A high fat diet induces sex-specific differences in hepatic lipid metabolism and nitrite/nitrate in rats

This work is supported by the grants No.173033 and III41028 from the Ministry of Science, Republic of Serbia.Men and women differ substantially in regard to the severity of insulin resistance (IR) but the underlying mechanism(s) of how this occurs is poorly characterized. We investigated whether a high fat (HF) diet resulted in sex-specific differences in nitrite/nitrate production and lipid metabolism and whether these variances may contribute to altered obesity-induced IR. Male and female Wistar rats were fed a standard laboratory diet or a HF diet for 10 weeks. The level of plasma nitrite/nitrate, as well as free fatty acid (FFA), in both plasma and liver lysates were assessed. The levels of inducible nitric oxide (NO) synthase (iNOS), p65 subunit of NFκB, total and phosphorylated forms of Akt, mTOR and PDK-1 in lysates, and the levels of glucose transporter 2 (Glut-2) and fatty acid translocase/cluster of differentiation 36 (FAT/CD36) in plasma membrane fractions of liver were assessed. HF-fed male rats exhibited a significant increase in plasma nitrite/nitrate, and hepatic FFA and FAT/CD36 levels compared with controls. They also displayed a relative decrease in iNOS and Glut-2 levels in the liver. Phosphorylation of Akt (at Ser473 and Thr308), mTOR and PDK-1 was also reduced. HF-fed female rats exhibited increased levels of NFκB-p65 in liver compared with controls, while levels of Glut-2, FAT/CD36 and Akt phosphorylation at Thr308 and PDK-1 were decreased. Our results reveal that altered lipid and glucose metabolism in obesity, lead to altered iNOS expression and nitrite/nitrate production. It is likely that this mechanism contributes to sex-specific differences in the development of IR.PostprintPeer reviewe

Puncture site bleeding complications in patients with Clopidogrel hyper-response: Three case reports

Dual antiplatelet therapy (clopidogrel and acetylsalicylic acid) is a standard for the embolization of planned intracranial aneurysms with CNS stent due to the possibility of stent thrombus formation. All anti-aggregation drugs, including those listed, have bleeding as a side effect. Three patients with aneurysm had an elevated response to antiplatelet therapy with clopidogrel, which was confirmed by a multiplate test on the "VerifyNow" system. After reducing the dose of clopidogrel or after interrupting it, with the introduction of low molecular weight heparin for the duration of five days, aneurysms were successfully resolved by intracranial implantation of the stent. Perioperative angiograms and postoperative CT angiograms have verified hematomas at the place of punction of the femoral artery. Bleeding was resolved by the femoral artery suture by a vascular surgeon. All patients were discharged home without further complications and with dual antiplatelet therapy. By measuring the platelet function in vitro, the degree of inhibition of platelet activity achieved by the action of the drug can be assessed. A specific test can identify those patients who are highly responsive to the drug with increased platelet reactivity and the possibility of increased risk of bleeding. Our suggestion is to reduce the dosage of clopidogrel or to leave it out for 24 hours with preventive doses of low molecular weight heparin or to change the strategy of treatment of intracranial aneurysm, i.e. avoiding implantation of CNS stent

Exploring unmet needs and preferences of young adult stroke patients for post-stroke care through PROMs and gender differences

BackgroundStroke incidence among young adults of working age (under 65 years of age) has significantly increased in the past decade, with major individual, social, and economic implications. There is a paucity of research exploring the needs of this patient population. This study assessed: (1) young adult stroke patients' physical, psychological, and occupational functioning and health-related quality of life (HRQoL); and (2) post-stroke care preferences using patient-reported outcome measures (PROMs), with attention to gender differences.MethodsA cross-sectional pilot study was conducted. Sociodemographic and clinical characteristics were collected through chart review and data on occupational function, physical, psychological, and social wellbeing >90 days post-stroke through a self-reported survey. Descriptive statistics, gender-based, and regression analyses were conducted.ResultsThe sample included 85 participants. Participants reported impairments in both, occupational functioning, with 58.7% not returned to work (RTW), and HRQoL, specifically with social activities (37%), anxiety (34%), and cognitive function (34%). Women had significantly (p < 0.05) worse physical symptoms (sleep disturbance and fatigue), emotional health (depression, stigma, emotional dyscontrol) scores, and sense of self-identify post-stroke. Over 70% of participants preferred in-person post-stroke care led by health care providers and felt they would have benefited from receiving information on physical health (71.4%), emotional and psychological health (56.0%), RTW (38.1%), and self-identity (26.2%) post-stroke. Women preferred cognitive behavioral therapy (p = 0.018) and mindfulness-based stress reduction therapy (p = 0.016), while men preferred pharmacotherapy (p = 0.02) for psychological symptoms.ConclusionThis is the first study to report impaired HRQoL, psychological and occupational functioning using PROMs, with significant gender differences and preferences for post-stroke care delivery among young adult stroke patients at >90 days after stroke. The findings highlight the importance of needs, gender, and age-specific post-stroke education and interventions

Spontaneous cerebrospinal fluid rhinorrhea in a patient with Pallister–Hall syndrome

Pallister-Hall syndrome (PHS) is extremely rare autosomal dominant disorder with typical clinical features such as presence of polydactyly, hypothalamic hamartoma, bifid epiglottis, anal, renal, genitourinary and pulmonary abnormalities, mainly located in the midline of the body. Spontaneous cerebrospinal fluid (CSF) rhinorrhea is also a rare condition, and it is used to describe nasal discharge of CSF unrelated to previous trauma, localized tumour, surgery, or previous radiation therapy. The exact cause is not yet fully understood. We report a case of adult female patient previously diagnosed with PHS and late onset of spontaneous nasal liquorrhea, due to defect in the anterior skull base. Although it can be incidental finding, we believe that described defect in the body midline can be another presentation of congenital craniofacial abnormality which are common in PHS

17ß-Estradiol protects against the effects of a high fat diet on cardiac glucose, lipid and nitric oxide metabolism in rats

This work is supported by the grant No.173033 (to E.R.I.) from the Ministry of Education, Science and Technological Development, Republic of Serbia.The aim of this study was to investigate the in vivo effects of estradiol (E2) on myocardial metabolism and inducible nitric oxide synthase (iNOS) expression/activity in obese rats. Male Wistar rats were fed with a normal or a high fat (HF) diet (42% fat) for 10 weeks. Half of the HF fed rats were treated with a single dose of E2 while the other half were placebo-treated. 24h after treatment animals were sacrificed. E2 reduced cardiac free fatty acid (FFA) (p<0.05), L-arginine (p<0.01), iNOS mRNA (p<0.01), and protein (p<0.05) levels and translocation of the FFA transporter (CD36) (p<0.01) to the plasma membrane (PM) in HF fed rats. In contrast, Akt phosphorylation at Thr308 (p<0.05) and translocation of the glucose transporter GLUT4 (p<0.05) to the PM increased after E2 tretment in HF rats. Our results indicate that E2 acts via PI3K/Akt signaling pathway to partially protect myocardial metabolism by attenuating the detrimental effects of increased iNOS expression/activity in HF fed rats.PostprintPeer reviewe

Influence of a high-fat diet on cardiac iNOS in female rats

Overexpression of inducible nitric oxide synthase (iNOS) is a key link between high-fat (HF) diet induced obesity and cardiovascular (CV) disease. Several studies have reported that oestradiol has cardioprotective effects that may be mediated through reduction of iNOS activity/expression. In the present study, female Wistar rats were fed a standard diet or a HF diet (balanced diet for laboratory rats enriched with 42% fat) for 10 weeks. Gene and protein expression of iNOS were measured in heart tissue. HF diet-fed rats exhibited a significant increase in cardiac iNOS mRNA by 695% (p<0.05), iNOS protein level by 248% (p<0.01), without changes in nitrate/nitrite levels. Expression of CD36 protein in plasma membranes was increased by 37% (p<0.05), while the concentration of free fatty acids (FFA) was reduced by 25% (p<0.01) in HF diet-fed rats. Expression of the p50 subunit of nuclear factor-κB (NFκB-p50) in heart lysate was increased by 77% (p<0.01) in HF diet-fed rats. Expression and phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinases 1/2 (ERK1/2) in control and HF diet-fed rats were also examined. Expression of Akt and ERK1/2 were unchanged between the groups. There was a significant increase in the ratio of phospho-Akt/total Akt but not for phospho-ERK1/2/total ERK1/2/ in HF-fed rats. Estrogen receptor-α levels (by 50%; p<0.05) and serum oestradiol concentrations (by 35%; p<0.05) were examined and shown to be significantly reduced in HF diet-fed rats. Our results revealed that a HF diet led to increased iNOS expression, most likely via a mechanism involving Akt and NFκB-p50 proteins. Decreased levels of oestradiol and ERα protein in the HF-fed group, in combination with increased iNOS levels are consistent with the hypothesis that oestradiol has a cardioprotective effect through its ability to regulate iNOS expression.PostprintPeer reviewe

Insights into the Impact of Med Rec Implementation at admission in Acute and Long Term Care Settings in Alberta

Introduction: In Canada, adverse drug events (ADEs) pose a significant public health problem. Various clinical tools have been created to mitigate ADEs and/or their impacts. Medication reconciliation (Med Rec) has been created as a clinical process intended to address the limitations associated with the use of previous clinical tools. Typically, Med Rec interventions have been implemented and evaluated at a single hospital ward and/or among vulnerable patient populations, thus limiting the generalizability of findings. In Alberta, a medication reconciliation intervention, the Medication Reconciliation Alberta (MRQA Med Rec), has been concurrently implemented in acute care hospitals and continuing care facilities with the aim of enhancing medication safety. The intervention has the potential to reduce ADE-related healthcare utilization by ensuring that all medication changes are adequately documented. Primary Objective: To evaluate the effectiveness of MRQA Med Rec in Alberta’s healthcare settings. Secondary Objectives: 1) To characterize Alberta’s healthcare institutions participating in the MRQA Med Rec intervention and compare with non-participating institutions; 2) To determine the consistency (fidelity) of MRQA Med Rec implementation by assessing the Quality Audit Bundle Compliance at Admission; 3) To evaluate whether the impact of the MRQA Med Rec intervention differs among care settings; and 4) To assess the impact of organizational factors on the effectiveness of MRQA Med Rec interventions both between and within healthcare settings. Study population: Cohort consisted of Alberta’s acute care hospital units and LTC facilities, participating in the initiative as of June 2014. Data collection: Administrative data from the following sources were linked by facility identifier: NACRS; DAD; Guide to Canadian Health facilities database; and MRQA Med Rec dataset. Data was obtained from the period between June 1st 2013 and March 31st, 2015. Analysis: Continuous variables were described with measures of central tendency and dispersion and categorical variables were described using contingency tables. Outcomes associated with ADE related healthcare utilization (ADE related ED visits and ADE related hospitalizations), consistently measured over time, were analyzed using repeated measures with the generalized linear mixed model procedures in SAS. For all parameter tests, α level was set to 0.05. Results: Alberta has 328 healthcare facilities, whereas as of June 2014, 116 healthcare organizations have implemented MRQA Med Rec including: hospitals (n=52); hospice (n=1) and publicly funded LTC facilities (n=63). MRQA Med Rec implementation in hospitals was not associated with changes in number of ADE related ED visits (p-value =0.1090) yet organizational factor analysis found that intervention’s positive effect may be more pronounced in hospitals with fewer than 50 beds (p-valuePh.D

Importance of revealing a rare case of breast cancer in a female to male transsexual after bilateral mastectomy

Abstract The incidence of breast carcinoma following prophylactic mastectomy is probably less than 2%. We present a 43-year-old female to male transsexual who developed breast cancer 1 year after bilateral nipple- sparing subcutaneous mastectomy as part of female to male gender reassignment surgery. In addition to gender reassignment surgery, total abdominal hysterectomy with bilateral salpingo-oophorectomy (to avoid the patient from entering menopause and to eliminate any subsequent risk of iatrogenic endometrial carcinoma), colpocleisys, metoidioplasty, phalloplasty, urethroplasty together with scrotoplasty/placement of testicular prosthesis and perineoplasty were also performed. Before the sex change surgery, the following diagnostic procedures were performed: breast ultrasound and mammography (which were normal), lung radiography (also normal) together with abdominal ultrasound examination, biochemical analysis of the blood and hormonal status. According to medical literature, in the last 50 years only three papers have been published with four cases of breast cancer in transsexual female to male patients. All hormonal pathways included in this complex hormonal and surgical procedure of transgender surgery have important implications for women undergoing prophylactic mastectomy because of a high risk of possible breast cancer.</p

A high fat diet induces sex-specific differences in hepatic lipid metabolism and nitrite/nitrate in rats

Men and women differ substantially in regard to the severity of insulin resistance (IR) but the underlying mechanism(s) of how this occurs is poorly characterized. We investigated whether a high fat (HF) diet resulted in sex-specific differences in nitrite/nitrate production and lipid metabolism and whether these variances may contribute to altered obesity-induced IR.Male and female Wistar rats were fed a standard laboratory diet or a HF diet for 10 weeks. The level of plasma nitrite/nitrate, as well as free fatty acid (FFA), in both plasma and liver lysates were assessed. The levels of inducible nitric oxide (NO) synthase (iNOS), p65 subunit of NFκB, total and phosphorylated forms of Akt, mTOR and PDK-1 in lysates, and the levels of glucose transporter 2 (Glut-2) and fatty acid translocase/cluster of differentiation 36 (FAT/CD36) in plasma membrane fractions of liver were assessed.HF-fed male rats exhibited a significant increase in plasma nitrite/nitrate, and hepatic FFA and FAT/CD36 levels compared with controls. They also displayed a relative decrease in iNOS and Glut-2 levels in the liver. Phosphorylation of Akt (at Ser473 and Thr308), mTOR and PDK-1 was also reduced. HF-fed female rats exhibited increased levels of NFκB-p65 in liver compared with controls, while levels of Glut-2, FAT/CD36 and Akt phosphorylation at Thr308 and PDK-1 were decreased.Our results reveal that altered lipid and glucose metabolism in obesity, lead to altered iNOS expression and nitrite/nitrate production. It is likely that this mechanism contributes to sex-specific differences in the development of IR