Diet and physical activity behaviors: how are they related to illness perceptions, coping, and health-related quality of life in young people with hereditary cancer syndromes?

Individuals with inherited cancer syndromes, such as Li-Fraumeni syndrome (LFS), may be motivated to adopt health-protective behaviors, such as eating more fruits and vegetables and increasing physical activity. Examining these health behaviors among young people with high lifetime genetic cancer risk may provide important insights to guide future behavioral interventions that aim to improve health-related quality of life (HRQOL). We used a self-regulatory framework to investigate relationships among diet and physical activity behaviors and psychosocial constructs (e.g., illness perceptions, coping, HRQOL) in adolescents and young adults (AYAs; aged 15-39 years) with LFS. This longitudinal mixed-methods study included 57 AYAs aged 16-39 years at enrollment), 32 (56%) of whom had a history of one or more cancers. Participants completed one or two telephone interviews and/or an online survey. We thematically analyzed interview data and conducted regression analyses to evaluate relationships among variables. AYAs described adopting healthy diet and physical activity behaviors to assert some control over health and to protect HRQOL. More frequent use of active coping strategies was associated with greater reported daily fruit and vegetable intake. Greater reported physical activity was associated with better quality of psychological health. Healthy diet and physical activity behaviors may function as LFS coping strategies that confer mental health benefits. Clinicians might emphasize these potential benefits and support AYAs in adopting health behaviors that protect multiple domains of health. Future research could use these findings to develop behavioral interventions tailored to AYAs with high genetic cancer risk.

Do published trial results influence physician prescribing patterns? Intravitreal antivascular endothelial growth factor usage by the United States Ophthalmologists before and after Protocol T study.

PURPOSE OF REVIEW: Clinical trial publications may influence physician prescribing patterns. The Diabetic Retinopathy Clinical Research Network (DRCR.net) Protocol T study, published in 2015, examined outcomes of intravitreal antivascular endothelial growth factor (VEGF) medications for treatment of diabetic macular oedema (DME). This study investigates if the Protocol T 1-year results were associated with changes in prescribing patterns. RECENT FINDINGS: Anti-VEGF agents have revolutionized treatment of DME by blocking angiogenesis signalled by VEGF. Three commonly used anti-VEGF agents are on-label aflibercept (Eylea, Regeneron) and ranibizumab (Lucentis, Genentech) and off-label bevacizumab (Avastin, Genentech). SUMMARY: From 2013 to 2018, there was a significant positive trend in the average number of aflibercept injections for any indication ( P  < 0.002). There was no significant trend in the average number of bevacizumab ( P  = 0.09) and ranibizumab ( P  = 0.43) for any indication. The mean proportion of aflibercept injections per provider per year was 0.181, 0.217, 0.311, 0.403, 0.419 and 0.427; each year-by-year comparison was significant (all P  < 0.001), and the largest increase was in 2015, the year of publication of Protocol T 1-year results. These results imply and reinforce that clinical trial publications may have significant effects on ophthalmologist prescribing patterns.

Telehealth Utilization Among Occupational Therapists in Oncology: Results From a National Survey.

While the COVID-19 pandemic introduced wide expansion of telehealth access in health care, evidence concerning telehealth use in occupational therapy (OT) for cancer survivors remains limited. The objective of this study was to identify the prevalence and perceptions of telehealth services among occupational therapy practitioners (OTPs) in oncology. Descriptive statistics and qualitative content analysis were used to analyze data from a pre-pandemic national survey of OTPs (n = 126) focusing on telehealth. Most OTPs in oncology settings support telehealth use, despite a dearth of access prior to the pandemic. The highest levels of telehealth endorsement among OTPs related to ease of accessibility (48%). Treatments rated as best suited for OT oncology telehealth sessions included education (41%), quality of life/well-being/lifestyle (21%), and psychosocial interventions (19%). These data suggest widespread benefits of telehealth-delivered OT treatment in oncology. Advocacy is needed to ensure the continuation of legislation allowing expanded telehealth access and reimbursement for OT.

Comparison of Permanent Hair Removal Procedures before Gender-Affirming Vaginoplasty: Why We Should Consider Laser Hair Removal as a First-Line Treatment for Patients Who Meet Criteria.

INTRODUCTION: Permanent genital hair removal is required before gender-affirming vaginoplasty to prevent hair-related complications. No previous studies have directly compared the relative efficacy, costs, and patient experiences with laser hair removal (LHR) vs electrolysis treatments. Food and Drug Administration (FDA) oversight of medical devices is poorly understood and commonly misrepresented, adversely affecting patient care. AIM: This study compares treatment outcomes of electrolysis and LHR for genital hair removal and investigates FDA regulation of electrolysis and LHR devices. METHODS: Penile-inversion vaginoplasty and shallow-depth vaginoplasty patients completed surveys about their preoperative hair removal, including procedure type, number/frequency of sessions, cost, and discomfort. Publicly available FDA-review documents and databases were reviewed. MAIN OUTCOMES MEASURE: Compared to electrolysis, LHR was associated with greater efficiency, decreased cost, decreased pain, and improved patient satisfaction. RESULTS: Of 52 total (44 full-depth and 8 shallow-depth) vaginoplasty patients, 22 of 52 underwent electrolysis only, 15 of 52 underwent laser only, and 15 of 52 used both techniques. Compared to patients that underwent LHR only, patients that underwent only electrolysis required a significantly greater number of treatment sessions (mean 24.3 electrolysis vs 8.1 LHR sessions, P < .01) and more frequent sessions (every 2.4 weeks for electrolysis vs 5.3 weeks for LHR, P < .01) to complete treatment (defined as absence of re-growth over 2 months). Electrolysis sessions were significantly longer than LHR sessions (152 minutes vs 26 minutes, P < .01). Total treatment costs for electrolysis ($5,161) were significantly greater than for laser ($981, P < .01). Electrolysis was associated with greater pain and significantly increased need for pretreatment analgesia, which further contributed to higher net costs for treatment with electrolysis vs laser. Many LHR and electrolysis devices have been FDA-cleared for safety, but the FDA does not assess or compare clinical efficacy or efficiency. CLINICAL IMPLICATIONS: For patients with dark-pigmented hair, providers should consider LHR as the first-line treatment option for preoperative hair removal before gender-affirming vaginoplasty. STRENGTH AND LIMITATIONS: This is the first study to compare electrolysis and LHR for genital hair removal. The discussion addresses FDA review/oversight of devices, which is commonly misrepresented. Limitations include the survey format for data collection. CONCLUSION: When compared with electrolysis, LHR showed greater treatment efficiency (shorter and fewer treatment sessions to complete treatment), less pain, greater tolerability, and lower total cost. Our data suggests that, for patients with dark genital hair, providers should consider recommending laser as the first-line treatment for permanent genital hair removal before vaginoplasty. Yuan N, Feldman A, Chin P, et al. Comparison of Permanent Hair Removal Procedures before Gender-Affirming Vaginoplasty: Why We Should Consider Laser Hair Removal as a First-Line Treatment for Patients Who Meet Criteria. Sex Med 2022;10:100545.

Liver-related Mortality is Increased in Lean Subjects with Non- alcoholic Fatty Liver Disease Compared to Overweight and Obese Subjects.

BACKGROUND AND AIMS: Although non-alcoholic fatty liver disease (NAFLD) is linked to obesity, a proportion of lean subjects also have NAFLD with potentially distinct clinical features. We studied the outcome of lean NAFLD subjects. METHODS: 299 consecutive patients (215 male, 84 female, 49.5 ± 13.5years) with biopsy-proven NAFLD and a follow-up of 8.4 years (±4.1; range: 0.9-18.0) were stratified by body mass index (BMI) at the time of liver biopsy: lean (BMI ≤25.0 kg/m, n=38), overweight (BMI 25.0-29.9 kg/m2, n=165), obese (BMI ≥30.0 kg/m2, n=93). A control group of 1,013 subjects (547 male, 52.4 ± 5.8) was used for comparison. The time to the event was recorded. Multivariable Cox regression analyses were performed to assess associations with 10-year-mortality. Hazard ratios (HR) and adjusted hazard ratios (aHR) with 95% confidence intervals (CI) were calculated. RESULTS: Age and gender were similar, while components of the metabolic syndrome were less frequent in lean subjects. The proportion of subjects with significant fibrosis and the number of subjects with cirrhosis was increased in lean subjects while the proportion of non-alcoholic steatohepatitis was not different. Mortality in the NAFLD groups was significantly higher than in the control group. Multivariable analysis adjusting for age, gender, and glucose confirmed lower mortality in overweight (aHR 0.21; 95% CI 0.07-0.62, p=0.005) and in obese (aHR 0.22; 95% CI 0.06-0.76, p=0.02) compared to lean subjects. Further adjustment for fibrosis weakened the difference between lean and obese (p=0.12) while the difference to overweight subjects remained intact (p=0.01). CONCLUSION: Lean subjects with NAFLD have a high risk of liver-related death. Our data support that lean NAFLD subjects deserve particular attention with regard to clinical follow-up.

How Accessible Is Genital Gender-Affirming Surgery for Transgender Patients With Commercial and Public Health Insurance in the United States? Results of a Patient-Modeled Search for Services and a Survey of Providers.

INTRODUCTION: In the United States, 1.4-1.65 million people identify as transgender, many of whom will seek genital gender-affirming surgery (GAS). The number of surgeons, geographic proximity thereof, and exclusionary insurance policies has limited patient access to genital GAS. AIM: To assess the accessibility of both feminizing and masculinizing genital GAS (vaginoplasty, metoidioplasty, and phalloplasty) by identifying the location of GAS surgeons, health insurance, or payment forms accepted. METHODS: Between February and April 2018, genital GAS surgeons were identified via Google search. Surgeons' offices were contacted by telephone or e-mail. MAIN OUTCOME MEASURE: We queried the type of genital GAS performed, the health insurance or payment forms accepted, and the type of medical practice (academic, private, or group managed-care practice). RESULTS: We identified 96 surgeons across 64 individual medical centers offering genital GAS. The survey response rate was 83.3%. Only 61 of 80 (76.3%) surgeons across 38 of 53 (72%) locations confirmed offering genital GAS. Only 20 (40%) U.S. states had at least one genital GAS provider. 30 of 38 (79%) locations reported accepting any form of insurance. Only 24 of 38 (63%) locations (14 academic; 10 private/group) accepted Medicaid (P = .016); 18 of 38 (47%) locations (13 academic; 5 private/group) accepted Medicare (P = .001). CLINICAL TRANSLATION: Reconciliation of the public policies regarding insurance coverage for GAS with the actual practices of the providers is necessary for improving access to GAS for transgender individuals. STRENGTHS & LIMITATIONS: We purposefully used a methodology mirroring how a patient would find GAS surgeons, which also accounts for key limitations: only surgeons whose services were featured on the internet were identified. We could not verify the services or insurance-related information surgeons reported. CONCLUSION: This study suggests that access to genital GAS is significantly limited by the number of providers and the uneven geographic distribution across the United States, in which only 20 of 50 U.S. states have at least one genital GAS surgeon. Feldman AT, Chen A, Poudrier G, et al. How Accessible Is Genital Gender-Affirming Surgery for Transgender Patients With Commercial and Public Health Insurance in the United States? Results of a Patient-Modeled Search for Services and a Survey of Providers. Sex Med 2020;8:664-672.

Mesenchymal iron deposition is associated with adverse long-term outcome in non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Approximately one-third of patients with non-alcoholic fatty liver disease (NAFLD) show signs of mild-to-moderate iron overload. The impact of histological iron deposition on the clinical course of patients with NAFLD has not been established. METHODS & RESULTS: For this retrospective study, 299 consecutive patients with biopsy-proven NAFLD and a mean follow-up of 8.4 (±4.1; range: 0.3-18.0) years were allocated to one of four groups according to presence of hepatic iron in the reticuloendothelial system (RES) and/or hepatocytes (HC): 156 subjects (52%) showed no stainable iron (NONE), 58 (19%) exclusively reticuloendothelial (xRES), 19 (6%) exclusively hepatocellular (xHC) and 66 (22%) showed a mixed (HC/RES) pattern of iron deposition. A long-term analysis for overall survival, hepatic, cardiovascular or extrahepatic-malignant events was conducted. Based on multivariate Cox proportional hazards models any reticuloendothelial iron was associated with fatal and non-fatal hepatic events. Specifically, xRES showed a cause-specific hazard ratio (csHR) of 2.4 (95%-CI, 1.0-5.8; P = .048) for hepatic as well as cardiovascular fatal and non-fatal events combined (csHR 3.2; 95%-CI, 1.2-8.2; P = .015). Furthermore, the mixed HC/RES iron pattern showed a higher rate of combined hepatic fatal and non-fatal events (csHR 3.6; 95%-CI, 1.4-9.5; P = .010), while xHC iron deposition was not associated with any defined events. CONCLUSIONS: The presence of reticuloendothelial-accentuated hepatic iron distribution patterns is associated with detrimental long-term outcomes reflected in a higher rate of both liver-related and cardiovascular fatal and non-fatal events.

Heterozygous carriage of the alpha1-antitrypsin Pi*Z variant increases the risk to develop liver cirrhosis.

OBJECTIVE: Homozygous alpha1-antitrypsin (AAT) deficiency increases the risk for developing cirrhosis, whereas the relevance of heterozygous carriage remains unclear. Hence, we evaluated the impact of the two most relevant AAT variants ('Pi*Z' and 'Pi*S'), present in up to 10% of Caucasians, on subjects with non-alcoholic fatty liver disease (NAFLD) or alcohol misuse. DESIGN: We analysed multicentric case-control cohorts consisting of 1184 people with biopsy-proven NAFLD and of 2462 people with chronic alcohol misuse, both cohorts comprising cases with cirrhosis and controls without cirrhosis. Genotyping for the Pi*Z and Pi*S variants was performed. RESULTS: The Pi*Z variant presented in 13.8% of patients with cirrhotic NAFLD but only in 2.4% of counterparts without liver fibrosis (p<0.0001). Accordingly, the Pi*Z variant increased the risk of NAFLD subjects to develop cirrhosis (adjusted OR=7.3 (95% CI 2.2 to 24.8)). Likewise, the Pi*Z variant presented in 6.2% of alcohol misusers with cirrhosis but only in 2.2% of alcohol misusers without significant liver injury (p<0.0001). Correspondingly, alcohol misusers carrying the Pi*Z variant were prone to develop cirrhosis (adjusted OR=5.8 (95% CI 2.9 to 11.7)). In contrast, the Pi*S variant was not associated with NAFLD-related cirrhosis and only borderline with alcohol-related cirrhosis (adjusted OR=1.47 (95% CI 0.99 to 2.19)). CONCLUSION: The Pi*Z variant is the hitherto strongest single nucleotide polymorphism-based risk factor for cirrhosis in NAFLD and alcohol misuse, whereas the Pi*S variant confers only a weak risk in alcohol misusers. As 2%-4% of Caucasians are Pi*Z carriers, this finding should be considered in genetic counselling of affected individuals.

Lean Patients with Non-Alcoholic Fatty Liver Disease Have a Severe Histological Phenotype Similar to Obese Patients.

A small proportion of lean patients develop non-alcoholic fatty liver disease (NAFLD). We aimed to report the histological picture of lean NAFLD in comparison to overweight and obese NAFLD patients. Biopsy and clinical data from 466 patients diagnosed with NAFLD were stratified to groups according to body mass index (BMI): lean (BMI ≤ 25.0 kg/m², n confirmed to be appropriate = 74), overweight (BMI > 25.0 ≤ 30.0 kg/m², n = 242) and obese (BMI > 30.0 kg/m², n = 150). Lean NAFLD patients had a higher rate of lobular inflammation compared to overweight patients (12/74; 16.2% vs. 19/242; 7.9%; p = 0.011) but were similar to obese patients (25/150; 16.7%). Ballooning was observed in fewer overweight patients (38/242; 15.7%) compared to lean (19/74; 25.7%; p = 0.014) and obese patients (38/150; 25.3%; p = 0.006). Overweight patients had a lower rate of portal and periportal fibrosis (32/242; 13.2%) than lean (19/74; 25.7%; p = 0.019) and obese patients (37/150; 24.7%; p = 0.016). The rate of cirrhosis was higher in lean patients (6/74; 8.1%) compared to overweight (4/242; 1.7%; p = 0.010) and obese patients (3/150; 2.0% p = 0.027). In total, 60/466; 12.9% patients were diagnosed with non-alcoholic steatohepatitis (NASH). The rate of NASH was higher in lean (14/74; 18.9% p = 0.01) and obese (26/150; 17.3%; p = 0.007) compared to overweight patients (20/242; 8.3%)). Among lean patients, fasting glucose, INR and use of thyroid hormone replacement therapy were independent predictors of NASH in a multivariate model. Lean NAFLD patients were characterized by a severe histological picture similar to obese patients but are more progressed compared to overweight patients. Fasting glucose, international normalized ratio (INR) and the use of thyroid hormone replacement may serve as indicators for NASH in lean patients.

Metabolomic profiling identifies potential pathways involved in the interaction of iron homeostasis with glucose metabolism.

OBJECTIVE: Elevated serum ferritin has been linked to type 2 diabetes (T2D) and adverse health outcomes in subjects with the Metabolic Syndrome (MetS). As the mechanisms underlying the negative impact of excess iron have so far remained elusive, we aimed to identify potential links between iron homeostasis and metabolic pathways. METHODS: In a cross-sectional study, data were obtained from 163 patients, allocated to one of three groups: (1) lean, healthy controls (n = 53), (2) MetS without hyperferritinemia (n = 54) and (3) MetS with hyperferritinemia (n = 56). An additional phlebotomy study included 29 patients with biopsy-proven iron overload before and after iron removal. A detailed clinical and biochemical characterization was obtained and metabolomic profiling was performed via a targeted metabolomics approach. RESULTS: Subjects with MetS and elevated ferritin had higher fasting glucose (p < 0.001), HbA1c (p = 0.035) and 1 h glucose in oral glucose tolerance test (p = 0.002) compared to MetS subjects without iron overload, whereas other clinical and biochemical features of the MetS were not different. The metabolomic study revealed significant differences between MetS with high and low ferritin in the serum concentrations of sarcosine, citrulline and particularly long-chain phosphatidylcholines. Methionine, glutamate, and long-chain phosphatidylcholines were significantly different before and after phlebotomy (p < 0.05 for all metabolites). CONCLUSIONS: Our data suggest that high serum ferritin concentrations are linked to impaired glucose homeostasis in subjects with the MetS. Iron excess is associated to distinct changes in the serum concentrations of phosphatidylcholine subsets. A pathway involving sarcosine and citrulline also may be involved in iron-induced impairment of glucose metabolism.

The VEGF rise in blood of bevacizumab patients is not based on tumor escape but a host-blockade of VEGF clearance.

Vascular endothelial growth factor (VEGF) has become a major target in cancer treatment as it promotes tumor angiogenesis. Therapy with anti-VEGF antibody bevacizumab reportedly induces high levels of circulating VEGF which may potentially contribute to resistance. Based on animal or computational models, mechanisms of VEGF induction by bevacizumab have been proposed but not verified in the clinical setting. Hence, we evaluated sixty patients with colorectal cancer metastases for changes in plasma VEGF during neoadjuvant/conversion and adjuvant chemotherapy with or without bevacizumab. VEGF expression was assessed in tissue sections of liver metastases. The VEGF source was investigated with in vitro cultures of tumor, endothelial cells, fibroblasts and platelets, and potential protein stabilization due to anti-VEGF therapy was addressed. A VEGF rise was observed in blood of bevacizumab patients but not in chemotherapy controls, and VEGF was found to be largely complexed by the antibody. A comparable VEGF increase occurred in the presence (neoadjuvant) and absence of the tumor (adjuvant). Accordingly, VEGF expression in tumor tissue was not determined by bevacizumab treatment. Investigations with isolated cell types did not reveal VEGF production in response to bevacizumab. However, antibody addition to endothelial cultures led to a dose-dependent blockade of VEGF internalization and hence stabilized VEGF in the supernatant. In conclusion, the VEGF rise in cancer patients treated with bevacizumab is not originating from the tumor. The accumulation of primarily host-derived VEGF in circulation can be explained by antibody interference with receptor-mediated endocytosis and protein degradation. Thus, the VEGF increase in response to bevacizumab therapy should not be regarded as a tumor escape mechanism.

Chemotherapy of colorectal liver metastases induces a rapid rise in intermediate blood monocytes which predicts treatment response.

We have previously reported that intermediate monocytes (CD14(++)/CD16(+)) were increased in colorectal cancer (CRC) patients, while the subset of pro-angiogenic TIE2-expressing monocytes (TEMs) was not significantly elevated. This study was designed to evaluate changes in frequency and function of intermediate monocytes and TEMs during chemotherapy and anti-angiogenic cancer treatment and their relation to treatment response. Monocyte populations were determined by flow cytometry in 60 metastasized CRC (mCRC) patients who received neoadjuvant chemotherapy with or without bevacizumab. Blood samples were taken before treatment, after two therapy cycles, at the end of neoadjuvant therapy and immediately before surgical resection of liver metastases. Neoadjuvant treatment resulted in a significant increase in circulating intermediate monocytes which was most pronounced after two cycles and positively predicted tumor response (AUC = 0.875, p = 0.005). With a cut-off value set to 1% intermediate monocytes of leukocytes, this parameter showed a predictive sensitivity and specificity of 75% and 88%. Anti-angiogenic therapy with bevacizumab had no impact on monocyte populations including TEMs. In 15 patients and six healthy controls, the gene expression profile and the migratory behavior of monocyte subsets was evaluated. The profile of intermediate monocytes suggested functions in antigen presentation, inflammatory cytokine production, chemotaxis and was remarkably stable during chemotherapy. Intermediate monocytes showed a preferential migratory response to tumor-derived signals in vitro and correlated with the level of CD14(+)/CD16(+) monocytic infiltrates in the resected tumor tissue. In conclusion, the rapid rise of intermediate monocytes during chemotherapy may offer a simple marker for response prediction and a timely change in regimen.

Natural course of subjects with elevated liver tests and normal liver histology.

BACKGROUND & AIMS: Liver biopsy (LB) is performed if non-invasive work-up of liver disease is inconclusive. The examination of liver tissue occasionally reveals normal histology. Long-term follow-up of such patients has not been performed. METHODS: We identified a total 70 subjects from our LB database with elevated liver tests and normal liver histology after a mean of 90.5 ± 52.3 (range 15-216) months and conducted reassessment of medical history, physical examination, laboratory testing, ultrasound, transient elastography and LB if indicated. RESULTS: At follow-up examination, 15 (7 females (f)/8 males (m); 21.4%) subjects had normal liver tests and no further evidence of liver disease. A subset of 37 (29 f/8 m; 52.9%) subjects had persistently elevated liver tests without evidence indicating progressive liver disease but the cause thereof remained unexplained also at the follow-up visit. Three (0 f/3 m; 4.3%) subjects had consumed excessive alcohol with indicators of alcoholic liver disease. Eleven subjects (4 f/7 m; 15.7%) had developed steatosis on ultrasound examination along with weight gain and/or biochemical features of the metabolic syndrome. In addition, three (2 f/1 m) patients developed autoimmune hepatitis, one female presented with primary biliary cirrhosis. One male was diagnosed with cholangiocellular carcinoma 3 months after the initial evaluation. CONCLUSION: The clinical course of most patients was benign, but in approximately 20% of the subjects a liver disease developed. Particular attention should be given to autoimmune liver diseases in subjects with positive autoantibodies. In addition, lifestyle factors such as weight gain and alcohol consumption were associated with the manifestation of liver diseases.

The Potential Role of Iron and Copper in Pediatric Obesity and Nonalcoholic Fatty Liver Disease.

Obesity is a rapidly growing health problem and is paralleled by a multitude of comorbidities, including nonalcoholic fatty liver disease (NAFLD). NAFLD has become the most common chronic liver disease in both adults and children. The current understanding of NAFLD is still fragmentary. While simple steatosis is characterized by the interplay between excessive free fatty acid accumulation and hepatic insulin resistance, the progression to NASH has been related to oxidative stress and a proinflammatory state with dysbalanced adipokine, cytokine levels, and endotoxin-mediated immune response. In addition, oxidative stress has been suggested to play a central role for the sequelae leading to NASH. Trace elements are critical in regulatory, immunologic, and antioxidant functions resulting in protection against inflammation and peroxidation and consequently against the known comorbidities of obesity. Disruptions of the metal detoxification processes located in the liver are plausibly related to NAFLD development via oxidative stress. Perturbations of iron and copper (Cu) homeostasis have been shown to contribute to the pathogenesis of NAFLD. This review presents current data from pediatric studies. In addition, data from adult studies are summarized where clinical relevance may be extrapolated to pediatric obesity and NAFLD.

Obesity as an emerging risk factor for iron deficiency.

Iron homeostasis is affected by obesity and obesity-related insulin resistance in a many-facetted fashion. On one hand, iron deficiency and anemia are frequent findings in subjects with progressed stages of obesity. This phenomenon has been well studied in obese adolescents, women and subjects undergoing bariatric surgery. On the other hand, hyperferritinemia with normal or mildly elevated transferrin saturation is observed in approximately one-third of patients with metabolic syndrome (MetS) or nonalcoholic fatty liver disease (NAFLD). This constellation has been named the "dysmetabolic iron overload syndrome (DIOS)". Both elevated body iron stores and iron deficiency are detrimental to health and to the course of obesity-related conditions. Iron deficiency and anemia may impair mitochondrial and cellular energy homeostasis and further increase inactivity and fatigue of obese subjects. Obesity-associated inflammation is tightly linked to iron deficiency and involves impaired duodenal iron absorption associated with low expression of duodenal ferroportin (FPN) along with elevated hepcidin concentrations. This review summarizes the current understanding of the dysregulation of iron homeostasis in obesity.

Endogenous H2O2 produced by Streptococcus pneumoniae controls FabF activity.

FabF elongation condensing enzyme is a critical factor in determining the spectrum of products produced by the FASII pathway. Its active site contains a critical cysteine-thiol residue, which is a plausible target for oxidation by H2O2. Streptococcus pneumoniae produces exceptionally high levels of H2O2, mainly through the conversion of pyruvate to acetyl-P via pyruvate oxidase (SpxB). We present evidence showing that endogenous H2O2 inhibits FabF activity by specifically oxidizing its active site cysteine-thiol residue. Thiol trapping methods revealed that one of the three FabF cysteines in the wild-type strain was oxidized, whereas in an spxB mutant, defective in H2O2 production, none of the cysteines was oxidized, indicating that the difference in FabF redox state originated from endogenous H2O2. In vitro exposure of the spxB mutant to various H2O2 concentrations further confirmed that only one cysteine residue was susceptible to oxidation. By blocking FabF active site cysteine with cerulenin we show that the oxidized cysteine was the catalytic one. Inhibition of FabF activity by either H2O2 or cerulenin resulted in altered membrane fatty acid composition. We conclude that FabF activity is inhibited by H2O2 produced by S. pneumoniae.

Apoptosis of Hodgkin-Reed-Sternberg cells in classical Hodgkin lymphoma revisited.

We scrutinized the role of apoptosis of the Hodgkin-Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) and critically reviewed its features in the light of conflicting evidence. In this study, we found that tumor cells in this neoplasm showed inhibition of apoptosis in 55% of the 217 cHL cases only. It is also suggested that the two factors considered responsible for apoptosis inhibition in HRS cells, nuclear factor-kappaB and the latent membrane protein-1 of the Epstein-Barr virus, do not correlate with apoptosis inhibition, in contrast with the findings in the consensual pathogenetic scheme. The most significant association of HRS cell apoptosis was with p53, the negative expression of which related with a high apoptotic index (p = 0.001). These findings support our contention that the role of apoptosis in the HRS cells of Hodgkin lymphoma has not been completely elucidated and is at variance with that in the consensus.