Organic Cation Transporter 3 (OCT3) Is Localized to Intracellular and Surface Membranes in Select Glial and Neuronal Cells Within the Basolateral Amygdaloid Complex of Both Rats and Mice

Organic cation transporter 3 (OCT3) is a high-capacity, low-affinity transporter that mediates corticosterone-sensitive uptake of monoamines including norepinephrine, epinephrine, dopamine, histamine and serotonin. OCT3 is expressed widely throughout the amygdaloid complex and other brain regions where monoamines are key regulators of emotional behaviors affected by stress. However, assessing the contribution of OCT3 to the regulation of monoaminergic neurotransmission and monoamine-dependent regulation of behavior requires fundamental information about the subcellular distribution of OCT3 expression. We used immunofluorescence and immuno-electron microscopy to examine the cellular and subcellular distribution of the transporter in the basolateral amygdaloid complex of the rat and mouse brain. OCT3-immunoreactivity was observed in both glial and neuronal perikarya in both rat and mouse amygdala. Electron microscopic immunolabeling revealed plasma membrane-associated OCT3 immunoreactivity on axonal, dendritic, and astrocytic processes adjacent to a variety of synapses, as well as on neuronal somata. In addition to plasma membrane sites, OCT3 immunolabeling was also observed associated with neuronal and glial endomembranes, including Golgi, mitochondrial and nuclear membranes. Particularly prominent labeling of the outer nuclear membrane was observed in neuronal, astrocytic, microglial and endothelial perikarya. The localization of OCT3 to neuronal and glial plasma membranes adjacent to synaptic sites is consistent with an important role for this transporter in regulating the amplitude, duration, and physical spread of released monoamines, while its localization to mitochondrial and outer nuclear membranes suggests previously undescribed roles for the transporter in the intracellular disposition of monoamines

Dietary Patterns and Risk of Pancreatic Cancer in a Large Population-Based Case-Control Study in the San Francisco Bay Area

Pancreatic cancer is highly lethal, and identifying modifiable risk factors could have substantial public health impact. In this population-based case-control study (532 cases, 1701 controls), we used principal component analysis and multivariable unconditional logistic regression models to examine whether a particular dietary pattern was associated with risk of pancreatic cancer, adjusting for other known risk factors. A prudent dietary pattern, characterized by greater intake of vegetables, fruit, fish, poultry, whole grains, and low-fat dairy, was associated with an approximate 50% reduction in pancreatic cancer risk among men [odds ratio (OR) = 0.51, 95% confidence intervals (CI) = 0.31-0.84, P trend = 0.001] and women (OR = 0.51, 95% CI = 0.29-0.90, P trend = 0.04). A Western dietary pattern, characterized by higher intake of red and processed meats, potato chips, sugary beverages, sweets, high fat dairy, eggs, and refined grains, was associated with a 2.4-fold increased risk of pancreatic cancer among men (95% CI = 1.3-4.2, P trend = 0.008) but was not associated with risk among women. Among men, those in the upper quintiles of the Western diet and lower quintiles of the prudent diet had a threefold increased risk. Consistent with what has been recommended for several other chronic diseases, consuming a diet rich in plant-based foods, whole grains, and white meat, might reduce risk of pancreatic cancer

Selenium Supplementation and Prostate Cancer Mortality

BackgroundFew studies have evaluated the relation between selenium supplementation after diagnosis and prostate cancer outcomes.MethodsWe prospectively followed 4459 men initially diagnosed with nonmetastatic prostate cancer in the Health Professionals Follow-Up Study from 1988 through 2010 and examined whether selenium supplement use (from selenium-specific supplements and multivitamins) after diagnosis was associated with risk of biochemical recurrence, prostate cancer mortality, and, secondarily, cardiovascular disease mortality and overall mortality, using Cox proportional hazards models. All P values were from two-sided tests.ResultsWe documented 965 deaths, 226 (23.4%) because of prostate cancer and 267 (27.7%) because of cardiovascular disease, during a median follow-up of 8.9 years. In the biochemical recurrence analysis, we documented 762 recurrences during a median follow-up of 7.8 years. Crude rates per 1000 person-years for prostate cancer death were 5.6 among selenium nonusers and 10.5 among men who consumed 140 or more μg/day. Crude rates per 1000 person-years were 28.2 vs 23.5 for all-cause mortality and 28.4 vs 29.3 for biochemical recurrence, for nonuse vs highest-dose categories, respectively. In multivariable analyses, men who consumed 1 to 24 μg/day, 25 to 139 μg/day, and 140 or more μg/day of supplemental selenium had a 1.18 (95% confidence interval [CI] = 0.73 to 1.91), 1.33 (95% CI = 0.77 to 2.30), and 2.60-fold (95% CI = 1.44 to 4.70) greater risk of prostate cancer mortality compared with nonusers, respectively, P trend = .001. There was no statistically significant association between selenium supplement use and biochemical recurrence, cardiovascular disease mortality, or overall mortality.ConclusionSelenium supplementation of 140 or more μg/day after diagnosis of nonmetastatic prostate cancer may increase risk of prostate cancer mortality. Caution is warranted regarding usage of such supplements among men with prostate cancer

A Price Worth Paying: The Case for Controlling Marine Emissions in the Pearl River Delta

The Pearl River Delta (PRD) is a region with a single airshed, but different administrative and legal practices for controlling air quality. Under the Regional Cooperation Plan on Building a Quality Living Area (QLA Plan) released in June 2012 the Governments of Hong Kong, Guangdong and Macau have outlined a strategy to collaborate in reducing emissions from vessels throughout the PRD. This report provides evidence designed to assist policymakers in the region with this objective. It focuses on regulating toxic exhaust emissions from ocean-going vessels (OGVs) -- the most significant contributors of marine emissions. The findings show that marine sources of sulphur dioxide (SO2) emissions currently account for 519 premature deaths per annum in the PRD. These deaths could be reduced by 91% should an Emission Control Area (ECA) mandating the use of fuels with lower sulphur content be introduced. The report also demonstrates that three less comprehensive control measures would also reduce OGV emissions and associated public health impacts by 41-62%. Policymakers are encouraged to introduce these measures as stepping-stones on the way to establishment of an ECA for the PRD

Development and pilot evaluation of a personalized decision support intervention for low risk prostate cancer patients.

ObjectivesDevelopment and pilot evaluation of a personalized decision support intervention to help men with early-stage prostate cancer choose among active surveillance, surgery, and radiation.MethodsWe developed a decision aid featuring long-term survival and side effects data, based on focus group input and stakeholder endorsement. We trained premedical students to administer the intervention to newly diagnosed men with low-risk prostate cancer seen at the University of California, San Francisco. Before the intervention, and after the consultation with a urologist, we administered the Decision Quality Instrument for Prostate Cancer (DQI-PC). We hypothesized increases in two knowledge items from the DQI-PC: How many men diagnosed with early-stage prostate cancer will eventually die of prostate cancer? How much would waiting 3 months to make a treatment decision affect chances of survival? Correct answers were: "Most will die of something else" and "A little or not at all."ResultsThe development phase involved 6 patients, 1 family member, 2 physicians, and 5 other health care providers. In our pilot test, 57 men consented, and 44 received the decision support intervention and completed knowledge surveys at both timepoints. Regarding the two knowledge items of interest, before the intervention, 35/56 (63%) answered both correctly, compared to 36/44 (82%) after the medical consultation (P = .04 by chi-square test).ConclusionsThe intervention was associated with increased patient knowledge. Data from this pilot have guided the development of a larger scale randomized clinical trial to improve decision quality in men with prostate cancer being treated in community settings

Development of a Rapid and High-Throughput Multiplex Real-Time PCR Assay for Mycoplasma hominis and Ureaplasma Species

Bacterial commensals of the human genitourinary tract, Mycoplasma hominis and Ureaplasma species (parvum and urealyticum) can be sexually transmitted, and may cause nongonococcal urethritis, pelvic inflammatory disease, and infertility. Mycoplasma hominis and Ureaplasma species may also cause severe invasive infections in immunocompromised patients. Current culture-based methods for Mycoplasma/Ureaplasma identification are costly and laborious, with a turnaround time between 1 and 2 weeks. We developed a high-throughput, real-time multiplex PCR assay for the rapid detection of M. hominis and Ureaplasma species in urine, genital swab, body fluid, and tissue. In total, 282 specimens were tested by PCR and compared with historic culture results; a molecular reference method was used to moderate discrepancies. Overall result agreement was 99% for M. hominis (97% positive percentage agreement and 100% negative percentage agreement) and 96% for Ureaplasma species (96% positive percentage agreement and 97% negative percentage agreement). Specimen stability was validated for up to 7 days at room temperature. This multiplex molecular assay was designed for implementation in a high-complexity clinical microbiology laboratory. With this method, >90 samples can be tested in one run, with a turnaround time of 4 to 5 hours from specimen extraction to reporting of results. This PCR test is also more labor effective and cheaper than the conventional culture-based test, thus improving laboratory efficiency and alleviating labor shortages

Fat intake after prostate cancer diagnosis and mortality in the Physicians’ Health Study

PurposeDiet after prostate cancer diagnosis may impact disease progression. We hypothesized that consuming saturated fat after prostate cancer diagnosis would increase risk of mortality, and consuming vegetable fat after diagnosis would lower the risk of mortality.MethodsThis was a prospective study among 926 men with non-metastatic prostate cancer in the Physicians' Health Study who completed a food frequency questionnaire a median of 5 years after diagnosis and were followed for a median of 10 years after the questionnaire. We examined post-diagnostic saturated, monounsaturated, polyunsaturated, and trans fat, as well as animal and vegetable fat, intake in relation to all-cause and prostate cancer-specific mortality. Hazard ratios (HR) and 95 % confidence intervals (CI) were estimated using multivariate Cox proportional hazards regression.ResultsWe observed 333 deaths (56 prostate cancer deaths) during follow-up. Men who obtained 5 % more of their daily calories from saturated fat and 5 % less of their daily calories from carbohydrate after diagnosis had a 1.8-fold increased risk of all-cause mortality (HR 1.81; 95 % CI 1.20, 2.74; p value 0.005) and a 2.8-fold increased risk of prostate cancer-specific mortality (HR 2.78; 95 % CI 1.01, 7.64; p value 0.05). Men who obtained 10 % more of their daily calories from vegetable fats and 10 % less of their daily calories from carbohydrates had a 33 % lower risk of all-cause mortality (HR 0.67; 95 % CI 0.47, 0.96; p value 0.03).ConclusionsAmong men with non-metastatic prostate cancer, saturated fat intake may increase risk of death and vegetable fat intake may lower risk of death

THE IMPACT OF OBESITY ON HEALTH RELATED QUALITY OF LIFE BEFORE AND AFTER RADICAL PROSTATECTOMY (DATA FROM CaPSURE)

PurposeHealth related quality of life (HRQOL) is an important measure of outcomes among patients with prostate cancer due to disease related and treatment related effects on physical and emotional health. We determined if there are differences in the HRQOL of obese men at diagnosis and after radical prostatectomy compared to the HRQOL of men with normal body mass index (BMI).Materials and methodsData were abstracted from Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE), a disease registry of 10,018 men with prostate cancer. A total of 1,884 men were included in study who were treated with radical prostatectomy between 1989 and 2002, had BMI information available and had completed 1 initial HRQOL questionnaire. Of these men 672 who completed at least 2 followup questionnaires were assessed further.ResultsThe BMI (kg/m) distributions were 24% normal (less than 24.9 kg/m), 56% overweight (25 to 29.9), 16% obese (30 to 34.9) and 4% very obese (greater than 35 kg/m). Higher BMI was associated with worse physical function, bodily pain, general health, vitality and role physical, but better bowel bother at diagnosis independent of race. Higher BMI was also associated with worse HRQOL after radical prostatectomy for physical function, general health and vitality, but better bowel bother. HRQOL differences between BMI groups were similar among times for all measured variables. Compared to the normal group, the higher BMI groups had similar HRQOL after radical prostatectomy.ConclusionsIn the majority of domains men with higher BMI had lower HRQOL at diagnosis than men of normal BMI. Obese men have a similar recovery pattern of HRQOL after radical prostatectomy, with minimal additive long-term impairment in HRQOL relative to men of normal weight

Management of locally recurrent nasopharyngeal carcinoma

As a consequence of the current excellent loco-regional control rates attained using the generally accepted treatment paradigms involving intensity-modulated radiotherapy for nasopharyngeal carcinoma (NPC), only 10-20% of patients will suffer from local and/or nodal recurrence after primary treatment. Early detection of recurrence is important as localized recurrent disease is still potentially salvageable, but this treatment often incurs a high risk of major toxicities. Due to the possibility of radio-resistance of tumors which persist or recur despite adequate prior irradiation and the limited tolerance of adjacent normal tissues to sustain further additional treatment, the management of local failures remains one of the greatest challenges in this disease. Both surgical approaches for radical resection and specialized re-irradiation modalities have been explored. Unfortunately, available data are based on retrospective studies, and the majority of them are based on a small number of patients or relatively short follow-up. In this article, we will review the different salvage treatment options and associated prognostic factors for each of them. We will also propose a treatment algorithm based on the latest available evidence and discuss the future directions of treatment for locally recurrent NPC.Peer reviewe