risk assessment, and strategy of exogenous pyrrolizidine alkaloids in tea

Background and aimPyrrolizidine alkaloids (PAs) are secondary metabolites produced by plants. At present, more than 660 PAs have been identified in more than 6000 plants, mainly belonging to the families Boraginaceae, Compositae, Leguminosae, and so forth. PAs and their corresponding nitrogen oxides have variedtoxicities, including hepatotoxicity, pulmonary toxicity, and genotoxicity. The long-term intake of PAs can lead to cancer. This study aimed to review the literature on tea derived from C. sinensis only. ResultsTea is one of the most frequently items usedas both medicine and food. In recent years, PAs have been frequently detected in tea. The tea plant itself does not produce PAs, theymainly come from soil contamination caused by weeds in the tea garden. ConclusionsThis study reviewed data published in recent years on the distribution, detection, risk assessment, strategy, and prospects of PAs in tea. The findings of this study mightfacilitate the qualityimprovementand safe use of PAs in tea.

#3406 CARDIOPROTECTIVE EFFECT OF SOY PROTEIN ON LONG-TERM HIGH-SALT DIET IN CYNOMOLGUS MONKEYS

Abstract Background and Aims A high salt content in the diet is one of the reasons for the increase in blood pressure (BP) and the development of cardiovascular disorders. However, high intake of sodium chloride does not always lead to an increase in blood pressure, but causes endothelial dysfunction and cardiac remodeling. It has been established that the introduction of soy products into the diet can have a nephro- and cardioprotective effect in chronic kidney disease. At the same time, it is not clear whether the damaging effect of a high-salt diet on the cardiovascular system can be offset by other dietary interventions, in particular, soy proteins. In this regard, the aim of the study was to study the effect of long-term use of diets with different content of sodium chloride and soy protein on myocardial remodeling in cynomolgus monkeys. Method A total of 18 cynomolgus male monkeys with age 6–8 years were studied. The animals were divided into three groups (six in each group). The first (control) group received the standard diet. The second group received the diet rich in common salt (8 g of NaCl/kg), and the third, the high salt diet in combination with soy protein SUPRO 760 (200 g/kg; Protеin Tеchnology Intеrnational, USA). Systolic (BP) and diastolic (BPd) blood pressure (BP) in monkeys was recorded by oscillometric method on a veterinary tonometer ML-410 VET (Microlux, Russia) under anesthesia. After registration of blood pressure, an echocardiographic study (EchoCG) was performed with a sector sensor with a frequency of 3-5 MHz on an ultrasound system Chison SonoTouch 60 (China). Echocardiography was performed in B-mode (two-dimensional scanning), M-mode (one-dimensional scanning), as well as in pulsed and tissue Doppler modes. Echocardiography and blood pressure measurements were performed at baseline, after 4 and 12 months of follow-up. Results BP values (group 1 - BPs: 109±10.09, BPd: 60±7.42; group 2 - BPs: 109±25.14, BPd: 57±11.86; group 3 - BPs: 101±8, 59, BPd: 57±6.92 mm Hg, all p>0.05) and heart rate (group 1 - 77±12.61, group 2 - 81±18.07, group 3-80±19.9 beats/min, all p>0.05) in macaques did not undergo significant changes over 12 months of the experiment in any of the groups. In group 1, there were also no significant changes in echocardiographic parameters. Group 2 monkeys showed no early changes in LV shortening fraction (FU) and ejection fraction (EF). However, after 12 months, FU decreased by an average of 26.6%, and EF by 12.8% compared with the indicator for a period of 4 months. In addition, the speed of the transmitral flow in early diastole (E) decreased by 19.1% compared with the baseline. Long-term intake of soy proteins prevented a decrease in LV FU in macaques on a high-salt diet. Its value was 25.1% greater than in group 2. In group 3 monkeys, after 12 months, the magnitude of systolic excursion of the mitral annulus plane and the maximum rate of excursion of the fibrous annulus of the mitral valve in early diastole (e') increased, the thickness of the interventricular septum in diastole decreased, and E/e' ratio. In group 3, the thickness of the posterior wall of the left ventricle decreased in systole (0.57±0.056 mm), the mass of the LV myocardium (14.9±2.94 g/m2), the average diameter of the base of the right ventricle (1.20±0.115 mm) compared with group 2 (0.69±0.040 mm, 19.6±2.83 g/m2, 1.40±0.111 mm, respectively; all p<0.01). Conclusion The obtained results can be considered as confirmation of the hypothesis that high consumption of sodium chloride leads to adverse structural and functional changes in the heart and blood vessels, not associated with an increase in blood pressure. The inclusion of isolated soy proteins in the diet is likely to reduce the effects of this negative impact. The specific mechanisms of this cardioprotective effect remain to be explored. Statistical analysis used One-way analysis of variance for unrelated samples when comparing the data of 3 studied groups and one-way analysis of variance for related samples when studying the dynamics of the indicator in each of the groups during 12 months of observation. Results are presented as mean ± standard deviation (M ± SD). Differences were considered significant at p<0.05.

Dietary Patterns and Their Associations with Symptom Levels Among People with Multiple Sclerosis: A Real-World Digital Study.

The objective of the study was to investigate long-term food intake patterns and establish possible associations between the inferred dietary habits and levels of reported symptoms among people with multiple sclerosis (MS) in Denmark. The present study was designed as a prospective cohort study. Participants were invited to register daily food intake and MS symptoms and were observed during a period of 100days. Dropout and inclusion probabilities were addressed using generalized linear models. Dietary clusters were identified among 163 participants using hierarchical clustering on principal component scores. Associations between the dietary clusters and the levels of self-assessed MS symptoms were estimated using inverse probability weighting. Furthermore, the effect of a person's position on the first and second principal dietary component axis on symptom burden was investigated. Three dietary clusters were identified: a Western dietary cluster, a plant-rich dietary cluster and a varied dietary cluster. Analyses further indicated a vegetables-fish-fruit-whole grain axis and a red-meat-processed-meat axis. The plant-rich dietary cluster showed reduction in symptom burden in nine pre-defined MS symptoms compared to the Western dietary cluster (between 19 and 90% reduction). This reduction was significant for pain and bladder dysfunction as well as across all nine symptoms (pooled p value = 0.012). Related to the two dietary axes, high intake of vegetables resulted in 32-74% reduction in symptom burden compared to low levels of vegetable intake. Across symptoms, this was significant (pooled p value = 0.015), also regarding walking difficulty and fatigue. Three dietary clusters were identified. Compared to levels of self-assessed MS-related symptoms, and adjusted for potential confounders, the results suggested less symptom burden with increased intake of vegetables. Although the research design limits the possibilities of establishing causal inference, the results indicate that general guidelines for healthy diet may be relevant as a tool in coping with MS symptoms.

Salidroside ameliorates memory impairment following long-term ethanol intake in rats by modulating the altered intestinal microbiota content and hippocampal gene expression.

Salidroside (Sal), the main component of a famous herb Rhodiola rosea L, enhances memory performance and reduces fatigue. Therefore, this study assessed the effect of Sal on memory impairment induced by a long-term intake of ethanol (EtOH) in rats and investigated its relevant mechanisms using gut microbiota metagenomic analysis and hippocampal transcriptomic analysis. Eighteen male SD rats were divided into the normal control group (CON group), EtOH model group (Model group), and Sal treatment group (Sal group). The rats in the Model and Sal groups intragastrically (i.g.) received 2 g/kg EtOH for 30 consecutive days, whereas the CON group was given an equal volume of distilled water. Meanwhile, the rats in the Sal group were administered i.g. 30 mg/kg Sal 60 min after EtOH intake. All rats were tested in the eight-arm maze for their memory function every 3 days. On the 30th day, metagenomic analyses of gut microbiota and transcriptomic analyses of the hippocampus were performed. Compared with the Model group, Sal treatment reduced the total time to complete the eight-arm maze task, decreased the number of arm entries, and abated the working memory error that was significant from the 9th day. Additionally, Sal intervention improved the gut microbiota composition, such as the increased abundance of Actinobacteria and Bifidobacterium, which was related to the metabolism of amino acids and terpenoid carbohydrate, endocrine function, and signal transduction by neurotransmitters. In the hippocampus, the EtOH intake differentially expressed 68 genes (54 genes increased, whereas 14 genes decreased), compared with the CON group, whereas Sal intervention affected these changes: 15 genes increased whereas 11 genes decreased. And, enrichment analyses revealed these genes were related to the structural components of the ribosome, mRNA splicing process, protein translation, mitochondria function, and immunological reaction. Finally, a correlation analysis found the memory impairment was positively correlated with the abnormal upregulation of Tomm7 but negatively correlated with decreased abundance of gut Alistipes_indistinctus, Lactobacillus_taiwanensis, Lactobacillus_paragasseri, and Lactobacillus johnsonii. Sal improved memory impairment caused by long-term EtOH intake in rats, which may be related to its regulation of gut dysbiosis and hippocampal dysfunction.

Long-Term Intake of Linezolid Elevates Drug Exposure and Reduces Drug Clearance and Elimination in Adults With Drug-Resistant Pulmonary Tuberculosis.

Pharmacokinetic (PK) studies are critical for dose optimization, and there is a paucity of linezolid (LZD) PK data for prolonged use in drug-resistant tuberculosis (DR-TB). Therefore, the authors evaluated the pharmacokinetics of LZD at two-time intervals in DR-TB during long-term use. PK evaluation of LZD was performed at the end of the 8th and 16th weeks of treatment in a randomly selected subset of adult pre-extensively drug-resistant pulmonary tuberculosis patients (n = 18) from a multicentric interventional study (Building Evidence to Advance Treatment of TB/BEAT study; CTRI/2019/01/017310), wherein a daily dose of 600 mg LZD was used for 24 weeks. Plasma LZD levels were measured using a validated high-pressure liquid chromatography (HPLC) method. The LZD median plasma C max was comparable between the 8th and 16th weeks [18.3 mg/L, interquartile range (IQR: 15.5-20.8 and 18.8 mg/L, IQR: 16.0-22.7, respectively)]. However, the trough concentration increased significantly in the 16th week (3.16 mg/L, IQR: 2.30-4.76), compared with the 8th week (1.98 mg/L, IQR: 0.93-2.75). Furthermore, compared with the 8th week, in the 16th week, there was a significant increase in drug exposure (AUC 0-24 = 184.2 mg*h/L, IQR: 156.4-215.8 versus 233.2 mg*h/L, IQR: 187.9-277.2), which corroborated with a longer elimination half-life (6.94 hours, IQR: 5.55-7.99 versus 8.47 hours, IQR:7.36-11.35) and decreased clearance (2.91 L/h, IQR: 2.45-3.33 versus 2.19 L/h, IQR: 1.49-2.78). Long-term daily intake of 600 mg LZD resulted in a significant elevation in trough concentration (>2.0 mg/L) in 83% of the study participants. Furthermore, increased LZD drug exposure may be partly because of decreased clearance and elimination. Overall, the PK data underscore the need for dose adjustment when LZDs are intended for long-term treatment.

A very high-carbohydrate diet differentially affects whole-body glucose tolerance and hepatic insulin resistance in rats

ObjectivesThis study was performed to assess the effects of long-term intake of a very high carbohydrate (VHCHO) diet (76% of total energy from carbohydrate [CHO]) on whole-body glucose tolerance and hepatic insulin resistance. Methods and MaterialsMale Sprague Dawley rats were fed either a control high-CHO diet (59% total energy from CHO; n = 8) or a VHCHO diet (76% total energy from CHO; n = 8) for 17 wk. At 4, 8, 12, and 16 wk of the dietary intervention, oral glucose tolerance test and homeostasis model assessment of insulin resistance (HOMA-IR) measurements were taken to assess whole-body glucose tolerance and hepatic insulin resistance, respectively. The triacylglycerol concentration in the liver was measured at the end of the 17-wk intervention period. ResultsThe VHCHO diet group showed significantly higher muscle glucose transporter 4 content and a smaller area under the curve for plasma glucose, but not insulin, in the oral glucose tolerance test compared with the control group. On the other hand, the VHCHO diet group had a significantly higher hepatic triacylglycerol concentration and HOMA-IR measurement compared with the control group. The hepatic triacylglycerol concentration was significantly and positively correlated with HOMA-IR. ConclusionsThe results of the present study suggest that long-term intake of a VHCHO diet exerts differential effects on whole-body glucose tolerance and hepatic insulin resistance.

Modification of the existing maximum residue levels and setting of import tolerances for fluopyram in various crops.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Bayer AG Crop Science Division submitted a request to the competent national authority in Italy to modify the existing maximum residue level (MRL) for the active substance fluopyram in kiwi. Additionally, the applicants Bayer Crop Science SA and Bayer SAS Crop Science Division submitted two applications to the competent national authority in Germany to modify the MRLs for fluopyram in certain stem vegetables, seed spices, apples and soyabeans based on intended EU uses as well as to lower the existing EU MRL in pome fruits and to raise the existing EU MRL in peanuts on the basis of authorised use of fluopyram in the USA. The data submitted in support of the request were found to be sufficient to derive MRL proposals for all the crops under assessment except for palm hearts and bamboo shoots. Adequate analytical methods for enforcement are available to control the residues of fluopyram in commodities under consideration at the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the short-term intake of residues resulting from the use of fluopyram according to the reported agricultural practices is unlikely to present a risk to consumer health. A long-term consumer intake concern is identified if the current MRL of 0.8 mg/kg in pome fruits is maintained and new MRLs for other commodities under consideration are supported, with apples being the highest contributing commodity to the diet for which exposure exceedances were noted. The chronic risk for consumers is unlikely if a lower MRL of 0.6 mg/kg in pome fruits proposed by the applicant is considered. Further risk manager considerations are required.

Setting of import tolerance for pyraclostrobin in papayas.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant BASF SE submitted a request to the competent national authority in Germany to set an import tolerance for the active substance pyraclostrobin in papayas imported from Brazil. The data submitted in support of the request were found to be sufficient to derive a maximum residue level (MRL) proposal for papayas. Adequate analytical methods for enforcement are available to control the residues of pyraclostrobin on the commodity under consideration at or above the validated limit of quantification (LOQ) of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues resulting from the use of pyraclostrobin on papayas imported from Brazil according to the reported agricultural practices is unlikely to present a risk to consumer health.

Safety outcomes of direct oral anticoagulants in older adults with atrial fibrillation: a systematic review and meta-analysis of (subgroup analyses from) randomized controlled trials

Balancing stroke prevention and risk of bleeding in patients with atrial fibrillation (AF) is challenging. Direct oral anticoagulants (DOACs) are by now considered standard of care for treating patients with AF in international guidelines. Our objective was to assess the safety of long-term intake of DOACs in older adults with AF. We included RCTs in elderly (≥ 65 years) patients with AF. A systematic search in MEDLINE and EMBASE was performed on 19 April 2022. For determination of risk of bias, the RoB 2 tool was applied. We pooled outcomes using random-effects meta-analyses. The quality of evidence was assessed using GRADE. Eleven RCTs with a total of 63,374 patients were identified. Two RCTs compared apixaban with either warfarin or aspirin, four edoxaban with either placebo, aspirin, or vitamin K antagonists (VKAs), two dabigatran with warfarin and three rivaroxaban with warfarin. DOACs probably reduce mortality in elderly patients with AF (HR 0.89 95%CI 0.77 to 1.02). Low-dose DOACs likely reduce bleeding compared to VKAs (HR ranged from 0.47 to 1.01). For high-dose DOACS the risk of bleeding varied widely (HR ranged from 0.80 to 1.40). We found that low-dose DOACs probably decrease mortality in AF patients. Moreover, apixaban and probably edoxaban are associated with fewer major or clinically relevant bleeding (MCRB) events compared to VKAs. For dabigatran and rivaroxaban, the risk of MCRB varies depending on dose. Moreover, subgroup analyses indicate that in the very old (≥ 85) the risk for MCRB events might be increased when using DOACs.Registration: PROSPERO: CRD42020187876.

Determination of seven paraben preservatives in aquatic seasoning using solid-phase extraction coupled with high performance liquid chromatography

Seven parabens are widely used in soy sauce, vinegar, jam, oyster sauce, stuffing, and other foods. The long-term intake of large amounts of parabens and similar substances may be harmful to the human body. Therefore, the addition of paraben preservatives to food should be strictly controlled. The current detection method is applicable to single target compound and several food categories, and the experimental pretreatment method involves extraction with anhydrous ethyl ether, which is a toxic reagent. Moreover, interferences in the analysis of parabens via gas chromatography limit the versatility and accuracy of the detection method. Herein, a novel method based on solid-phase extraction (SPE) coupled with high performance liquid chromatography (HPLC) was developed for the determination of seven paraben preservatives (methyl p-hydroxybenzoate, ethyl p-hydroxybenzoate, propyl p-hydroxybenzoate, butyl p-hydroxybenzoate, isopropyl p-hydroxybenzoate, isobutyl p-hydroxybenzoate, and heptyl p-hydroxybenzoate) in oyster sauce, shrimp sauce, and fish sauce. Compared with the conventional method, the proposed work enables the determination of more compounds, thereby expanding its scope of application to different food types. This strategy also optimizes the pretreatment method and device parameters. The samples were extracted with methanol and 20% methanol aqueous solution by ultrasonication, respectively, and then centrifuged. The experimental pretreatment method was enriched, and sample clean-up was conducted using a MAX SPE column. The seven parabens were separated using a Chromcore 120 C18 column (150 mm×4.6 mm, 3.0 μm). Gradient elution was performed with acetonitrile-5 mmol/L ammonium acetate aqueous solution as the mobile phase (initial mobile phase volume ratio, 30∶70). The flow rate was 0.7 mL/min, and the column temperature was 35 ℃. A diode array detector with a detection wavelength of 254 nm was also used. The seven paraben preservatives showed good linearity in the range of 0.5-50.0 mg/L, with correlation coefficients greater than 0.9999. The limits of detection (LODs) and quantification (LOQs) for the seven paraben preservatives were 0.2-0.4 mg/kg and 0.5-1.3 mg/kg, respectively. A spiked recovery test was conducted using oyster sauce, shrimp sauce, and fish sauce at three spiked levels of 2, 40, and 200 mg/kg. Good recoveries for the seven paraben preservatives were obtained and the recoveries of the analytes in oyster sauce, shrimp sauce, and fish sauce were 91.0%-102%, 95.5%-106%, and 95.0%-105%, respectively, with relative standard deviations of ≤6.97%. Compared with the liquid-liquid extraction method, the proposed method demonstrated better purification effects. The recoveries of the seven paraben preservatives extracted using this method were also much higher than those obtained from liquid-liquid extraction. We determined the contents of these preservatives in 135 food products using the method established in this study and detected methyl p-hydroxybenzoate and ethyl p-hydroxybenzoate in soy sauce, vinegar, and pickles. Thus, the established method can be used for the effective determination of seven parabens in aquatic seasoning such as oyster sauce, shrimp sauce, and fish sauce.

Setting of import tolerances for sulfoxaflor in various crops.

In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant Dow AgroSciences Ltd submitted a request to the competent national authority in Greece to set an import tolerance for the active substance sulfoxaflor in various crops. The data submitted in support of the request were found to be sufficient to derive import tolerance proposals for cane fruits, blueberries, avocados, mangoes, pineapples, asparagus, globe artichokes, sunflower seeds and coffee beans. Adequate analytical methods for enforcement are available to control the residues of sulfoxaflor in plant matrices under consideration at the validated LOQ of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the short-term and long-term intake of residues resulting from the use of sulfoxaflor according to the reported agricultural practices is unlikely to present a risk to consumer health.

SP06. Regenerative Peripheral Nerve Interface Surgery and its Four-year Pain and Medication Intake Outcomes for Treatment or Prevention of Postamputation Pain

PURPOSE: Regenerative peripheral nerve interface (RPNI) surgery is a validated method for mitigating pain in postamputation patients. However, the long-term efficacy of RPNI surgery has yet to be fully characterized. The purpose of this clinical study was to assess long-term pain outcomes and opioid medication intake in amputation patients who have undergone RPNI surgery for the treatment or prevention of postamputation pain. METHODS: Patients included in this study underwent RPNI surgery between 2014 and 2021 for the treatment or prevention of postamputation pain and had at least one-year follow-up. A retrospective review was performed to collect preoperative demographic and clinical information. Outcomes for neuroma pain and PLP were assessed from the medical records at both the 1-year and the most recent follow-up visits. Postoperative pain was compared to preoperative pain and categorized into the following outcomes: no symptoms, improved symptoms, stable symptoms, or worsened symptoms. Opioid prescriptions were obtained through the EMR at preoperative and follow-up visits and converted to morphine milliequivalents (MME) based on dosage and type of opioid medication. RESULTS: Seventy-seven patients met inclusion criteria in this study. Thirty-seven patients underwent RPNI surgery to treat preexisting postamputation pain (treatment group) and 40 patients underwent prophylactic RPNI surgery at the time of amputation (prophylactic group). Fifty-five patients (26 in the treatment group and 29 in the prophylactic group) had additional follow-up visits after the one-year postop time frame. Average time from surgery at most recent follow-up was 50 months (4.2 years). For the treatment group, at time of most recent follow-up, favorable neuroma pain and PLP outcomes (no reported symptoms or improved symptoms) were seen in 77% and 61% of patients, respectively. For patients treated prophylactically, 97% of patients had no recorded neuroma pain or PLP at time of most recent follow-up visit. Average MME at time of most recent follow-up was also lower for both the treatment group (-12 +/- 83) and prophylactic group (-40 +/- 103). CONCLUSIONS: This study demonstrates the long-term clinical benefits of RPNI surgery on improving neuroma pain and PLP as well as a reduction of opioid intake for amputation patients who underwent the procedure. These findings suggest that the benefits of RPNI surgery on pain outcomes are highly favorable, and thus this surgery should be considered for all amputation patients.

Development and validity of a short web-based semi-quantitative Food Frequency Questionnaire applicable in both clinical and research setting: an evolution over time.

Assessing dietary intake is valuable both in clinical practice and in research. In research and in clinical practice, long-term habitual dietary intake is most often of interest. Therefore, a web-based semi-quantitative Food Frequency Questionnaire (FFQ) was developed to measure habitual intake of nutrients and foods. This study aimed to assess content validity, convergent validity, and reliability of a 32-item semi-quantitative FFQ for adults. A total of three different cohorts of Flemish adults were recruited in the past 10 years. The first cross-sectional validation study took place in 2013, consequently in 2019 and 2021. Content validity was assessed in 2019 through a semi-structured cognitive interview. Convergent validity was assessed by examining mean differences, Wilcoxon signed-rank test, Spearman's correlation coefficients (SCC), and Bland-Altman analysis for energy, nutrient, and food group intake compared with a 3-day food record (FR). Additionally, consumers-only analysis was performed together with cross-classification analysis by assessing the ranking capabilities of the FFQ into quartiles and weighted kappa. Reliability was assessed through the evaluation of SCC and intra-class correlation (ICC) of test-retest assessment of the FFQ. Spearman's correlation coefficient (SCC) for energy and absolute nutrient intake between the FFQ and the FR ranged from 0.02 to 0.54. Compared with absolute macronutrients, higher SCC was found for the majority of the relative macronutrient intake and most food groups. Bland-Altman plots showed improved agreement and decreasing bias between the FFQ and the FR over time. Misclassification of the FFQ for nutrients was acceptable and decreased over time (7.4, 7.5, and 6.8% in 2013, 2019, and 2021, respectively), but weighted kappa remained mostly fair (κ ≤ 0.20). The reliability of the FFQ was good and improved over time (mean SCC of 0.65 and 0.66 p <0.001 in 2013 and 2019). The short web-based FFQ is an easy, low-cost, and feasible tool with good reliability, low misclassification, and acceptable validity to compare nutrient densities and food group intake at the population level. The measurement of absolute intake remains debatable.

Normal 24-hour urine calcium concentrations after long-term daily oral intake of vitamin D in doses ranging from 5000 to 50,000 international units in 14 adult hospitalized psychiatric patients

Many controversies exist regarding vitamin D3 supplementation. These include not only diseases that are responsive to vitamin D supplementation, but also the long-term safety of prolonged daily oral vitamin D3 intake above 4000–10,000 International Units (IU). In particular, supplementation levels that do not result in adverse events, and the upper limits of safe serum 25-hydroxyvitamin D (25OHD) concentrations. Adverse reactions reported to occur with excessive vitamin D intake include hypercalcemia, renal failure, calcium crystal formation, undetectable parathyroid hormone concentrations, and hypercalciuria, all of which are reported to be reversible. To address the long-term safety of vitamin D supplementation, we previously reported data from patients in our hospital who have been voluntarily supplemented with vitamin D3 ranging from 5,000 to 10,000 IU/day since July 2011 as a standard of care for the prevention and treatment of vitamin D deficiency. Historically 90% of patients have agreed to daily supplementation, with most taking 10,000 IU/day. These data indicate no evidence for hypercalcemia, renal failure, calcium crystal formation, nephrolithiasis. or undetectable parathyroid hormone concentrations in patients taking 5000 or 10,000 IU/day for extended periods of time. As another measure for potential vitamin D toxicity, we retrospectively assessed 24-hour urine calcium excretion in 14 individuals on long-term daily oral vitamin D intake ranging from 5000 to 50,000 IU/day to further assess the safety of supplementation using these doses. This included patients taking either 5000 (4), 10,000 (9), or 50,000 (1) IU/day. Time on supplementation ranged from 10 to 102 months. A patient taking 400 IU/day and getting frequent sun exposure was also included. All fifteen 24-hour urine calcium measurements were normal. The current findings complement our experience with over 7000 patients in the past 13 years, indicating that prolonged daily oral intake of vitamin D3 ranging from 5000 to 10,000 IU/day is safe.

Low prevalence of Clostridioides difficile infection in acute severe ulcerative colitis: A retrospective cohort study from northern India.

The incidence of Clostridioides difficile infection (CDI) is high in ulcerative colitis and is associated with disease flares and adverse outcomes. However, the data on the dynamics of CDI in patients with acute severe ulcerative colitis (ASUC) is rather scarce. We evaluated the prevalence of CDI in patients with ASUC. This retrospective analysis of a prospectively maintained cohort admitted to the All India Institute of Medical Sciences, India, from May 2016 to December 2021, included patients with ASUC (as per Truelove and Witts criteria) who were tested for CDI. CDI testing was performed using enzyme-linked immunoassay for toxins A and B. Risk factors for developing CDI were analyzed along with short-term outcomes of ASUC. Steroid failure was defined as the need for medical rescue therapy or colectomy. Total 153 patients with ASUC were included (mean age 34.92 ± 12.24years; males 56.2%; disease duration 36 (IQR: 16-55.5) months, pancolitis 67.3%). Ninety-eight (63.4%), 72 (47%) and 10 (6.5%) patients, respectively, had received steroids, azathioprine and biologics in the past. Forty patients (26.14%) had a prior history of ASUC. Among risk factors for CDI, 14% of the patients had prior admission within 30days, 22.2% had a recent history of antibiotics and 3.9% had long-term non-steroidal anti-inflammatory drug intake. Only one sample was positive for Clostridioides difficile toxin assay. Tissue Cytomegalovirus DNA-PCR positivity was noted in 57 patients (37.3%). Fifty-seven patients (37.3%) had steroid failure, 35 required medical rescue therapy and 30 (19.6%) required colectomy (eight after medical rescue therapy failure). Despite antecedent risk factors for CDI, the overall prevalence of CDI in ASUC was low and theoutcomes were determined by underlying disease severity.

Dietary Isoquercetin Reduces Hepatic Cholesterol and Triglyceride in NAFLD Mice by Modulating Bile Acid Metabolism via Intestinal FXR-FGF15 Signaling

Isoquercetin, a monosaccharide flavonoid, was recently reported to have significant amelioration effects on high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) of mice. However, the underlying mechanism of hepatic cholesterol and triglyceride improvement in mice fed HFD by isoquercetin remains unclear. Here, a combination of 16S rRNA gene sequencing, targeted quantification of bile acids (BAs), and biological assays was employed to investigate the beneficial effects of isoquercetin on NAFLD in mice. The results showed that dietary isoquercetin markedly modulated the BAs profiling in various samples such as liver, serum, intestine, and feces. We found that dietary isoquercetin promoted BA biosynthesis via the activation of alternative pathways and inhibition of intestinal FXR-Fgf15 signaling, thus reducing 13.2% hepatic cholesterol and 16.05% triglyceride in NAFLD mice. Dietary isoquercetin also regulated a series of receptors mediating correspondent processes of BA transportation, reabsorption, and excretion. Of particular note, dietary isoquercetin significantly modulated cross-talk between BAs and specific gut bacteria of NAFLD mice. These findings revealed that long-term intake of isoquercetin plays beneficial roles in the prevention or intervention of fatty liver disease.

Dam Body Condition Score Alters Offspring Circulating Cortisol and Energy Metabolites in Holstein Calves but Did Not Affect Neonatal Leptin Surge.

The neonatal leptin surge is important for hypothalamic development, feed intake regulation, and long-term metabolic control. In sheep, the leptin surge is eliminated with maternal overnutrition and an elevated dam body condition score (BCS), but this has not been assessed in dairy cattle. The aim of this study was to characterize the neonatal profile of leptin, cortisol and other key metabolites in calves born to Holstein cows with a range of BCS. Dam BCS was determined 21 d before expected parturition. Blood was collected from calves within 4 h of birth (d 0), and on days 1, 3, 5, and 7. Serum was analyzed for concentrations of leptin, cortisol, blood urea nitrogen, β-hydroxybutyrate (BHB), free fatty acids (FFA), triglycerides, and total protein (TP). Statistical analysis was performed separately for calves sired by Holstein (HOL) or Angus (HOL-ANG) bulls. Leptin tended to decrease after birth in HOL calves, but there was no evidence of an association between leptin and BCS. For HOL calves, the cortisol level increased with an increasing dam BCS on day 0 only. Dam BCS was variably associated with the calf BHB and TP levels, depending on the sire breed and day of age. Further investigation is required to elucidate the impacts of maternal dietary and energy status during gestation on offspring metabolism and performance, in addition to the potential impact of the absence of a leptin surge on long-term feed intake regulation in dairy cattle.

An iodine balance study in Chinese school-age children.

Few iodine balance studies have been conducted in school-age children. This study aimed to conduct an iodine balance study in school-aged children. We measured daily iodine intake, excretion, and retention for three consecutive days without any dietary interventions in school-age children. Linear mixed-effects models were used to fit the relationship between total iodine intake (TII) and iodine retention (IR). 29 children aged 7-12 years (mean age 10.2 ± 1.4 years) with normal thyroid function and thyroid volume (Tvol) were recruited. The zero balance value (iodine intake = iodine excretion, iodine retention = 0 μg/d) shifted with iodine intake in an iodine sufficient population. The zero balance value for school-aged children with an iodine intake of 235 (133, 401) μg/d is 164 μg/d. Children aged 7-12 years with iodine intake >400 μg/d were almost in a positive iodine state. An iodine intake of 235 (133, 401) μg/d for children aged 7-10 years achieved a zero balance value of 164 μg/d. Long-term iodine intake of >400 μg/d is not recommended.