Elevated parathyroid hormone (PTH) levels usually suggest an underlying parathyroid disorder. However, immunoassay interference, such as macro-PTH, can result in falsely elevated readings, leading to diagnostic inaccuracy. Here, we report the case of a 27-year-old woman with persistently elevated PTH levels despite normal serum calcium, phosphate, and vitamin D. Aside from a history of nephrolithiasis, the patient was asymptomatic and exhibited no parathyroid abnormalities detected on ultrasound, sestamibi scintigraphy, or choline positron emission tomography-computed tomography (PET-CT) scans. To investigate potential immunoassay interference, a polyethylene glycol (PEG) 6000 precipitation assay was performed, which showed a decrease of PTH levels from >1200 pg/mL to approximately 40 pg/mL, corresponding to a 97% reduction. To validate the specificity of this technique, the same procedure was conducted on sera from two patients with elevated PTH levels due to known parathyroid pathologies. PTH levels decreased from 771 to 271 pg/ml and 527 to 146 pg/ml, corresponding to 65 and 72% reduction, respectively. The following results indicated that the PEG precipitation primarily affected the macro-PTH in our patient’s sample while leaving intact PTH relatively unaffected in the control group. This report suggests that unexpectedly high PTH levels in the presence of otherwise normal laboratory values and imaging results could indicate the possibility of immunoassay interference. PEG 6000 precipitation is a valuable diagnostic tool for macro-PTH detection, although further refinement of immunoassay techniques may be needed to enhance the reliability of PTH measurements in clinical practice.

Lung damage caused by SARS-CoV-2 infection has been described in the literature as resulting from direct cytopathic effects on type II pneumocytes, playing a critical role in the extent and progression of pulmonary injury. This study aimed to evaluate the prognostic value of the mucin glycoprotein KL-6 in predicting clinical outcomes in COVID-19 patients. We prospectively enrolled 260 COVID-19 patients admitted to specialized hospitals in Naples under the ASL Napoli 1 Centro between March 20, 2020, and March 31, 2022, when the state of emergency ended. Our institution, part of the Coronet Lab network designated by the Campania Region and the Ministry of Health, performed 203,368 molecular tests for COVID-19 during this period, identifying 17,650 positive cases (8.67%). The study cohort had a median age (IQR) of 63 years (54–72), comprising 199 males and 61 females. All patients underwent clinical, radiological, and functional assessments in the emergency department. Serum KL-6 levels were measured at admission, after detecting interstitial lung damage, and during hospitalization. Elevated KL-6 concentrations were observed in patients with pulmonary abnormalities, and baseline levels demonstrated good accuracy in identifying those with radiologically documented fibrotic sequelae. In hospitalized COVID-19 patients, serum KL-6 levels also correlated with severe cases requiring mechanical ventilation and predicted the development of fibrotic lung sequelae during follow-up. Finally, KL-6 proved to be an effective predictive marker of disease severity, emphasizing its potential role in guiding clinical management and prognosis.

Background/Objectives: In the present study, the changes in oxytocin (OXT) and serotonin (5-HT), as hormones involved in social relationships and mood regulation, respectively, were measured in dialysis patients involved in Animal Assisted Activity (AAA) interventions. Methods: Thirty patients (15 men and 15 women) with chronic kidney disease, undergoing hemodialysis three times per week, for 4 h, were enrolled. The patients were divided into three groups: two experimental groups who received the AAA intervention and a control group that never received the AAA intervention. A specific dog-zootherapist vet pair was assigned for each experimental group. All sessions of the two experimental groups were performed weekly, for a total period of 3 months (12 sessions). Blood samples were collected at the beginning and end of each session (T0 and T1), lasting about one hour. The interaction time with the dog was approximately 40 min. The samples were then analyzed to measure the levels of oxytocin and serotonin and processed using analysis of variance with mixed effects models. Results: The results obtained showed that both dog-zootherapist vet dyads caused a statistically significant overall effect of both oxytocin and serotonin, increasing during the sessions, compared to the control group. In addition, it was observed progressively increasing effect between two consecutive weeks. Conclusions: The results from this study showed that the AAA represents a positive stimulus for patients on dialysis. Thus, our study suggests that structured AAA intervention in a hemodialysis center can improve patients' quality of life during the dialysis cycle.

IntroductionPostmenopausal hyperandrogenism (PH) is a rare clinical condition caused by relative or absolute androgen excess after menopause. Tumorous or non-tumorous ovarian diseases can cause PH.MethodsIn this two-section hybrid study, the first section describes the case of a patient with PH caused by an ovarian disease and surgically treated. The second section shows the results of a scoping review with individual patient data (IPD) analysis, which was performed to define the biochemical and clinical features of PH patients with tumorous or non-tumorous ovarian diseases surgically treated. All PH cases caused by anything but ovarian disease and/or without surgical indication and/or without histological diagnosis were excluded.ResultsDue to imaging suspicion, our PH patient underwent robotic hysterectomy with bilateral ovariectomy. A Leydig cell tumor stage 1A was diagnosed. At 6 months after surgery, the PH was resolved. Overall, the IPD analysis included 280 PH patients with ovarian diseases (oPH) surgically treated. Among them, histological examination showed 174 tumorous oPH and 106 non-tumorous oPH. Patients with tumorous oPH showed lower body mass index and lower levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as higher levels of testosterone, dehydroepiandrosterone sulfate (DHEA-S), 17-OH progesterone, and estradiol compared with non-tumorous oPH patients. We defined the levels of testosterone (≥9.8 nmol/L), LH (≤15 mUI/ml), FSH (≤35 mUI/ml), and DHEA-S (≥1.6 μmol/L) able to differentiate between tumorous and non-tumorous oPH patients with suitable sensitivity (≥68.6%) and specificity (≥72.7%). No PH recurrence was described after surgery.DiscussionThe study results provide useful biochemical parameters to support the diagnosis of ovarian tumor in patients with oPH.

Introduction:Autologous platelet concentrates (APC) are widely used in the infiltrative treatment of knee osteoarthritis (OA) to enhance tissue healing and relieve pain. Aim of this study was to identify predictive biomarkers for clinical outcomes in patients with grade I knee OA. Methods:A panel of growth factors (GFs) and cytokines was determined in peripheral blood (PB) and APC. The Numeric Pain Rating Scale (NPRS) was used as a clinical readout before and after the APC infiltration. Results:A lower white blood cell (WBC) count and higher Monocyte-chemoattractant Protein-1 levels in PB were associated with APC-induced pain relief. Platelet-derived Growth Factor (PDGF) levels in APC were significantly higher in OA patients displaying a larger NPRS reduction, independent of platelet count. Finally, the simultaneous determination of PDGF, Vascular Endothelial Growth Factor, and Macrophage Inflammatory Protein-1α in APC discriminated OA patients with very poor or no response. Conclusion:Platelet-released GFs rather than platelet counts may predict clinical outcomes in grade 1 knee OA.

Skeletal anomalies represent a characteristic feature of type 1 Gaucher disease (GD1). Here we evaluated the impact of an integrated therapy comprising enzyme-replacement therapy (ERT), cholecalciferol, and a normocalcemic-normocaloric-hyposodic diet (bone diet) on bone health in GD1 patients. We also performed a systematic review to compare our results with available data. From January 1, 2015 to February 28, 2019, all GD1 patients referred to Federico II University were enrolled and treated with the integrated therapy. Bone turnover markers and bone mineral density (BMD) were evaluated at baseline (T0) and after 24 months (T24). We enrolled 25 GD1 patients, all showing 25-hydroxy vitamin D (25OHD) levels < 50 nmol/l (hypovitaminosis D) at T0. Response to cholecalciferol treatment was effective, showing a direct relationship between 25OHD levels before and after treatment. At T0, 2 GD1 patients showed fragility fractures, 5 the Erlenmeyer flask deformity, 3 osteonecrosis, and 7 a BMD Z-score <= -2. Overall, GD1 patients with bone anomalies showed higher C-terminal telopeptide levels compared with those without bone anomalies. No new bone anomalies occurred during 2 years of follow-up. At T24, BMD remained stable across the entire study cohort, including in patients with bone anomalies. The systematic review showed that our study is the first that evaluated all bone health parameters. Hypovitaminosis D is prevalent in GD1 patients. The response to cholecalciferol treatment was effective but different to healthy subjects and in patients with metabolic bone disorders. Integrated therapy including ERT, cholecalciferol, and bone diet guarantees bone health. Graphical Abstract

Marine natural products constitute a great source of potential new antidiabetic drugs. The aim of this study was to evaluate the role of phosphoeleganin (PE), a polyketide purified from the Mediterranean ascidian Sidnyum elegans, and its derivatives PE/2 and PE/3 on insulin sensitivity in human hepatocellular carcinoma (HepG2) cells. In our experiments, insulin stimulates the phosphorylation of its receptor (INSR) and AKT by 1.5- and 3.5-fold, respectively, whereas in the presence of PE, PE/2, and PE/3, the insulin induced INSR phosphorylation is increased by 2.1-, 2-, and 1.5-fold and AKT phosphorylation by 7.1-, 6.0-, and 5.1-fold, respectively. Interestingly, PE and PE/2 have an additive effect on insulin-mediated reduction of phosphoenolpyruvate carboxykinase (PEPCK) expression. Finally, PE and PE/2, but not PE/3, decrease interleukin 6 (IL6) secretion and expression before and after palmitic acid incubation, while in the presence of high glucose (HG), only PE reduces IL6. Levels of other cytokines are not significantly affected by PE and its derivates. All these data suggest that PE and its synthetic-derived compound, PE/2, significantly decrease IL6 and improve hepatic insulin signaling. As IL6 impairs insulin action, it could be hypothesized that PE and PE/2, by inhibiting IL6, may improve the hepatic insulin pathway.

Semaphorin 3A (SEMA3A) plays a crucial role in the development, differentiation, and plasticity of specific types of neurons that secrete Gonadotropin-Releasing Hormone (GnRH) and regulates the acquisition and maintenance of reproductive competence in humans and mice. Its insufficient expression has been linked to reproductive disorders in humans, which are characterized by reduced or failed sexual competence. Various mutations, polymorphisms, and alternatively spliced variants of SEMA3A have been associated with infertility. One of the common causes of infertility in women of reproductive age is diminished ovarian reserve (DOR), characterized by a reduced ovarian follicular pool. Despite its clinical significance, there are no universally accepted diagnostic criteria or therapeutic interventions for DOR. In this study, we analyzed the SEMA3A plasma levels in 77 women and investigated their potential role in influencing fertility in patients with DOR. The results revealed that the SEMA3A levels were significantly higher in patients with DOR than in healthy volunteers. Furthermore, the SEMA3A levels were increased in patients who underwent fertility treatment and had positive Beta-Human Chorionic Gonadotropin (βHCG) values (β+) after controlled ovarian stimulation (COS) compared to those who had negative βHCG values (β−). These findings may serve as the basis for future investigations into the diagnosis of infertility and emphasize new possibilities for the SEMA3A-related treatment of sexual hormonal dysfunction that leads to infertility.

BACKGROUND: Intensive physical activity and rigid dietary regimes can act as modifiers of neuroendocrine axes in women, inducing hormonal disorders and related menstrual irregularities such as functional hypothalamic amenorrhea (FHA). It would be important to evaluate if such disturbances may worsen female fertility. The aim of this study was to evaluate ovarian reserve markers and neuroendocrine axis in young military academy female cadets with years of training and occurrence of FHA. METHODS: This is a prospective pilot study involving young female cadets from the Military Academy training program. Ovarian reserve markers and metabolic and neuroendocrine factors in the early follicular phase were measured with blood tests and transvaginal ultrasound. RESULTS: The study group consisted of 11 women belonging to the first year of training and the control group of 33 women belonging to the second to sixth year of training. No differences were found about ovarian reserve markers between the two groups. Moreover, the occurrence of FHA did not modify the ovarian reserve compared to eumenorrhea in both groups. Women from the study group showed significantly higher levels of fasting Insulin (42.18 +/- 26.14 uUI/mL versus 11.9 +/- 10.2 ng/mL, P value <0.001) and insulin-like growth factor 1 (310.06 +/- 67.90 uUI/mL versus 248.67 +/- 61.57 uUI/mL, P value = 0.015) compared with control group. CONCLUSIONS: Both intense physical training and FHA do not appear to impact the ovarian reserve of young female cadets. Although preliminary, these findings seem reassuring about the reproductive health of these women and their future fertility.

Background: In the present study, the changes in oxytocin (OXT) and serotonin (5-ht) were measured in dialysis patients involved in Animal Assisted Activity (AAA) interventions. Methods: Thirty patients (15 men and 15 women) with chronic kidney disease, undergoing hemodialysis three times per week, for 4 hours were enrolled. The patients were at random divided into 3 groups: 2 experimental groups who received the AAA intervention and a control group who never received the AAA intervention. A specific dog-zootherapist vet pair was assigned for each experimental group. All sessions of the two experimental groups were weekly performed, for a total period of 3 months (12 sessions). Blood samples were taken at the beginning and end of each session (T0 and T1), lasting about one hour. The samples were then analyzed to measure the levels of oxytocin and serotonin. Data obtained were processed using analysis of variance with mixed effects models. Results: The emerged results showed that both dog-zootherapist vet dyad caused a statistically significant overall effect of both oxytocin and serotonin, increasing during the sessions, compared to the control group. In addition, it was observed progressively increasing effect between two consecutive weeks. Conclusion: The results that emerged showed that the AAA represents a positive stimulus for patients on dialysis. Thus, our study suggests that structured AAA intervention in a hemodialysis center can improve patients' quality of life.

In March 2020, the World Health Organization Department declared the coronavirus (COVID-19) outbreak a global pandemic, as a consequence of its rapid spread on all continents. The COVID-19 pandemic has been not only a health emergency but also a serious general problem as fear of contagion and severe restrictions put economic and social activity on hold in many countries. Considering the close link between human and animal health, COVID-19 might infect wild and companion animals, and spawn dangerous viral mutants that could jump back and pose an ulterior threat to us. The purpose of this review is to provide an overview of the pandemic, with a particular focus on the clinical manifestations in humans and animals, the different diagnosis methods, the potential transmission risks, and their potential direct impact on the human–animal relationship.

Background: Insufficient serum 25-hydroxyvitamin D [25(OH)D] levels are a global public health issue, and pregnant women are a significant at-risk group. We aimed to assess maternal serum 25(OH)D concentrations in a cohort of Neapolitan pregnant women and the association with dietary habits, to define which patients are at increased risk of hypovitaminosis and how we can identify them. Methods: This was a prospective observational study. We included 103 pregnant women attending a routine third trimester obstetric examination. Information on obstetrical history and socio-demographic characteristics were obtained through interviews and medical records. Vitamin D intake was assessed using a food frequency questionnaire. Serum 25(OH)D concentration was measured by DiaSorin Liaison and the cut-off value for deficiency was set at 20 ng/mL. Results: Among the 103 pregnant women recruited, 71 (68.9%) were Vitamin D deficient (mean value 12.6 ± 0.5 ng/mL). No statistically significant differences were found between the women involved in the study for: maternal age, pre-pregnancy body mass index (BMI), gestational weight gain, and gestational age at investigation. Women with hypovitaminosis reported a significantly lower intake of milk/yoghurt, cheeses/dairy products and fish. Maternal hypovitaminosis D significantly correlated with low birth weight. Conclusions: Our study confirms that Vitamin D deficiency is a common finding also in sunny areas. Patients with low level of Vitamin D reported a lower intake of food rich of this micronutrient. An accurate anamnesis can be an easy way to identify pregnant women at risk of hypovitaminosis D for whom screening and supplementation can be suitable.

Visceral obesity is linked to the progression of fatty liver to nonalcoholic steatohepatitis (NASH). Cytokeratin-18 (CK18) epitopes M30 (CK18M30) and M65 (CK18M65) represent accurate markers for detecting NASH. The aim of this study was to evaluate the association of CK18M30 and CK18M65 levels with anthropometric and metabolic characteristics, liver stiffness, and liver indices of steatosis and fibrosis in a cohort of subjects with visceral obesity; in this cross-sectional study, transient elastography (TE-Fibroscan®), anthropometric measurements, metabolic parameters, High Sensitivity C-Reactive Protein (hsCRP), and CK18M30 and CK18M65 levels (Apoptosense ELISA, PEVIVA, Germany) were evaluated. Fatty Liver Index (FLI), Fibrosis 4 (FIB-4), and Aspartate transaminase (AST)-platelet ratio index (APRI) were calculated; among 48 subjects, 47.2% presented metabolic syndrome, 93.8% hepatic steatosis, 60.4% high liver stiffness, and 14.6% hypertransminasemia, while FIB-4 and APRI were normal. CK18M30 and CK18M65 levels were significantly correlated with waist circumference, AST, ALT, HoMA-IR, liver stiffness, and APRI (p < 0.001). Subjects with CK18 fragments above the median values showed significantly higher waist circumference, HbA1c, AST, ALT, HoMA-IR, FLI, and APRI compared to those with values below the median; CK18M30 and CK18M65 levels correlated well with anthropometric and metabolic characteristics, representing good biomarkers for early identification of NASH in subjects with visceral obesity.

[This corrects the article DOI: 10.1371/journal.pone.0082099.].

Low-grade chronic inflammation (LGCI) is a common feature of non-communicable diseases. Cytokines play a crucial role in LGCI. This study aimed to assess how LGCI risk factors [e.g., age, body mass index (BMI), smoke, physical activity, and diet] may impact on specific cytokine levels in a healthy population. In total, 150 healthy volunteers were recruited and subjected to questionnaires about the last 7-day lifestyle, including smoking habit, physical activity, and food frequency. A panel of circulating cytokines, chemokines, and growth factors was analyzed by multiplex ELISA. BMI showed the heaviest impact on the correlation between LGCI-related risk factors and cytokines and was significantly associated with CRP levels. Aging was characterized by an increase in IL-1b, eotaxin, MCP-1, and MIP-1α. Smoking was related to higher levels of IL-1b and CCL5/RANTES, while physical activity was related to MIP-1α. Within the different eating habits, CRP levels were modulated by eggs, red meat, shelled fruits, and greens consumption; however, these associations were not confirmed in a multivariate model after adjusting for BMI. Nevertheless, red meat consumption was associated with an inflammatory pattern, characterized by an increase in IL-6 and IL-8. IL-8 levels were also increased with the frequent intake of sweets, while a higher intake of shelled fruits correlated with lower levels of IL-6. Moreover, IL-6 and IL-8 formed a cluster that also included IL-1b and TNF-α. In conclusion, age, BMI, smoke, physical activity, and dietary habits are associated with specific cytokines that may represent potential markers for LGCI.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia, responsible for the onset of several long-term complications. Recent evidence suggests that cognitive dysfunction represents an emerging complication of DM, but the underlying molecular mechanisms are still obscure. Dopamine (DA), a neurotransmitter essentially known for its relevance in the regulation of behavior and movement, modulates cognitive function, too. Interestingly, alterations of the dopaminergic system have been observed in DM. This review aims to offer a comprehensive overview of the most relevant experimental results assessing DA's role in cognitive function, highlighting the presence of dopaminergic dysfunction in DM and supporting a role for glucotoxicity in DM-associated dopaminergic dysfunction and cognitive impairment. Several studies confirm a role for DA in cognition both in animal models and in humans. Similarly, significant alterations of the dopaminergic system have been observed in animal models of experimental diabetes and in diabetic patients, too. Evidence is accumulating that advanced glycation end products (AGEs) and their precursor methylglyoxal (MGO) are associated with cognitive impairment and alterations of the dopaminergic system. Further research is needed to clarify the molecular mechanisms linking DM-associated dopaminergic dysfunction and cognitive impairment and to assess the deleterious impact of glucotoxicity.

Background Excessive adiposity provides an inflammatory environment. However, in people with severe obesity, how systemic and local adipose tissue (AT)-derived cytokines contribute to worsening glucose tolerance is not clear. Methods Ninty-two severely obese (SO) individuals undergoing bariatric surgery were enrolled and subjected to detailed clinical phenotyping. Following an oral glucose tolerance test, participants were included in three groups, based on the presence of normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or type 2 diabetes (T2D). Serum and subcutaneous AT (SAT) biopsies were obtained and mesenchymal stem cells (MSCs) were isolated, characterized, and differentiated in adipocytes in vitro. TNFA and PPARG mRNA levels were determined by qRT-PCR. Circulating, adipocyte- and MSC-released cytokines, chemokines, and growth factors were assessed by multiplex ELISA. Results Serum levels of IL-9, IL-13, and MIP-1β were increased in SO individuals with T2D, as compared with those with either IGT or NGT. At variance, SAT samples obtained from SO individuals with IGT displayed levels of TNFA which were threefold higher compared to those with NGT, but not different from those with T2D. Elevated levels of TNFα were also found in differentiated adipocytes, isolated from the SAT specimens of individuals with IGT and T2D, compared to those with NGT. Consistent with the pro-inflammatory milieu, IL-1β and IP-10 secretion was significantly higher in adipocytes from individuals with IGT and T2D. Moreover, increased levels of TNFα, both mRNA and secreted protein were detected in MSCs obtained from IGT and T2D, compared to NGT SO individuals. Exposure of T2D and IGT-derived MSCs to the anti-inflammatory flavonoid quercetin reduced TNFα levels and was paralleled by a significant decrease of the secretion of inflammatory cytokines. Conclusion In severe obesity, enhanced SAT-derived inflammatory phenotype is an early step in the progression toward T2D and maybe, at least in part, attenuated by quercetin.

No clear consensus on the need to perform an intracorporeal anastomosis (IA) after laparoscopic right colectomy is currently available. One of the potential benefits of intracorporeal anastomosis may be a reduction in surgical stress. Herein, we evaluated the surgical stress response and the metabolic response in patients who underwent right colonic resection for colon cancer. Fifty-nine patients who underwent laparoscopic resection for right colon cancer were randomized to receive an intracorporeal or an extracorporeal anastomosis (EA). Data including demographics (age, sex, BMI and ASA score), pathological (AJCC tumour stage and tumour localization) and surgical results were recorded. Moreover, to determine the levels of the inflammatory response, mediators, such as C-reactive protein (CRP), tumour necrosis factor (TNF), interleukin 1β (IL-1β), IL-6, IL-10, and IL-13, were evaluated. Similarly, cortisol and insulin levels were evaluated as hormonal responses to surgical stress. We found that the proinflammatory mediator IL-6, CRP, TNF and IL-1β levels, were significantly reduced in IA compared to EA. Concurrently, an improved profile of the anti-inflammatory cytokines IL-10 and IL-13 was observed in the IA group. Relative to the hormone response to surgical stress, cortisol was increased in patients who underwent EA, while insulin was reduced in the EA group. Based on these results, s urgical stress and metabolic response to IA justify advocating the adoption of a totally laparoscopic approach when performing a right colectomy for cancer. This trial is registered on ClinicalTrials.gov (ID: NCT03422588).

Background Excessive adiposity provides an inflammatory environment. However, in people with severe obesity, how systemic and local adipose tissue (AT)-derived cytokines contribute to worsening glucose tolerance is not clear. Methods 92 severely obese (SO) individuals undergoing bariatric surgery were enrolled and subjected to detailed clinical phenotyping. Following an Oral Glucose Tolerance Test, participants were included in three groups, based on the presence of normal glucose tolerance (NGT), impaired glucose tolerance (IGT) or Type 2 Diabetes (T2D). Serum and subcutaneous AT (SAT) biopsies were obtained and Mesenchymal Stem Cells (MSCs) were isolated, characterized and differentiated in adipocytes in vitro. TNFA and PPARG mRNA levels were determined by qRT-PCR. Circulating, adipocyte- and MSC-released cytokines, chemokines and growth factors were assessed by multiplex ELISA. Results Serum levels of IL-9, IL-13 and MIP-1β were increased in SO individuals with T2D, as compared with those with either IGT or NGT. At variance, SAT samples obtained from SO individuals with IGT displayed levels of TNFA which were 3-fold higher compared to those with NGT, but not different from those with T2D. Elevated levels of TNFα were also found in differentiated adipocytes, isolated from the SAT specimens of individuals with IGT and T2D, compared to those with NGT. Consistent with the pro-inflammatory milieu, IL-1β and IP-10 secretion was significantly higher in adipocytes from individuals with IGT and T2D. Moreover, increased levels of TNFα, both mRNA and secreted protein, were detected in MSCs obtained from IGT and T2D, compared to NGT SO individuals. Exposure of T2D and IGT–derived MSCs to quercetin reduced TNFα levels and was paralleled by a significant decrease of the secretion of inflammatory cytokines. Conclusion In severe obesity, enhanced SAT-derived inflammatory phenotype is an early step in the progression toward T2D and may be, at least in part, attenuated by quercetin.