Adenosine receptors in breast cancer.

Adenosine receptors are important in the normal physiological function of cells and the pathogenesis of various cancer cells, including breast cancer cells. The activity of adenosine receptors in cancer cells is related to cell proliferation, angiogenesis, metastasis, immune system evasion, and interference with apoptosis. Considering the different roles of adenosine receptors in cancer cells, we intend to investigate the function of adenosine receptors and their biological pathways in breast cancer to improve understanding of therapeutically relevant signaling pathways.

Hs-CRP and TNF-α Effects on Postnatal Umbilical Coiling: Impact Assessment of the Gestational Diabetes Mellitus.

Background: No study has been conducted to specifically demonstrate the relationship between gestational diabetes mellitus (GDM) status, inflammatory factors, and postnatal umbilical coiling index (pUCI). Understanding this relationship could help select the best interventions to save the fetus. To evaluate the effects of maternal venous and umbilical cord blood levels of high sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-alpha (TNF-alpha) on pUCI in GDM and non-GDM groups. Methods: This prospective observational study included 40 participants in each of the GDM and non-GDM groups, matched for maternal age, ethnicity, and parity. The GDM diagnosis was confirmed by 24 to 28 weeks of gestation (WOG) and a 2-step strategy. The covariates of interest were maternal hs-CRP and TNF-α, measured at 37 to 40 WOG, and their UC analogous was measured during delivery. The gross morphologies were assessed immediately after delivery. The UC coiling was quantitatively assessed by the pUCI. To compare the GDM and non-GDM groups, the t test and the Mann-Whitney test were used for normal and non-normal variables, respectively. Results: There was not a significant difference in hs-CRP and TNF-a levels in maternal venous blood or UC blood between the GDM and non-GDM groups. The mean (SD) of pUCI in the GDM and non-GDM groups were 0.28 (0.15) and 0.24 (0.21) (P = 0.441), respectively. In the GDM group, none of the 4 covariates of interest had significant effects on the UCI. Among the non-GDM participants, merely the UC hs-CRP had a direct association with the pUCI, with a Pearson correlation of 0.54 (P = 0.001). Impacts of hs-CRP and TNF-α on the pUCI were assessed using Poisson regression models and no significant findings were detected (95% CI, 0.999-1.001, for all parameters). Conclusion: In the GDM group, no apparent association was observed between inflammatory factors and pUCI, although a direct association was detected between UC hs-CRP and pUCI in the non-GDM.

Evaluation of the expression of necroptosis pathway mediators and its association with tumor characteristics in functional and non-functional pituitary adenomas.

BACKGROUND: Pituitary adenomas impose a burden of morbidity on patients and characterizing the molecular mechanisms underlying its pathogenesis received remarkable attention. Despite the appealing role of necroptosis as an alternative cell death pathway in cancer pathogenesis, its relevance to pituitary adenoma pathogenesis has yet to be determined that is perused in the current study. METHODS: The total number of 109 specimens including pituitary adenomas and cadaveric healthy pituitary tissues were enrolled in the current study. Tumor and healthy pituitary tissues were subjected to RNA extraction and gene analysis using Real-Time PCR. The expression levels of necroptosis markers (RIP1K, RIP3K and, MLKL) and their association with the patient's demographic features were evaluated, also the protein level of MLKL was assessed using immunohistochemistry in tissues. RESULTS: Based on our data, the remarkable reduction in RIP3K and MLKL expression were detected in nonfunctional and GH-secreting pituitary tumors compared to pituitary normal tissues. Invasive tumors revealed lower expression of RIP3K and MLKL compared to non-invasive tumors, also the attenuated level of MLKL was associated with the tumor size in invasive NFPA. The simultaneous down-regulation of MLKL protein in pituitary adenoma tissues was observed which was in line with its gene expression. While, RIP1K over-expressed significantly in both types of pituitary tumors which showed no significant correlation with patient's age, gender and tumor size in GHPPA and NFPA group. Notably, MLKL and RIP3K gene expression was significantly correlated in the GHPPA group. CONCLUSIONS: According to our data, the reduced expression of necroptosis mediators (RIP3K, MLKL) in pituitary adenoma reinforces the hypothesis that the necroptosis pathway can be effective in regulating the proliferation and growth of pituitary tumor cells and tumor recurrence.

Clinical features, risk factors and a prediction model for in-hospital mortality among diabetic patients infected with COVID-19: data from a referral centre in Iran.

OBJECTIVES: The aim of this study was to identify risk factors of in-hospital mortality among diabetic patients infected with COVID-19. STUDY DESIGN: This is a retrospective cohort study. METHODS: Using logistic regression analysis, the independent association of potential prognostic factors and COVID-19 in-hospital mortality was investigated in three models. Model 1 included demographic data and patient history; model 2 consisted of model 1, plus vital signs and pulse oximetry measurements at hospital admission; and model 3 included model 2, plus laboratory test results at hospital admission. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were reported for each predictor in the different models. Moreover, to examine the discriminatory powers of the models, a corrected area under the receiver-operating characteristic curve (AUC) was calculated. RESULTS: Among 560 patients with diabetes (men = 291) who were hospitalised for COVID-19, the mean age of the study population was 61.8 (standard deviation [SD] 13.4) years. During a median length of hospitalisation of 6 days, 165 deaths (men = 93) were recorded. In model 1, age and a history of cognitive impairment were associated with higher mortality; however, taking statins, oral antidiabetic drugs and beta-blockers was associated with a lower risk of mortality (AUC = 0.76). In model 2, adding the data for respiratory rate (OR 1.07 [95% CI 1.00-1.14]) and oxygen saturation (OR 0.95 [95% CI 0.92-0.98]) slightly increased the AUC to 0.80. In model 3, the data for platelet count (OR 0.99 [95% CI 0.99-1.00]), lactate dehydrogenase (OR 1.002 [95% CI 1.001-1.003]), potassium (OR 2.02 [95% CI 1.33-3.08]) and fasting plasma glucose (OR 1.04 [95% CI 1.02-1.07]) significantly improved the discriminatory power of the model to AUC 0.86 (95% CI 0.83-0.90). CONCLUSIONS: Among patients with type 2 diabetes, a combination of past medical and drug history and pulse oximetry data, with four non-expensive laboratory measures, was significantly associated with in-hospital COVID-19 mortality.

Cyclooxygenase enzyme and PGE2 expression in patients with functional and non-functional pituitary adenomas.

BACKGROUND: Pituitary adenomas as multifactorial intracranial neoplasms impose a massive burden of morbidity on patients and characterizing the molecular mechanism underlying their pathogenesis has received considerable attention. Despite the appealing role of cyclooxygenase enzymes and their bioactive lipid products in cancer pathogenesis, their relevance to pituitary adenoma pathogenesis is debated and yet to be determined. Thus, the current study perused this relevance. METHODS: The expression level of the isoforms of cyclooxygenase (COX-1 and COX-2) was evaluated in hormone-secreting and in-active pituitary adenoma tumors and normal pituitary tissues through Real-Time PCR. The level of PGE2, as the main product of enzymes, was assessed using enzyme immunoassay kits in patients and healthy subjects. RESULTS: The results of the current study demonstrated that COX-1 and COX-2 expression levels were increased in pituitary tumors including non-functional pituitary adenoma (NFPA), acromegaly, Cushing's disease and prolactinoma compared with normal pituitary tissues. A significant expression level of COX-2 was observed in NFPA compared with the other pituitary tumors. Furthermore, the COX-2 expression level was significantly increased in macroadenoma and invasive tumors. The level of PGE2 was consistent with COX enzymes enhanced in pituitary adenoma tumors compared with healthy pituitary tissue. A significant elevation in the PGE2 level was detected in NFPA compared with hormone-secreting pituitary tumors. Additionally, the PGE2 level was increased in macroadenoma compared with microadenoma and in invasive compared with non-invasive pituitary tumors. The diagnostic values of cyclooxygenase isoforms and PGE2 were considerable between patients and healthy groups; however, COX-2 revealed more value in distinguishing endocrinologically active and non-active pituitary tumors. CONCLUSIONS: Data from the current study provides expression patterns of COX-1, COX-2 and PGE2 in prevalent pituitary tumors and their association with patients' clinical features which may open up new molecular targets for early diagnosis/follow up of pituitary tumor growth.

Does intramuscular ondansetron have an effect on intramuscular ketamine-associated vomiting in children? A prospective, randomized, double blind, controlled study.

OBJECTIVE: This study was conducted to determine the effect of intramuscular ondansetron on ketamine-associated vomiting in children undergoing procedural sedation. METHODS: This randomized, double-blind, placebo-controlled, parallel-group clinical trial was conducted at the emergency departments of two university-affiliated tertiary care hospitals. Eligible participants included all 6-month to 16-year-old children who received IM ketamine for PSA in the ED. A convenience sampling approach was used and a block randomization method was applied (blocks of four) using a computer-generated random sequence. Patients received ketamine 4 mg/kg or ketamine 4 mg/kg plus ondansetron 0.1 mg/kg intramuscularly. All findings including the occurrence of vomiting and its frequency were then recorded in the data collection sheets. RESULTS: Of 56 patients who received ondansetron plus ketamin, 7 (12.5%) and 1 (1.8%) experienced vomiting during recovery and before discharge and Of 65 patients in the control group, 14 (21.5%) and 6 (9.2%) experienced vomiting during recovery and before discharge, respectively. The observed differences in the rates of vomiting during recovery and at discharge were statistically significant between the two groups (P-value of 0.03 and <0.001, respectively). CONCLUSION: Intramuscular ondansetron is effective in controlling ketamine-associated vomiting.

Usefulness of prolactin measurement in inferior petrosal sinus sampling with desmopressin for Cushing's syndrome.

Background: Bilateral inferior petrosal sinus sampling (IPSS) is used to distinguish pituitary from ectopic adrenocorticotropin (ACTH) excess in patients with ACTH-dependent Cushing's syndrome. Our objective was to examine the utility of prolactin measurement during IPSS with desmopressin (DDAVP) stimulation in localization of the source of ACTH excess.Method: Retrospective review of 20 patients with ACTH-dependent Cushing's syndrome who underwent IPSS with DDAVP stimulation. Baseline, DDAVP-stimulated, and prolactin-normalized ACTH IPS:P (inferior petrosal sinus to peripheral) ratios were calculated. Cut-off values for each test were obtained from receiver-operating characteristic (ROC) curve analysis.Results: Fifteen patients had Cushing disease (CD), and five were diagnosed with ectopic ACTH syndrome (EAS). For the baseline ACTH IPS:P ratio of ≥2, the diagnostic sensitivity (80%), specificity (100%), positive predictive value (PPV) (100%) and negative predictive value (NPV) (62.5%) were calculated. These values for DDAVP-stimulated IPS:P ACTH ratio ≥ 3, were 86.7%, 100%, 100% and 71.4%, respectively. The corresponding value for the prolactin-normalized ACTH IPS:P ratio ≥ 0.8 were 86.6%, 80%, 92.8% and 66.7%. The cut-off value for the baseline, DDAVP-stimulated and prolactin-normalized ACTH IPS:P ratios were 1.76, 3.9, and 0.33, respectively.Conclusion: Prolactin-normalized ACTH IPS:P ratio measurement showed comparable sensitivity and less specificity than baseline/DDAVP-stimulated IPS/P ACTH ratios. Moreover, when baseline and stimulated IPS/P ACTH tests were discordant, prolactin-normalized ACTH IPS: P ratio correctly localized the source of ACTH excess. The sensitivity of the test increased, applying a prolactin-normalized ACTH IPS: P ratio ≥0.33.

Up-regulation of 15-lipoxygenase enzymes and products in functional and non-functional pituitary adenomas.

BACKGROUND: Pituitary adenoma accounts as a complex and multifactorial intracranial neoplasm with wide range of clinical symptoms which its underlying molecular mechanism has yet to be determined. The bioactive lipid mediators received attentions toward their contribution in cancer cell proliferation, progression and death. Amongst, 15-Lipoxygense (15-Lox) enzymes and products display appealing role in cancer pathogenesis which their possible effect in pituitary adenoma tumor genesis is perused in the current study. METHODS: The 15-Lipoxygenses isoforms expression level was evaluated in tumor tissues of prevalent functional and non-functional pituitary adenomas and normal pituitary tissues via Real-Time PCR. The circulating levels of 15(S) HETE and 13(S) HODE as 15-Lox main products were assessed in serum of patients and healthy subjects using enzyme immunoassay kits. RESULTS: Our results revealed that 15-Lox-1 and 15-Lox-2 expression levels were elevated in tumor tissues of pituitary adenomas comparing to normal pituitary tissues. The elevated levels of both isoforms were accompanied with 15(S) HETE and 13(S) HODE elevation in the serum of patients. The 15-Lox-1 expression and activity was higher in invasive tumors as well as tumors with bigger size indicating the possible pro-tumorigenic role of 15-Lox-1, more than 15-Lox-2 in pituitary adenomas. The diagnostic value of 15-Lipoxygense isoforms and products were considerable between patients and healthy groups. CONCLUSION: The possible involvement of 15-Lipoxygense pathway especially 15-Lox-1 in the regulation of pituitary tumor growth and progression may open up new molecular mechanism regarding pituitary adenoma pathogenesis and might shed light on its new therapeutic strategies.

COMPARISON OF CABERGOLINE VERSUS RALOXIFENE ADD-ON THERAPY TO LONG-ACTING SOMATOSTATIN ANALOGUE IN PATIENTS WITH INADEQUATELY CONTROLLED ACROMEGALY: A RANDOMIZED OPEN LABEL CLINICAL TRIAL.

OBJECTIVE: The present study aimed to evaluate the efficacy of add-on therapy of cabergoline versus raloxifene to long-acting somatostatin analogues (SAs) in patients with inadequately controlled acromegaly. METHODS: This was a prospective, randomized open label clinical trial. Forty-four patients (22 per group) completed the study; where participants received either cabergoline (3 mg/week) or raloxifene (60 mg twice daily) add-on therapy for 12 weeks in a parallel manner. The primary outcome was the rate of reduction in serum insulin-like growth factor 1 (IGF-1) from baseline. Secondary outcomes comprised normalization of serum IGF-1 for age and sex. RESULTS: Serum IGF-1 was significantly decreased in both the cabergoline (40.3 ± 25.6%, P<.001) and raloxifene (31.5 ± 24.6%, P<.001) groups, with no significant difference between arms ( P>.05). Normalization in serum IGF-1 values occurred in 40.9% of patients who were on cabergoline compared to 45.5% of those receiving raloxifene ( P = .76). The subsequent logistic regression analysis highlighted baseline IGF-1 as a significant predictor of IGF-1 normalization (odds ratio, 0.995; 95% confidence interval, 0.990-0.999; P = .02). Using the receiver operating characteristic (ROC) curve analysis for the entire group, the baseline IGF-1 value of 1.47 the upper limit of normal (ULN) was the best cut-off point to identify patients with normal IGF-1 at the end of the study (sensitivity: 52.6%, specificity: 84.0%, Yoden's index: 0.366). Full biochemical control of acromegaly was achieved in 22.7% of patients in the cabergoline group compared to 13.6% of those in the raloxifene group ( P = .43). CONCLUSION: Cabergoline and raloxifene add-on therapy could effectively decrease serum IGF-1 level in patients with inadequately controlled acromegaly. The efficacy profiles of both drugs are comparable. ABBREVIATIONS: DA = dopamine agonist; FBG = fasting blood glucose; GH = growth hormone; IGF1 = insulin-like growth factor-1; IQR = interquartile range; OR = odds ratio; ROC = receiver operating characteristic; SA = somatostatin analogue; SERM = selective estrogen modulator receptor; ULN = upper limit of normal.

Clinical outcomes of endoscopic versus microscopic trans-sphenoidal surgery for large pituitary adenoma.

OBJECTIVE: To compare clinical outcomes of large pituitary adenomas (≥3 cm in maximum diameter), operated on by Endoscopic Transsphenoidal Surgery (ETS), versus Microscopic Transsphenoidal Surgery (MTS). METHODS: Medical records and MRI Scans of patients with a diagnosis of pituitary adenoma for whom transphenoidal surgery was done were reviewed. Complete pre and post-operative data were available for 121 patients. Thirty five patients had large pituitary adenoma and were enrolled in this study. ETS was done in 16 patients, and 19 underwent MTS. All patients were followed for at least six months. Clinical and imaging characteristics were reported in details. Post-operative clinical outcomes were defined as clinical outcomes persisted 6 months after surgery. RESULTS: The average tumor size was 36.3 ± 4.4 mm in ETS group, and 34.0 ± 4.6 mm in MTS group, (p = .46). Six months after surgery, tumor size was 4.6 ± 6.6 mm in ETS and 17.7 ± 12.2 mm in MTS group, (p = .002). Gross total resection (GTR) was observed in the 81.2% of the patient in the ETS group. In the MTS group, GTR was observed in 15.8%. Post-operative clinical outcomes including new onset hypopituitarism, visual impairment, and permanent diabetes insipidus (DI) were comparable between the two groups. CONCLUSION: ETS is superior to MTS in treatment of large pituitary adenomas with comparable post-operative complications.

Metabolic effects of dopamine-agonists treatment among patients with prolactinomas.

PURPOSE: To evaluate the effect of cabergoline treatment on metabolic parameters including the Triglyceride-glucose (TyG) index in newly diagnosed patients with prolactinoma. METHODS: 71 consecutive nondiabetic patients with prolactinoma were enrolled. Anthropometric and laboratory tests including TyG index were measured at baseline, 3 and 6 months visits. Treatment with cabergoline at the dose of 0.25 mg twice weekly was started and increased according to prolactin levels and continued for 6 months. RESULTS: At the baseline examination, the mean (SD) age, body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), and diastolic blood pressure (DBP) of patients were 36.2 (10.5) years, 29.2 (5.0) kg/m2, 98.2 (13.7) cm, 115.3 (13.3) mmHg, and 71.4 (8.1) mmHg, respectively. Forty-one (57.7%) of patients were women and 46 (64.8%) had microadenoma. Cabergoline treatment significantly improved anthropometric and metabolic measures including BMI, WC, fasting plasma glucose, triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, uric acid (only among women), TyG index, and hypogonadism. Blood pressure (both systolic and diastolic) levels remained steady except for a significant decrease in DBP after 6 months of treatment only among women. A declining trend in MetS prevalence was found from baseline to a 3-month evaluation in both genders which was statistically significant among men. CONCLUSION: Short-term treatment with cabergoline can significantly improve cardiovascular risk factors except for blood pressure. Moreover, the TyG index as a surrogate marker of insulin resistance decreased significantly after the reduction of prolactin by treatment. Generally, results were similar among both genders.

Evaluation of dry solid waste recycling from municipal solid waste: case of Mashhad city, Iran.

The recycling for recovery and reuse of material and energy resources undoubtedly provides a substantial alternative supply of raw materials and reduces the dependence on virgin feedstock. The main objective of this study was to assess the potential of dry municipal solid waste recycling in Mashhad city, Iran. Several questionnaires were prepared and distributed among various branches of the municipality, related organizations and people. The total amount of solid waste generated in Mashhad in 2008 was 594, 800 tons with per capita solid waste generation rate of 0.609 kg person(-1) day(-1). Environmental educational programmes via mass media and direct education of civilians were implemented to publicize the advantages and necessity of recycling. The amount of recycled dry solid waste was increased from 2.42% of total dry solid waste (2588.36 ton year(-1)) in 1999 to 7.22% (10, 165 ton year(-1)) in 2008. The most important fractions of recycled dry solid waste in Mashhad included paper and board (51.33%), stale bread (14.59%), glass (9.73%), ferrous metals (9.73%), plastic (9.73%), polyethylene terephthalate (2.62%) and non-ferrous metals (0.97%). It can be concluded that unfortunately the potential of dry solid waste recycling in Mashhad has not been considered properly and there is a great effort to be made in order to achieve the desired conditions of recycling.

Sequencing treatment of landfill leachate using ammonia stripping, Fenton oxidation and biological treatment.

Landfill leachates contain a wide variety of pollutants such as organic matter, refractory compounds, ammonia, particulate and dissolved solids and hazardous metals requiring application of advanced and well designed treatment processes before release to the environment. The main purpose of this research was to evaluate the efficiency of combined air stripping, Fenton oxidation and biological treatment in treating landfill leachate, especially the elimination of ammonia and refractory organics. The laboratory scale set-up consisted of three sequential but separate steps. The optimum conditions for air stripping and the Fenton oxidation were determined for landfill leachate from Karaj city, Iran. The final step was a moving bed bioreactor with HRTs of 18, 12 and 6 h. The highest NH(3)-N removal was 79% in the air stripping process at pH 10.5. At the optimum conditions for the Fenton reaction at a reaction time of 90 min, pH 3 and a H(2)O(2)/Fe(2+) mass ratio of 20, the COD removal was 61% and improved the BOD/COD ratio from 0.42 to 0.78. The overall COD removal including the final biological reactor with a HRT of 6 h resulted in an effluent COD concentration of less than 100 mg L(-1).

The return visit, outcome and predicting factors of return visit among suspected COVID-19 outpatients.

Rate of return visit, predicting factors of return visit and occurrence of adverse events in suspected to be or likely cases of COVID-19 patients who received outpatient treatment. This is a retrospective observational cohort study on patients (> 16 years), suspected to be or likely cases of COVID-19 who were visited in a respiratory emergency department and subsequently discharged home. Patients' baseline characteristics were extracted from medical charts. All patients were followed-up for 7 days after their first visit. Patients' outcomes during the7-day follow-up, as well as the severity of pulmonary involvement based on imaging were recorded. A total number of 601 patients (350 men and 251 women) were recruited. The rate of return visit was 27.74% (144 patients) with 6.74% (34 patients) experiencing a poor outcome. Six factors with a significant odds ratio were predictors of poor outcome in patients who received outpatient treatment, namely, older age [odds ratio = 3.278, 95% confidence interval: 1.115-9.632], days from onset of symptoms [1.068, 1.003-1.137], and history of diabetes [6.373, 2.271-17.883]). Predictors of favorable outcome were female gender [0.376, 0.158-0.894], oxygen saturation > 93% [0.862, 0.733-1.014], smoking habit [0.204, 0.045-0.934]. The findings of this study demonstrate that the rate of return visit with poor outcome in patients who received outpatient treatment was reasonably low. Age, male sex, diabetes mellitus and pulmonary disease are predicting factors of poor outcome in these COVID-19 patients who received outpatient management.

Mycobacterium avium subsp. paratuberculosis and Hashimoto's thyroiditis: Is MAP the trigger?

Hashimoto's thyroiditis (HT) is an autoimmune disorder of the thyroid gland that can cause hypothyroidism. As HT is a multifactorial disorder, activation of immune responses in genetically predisposed individuals exposed to some environmental factors can contribute to it. Microorganisms, as environmental factors, including Mycobacterium avium ssp. paratuberculosis (MAP) by molecular mimicry, can be important in this autoimmune disorder. This study aimed to investigate the association between MAP and HT. This case-control study included 110 participants consisting of 60 HT patients and 50 healthy controls (HCs). Blood samples were collected. Nested PCR of the IS900 gene determined the presence of MAP DNA. The enzyme-linked immunosorbent assay (ELISA) was designed to identify antibodies (Abs) against the MAP3865c epitope, which has a homologous sequence with ZnT8 in the sera. The demographic information of all participants was recorded. Anti-TG, anti-TPO, TSH, anemia, and ruminant exposure were higer in HT patients than in the HCs (p < 0.05). MAP IS900 was detected significantly more in the patients (46.6% consisting of 30, 8.3, and 8.3% in clinical, subclinical, and unknown) than in the HCs (14%). The sera showed a remarkable frequency of reactivity against MAP3865c in the patients (38.3%) in comparison to the HCs (10%) (p = 0.0001). Furthermore, a significantly higher rate of livestock contact and traditional dairy consumption was found in individuals with MAP or anti-MAP3865c Abs positive result (p < 0.05). This study suggests a possible link between MAP and HT. These findings indicated that MAP frequency was not statistically different in the severity of HT and its shift into the clinical and subclinical forms; therefore, it could be assumed that MAPs are the initiators of the process. The results imply on a possible zoonosis transmission route of MAP from livestock products to humans. Further research is needed to confirm these results in larger groups of HT patients.

A Novel ARMC5 Germline Variant in Primary Macronodular Adrenal Hyperplasia Using Whole-Exome Sequencing.

Background: Primary macronodular adrenocortical hyperplasia (PMAH) is a rare form of adrenal Cushing's syndrome with incomplete penetrance which may be sporadic or autosomal dominant. The inactivation of the ARMC5 gene, a potential tumor suppressor gene, is one of the associated causes of PMAH. This study aimed to identify the variant responsible for Iranian familial PMAH. Methods: The proband, a 44-year-old woman, was directed to whole-exome sequencing (WES) of the blood sample to discover a germline variant. In addition, the identified causative variant was confirmed and segregated in other and available unaffected family members. Results: The novel germline heterozygous missense variant, c.2105C>A in the ARMC5 gene, was found, and the same germline variant as the proband was confirmed in two affected sisters. This variant was detected in the brother of the proband with an asymptomatic condition and this considered because of incomplete penetrance and age-dependent appearance. The function of the ARMC5 protein would be damaged by the identified variant, according to in silico and computer analyses that followed. Conclusion: The new germline ARMC5 variation (c.2105C>A, (p. Ala702Glu)) was interpreted as a likely pathogenic variant based on ACMG and Sherloc standards. PMAH may be diagnosed early using genetic testing that shows inherited autosomal dominant mutations in the ARMC5 gene.

Cell proliferation, apoptosis, and angiogenesis in non-functional pituitary adenoma: association with tumor invasiveness.

PURPOSE: Non-functioning pituitary adenoma (NFPA) is the most prevalent pituitary macroadenoma. No prognostic marker has been found to explain the behavior of these tumors. We aimed to explore cell proliferation, apoptosis, proangiogenic markers, and microvascular density (MVD) in noninvasive and invasive NFPAs. METHODS: Adenoma invasiveness was defined according to Knosp and Hardy classifications based on preoperative magnetic resonance imaging scans. Cell proliferation was examined using Ki67 and P53. Tissue expression of Bcl-2 was used to assess the antiapoptosis pathway. CD34 and CD105 were measured to evaluate MVD, while VEGF expression was assessed as an indicator of pro-angiogenesis. Moreover, VEGF, bFGF, endocan, and endostatin were measured on preoperative serum samples. RESULTS: Tissue and serum markers were examined in 18 patients with invasive and 21 patients with noninvasive NFPAs. Ki67 less than 3% was reported in 10 invasive and 14 noninvasive NFPAs (P = 0.752). P53 staining was negative in all subjects. In addition, Bcl-2 staining was negative in 15 and 20 subjects, respectively (P = 0.718). VEGF-A expression 2+ or 3+ was reported in 9 invasive and 11 noninvasive macroadenomas (P = 0.83). Moreover, CD34 and CD105 positivity were comparable between the two groups. Furthermore, the comparison of serum markers showed no significant differences. CONCLUSION: Cell proliferation, apoptosis, and angiogenesis play a limited role in NFPA behavior.

Lateralization of inferior petrosal sinus sampling in Cushing's disease correlates with cavernous sinus venous drainage patterns, but not tumor lateralization.

BACKGROUND: Inferior petrosal sinus sampling (IPSS) is known as the gold standard to distinguish whether excessive adrenocorticotropin hormone (ACTH) production origins from the pituitary gland or an ectopic source. However, due to a number of factors, the value of IPSS for adenoma lateralization may be limited. Aim of this study was to evaluate the influence of parasellar venous drainage (VD) patterns on IPSS findings in predicting lateralization of pituitary microadenomas. METHODS: We retrospectively reviewed records of confirmed cases of Cushing's disease which were evaluated by IPSS prior to endoscopic tansnasal trans-sphenoidal surgery (ETSS) to assess the ability of IPSS to predict adenoma laterality. RESULTS: Seventeen patients with pathologically confirmed Cushing's disease were retrospectively reviewed. The median age of the included patients was 37 years. Laterality of parasellar VD perfectly associated with lateralization as measured by IPSS. Symmetrical VD was associated with symmetrical ACTH gradient on IPSS. However, lateralization measured by IPSS did not show any significant correlation with lateralization detected during ETSS. CONCLUSION: Our study suggests that IPSS lateralization results strongly depend on parasellar VD pattern but show no significant correlation with the adenoma lateralization found during ETSS. Thus, IPSS does not appear to be an appropriate modality to predict adenoma lateralization.

Post-traumatic stress disorder or emergence phenomena? A case of psychomotor agitation after procedural sedation and analgesia.

Background Psychomotor agitation can be problematic in an overcrowded emergency department (ED) during uncontrolled procedural sedation. Although emergence phenomena have been studied, various presentations may exist. Case presentation During procedural sedation, a 58-year-old man was sedated with a dissociative dose of ketamine in conjunction with propofol. His shoulder dislocation was reduced successfully but eventually, an exaggerated agitation occurred resembling a post-traumatic stress disorder (PTSD) flashback of past war scenes He was controlled by physical and chemical restraint with an intramuscular injection of 0.1 mg/kg midazolam. After resolution of sedation in rather stable psychiatric conditions, he left the ED with his relatives insisting for discharge against medical advice. Conclusions A PTSD flashback may occur from ketamine sedation in patients with a past history of military experience and can be a manifestation of psychologic adverse effects of ketamine.

Non-functioning pituitary macroadenoma: surgical outcomes, tumor regrowth, and alterations in pituitary function-3-year experience from the Iranian Pituitary Tumor Registry.

PURPOSE: The aim of this study was to assess clinical features and therapeutic outcomes in patients with clinically non-functioning pituitary macroadenomas (NFPMAs). METHOD: This is a retrospective cohort study of NFPMA patients treated surgically and followed periodically between 2015 and 2017 in a tertiary care center in Iran. Descriptive analysis was performed applying appropriate tests. Binary logistic regression models were used to determine the predictive factors for subtotal tumor resection (STR) and hormonal recovery. Data were analyzed by Stata software. RESULT: A total of 71 patients with a mean age of 50.6 ± 1.4 years were studied. The mean diameter of the adenoma was 26.8 ± 1.1 mm. The most frequent symptoms were headache (85.75%), visual field defect (VFD) (78.3%), and hypogonadal symptoms (40.3%). Gross total resection (GTR) was achieved in 45.1%. Preoperative hypopituitarism was observed in 50.7% of patients. Recovery of at least one axis occurred in 36.1% of the patients suffering from hypopituitarism preoperatively, while new-onset postoperative hormonal deficiency appeared in 14.3% of patients. Multivariate analyses showing preoperative tumor size (OR = 38.2; P = 0.008) and cavernous sinus extension (OR = 13.4; P = 0.020) were predictors of STR. Moreover, hormonal recovery was observed not to be related to age, gender, tumor size, or the extent of tumor resection. CONCLUSIONS: Tumor size and cavernous sinus extension are the main predictors for STR. Notably, recovery of the gonadal axis in a large proportion of patients supports the surgical resection of NFPAM in patients suffering from gonadal deficiency, even in the absence of VFD.