dysfunction and characteristic image of the ovaries in the ultrasound ( 2 ). A lot of data indicated that insulin resistance is a key factor in the development of metabolic disturbances in PCOS, for example, obesity, type 2 diabetes (T2D), cardiovascular
Agnieszka Adamska, Aleksandra Maria Polak, Anna Krentowska, Agnieszka Łebkowska, Justyna Hryniewicka, Monika Leśniewska, and Irina Kowalska
L M Mongioì, R A Condorelli, S La Vignera, and A E Calogero
3912 – 3922 . ( https://doi.org/10.1210/jc.2007-0685 ) 10.1210/jc.2007-0685 14 Løvås K Curran S Oksnes M Husebye ES Huppert FA Chatterjee VK. Development of a disease-specific quality of life questionnaire in Addison’s disease . Journal of Clinical
H A Booij, W D C Gaykema, K A J Kuijpers, M J M Pouwels, and H M den Hertog
stalk at the time of injury ( 4 ). This, and other secondary mechanisms after TBI, such as hypotension, hypoxia and raised intracranial pressure might be responsible for the development of PD ( 5 ). The same concept might be applied in part to brain
Sandrine Visentin, Gérard Michel, Claire Oudin, Béatrice Cousin, Bénédicte Gaborit, Inès Abdesselam, Marie Maraninchi, Marion Nowicki, René Valéro, Maxime Guye, Monique Bernard, Pascal Auquier, Hervé Chambost, Marie-Christine Alessi, and Sophie Béliard
). Given the high prevalence of MS, and despite a lower body weight among survivors who received TBI, we hypothesized that exposure to radiation leads to abnormal fat storage with ectopic fat deposition development deposition and insulin resistance
A Daniel Bird, Spencer Greatorex, David Reser, Gareth G Lavery, and Timothy J Cole
all stages of ovarian follicle development ( Fig. 5A and D ). Also shown are negative controls with no primary antibody (panel B) and an immunizing peptide, pre-incubation control (panel C). The mouse ovary, that should not express a HSD1L protein
Yun Hu, Na Li, Peng Jiang, Liang Cheng, Bo Ding, Xiao-Mei Liu, Ke He, Yun-Qing Zhu, Bing-li Liu, Xin Cao, Hong Zhou, and Xiao-Ming Mao
.1158/0008-5472.CAN-05-0934 ) 10.1158/0008-5472.CAN-05-0934 33 Fontenot JD Gavin MA Rudensky AY . Foxp3 programs the development and function of CD4+CD25+ regulatory T cells . Nature Immunology 2003 4 330 – 336 . ( https://doi.org/10.1038/ni904 ) 12612578 10
Thomas Crezee, Mirela Petrulea, Doina Piciu, Martin Jaeger, Jan Wa Smit, Theo S Plantinga, Carmen E. Georgescu, and Romana Netea-Maier
The PI3K-Akt-mTOR pathway plays a central role in the development of non-medullary thyroid carcinoma (NMTC). Although somatic mutations have been identified in these genes in NMTC patients, the role of germline variants has not been investigated. Here, we selected frequently occurring genetic variants in AKT1, AKT2, AKT3, PIK3CA and MTOR and have assessed their effect on NMTC susceptibility, progression and clinical outcome in a Dutch discovery cohort (154 patients, 188 controls) and a Romanian validation cohort (159 patients, 260 controls). Significant associations with NMTC susceptibility were observed for AKT1 polymorphisms rs3803304, rs2494732 and rs2498804 in the Dutch discovery cohort, of which the AKT1 rs3803304 association was confirmed in the Romanian validation cohort. No associations were observed between PI3K-Akt-mTOR polymorphisms and clinical parameters including histology, TNM staging, treatment response and clinical outcome. Functionally, cells bearing the associated AKT1 rs3803304 risk allele exhibit increased levels of phosphorylated Akt protein, potentially leading to elevated signaling activity of the oncogenic Akt pathway. All together, germline encoded polymorphisms in the PI3K-Akt-mTOR pathway could represent important risk factors in development of NMTC.
Dirk Weismann, Andreas Schneider, and Charlotte Höybye
Hyponatremia (HN) is a common condition, with a large number of etiologies and a complicated treatment. Although chronic HN has been shown to be a predictor of poor outcome, sodium-increasing treatments in chronic stable and asymptomatic HN have not proven to increase life expectancy. For symptomatic HN, in contrast, the necessity for urgent treatment has broadly been accepted to avoid the development of fatal cerebral edema. On the other hand, a too rapid increase of serum sodium in chronic HN may result in cerebral damage due to osmotic demyelinisation. Recently, administration of hypertonic saline bolus has been recommended as first-line treatment in patients with moderate-to-severe symptomatic HN. This approach is easy to memorize and holds the potential to greatly facilitate the initial treatment of symptomatic HN. First-line treatment of chronic HN is fluid restriction and if ineffective treatment with tolvaptan or in some patients other agents should be considered. A number of recommendations and guidelines have been published on HN. In the present review, the management of patients with HN in relation to everyday clinical practice is summarized with focus on the acute management.
Yali Cheng, Qiaoying Lv, Bingying Xie, Bingyi Yang, Weiwei Shan, Chengcheng Ning, Bing Li, Liying Xie, Chao Gu, Xuezhen Luo, Xiaojun Chen, and Qin Zhu
Unopposed estrogen stimulation and insulin resistance are known to play important roles in endometrial cancer (EC), but the interaction between these two factors and how they contribute to endometrial lesions are not completely elucidated. To investigate the endometrial transcriptome profile and the associated molecular pathway alterations, we established an ovariectomized C57BL/6 mouse model treated with subcutaneous implantation of 17-β estradiol (E2) pellet and/or high-fat diet (HFD) for 12 weeks to mimic sustained estrogen stimulation and insulin resistance. Histomorphologically, we found that both E2 and E2 + HFD groups showed markedly enlarged uterus and increased number of endometrial glands. The endometrium samples were collected for microarray assay. GO and KEGG analysis showed that genes regulated by E2 and/or HFD are mainly responsible for immune response, inflammatory response and metabolic pathways. Further IPA analysis demonstrated that the acute phase response signaling, NF-κB signaling, leukocyte extravasation signaling, PPAR signaling and LXR/RXR activation pathways are mainly involved in the pathways above. In addition, the genes modulated reciprocally by E2 and/or HFD were also analyzed, and their crosstalk mainly focuses on enhancing one another’s activity. The combination analysis of microarray data and TCGA database provided potential diagnostic or therapeutic targets for EC. Further validation was performed in mice endometrium and human EC cell lines. In conclusion, this study unraveled the endometrial transcriptome profile alterations affected by E2 and/or HFD that may disturb endometrial homeostasis and contribute to the development of endometrial hyperplasia.
Sweta Budyal, Swati Sachin Jadhav, Rajeev Kasaliwal, Hiren Patt, Shruti Khare, Vyankatesh Shivane, Anurag R Lila, Tushar Bandgar, and Nalini S Shah
Variable prevalence of subclinical Cushing's syndrome (SCS) has been reported in patients with type 2 diabetes mellitus (T2DM), making the need for screening in this population uncertain. It is unknown if this variability is solely due to study-related methodological differences or a reflection of true differences in ethnic predisposition. The objective of this study is to explore the prevalence of SCS in Asian Indian patients with T2DM. In this prospective single center study conducted in a tertiary care referral center, 993 T2DM outpatients without any discriminatory clinical features (easy bruising, facial plethora, proximal muscle weakness, and/or striae) of hypercortisolism underwent an overnight 1 mg dexamethasone suppression test (ODST). ODST serum cortisol ≥1.8 μg/dl was considered positive, and those with positive results were subjected to 48 h, 2 mg/day low dose DST (LDDST). A stepwise evaluation for endogenous hypercortisolism was planned for patients with LDDST serum cortisol ≥1.8 μg/dl. Patients with positive ODST and negative LDDST were followed up clinically and re-evaluated a year later for the development of clinically evident Cushing's syndrome (CS). In this largest single center study reported to date, we found 37 out of 993 (3.72%) patients had ODST serum cortisol ≥1.8 μg/dl. None of them had LDDST cortisol ≥1.8 μg/dl, nor did they develop clinically evident CS over a follow-up period of 1 year. Specificity of ODST for screening of CS was 96.3% in our cohort. None of the T2DM outpatients in our cohort had SCS, hence cautioning against routine biochemical screening for SCS in this cohort. We suggest screening be based on clinical suspicion only.