Purpose
Environmental endocrine-disrupting chemicals (EDCs) are a mixture of chemical compounds capable to interfere with endocrine axis at different levels and to which population is daily exposed. ...This paper aims to review the relationship between EDCs and breast, prostate, testicle, ovary, and thyroid cancer, discussing carcinogenic activity of known EDCs, while evaluating the impact on public health.
Methods
A literature review regarding EDCs and cancer was carried out with particular interest on meta-analysis and human studies.
Results
The definition of EDCs has been changed through years, and currently there are no common criteria to test new chemicals to clarify their possible carcinogenic activity. Moreover, it is difficult to assess the full impact of human exposure to EDCs because adverse effects develop latently and manifest at different ages, even if preclinical and clinical evidence suggest that developing fetus and neonates are most vulnerable to endocrine disruption.
Conclusion
EDCs represent a major environmental and health issue that has a role in cancer development. There are currently some EDCs that can be considered as carcinogenic, like dioxin and cadmium for breast and thyroid cancer; arsenic, asbestos, and dioxin for prostate cancer; and organochlorines/organohalogens for testicular cancer. New evidence supports the role of other EDCs as possible carcinogenic and pregnant women should avoid risk area and exposure. The relationship between EDCs and cancer supports the need for effective prevention policies increasing public awareness.
The metabolic cost of walking increases when mass is added to the legs, but the effects of load magnitude and location on the energetics and biomechanics of walking are unclear. We hypothesized that ...with leg loading 1) net metabolic rate would be related to the moment of inertia of the leg (I(leg)), 2) kinematics would be conserved, except for heavy foot loads, and 3) swing-phase sagittal-plane net muscle moments and swing-phase leg-muscle electromyography (EMG) would increase.
Five adult males walked on a force-measuring treadmill at 1.25 m.s(-1) with no load and with loads of 2 and 4 kg per foot and shank, 4 and 8 kg per thigh, and 4, 8, and 16 kg on the waist. We recorded metabolic rate and sagittal-plane kinematics and net muscle moments about the hip, knee, and ankle during the single-stance and swing phases, and EMG of key leg muscles.
Net metabolic rate during walking increased with load mass and more distal location and was correlated with I(leg) (r2 = 0.43). Thigh loading was relatively inexpensive, helping to explain why the metabolic rate during walking is not strongly affected by body mass distribution. Kinematics, single-stance and swing-phase muscle moments, and EMG were similar while walking with no load or with waist, thigh, or shank loads. The increase in net metabolic rate with foot loading was associated with greater EMG of muscles that initiate leg swing and greater swing-phase muscle moments.
Distal leg loads increase the metabolic rate required for swinging the leg. The increase in metabolic rate with more proximal loads may be attributable to a combination of supporting (via hip abduction muscles) and propagating the swing leg.
While males have dominated the physician lines over the last decades the recent female doctors' number increasing might progressively reduce this gender gap. This might be not fully true in the ...academic/research area. We aimed to analyze the gender distribution of first/senior Italian authors on neuroendocrine neoplasm papers published on peer reviewed journals.
Publications from January 2019 to September 2023 were reviewed; only papers with first and/or senior Italian authors were included. First/senior author gender, type of article, co-authorship with foreign authors were the variable analyzed.
742 papers with Italian first and/or senior authors were retrieved, 449 (60.5%) multicentric, 285 (38.4%) original articles. A female author was first and senior author in 386/742 (52%) and in 228/742 (31%) papers, respectively. 150 (20.2%) papers included foreign coauthors, being an Italian female researcher first author in 50 papers (33%), senior author in 28 (18.6%). The number of Italian female first/senior authors has been increasing over the years (22 in 2019, 113 in 2022; 16 in 2019, 62 in 2022, respectively). The first/senior female authors were mainly Oncologists/Endocrinologists/Pathologists rather than Gastroenterologists/Nuclear Medicine doctors/Surgeons/Radiologists.
There has been an increase in the prevalence of female authorship of published research in the neuroendocrine setting over the last 5 years, which partially reflects the current distributions in this field, taking into account that several specialties with different gender distribution are involved. However, senior authorship continues to be primarily men. Efforts should be made to improve proportionate gender representation in both clinical and academic/research setting.
Parathyroid diseases and metabolic syndrome Modica, R.; Liccardi, A.; Minotta, R. ...
Journal of endocrinological investigation,
06/2023, Letnik:
46, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Purpose
Parathyroid diseases are related to parathyroid hormone (PTH) dysregulation by parathyroid cells or alteration of PTH function. They include hyperparathyroidism (PTH excess), ...hypoparathyroidism (PTH deficiency) and pseudohypoparathyroidism (PTH resistance). Little is known about correlation between parathyroid diseases and metabolic syndrome (MetS).
Methods
An electronic-based search using PubMed was performed until October 2022 and articles were selected based on relevance of title, abstract, English language and publication in peer-reviewed journals.
Results
Possible association between PTH alterations and the diverse manifestation of MetS have been proposed and it could be supposed that MetS may negatively influence parathyroid diseases. Available data show significant association for hyperparathyroidism and pseudohypoparathyroidism.
Conclusions
This review highlights the possible implications between MetS and parathyroid diseases. Given the increasing MetS global prevalence and the higher parathyroid diseases awareness and diagnosis, it may be interesting to further explore the possible role of alterations in parathyroid homeostasis in the development of MetS components with dedicated prospective studies.
•Two long-acting somatostatin analogs (SSA) are available in clinical practice for NET.•Octreotide and lanreotide are approved for clinical syndrome and tumor growth control.•However, some clinical ...indications of approved SSA remain controversial.•A group of NET-specialists, critically addressed ten challenging questions on SSA use.
Octreotide and lanreotide are the two somatostatin analogs (SSA) currently available in clinical practice. They have been approved first to control the clinical syndrome (mainly carcinoid syndrome) associated with functioning neuroendocrine tumors (NET) and later for tumor growth control in advanced low/intermediate grade NET. Although evidence regarding their role, especially as antiproliferative therapy, has been increasing over the years some clinical indications remain controversial. Solicited by AIOM (Italian Association of Medical Oncology) a group of clinicians from various specialties, including medical oncology, endocrinology, and gastroenterology, deeply involved in NET for their clinical and research activity, addressed eight open questions, critically reviewing evidence and guidelines and sharing clinical take-home messages. The questions regarded the use of long-acting octreotide and lanreotide in the following settings: functioning and non-functioning NET refractory to label dose, first-line metastatic pulmonary NET, combination with other therapy with an antiproliferative intent, maintenance in NET responding to other therapies, adjuvant treatment, Ki-67-related cut-off, somatostatin receptor imaging, safety, and feasibility. The level of evidence is not absolute for the majority of these clinical contexts, so it is recommended to distinguish routine versus sporadic utilization in very selected cases. Mention of such specific issues by the main European guidelines (ENETS, European Neuroendocrine Tumor Society, and ESMO, European Society for Medical Oncology) was explored and their position reported. However, different clinical decisions on single patients could be made if the case is carefully discussed within a NET-dedicated multidisciplinary team.
Purpose
Risk factors for sporadic GEP-NENs are still not well defined. To identify the main clinical risk factors represents the aim of this study performed by three Italian referral centers for ...NENs.
Methods
We performed a retrospective case–control study including 148 consecutive sporadic GEP-NENs and 210 age- and sex-matched controls. We collected data on clinical features, cancer family history and other potential risk factors.
Results
Mean age was 58.3 ± 15.8 years; 50% males, primary site was pancreas (50.7%), followed by ileum (22.3%). The 62.8% and 29.1% of cases were G1 and G2, respectively; the 40% had locally advanced or metastatic disease at diagnosis. Independent risk factors for GEP-NENs were: family history of non-neuroendocrine GEP cancer (OR 2.16, 95% CI 1.31–3.55,
p
= 0.003), type 2 diabetes mellitus (T2DM) (OR 2.5, 95% CI 1.39–4.51,
p
= 0.002) and obesity (OR 1.88, 95% CI 1.18–2.99,
p
= 0.007). In the T2DM subjects, metformin use was a protective factor (OR 0.28, 95% CI 0.08–0.93,
p
= 0.049). T2DM was also associated with a more advanced (OR 2.39, 95% CI 1.05–5.46,
p
= 0.035) and progressive disease (OR 2.47, 95% CI 1.08–5.34,
p
= 0.03). Stratifying cases by primary site, independent risk factors for pancreatic NENs were T2DM (OR 2.57, 95% CI 1.28–5.15,
p
= 0.008) and obesity (OR 1.98, 95% CI 1.11–3.52,
p
= 0.020), while for intestinal NENs family history of non-neuroendocrine GEP cancer (OR 2.46, 95% CI 1.38–4.38,
p
= 0.003) and obesity (OR 1.90, 95% CI 1.08–3.33,
p
= 0.026).
Conclusion
This study reinforces a role for family history of non-neuroendocrine GEP cancer, T2DM and obesity as independent risk factors for GEP-NENs and suggests a role of metformin as a protective factor in T2DM subjects. If confirmed, these findings could have a significant impact on prevention strategies for GEP-NENs.
PRRT: identikit of the perfect patient Albertelli, M.; Dotto, A.; Di Dato, C. ...
Reviews in endocrine & metabolic disorders,
09/2021, Letnik:
22, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Peptide receptor radionuclide therapy (PRRT) has been strengthened since the publication of NETTER-1. Nevertheless, the correct positioning in the therapeutic algorithm is debated, and no optimal ...sequence has yet been standardized. Possible criteria to predict the response to PRRT in neuroendocrine tumors (NET) have been proposed. The aim of this review is to define the perfect identity of the eligible patient who can mostly benefit from this therapy. Possible predictive criteria which have been analysed were: primary tumor site, grading, tumor burden, FDG PET and
68
Ga-PET uptake. Primary tumor site and
68
Ga-PET uptake do not play a pivotal role in predicting the response, while tumor burden, FDG PET uptake and grading seem to represent predictive/prognostic factors for response to PRRT. The heterogeneity in trial designs, patient populations, type of radionuclides, previous therapies and measurement of outcomes, inevitably limits the strength of our conclusions, therefore care must be taken in applying these results to clinical practice. In conclusion, the perfect patient, selected by
68
Ga-PET uptake, will likely have a relatively limited liver tumor burden, a ki67 index <20% and will respond to PRRT irrespective to primary tumor. Nevertheless, we have mostly prognostic than predictive factors to predict the efficacy of PRRT in individual patients, while a promising tool could be the NETest. However, to date, the identikit of the perfect patient for PRRT is a puzzle without some pieces and still we cannot disregard a multidisciplinary discussion of the individual case to select the patients who will mostly benefit from PRRT.
Purpose
Scientific knowledge on health-related quality of life (HRQoL) in patients with neuroendocrine neoplasm (NEN) is still limited and longitudinal assessment of HRQoL over the time in NEN ...patients are scarce. The current study aimed to assess the role of clinical severity and heterogeneity of NEN, as well as resilience, in the HRQoL of NEN patients over the course of a year.
Methods
39 consecutive NEN patients (25 men and 14 women) aged from 29 to 73 years participated in a longitudinal Italian multicentric study. The main outcome measure concerned the severity and heterogeneity of NEN, HRQoL, and resilience.
Results
Over the course of a year, higher levels of the global health (GH) were associated to the absence of distant metastases, while the presence of metastases with higher levels of fatigue, diarrhea, and financial difficulties. Higher levels of resilience are still associated with better GH and lower levels of fatigue, diarrhea, and financial difficulties, but no longer with constipation. Furthermore, patients with gastroenteropancreatic NEN still have higher scores on constipation, but not on GH, fatigue, diarrhea, and financial difficulties. Patients with hereditary NEN continue to have greater GH than those with a sporadic NEN and lower fatigue, diarrhea, and financial difficulties.
Conclusion
These findings showed that the effects of severity and clinical heterogeneity of the NEN on HRQoL may change over time. This evidence should lead clinicians to monitor the HRQoL of NEN patients throughout the course of the disease and psychologists to implement evidence-based resilience interventions.
Unexpected threshold voltage (<inline-formula> <tex-math notation="LaTeX">{V}_{\text {TH}} </tex-math></inline-formula>) behaviors are experimentally observed in gallium nitride (GaN)-on-Si ...metal-oxide-semiconductor-channel high electron mobility transistors (MOSc-HEMTs) with fully recessed gate and back-barrier (BB): 1) <inline-formula> <tex-math notation="LaTeX">{V}_{\text {TH}} </tex-math></inline-formula> increases with decreasing gate length (<inline-formula> <tex-math notation="LaTeX">{L}_{G} </tex-math></inline-formula>) (<inline-formula> <tex-math notation="LaTeX">{V}_{\text {TH}} </tex-math></inline-formula> roll-up); 2) discrepancies between <inline-formula> <tex-math notation="LaTeX">{V}_{\text {TH}} </tex-math></inline-formula> values extracted from drain current characteristics <inline-formula> <tex-math notation="LaTeX">{I}_{\text {D}} </tex-math></inline-formula>(<inline-formula> <tex-math notation="LaTeX">{V}_{\text {G}} </tex-math></inline-formula>) (<inline-formula> <tex-math notation="LaTeX">{V}_{\text {TH}\_\text{IV}} </tex-math></inline-formula>) and from gate-to-channel capacitance characteristics <inline-formula> <tex-math notation="LaTeX">{C}_{\text {GC}}{(}{V}_{\text {G}} </tex-math></inline-formula>) (<inline-formula> <tex-math notation="LaTeX">{V}_{\text {TH}\_\text{CV}} </tex-math></inline-formula>); and 3) significant dependence of <inline-formula> <tex-math notation="LaTeX">{V}_{\text {TH}\_\text{CV}} </tex-math></inline-formula> with frequency. Using TCAD simulations and experimental measurements, it is demonstrated that conduction band confinement, especially at gate corners, is responsible for these peculiar <inline-formula> <tex-math notation="LaTeX">{V}_{\text {TH}} </tex-math></inline-formula> behaviors. This band confinement is strengthened by the fully recessed gate configuration coupled with the proximity of a BB. It depends on recessed gate topology and BB efficiency.
In this article, threshold-voltage V TH instabilities under positive gate voltage stress V GStress in GaN-on-Si devices are thoroughly investigated. Measurement-stress-measurement pBTI technique ...using ultrafast V G ramp was applied in this study. PBTI transients performed at different V GStress and several temperatures highlight the influence of two trap populations, one being related to Al 2 O 3 gate oxide defects and the other one to C N acceptors in GaN lattice. Both trap populations are located close to the Al 2 O 3 /GaN interface and lead to V TH instabilities via two different underlying mechanisms simulated by TCAD. PBTI transients obtained under several dc and ac stress conditions have also been modeled using capture emission time (CET) maps and allowed the identification of the two trap populations. Analysis of the temperature-dependent CET maps gives an activation energy of 0.8-0.9 eV related to C N traps and an energy range between 0.7 and 1.5 eV ascribed to Al 2 O 3 defects above the GaN conduction band energy. This study provides a better understanding of the underlying physical mechanisms, leading to BTI degradation in GaN-HEMT technologies.
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