The Burden of Leadership: a Survey of Burnout Experiences Among Psychiatry Program Directors.

OBJECTIVE: The objectives of this study were to examine the prevalence of burnout, specify contributors to and protective factors against burnout, and gather suggestions to improve well-being in psychiatry Program Directors. METHODS: A survey regarding burnout and wellness was distributed to psychiatric Program Directors through the email listserv of the American Association of Directors of Psychiatric Residency Training (AADPRT). RESULTS: The survey response rate was 273 responses out of 880 members surveyed (31%). The majority of respondents were current residency or fellowship Program Directors or Associate Program Directors or had another current educational role (93%, 227/245). Almost half of current Program Directors or Associate Program Directors reported feeling burned out almost daily or once a week (44%, 93/210). These Program Directors reported a desire to resign (77%), experienced discrimination within the past 5 years (66%), and struggled with finding meaning in their job (44%). The most frequently endorsed contributors to burnout were increasing administrative burden and insufficient support. CONCLUSIONS: The survey findings confirm that burnout characteristics are common among respondents, associated with a desire to resign and a struggle to find meaning in the highly demanding position of Program Director or Associate Program Director. Advocacy for resources, decreased administrative overload, and increased protected time would enhance well-being in Program Directors. Most striking was the frequency of discrimination reported and its relationship to burnout. Departments may benefit from a careful review of policies, procedures, and training to decrease hostile workplaces for women, international medical graduate, and under-represented in medicine Program Directors.

pNaKtide Inhibits Na/K-ATPase Signaling and Attenuates Obesity.

Obesity is a growing public health crisis across the world and has been recognized as an underlying risk factor for metabolic syndrome. Growing evidence demonstrates the critical role of oxidative stress in the pathophysiological mechanisms of obesity and related metabolic dysfunction. As we have established previously that Na/K-ATPase can amplify oxidative stress signaling, we aimed to explore the effect of inhibition of this pathway on obesity phenotype using the peptide antagonist, pNaKtide. The experiments performed in murine preadipocytes showed the dose-dependent effect of pNaKtide in attenuating oxidant stress and lipid accumulation. Furthermore, these in vitro findings were confirmed in C57Bl6 mice fed a high-fat diet. Interestingly, pNaKtide could significantly reduce body weight, ameliorate systemic oxidative and inflammatory milieu and improve insulin sensitivity in obese mice. Hence the study demonstrates the therapeutic utility of pNaKtide as an inhibitor of Na/K-ATPase oxidant amplification signaling to alleviate obesity and associated comorbidities.

De Garengeot hernia masquerading as a painless groin lump: a case report.

De Garengeot's hernia is a rare subtype of femoral hernia in which the appendix is located within the herniated sac. These cases are important to report as both the diagnosis and treatment are quite challenging. We present a case of a 68-year-old gentleman with few months history of a lump in the right groin that gave him mild discomfort but no other symptoms. Initial investigations with an ultrasound did not prove to be helpful and so a plan was made to surgically explore the lump. The appendiceal tip was incarcerated within the hernial sac. The appendix was removed using an open inguinal incision with repair of the defect using a light weight partially absorbable mesh. It is important to consider the possibility of a De Garangeot's Hernia as a differential diagnosis for patients presenting with a groin lump.

Prospective Within-Patient Assessment of the Impact of an Unlabeled Octreotide Pre-dose on the Biodistribution and Tumor Uptake of 68Ga DOTATOC as Assessed by Dynamic Whole-body PET in Patients with Neuroendocrine Tumors: Implications for Diagnosis and Therapy.

PURPOSE: Gastroenteropancreatic neuroendocrine tumors (GEP NETs) are often associated with high expression of somatostatin receptors (SSTRs) which allows for PET/CT imaging with radiolabeled somatostatin analogs such as 68Ga-DOTATOC. The interplay between 68Ga-DOTATOC and the synthetic somatostatin analogs commonly used to manage patient symptoms may lead to competition between the labelled and unlabeled peptides for receptor binding sites and current product labelling recommends patients be taken off somatostatin analogs before imaging. In this study, we prospectively investigated in human patients the effect of a pre-dose of octreotide, a short-acting somatostatin analog, on the distribution of 68Ga-DOTATOC in GEP NETs and normal organs. PROCEDURE: Research participants with GEP NETs were studied on two occasions using dynamic whole-body 68Ga-DOTATOC PET/CT. The two imaging studies were performed within 21 days of each other, using an identical acquisition protocol except for the administration of 50 µg of short-acting octreotide (pre-dose) immediately before the second PET/CT. Paired t-tests were used to compare tracer uptake with and without octreotide, for tumor and various normal organs. RESULTS: Seven participants with a mean age of 53 ± 10 years were studied. Octreotide pre-dosing decreased radiotracer uptake in the normal liver and spleen by 25 % (p = 0.04) and 47 % (p = 0.05) respectively but did not significantly change uptake in tumor (p = 0.53), red marrow (p = 0.12), kidneys (p =0.57), or pituitary gland (p = 0.27). CONCLUSIONS: Our data indicate SSTR imaging can be improved with a pre-dose of unlabeled octreotide given just prior to injection of the radiotracer. These data suggest there may be no need to discontinue somatostatin analog therapy prior to PET/CT with 68Ga-DOTATOC, allowing for a simpler, less disruptive patient protocol. This approach warrants further study in a variety of settings.

Isolated perforated jejunal diverticulitis: a case report.

Jejunal diverticulosis is a rare phenomenon often identified either incidentally on imaging or intra-operatively. Complications of jejunal diverticulosis are associated with high rates of mortality. For this reason, it remains important that this pathology is considered amongst differentials for an acute abdomen. A 78-year old gentleman presented with a short history of generalized lower abdominal pain. Computer tomography scan revealed a large inflammatory abscess relating to a perforated jejunal diverticulum. The patient was taken to theatre where he underwent small bowel resection with primary anastomosis. Early cross sectional imaging is vital to allow early diagnosis and prompt management of this pathology. Small bowel resection with primary anastomosis was associated with an excellent clinical outcome.

The Na/K-ATPase α1 and c-Src form signaling complex under native condition: A crosslinking approach.

The protein-protein interactions amongst the Na/K-ATPase α1 subunit, c-Src, and caveolin-1 (cav-1) are essential for the Na/K-ATPase signaling functions. However, there are arguments concerning the interaction model. The present study aims to clarify the interactions amongst the endogenous native proteins in live cells under native resting condition. Under native condition, Blue Native-PAGE and Blue Native-PAGE/SDS-PAGE 2D analyses demonstrated co-existence of the α1 subunit and c-Src in same protein complex, as well as a direct interaction between the α1 subunit and c-Src. By comparison of cleavable and non-cleavable cysteine-cysteine crosslinked samples, capillary immunoblotting analysis demonstrated that depletion of Src kinase family members (c-Src, Yes, and Fyn) or cav-1 clearly reduced the interactions of the α1 subunit with proteins, but depletion of cav-1 did not affect the interaction of c-Src with the α1 subunit. The data indicated that there are direct interactions between the α1 subunit and c-Src as well as between the α1 subunit and cav-1, but argued about the interaction between c-Src and cav-1 under the condition. Furthermore, the data also indicated the existence of different protein complexes containing the α1 subunit and c-Src, which might have different signaling functions.

Metabolic Syndrome and Salt-Sensitive Hypertension in Polygenic Obese TALLYHO/JngJ Mice: Role of Na/K-ATPase Signaling.

We have demonstrated that Na/K-ATPase acts as a receptor for reactive oxygen species (ROS), regulating renal Na+ handling and blood pressure. TALLYHO/JngJ (TH) mice are believed to mimic the state of obesity in humans with a polygenic background of type 2 diabetes. This present work is to investigate the role of Na/K-ATPase signaling in TH mice, focusing on susceptibility to hypertension due to chronic excess salt ingestion. Age-matched male TH and the control C57BL/6J (B6) mice were fed either normal diet or high salt diet (HS: 2, 4, and 8% NaCl) to construct the renal function curve. Na/K-ATPase signaling including c-Src and ERK1/2 phosphorylation, as well as protein carbonylation (a commonly used marker for enhanced ROS production), were assessed in the kidney cortex tissues by Western blot. Urinary and plasma Na+ levels were measured by flame photometry. When compared to B6 mice, TH mice developed salt-sensitive hypertension and responded to a high salt diet with a significant rise in systolic blood pressure indicative of a blunted pressure-natriuresis relationship. These findings were evidenced by a decrease in total and fractional Na+ excretion and a right-shifted renal function curve with a reduced slope. This salt-sensitive hypertension correlated with changes in the Na/K-ATPase signaling. Specifically, Na/K-ATPase signaling was not able to be stimulated by HS due to the activated baseline protein carbonylation, phosphorylation of c-Src and ERK1/2. These findings support the emerging view that Na/K-ATPase signaling contributes to metabolic disease and suggest that malfunction of the Na/K-ATPase signaling may promote the development of salt-sensitive hypertension in obesity. The increased basal level of renal Na/K-ATPase-dependent redox signaling may be responsible for the development of salt-sensitive hypertension in polygenic obese TH mice.

A Mouse 5/6th Nephrectomy Model That Induces Experimental Uremic Cardiomyopathy.

Chronic kidney disease (CKD) is a great risk factor for cardiovascular disease events and mortality, and progressively develops to the clinical phenotype called "uremic cardiomyopathy". We describe here an experimental CKD mouse model, named 5/6th partial nephrectomy (PNx) with pole ligation, which developed uremic cardiomyopathy at four weeks post-surgery. This PNx model was performed by a two-step surgery. In step-one surgery, both poles of the left kidney were ligated. In step-two surgery, which was performed 7 days after the step-one surgery, the right kidney was removed. For the sham surgery, the same surgery procedures were performed but without pole ligation of the left kidney or removal of the right kidney. The surgical procedures are easier and less time-consuming, compared to other methods. However, the remnant functional renal mass is not as easily controlled as the renal artery ligation. Four weeks after surgery, in comparison with the sham-operated mice, the PNx mice developed impaired renal function, anemia, cardiac hypertrophy, cardiac fibrosis, and decreased heart systolic and diastolic function.

Protein Carbonylation of an Amino Acid Residue of the Na/K-ATPase α1 Subunit Determines Na/K-ATPase Signaling and Sodium Transport in Renal Proximal Tubular Cells.

BACKGROUND: We have demonstrated that cardiotonic steroids, such as ouabain, signaling through the Na/K-ATPase, regulate sodium reabsorption in the renal proximal tubule. By direct carbonylation modification of the Pro222 residue in the actuator (A) domain of pig Na/K-ATPase α1 subunit, reactive oxygen species are required for ouabain-stimulated Na/K-ATPase/c-Src signaling and subsequent regulation of active transepithelial (22)Na(+) transport. In the present study we sought to determine the functional role of Pro222 carbonylation in Na/K-ATPase signaling and sodium handling. METHODS AND RESULTS: Stable pig α1 knockdown LLC-PK1-originated PY-17 cells were rescued by expressing wild-type rat α1 and rat α1 with a single mutation of Pro224 (corresponding to pig Pro222) to Ala. This mutation does not affect ouabain-induced inhibition of Na/K-ATPase activity, but abolishes the effects of ouabain on Na/K-ATPase/c-Src signaling, protein carbonylation, Na/K-ATPase endocytosis, and active transepithelial (22)Na(+) transport. CONCLUSIONS: Direct carbonylation modification of Pro224 in the rat α1 subunit determines ouabain-mediated Na/K-ATPase signal transduction and subsequent regulation of renal proximal tubule sodium transport.

RETRACTED: pNaKtide inhibits Na/K-ATPase reactive oxygen species amplification and attenuates adipogenesis.

Obesity has become a worldwide epidemic and is a major risk factor for metabolic syndrome. Oxidative stress is known to play a role in the generation and maintenance of an obesity phenotype in both isolated adipocytes and intact animals. Because we had identified that the Na/K-ATPase can amplify oxidant signaling, we speculated that a peptide designed to inhibit this pathway, pNaKtide, might ameliorate an obesity phenotype. To test this hypothesis, we first performed studies in isolated murine preadipocytes (3T3L1 cells) and found that pNaKtide attenuated oxidant stress and lipid accumulation in a dose-dependent manner. Complementary experiments in C57Bl6 mice fed a high-fat diet corroborated our in vitro observations. Administration of pNaKtide in these mice reduced body weight gain, restored systemic redox and inflammatory milieu, and, crucially, improved insulin sensitivity. Thus, we propose that inhibition of Na/K-ATPase amplification of oxidative stress may ultimately be a novel way to combat obesity, insulin resistance, and metabolic syndrome.

Prognostic Value of FDG PET/CT-Derived Parameters in Pancreatic Adenocarcinoma at Initial PET/CT Staging.

OBJECTIVE: The purpose of this study is to evaluate the performance of PET-derived parameters as prognostic markers for overall survival (OS) and progression-free survival (PFS) outcome in patients with pancreatic adenocarcinoma. MATERIALS AND METHODS: We conducted a retrospective study of 106 patients (62 men and 44 women) with histologically proven pancreatic adenocarcinoma who underwent initial staging FDG PET/CT before treatment. Peak standardized uptake value (SUV), maximum SUV (SUVmax), metabolic tumor volume, and tumor glycolytic activity of the primary pancreatic tumor were measured. Two segmentation methods were performed to obtain the metabolic tumor volume and tumor glycolytic activity for all tumors: a gradient-based segmentation model (metabolic tumor volume and tumor glycolytic activity by gradient edge detection) and a fixed-threshold model with a threshold of 50% of the lesion's SUVmax and peak SUV. Univariate and multivariate Cox regression models were developed including clinical and imaging parameters for OS and PFS. RESULTS: Multivariate Cox regression analysis showed a statistically significant association between PFS and age, SUVmax, peak SUV, and tumor glycolytic activity by gradient edge detection. There was a statistically significant difference in PFS for patients with values above and below the median cutoff points for SUVmax (hazard ratio [HR], 1.12; p < 0.01), peak SUV (HR, 1.25; p < 0.02), and tumor glycolytic activity measured by gradient edge detection (HR, 1.00; p < 0.02) of the primary tumor. However, multivariate Cox regression analysis showed a statistically significant association only between tumor glycolytic activity by gradient edge detection and OS (p = 0.04), and there was a statistically significant difference in OS between patients with values above and below the median cutoff point for the tumor glycolytic activity by gradient edge detection of the primary tumor (HR, 1.42; p = 0.05). CONCLUSION: Age, SUVmax, peak SUV, and total lesion glycolysis (i.e., tumor glycolytic activity) of the primary tumor are associated with PFS, and tumor glycolytic activity is associated with OS in patients with pancreatic adenocarcinoma.

Evaluation of osseous metastasis in bone scintigraphy.

Bone scintigraphy (BS) is an imaging tool commonly used for screening patients with cancer, especially those with high prevalence of osseous metastases including the breast, prostate, lung, thyroid, and kidney, which account for 80% of osseous metastasis. BS has been shown to be of value in the initial and subsequent treatment strategy of various malignancies. The purpose of this article is to evaluate the technical and imaging aspects of BS and to examine the present research into improved detection of osseous metastasis.

Atypical Rocky Mountain spotted fever with polyarticular arthritis.

BACKGROUND: Rocky Mountain spotted fever (RMSF) is an acute, serious tick borne illness caused by Rickettsia rickettsi. Frequently, RMSF is manifested by headache, a typical rash and fever but atypical disease is common, making diagnosis difficult. Inflammatory arthritis as a manifestation is rare. The purpose of this study is to describe a patient with serologically proven RMSF who presented in an atypical manner with inflammatory arthritis of the small joints of the hands and to review the previously reported patients with rickettsial infection and inflammatory arthritis. METHODS: An 18-year-old woman presented with a rash that began on the distal extremities and spread centrally, along with hand pain and swelling. She had tenderness and swelling of the metacarpophlangeal joints on examination in addition to an erythematosus macular rash and occasional fever. RESULTS: Acute and convalescent serology demonstrated R rickettsi infection. She was successfully treated with doxycycline. CONCLUSIONS: Inflammatory arthritis is a rare manifestation of RMSF or other rickettsial infection with 8 previously reported patients, only 1 of whom had RMSF. Physician must have a high index of suspicion for RMSF because of atypical presentations.

Use of the trellis device in the management of deep vein thrombosis: a retrospective single-center experience.

OBJECTIVES: The Trellis thrombectomy system (Covidien) is one of the newer devices that incorporates isolated pharmacomechanical thrombectomy and thrombolysis (PMT) for treatment of deep venous thrombosis (DVT). We conducted a retrospective review of patients with upper- and lower-extremity DVT managed with the Trellis thrombectomy system at our center. METHODS: All patients with symptomatic DVT who presented to our center between April 2010 and April 2011 who underwent PMT by the Trellis device were included in this retrospective review. RESULTS: Twenty-eight patients (mean age, 46.4 ± 21.2 years) presented with symptoms with a mean duration of 1.3 ± 1.8 months. Eighty-six percent had 100% occlusion on admission, while 14.3% had 70%-90% stenosis. The mean lytic dose used was tPA 20.7 ± 12 mg. The mean Trellis treatment time was 25.1 ± 11.5 minutes. Grade 3 lysis was achieved in 23 of 28 patients (85.8%), while grade 2 lysis was achieved in 14.2%. Mean total hospital stay was 2.6 ± 2.7 days. Postprocedure symptom resolution was 100%, and there was no reocclusion in 78.6% of patients at 1 year. At 12 months, the patency rate (primary or secondary) was 80% as determined by Doppler ultrasound. CONCLUSIONS: In patients with DVT involving the ilio-femoral and the upper-extremity vessels, the use of the Trellis device was associated with a high technical success rate as well as a satisfactory 12-month patency rate. Moreover, this strategy was associated with reduced lytic dose, shorter treatment time and hospital stay, and no bleeding complications.

Takayasu's arteritis and its role in causing renal artery stenosis.

Takayasu's arteritis is a systemic vasculitis that involves medium- and large-sized arteries. Renal artery involvement is a potential manifestation of TA that occurs in 60% of the patients in India and the Far East. This manifestation can lead to renal failure and/or renovascular hypertension. Renovascular hypertension is generally resistant to medical therapy and often requires additional invasive management strategies, such as angioplasty or surgical bypass. In this review, we present the epidemiology, clinical manifestations, diagnosis and treatment of Takayasu's arteritis with particular emphasis on renal artery stenosis. The aim is to increase the awareness of this condition among clinicians because early diagnosis and the timely introduction of treatment can lead to improved outcomes in this poorly understood clinical enigma.

Obesity, brain natriuretic peptide levels and mortality in patients hospitalized with heart failure and preserved left ventricular systolic function.

BACKGROUND: An inverse relationship between brain natriuretic peptide (BNP) levels and body mass index (BMI) has been described for patients with left ventricular (LV) systolic dysfunction. In this study, the association of BMI, BNP levels and mortality in patients hospitalized for heart failure with preserved LV systolic function (HFpLVF) was investigated. METHODS: One hundred fifty consecutive patients (98% men) who were hospitalized with HFpLVF and had BNP levels measured on admission were analyzed. Patients were divided into categories of BMI: normal (BMI < 25 kg/m), overweight (BMI 25-29.9 kg/m) and obese (BMI ≥ 30 kg/m). Relevant clinical and echocardiographic characteristics and all-cause mortality were obtained through chart review. RESULTS: BNP levels were significantly lower in obese (median = 227 pg/mL) and overweight (median = 396 pg/mL) patients compared with those with normal BMI (median = 608 pg/mL, P = 0.003). Higher BMI predicted BNP levels of <100 pg/mL. Compared with patients with normal BMI, overweight and obese patients had a significantly lower risk of total mortality, even after adjusting for other clinical characteristics, including log-transformed BNP levels, atrial fibrillation, the use of beta-blockers at discharge, age, hemoglobin levels and the presence of pulmonary congestion on admission. Higher BNP levels also independently predicted mortality. CONCLUSIONS: An inverse relationship between BMI and BNP levels exists in patients hospitalized with HFpLVF. Higher BMI is associated with lower mortality, whereas higher BNP levels predict higher mortality in male patients with HFpLVF. These findings should be confirmed in a larger multicenter setting.

Inducibility of atrial fibrillation after GP ablations and "autonomic blockade": evidence for the pathophysiological role of the nonadrenergic and noncholinergic neurotransmitters.

BACKGROUND: Recent clinical reports that used cholinergic and adrenergic blockade (CAB) as an alternative to ganglionated plexi (GP) ablation to terminate atrial fibrillation (AF) showed mixed results. We investigated the role of other neurotransmitters in AF inducibility. METHODS: In 23 pentobarbital anesthetized dogs, a left and right thoracotomy allowed the attachment of electrode catheters to the left and right pulmonary veins and atrial appendages (AA). Programmed stimulation was used to determine the effective refractory periods (ERP) and AF inducibility, measured by the window of vulnerability (WOV). AF duration in response to acetylcholine (Ach; 100 mM) applied to the AA was measured before and after GP ablation + CAB and with vagus nerve stimulation (VNS). After GP ablation + CAB, Ach induced AF duration was determined in response to vasoactive intestinal peptide (VIP) and its specific antagonist ([Ac-Tyr1,D-phe2]-VIP). RESULTS: GP ablation + CAB significantly prolonged ERP, eliminated WOV, and suppressed the duration of Ach induced AF (P ≤ 0.01 for all). Also slowing of the heart rate by VNS was essentially blocked; however, with Ach 100 mM applied to the AA, VNS, and VIP applied to the AA markedly prolonged AF duration. This effect was blocked by the VIP antagonist. CONCLUSIONS: Neither GP ablation nor CAB can fully suppress AF inducibility arising from the atrial neural network. Our findings suggest that other neurotransmitters, such as VIP released during VNS, can promote sustained AF despite GP ablation and "autonomic blockade," which may further define the substrate for AF outside the pulmonary vein-atrial junctions.

The role of 18F-fluorodeoxyglucose positron emission tomography in the management of patients with pancreatic adenocarcinoma.

Pancreatic cancer continues to have a grim prognosis with 5-year survival rates at less than 5 %. It is a particularly challenging health problem given these poor survival outcomes, aggressive tumor biology, and late onset of symptoms. Most patients present with advanced unresectable cancer however, margin-negative resection provides a rare chance for cure for patients with resectable disease. The standard imaging modality for the diagnosis and management of pancreatic cancer is contrast-enhanced multidetector computed tomography. Remarkable advances in CT technology have led to improvements in the ability to detect small tumors and intricate vasculature involvement by the tumor, yet CT is still restricted to providing a morphological portrait of the tumor. Diagnosis can be challenging due to similar appearance of certain benign and malignant disease. Distant metastatic disease can be silent on CT leading to improper staging, and thus management, of certain patients. Furthermore, radiation-induced fibrosis and necrosis complicate assessment of treatment response by CT alone. F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is becoming a prevalent tool employed by physicians to improve accuracy in these clinical scenarios. Malignant transformation causes a high metabolic activity of cancer cells. 18F-FDG-PET captures this functional activity of malignancies by capturing areas with high glucose utilization rates. Imaging function rather than morphological appearance, 18F-FDG-PET has a unique role in the management of oncology patients with the ability to detect regions of tumor involvement that may be silent on conventional imaging. Literature on the sensitivity and specificity of 18F-FDG-PET fails to reach a consensus, and improvements resulting in hybridization of 18F-FDG-PET and CT imaging techniques are preliminary. Here we review the potential role of 18F-FDG-PET and PET/CT in improving accuracy in the initial evaluation and subsequent steps in the management of pancreatic cancer patients.