Pituitary Tumorigenesis-Implications for Management.

Pituitary neuroendocrine tumors (PitNETs), the third most common intracranial tumor, are mostly benign. However, some of them may display a more aggressive behavior, invading into the surrounding structures. While they may rarely metastasize, they may resist different treatment modalities. Several major advances in molecular biology in the past few years led to the discovery of the possible mechanisms involved in pituitary tumorigenesis with a possible therapeutic implication. The mutations in the different proteins involved in the Gsa/protein kinase A/c AMP signaling pathway are well-known and are responsible for many PitNETS, such as somatotropinomas and, in the context of syndromes, as the McCune-Albright syndrome, Carney complex, familiar isolated pituitary adenoma (FIPA), and X-linked acrogigantism (XLAG). The other pathways involved are the MAPK/ERK, PI3K/Akt, Wnt, and the most recently studied HIPPO pathways. Moreover, the mutations in several other tumor suppressor genes, such as menin and CDKN1B, are responsible for the MEN1 and MEN4 syndromes and succinate dehydrogenase (SDHx) in the context of the 3PAs syndrome. Furthermore, the pituitary stem cells and miRNAs hold an essential role in pituitary tumorigenesis and may represent new molecular targets for their diagnosis and treatment. This review aims to summarize the different cell signaling pathways and genes involved in pituitary tumorigenesis in an attempt to clarify their implications for diagnosis and management.

Infective endocarditis by Enterobacter cloacae: a systematic review and meta-analysis.

Enterobacter species are Gram-negative, non-spore-forming, facultative anaerobes typically motile due to the presence of peritrichous flagella. E. cloacae, the species responsible for the majority of Enterobacter infections in humans, is part of the intestinal microbiota and may cause infection in patients that have previously received antimicrobial therapy or who have been admitted to the Intensive Care Unit. E. cloacae may cause several infections, such as pneumonia, urinary tract, skin and soft tissue and intravascular infections. Infective Endocarditis (IE) is a rare disease with notable morbidity and mortality. Even though IE is rarely caused by E. cloacae, these infections can be problematic due to the relative lack of experience in their management. The purpose of this study was to systematically review all published cases of IE by E. cloacae in the literature. A systematic review of PubMed, Scopus and Cochrane library (through 14th November 2020) for studies providing epidemiological, clinical, microbiological as well as treatment data and outcomes of IE by E. cloacae was performed. A total of 20 studies, containing data of 20 patients, were included. A prosthetic valve was present in 27.8%. Mitral valve was the commonest infected site, followed by aortic valve. Diagnosis was facilitated by transthoracic and transesophageal echocardiography in 38.5% each, while the diagnosis was set at autopsy in 10%. Fever, sepsis, shock and immunologic phenomena were the most common clinical presentations, followed by heart failure. Aminoglycosides, cephalosporins and carbapenems were the most common antimicrobials used. Clinical cure was noted in 75%, while overall mortality was 30%. Development of shock and treatment with the combination of piperacillin with tazobactam were associated with overall mortality.

ERα36-GPER1 Collaboration Inhibits TLR4/NFκB-Induced Pro-Inflammatory Activity in Breast Cancer Cells.

Inflammation is important for the initiation and progression of breast cancer. We have previously reported that in monocytes, estrogen regulates TLR4/NFκB-mediated inflammation via the interaction of the Erα isoform ERα36 with GPER1. We therefore investigated whether a similar mechanism is present in breast cancer epithelial cells, and the effect of ERα36 expression on the classic 66 kD ERα isoform (ERα66) functions. We report that estrogen inhibits LPS-induced NFκB activity and the expression of downstream molecules TNFα and IL-6. In the absence of ERα66, ERα36 and GPER1 are both indispensable for this effect. In the presence of ERα66, ERα36 or GPER1 knock-down partially inhibits NFκB-mediated inflammation. In both cases, ERα36 overexpression enhances the inhibitory effect of estrogen on inflammation. We also verify that ERα36 and GPER1 physically interact, especially after LPS treatment, and that GPER1 interacts directly with NFκB. When both ERα66 and ERα36 are expressed, the latter acts as an inhibitor of ERα66 via its binding to estrogen response elements. We also report that the activation of ERα36 leads to the inhibition of breast cancer cell proliferation. Our data support that ERα36 is an inhibitory estrogen receptor that, in collaboration with GPER1, inhibits NFκB-mediated inflammation and ERα66 actions in breast cancer cells.

Vitamin D and Cathelicidin (LL-37) Status in Patients with Type 2 Diabetes and Staphylococcus aureus Nasal Carriage.

OBJECTIVE: Type 2 diabetes mellitus (T2D) is characterized by the dysregulation of innate immunity leading to higher rates of Staphylococcus aureus nasal carriage, an important risk factor for severe infections. 25-hydroxy vitamin D (25(OH)D) may contribute, via the production of the antimicrobial peptide cathelicidin (LL-37), to epithelial host defense against S. aureus. This study evaluated whether 25(OH)D and LL-37 levels determine S. aureus nasal carriage. METHODS: Two consecutive nasal swabs were obtained from 118 T2D patients to determine S. aureus nasal carriage status. Serum levels of 25(OH)D and LL-37 were measured using chemiluminescence immunoassay and enzyme-linked immunosorbent assay, respectively. Supplementation of vitamin D by a number of participants was taken into account and evaluated. RESULTS: Forty-two T2D patients (35.6%) were found to be colonized by S. aureus. Vitamin D deficiency was detected in sixty-nine patients (65.7%). Median value for LL-37 in T2D patients was 0.89 ng/ml (range 0.05-8.62 ng/ml). Circulating levels of LL-37 were higher in nasal carriers compared to non-carriers (1.25 ng/ml vs 0.72 ng/ml; p < 0.001). No difference was found in serum 25(OH)D levels between carriers and non-carriers. 25(OH)D and LL-37 serum levels correlated positively in non-carriers, while the relationship was inversed in the carrier group. Vitamin D supplementation was not associated with lower incidence of S. aureus nasal carriage (p = 0.706). CONCLUSIONS: T2D patients presented decreased serum levels of 25(OH)D and LL-37, indicating a potential impairment of innate immunity. Expression of LL-37 may be induced by S. aureus nasal carriage among people with diabetes. Vitamin D supplementation did not influence S. aureus nasal colonization in T2D patients.

Toxicity evaluation of an essential oil mixture from the Cretan herbs thyme, Greek sage and Cretan dittany.

The importance of herbal extracts on health, which was initially based on ethnopharmacological and traditional knowledge, becomes increasingly well documented by numerous experimental and intervention studies. The daily use of beverages from different aromatic plants which becomes more popular nowadays, has been a tradition in Crete, and a habit that has been linked to the longevity seen in the island. Additionally, a certain combination of aromatic plants has been used against common cold and influenza. Interestingly, when such a mixture of essential oils from Cretan herbs (Cretan Aromatic Plants essential oil, CAPeo, from thyme, Greek sage, and Cretan dittany) was formulated, significant antiviral properties were observed in vitro and a significant reduction in the duration and severity of symptoms of patients with upper respiratory tract infections was found in a clinical study. However, since many plants extracts can exert toxic effects, toxicity issues should be properly addressed. In the present work we present an acute and sub-chronic toxicity evaluation for this mixture of aromatic plants' essential oils in rats. In fact, it is the only toxicity study for Cretan dittany. We report absence of toxicity, rendering the use of the mixture of essential oils from Cretan dittany, Greek sage and thyme as safe.

Translating vitamin D transcriptomics to clinical evidence: Analysis of data in asthma and chronic obstructive pulmonary disease, followed by clinical data meta-analysis.

Vitamin D (VitD) continues to trigger intense scientific controversy, regarding both its bi ological targets and its supplementation doses and regimens. In an effort to resolve this dispute, we mapped VitD transcriptome-wide events in humans, in order to unveil shared patterns or mechanisms with diverse pathologies/tissue profiles and reveal causal effects between VitD actions and specific human diseases, using a recently developed bioinformatics methodology. Using the similarities in analyzed transcriptome data (c-SKL method), we validated our methodology with osteoporosis as an example and further analyzed two other strong hits, specifically chronic obstructive pulmonary disease (COPD) and asthma. The latter revealed no impact of VitD on known molecular pathways. In accordance to this finding, review and meta-analysis of published data, based on an objective measure (Forced Expiratory Volume at one second, FEV1%) did not further reveal any significant effect of VitD on the objective amelioration of either condition. This study may, therefore, be regarded as the first one to explore, in an objective, unbiased and unsupervised manner, the impact of VitD levels and/or interventions in a number of human pathologies.

Armillifer Infections in Humans: A Systematic Review.

Armillifer is a genus of obligate parasites belonging to the Pentastomida subclass that was first described as a cause of human disease in 1847. Human infection by Armillifer is rare and not widely known. These parasites are transmitted to humans by handling or eating undercooked meat from infected snakes, which are the definitive hosts, or oral uptake of environmental ova. The aim of this systematic review was to record all available evidence regarding infections by Armillifer in humans. A systematic review of PubMed (through 21 December 2018) for studies providing epidemiological, clinical, microbiological, as well as treatment data and outcomes of Armillifer infections was conducted. A total of 26 studies, containing data of 40 patients, were eventually included in the analysis. The most common sites of infection were the peritoneal cavity, the liver, the lower respiratory and the abdominal tract. The commonest infecting species was A. armillatus and most patients were asymptomatic; however, when symptoms occurred, the commonest was abdominal pain, even though unusual presentations occurred, such as hepatic encephalopathy or neurologic symptoms. Most cases were diagnosed at surgery or by imaging, and most patients were not treated. Mortality was low, but the majority of the cases with ocular infection lead to permanent loss of vision.

Rhodotorula species infections in humans: A systematic review.

BACKGROUND: Fungal infections by Rhodotorula species are increasingly reported in the literature and consist of bloodstream infections, especially in patients with central venous catheters (CVC), as well as central nervous system (CNS), ocular and other less frequent infections. OBJECTIVES: The aim of this systematic review was to record and evaluate all available evidence regarding infections by Rhodotorula species. METHODS: Systematic review of PubMed (through 9 August 2017) for studies providing epidemiological, clinical, microbiological, as well as treatment data and outcomes of Rhodotorula species infections. RESULTS: A total of 111 studies, containing data of 248 patients, were eventually included in the analysis. The most common Rhodotorula infections were those of bloodstream, CNS and ocular infections, as well as peritoneal dialysis-associated peritonitis. Epidemiology of each type of infection was different, with the bloodstream ones being more common in patients with malignancy and CVCs, while those of the CNS were more common in patients with AIDS. Mortality was variable being higher in CNS infections. Amphotericin B remains the most common agent used for treatment, irrespectively of the infection site. CONCLUSIONS: This systematic review thoroughly describes fungal infections by Rhodotorula species and provides information on their epidemiology, clinical picture, microbiology, treatment and outcomes.