Incidence of prostate, colorectal and male breast cancers in relation with statins and testosterone replacement therapy: SEER-Medicare 2007-2015.

INTRODUCTION: Statins and testosterone replacement therapy (TTh) have been inconsistently associated with a reduced risk of hormone-related cancers (HRCs, prostate [PCa], colorectal [CRC], and male breast cancers [BrCa]). Yet, the joint association of statins and TTh with the incidence of these cancers, and whether these associations vary by race, remains poorly understood. The objective of this retrospective cohort study is to examine the independent and joint effects of pre-diagnostic use of statins and TTh on the risk of HRCs, including PCa, CRC, and male BrCa. MATERIALS: and Methods: In 105,690 men (≥65 yrs) identified using the SEER-Medicare 2007-2015 data, we identified 82,578 White and 10,256 Black men. Pre-diagnostic prescription of statins and TTh was ascertained for this analysis and categorized into four groups (Neither users, statins alone, TTh alone and Dual users). Multivariable Time-varying Cox proportional hazards and Accelerated Failure Time (AFT) models were performed. RESULTS: We found inverse joint associations of statins and TTh with incident HRCs before (aHR: 0.39; 95 % CI: 0.35-0.44) and after 3 years of follow-up (aHR: 0.74; 95 % CI: 0.67-0.82). This included a lower risk for advanced stage HRC (only <3 years follow-up). Similar joint associations were identified with incident PCa, aggressive PCa, incident CRC, and its specific right- and left-sided CRC (only <3 years follow-up). In general, the inverse associations persisted among White (mainly <3 years follow-up) and Black men (high-grade HRC and <3 years follow-up). Findings from the AFT analysis were similar. DISCUSSION: Pre-diagnostic use of statins and TTh were, independently and jointly, associated with reduced risks of HRC and specific cancer sites at three years of follow-up overall, and among White and Black men. Greatest associations of HRCs risk reduction were observed among dual users (statins plus TTh). Further studies are needed to validate these findings, including larger samples of Black men, and male BrCa sites.

Heart Rate Variability and Coronary Artery Bypass Grafting: A Systematic Review.

Background: Coronary artery bypass grafting (CABG) is a well-established surgical procedure used to treat significant coronary artery disease. Nevertheless, unfavorable cardiovascular events and complications, including cardiac arrhythmias may be observed in patients after CABG. Previous studies have revealed a relationship between risk of cardiac arrhythmias and abnormal heart rate variability (HRV), which reflects adverse alterations in cardiac autonomic functioning, that may occur in patients after a CABG procedure. The aim of this article was to provide a systematic review of the major research findings in this area. Methods: A literature search was carried out using PubMed, Cochrane, and Embase databases and relevant articles, published in English, were analyzed in detail. Results: Studies performed so far have shown time depending changes in HRV after CABG. Time and frequency domain HRV decrease acutely after CABG but recover almost completely to pre-operative values by 6 months after surgery. Some preoperative clinical states such as: heart failure, type 2 diabetes mellitus and depression adversely affect post-CABG HRV. Finally, post-CABG cardiac rehabilitation appears to improve exercise capacity and speed up recovery of HRV. Conclusions: Generally, traditional time and frequency domain HRV parameters fail to predict complications post-CABG. Altered non-linear measures of HRV may identify subgroups of subjects at increased risk of potential complications, including atrial fibrillation post-CABG. However, data available currently does not appear to unequivocally support the hypothesis that early HRV assessment in post-CABG patients predicts long-term mortality.

Evaluating the impact of pre-diagnostic use of statins and testosterone replacement therapy on mortality outcomes in older men with hormone-related cancers: Surveillance, Epidemiology, and End Results-Medicare 2007-2015.

BACKGROUND: The link between the pre-diagnostic use of statins and testosterone replacement therapy and their impact on hormone-related cancers, prostate cancer, colorectal cancer, and male breast cancer survival remains a topic of controversy. Further, there is a knowledge gap concerning the joint effects of statins and testosterone replacement therapy on hormone-related cancer survival outcomes. OBJECTIVE: To examine the independent and joint effects of pre-diagnostic use of statins and testosterone replacement therapy on the risk of all-cause and cause-specific mortality among older men diagnosed with hormone-related cancers, including prostate cancer, colorectal cancer, and male breast cancer. METHODS: In 41,707 men (≥65 years) of Surveillance, Epidemiology, and End Results-Medicare 2007-2015, we identified 31,097 prostate cancer, 10,315 colorectal cancer, and 295 male breast cancer cases. Pre-diagnostic prescription of statins and testosterone replacement therapy was ascertained and categorized into four groups (Neither users, statins alone, testosterone replacement therapy alone, and Dual users). Multivariable-adjusted Cox proportional hazards and competing-risks (Fine-Gray subdistribution hazard) models were conducted. RESULTS: No significant associations were found in Cox-proportional hazard models for hormone-related cancers. However, in the Fine-Gray competing risk models among high-grade hormone-related cancers, statins alone had an 11% reduced risk of hormone-related cancer-specific death (hazard ratio: 0.89; 95% confidence interval: 0.81-0.99; p 0.0451). In the prostate cancer cohort with both statistical models, the use of testosterone replacement therapy alone had a 24% lower risk of all-cause death (hazard ratio: 0.76; 95% confidence interval: 0.59-0.97; p 0.0325) and a 57% lower risk of prostate cancer-specific death (hazard ratio: 0.43; 95% confidence interval: 0.24-0.75; p 0.0029). Similar inverse associations were found among aggressive prostate cancer cases with testosterone replacement therapy alone and statins alone. No significant associations were found in the colorectal cancer and male breast cancer sub-groups. CONCLUSION: Pre-diagnostic use of statins and testosterone replacement therapy showed a survival benefit with reduced mortality in high-grade hormone-related cancer patients (only statins) and aggressive prostate cancer patients in both statistical models. Findings of testosterone replacement therapy use in aggressive prostate cancer settings could facilitate clinical trials. Further studies with extended follow-up periods are needed to substantiate these findings.

The incremental yield of adenoma detection with I-Scan versus high-definition white light colonoscopy-a systematic review and meta-analysis of randomized studies.

INTRODUCTION: The incremental yield of I-Scan virtual chromoendoscopy compared to high-definition white light endoscopy (HD-WLE) in detection of colorectal adenomas has not been thoroughly elucidated. METHODS: A systematic search from inception to April 2023 was conducted to identify randomized controlled trials (RCTs) comparing I-Scan to HD-WLE for detection of adenomas. A random effects model was used to compute risk difference (RD) with corresponding 95% confidence intervals in adenoma detection rate (ADR). Influence analysis was done to assess robustness of findings. The number needed to diagnose was computed. Heterogeneity was assessed using the I2 statistic and explored further by subgroup analyses defined a priori. Certainty in effect estimates was assessed using the GRADE approach. RESULTS: We identified four studies (I-Scan n = 730, HD-WLE n = 765). I-Scan increased adenoma detection by 9% (risk difference (RD), 0.09; 0.04, 0.14; I2 02%; certainty, low). Influence analysis revealed that the gain in yield remained statistically significant with exclusion of all but one study. The number needed to capture one additional adenomatous polyp with I-Scan use was 11.2. I-Scan 1 use was associated with a statistically significant gain in ADR, whereas no significant difference in ADR was noted with I-Scan use on subgroup analysis. DISCUSSION: In conclusion, I-Scan increases the yield of adenoma detection by 9% compared to HD-WLE, with low certainty in the estimate of this effect. Data on the gain in yield of detecting large polyps, sessile serrated lesions, and on the impact of formally training endoscopists and trainees in I-Scan use and similar technology on adenoma detection rate are needed.

Virtual transitional pain service delivered via telehealth is effective in preventing new and persistent opioid use amongst post-surgical spine patients.

Opioid dependence is a national crisis, with 30 million patients annually at risk of becoming persistent opioid users after receiving opioids for post-surgical pain management. Translational Pain Services (TPS) demonstrate effectiveness for behavioral health improvements but its effectiveness in preventing persistent opioid use is less established, especially amongst opioid exposed patients. Prohibitive costs and accessibility challenges have hindered TPS program adoption. To address these limitations, we designed and implemented a remote telehealth TPS protocol focusing on preventing continued opioid use while improving behavioral health. Licensed therapists trained in the opioid-tapering CBT protocol delivered sessions reimbursed through standard payer reimbursement. Our prospective study evaluated the protocol's effectiveness on preventing persistent opioid use and behavioral health outcomes amongst both opioid naïve and exposed patients. In an opioid-naive patient cohort (n=67), 100% completely tapered off opioids, while in an opioid-exposed cohort (n =19) 52% completely tapered off opioids, demonstrating promising results. In both cohorts, we observed significant improvements in behavioral health scores, including pain. This opioid-tapering digital TPS is effective, adoptable, and incurs no out-of-pocket cost for healthcare systems. We provide the opioid-tapering CBT protocol in the supplement to facilitate adoption. Trial Registration Impact of Daily, Digital and Behavioral Tele-health Tapering Program for Perioperative Surgical Patients Exposed to Opioids and Benzodiazepines registered at clinicaltrials.gov, NCT04787692. https://clinicaltrials.gov/ct2/show/NCT04787692?term=NCT04787692&draw=2&rank=1.

Self-expanding metal stents for the treatment of malignant colon obstruction from extra-colonic malignancy versus intra-colonic malignancy: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The relative utility of self-expanding metal stent (SEMS) insertion for malignant colon obstruction (MCO) due to extra-colonic malignancy (ECM) versus intra-colonic malignancy (ICM) is understudied. METHODS: A systematic search was done from inception-April 2021 to identify reports of safety and efficacy of SEMS insertion for the treatment of MCO-ECM versus MCO-ICM. A meta-analysis of proportions, comparative meta-analysis to compute relative risks (RR), and mean differences (MD) was performed. Subgroup analyses and influence analyses were conducted. The certainty in estimates of effect(s) was assessed using the GRADE approach. RESULTS: Eight non-randomized studies were identified; 46% (39-53%) and 63% (59-67%) of patients in the ECM and ICM groups were male. Most obstructions were in the rectosigmoid colon in both ECM and ICM groups. SEMS insertion in MCO-ECM was associated with an increased risk of technical failure compared to MCO-ICM (RR 2.92; 1.13-7.54; Certainty: Very Low). Risk of clinical failure of SEMS was higher in MCO-ECM compared to MCO-ICM (RR 2.88; 1.58-2.52; Certainty: Very Low). The risk of clinical failure remained significant throughout the influence analysis, as well as on subgroup analysis. There was no significant difference in the risk of adverse events or luminal perforation with SEMS insertion among patients with MCO-ECM and MCO-ICM. On influence analysis, removal of one study unveiled a significant increase in the risk of luminal perforation in MCO-ECM (RR 3.22; 1.44-7.19; p = 0.004). CONCLUSION: SEMS for MCO-ECM may have a technical success rate comparable to or questionably worse than MCO-ICM, with low certainty in estimate of effects. SEMS deployment in MCO-ECM carries a higher risk of clinical failure, with a questionably higher risk of luminal perforation.

Factor Xa inhibitors versus low molecular weight heparin for the treatment of cancer associated venous thromboembolism; A meta-analysis of randomized controlled trials and non-randomized studies.

INTRODUCTION: We compared the safety and efficacy of Xa-inhibitors to LMWH for treatment of venous thromboembolism in mixed and gastrointestinal cancer cohorts (CA-VTE). METHODS: A systematic search identified RCTs and non-randomized studies (NRS) comparing Xa-inhibitors to LMWH for treating CA-VTE. Relative risks were computed. Certainty was assessed using the GRADE approach. RESULTS: Xa-inhibitors reduced the risk of recurrent VTE (RR0.64;0.49-0.84) and NRS (RR0.74;0.60-0.92;Moderate-Low Certainty). There was no significant difference in recurrent PE in RCTs (RR0.72;0.50-1.02) and NRS (1.43;0.65-3.12;Low-Very Low Certainty). Xa-inhibitors increased the risk of overall bleeding events in RCTs (RR1.45;1.05-2.01) and NRS (RR1.72;1.42-2.08;Moderate-Low Certainty), and the risk of major bleeding events in NRS (RR1.56;1.17-2.07), but not in RCTs (RR1.33;0.94-1.89; Low-Very Low Certainty). Similar results were detected in gastrointestinal cancer patients. CONCLUSION: Xa-inhibitors may reduce the risk of recurrent VTE, but not recurrent PE compared to LMWH. A higher overall bleeding risk, and a questionably higher major bleeding risk was found with Xa-inhibitor use.

Psychosocial stressors predict lower cardiovascular disease risk among Mexican-American adults living in a high-risk community: Findings from the Texas City Stress and Health Study.

The objective of this study was to examine the link between systemic and general psychosocial stress and cardiovascular disease (CVD) risk in a group of U.S. Latinos as a function of acculturation and education within the blended guiding conceptual framework of the biopsychosocial model of the stress process plus the reserve capacity model. We analyzed data from self-identifying Mexican-origin adults (n = 396, 56.9% female, Mage = 58.2 years, 55.5% < 12 years of education, 79% U.S.-born) from the Texas City Stress and Health Study. We used established measures of perceived stress (general stress), neighborhood stress and discrimination (systemic stress) to capture psychosocial stress, our primary predictor. We used the atherosclerotic CVD calculator to assess 10-year CVD risk, our primary outcome. This calculator uses demographics, cholesterol, blood pressure, and history of hypertension, smoking, and diabetes to compute CVD risk in the next 10 years. We also created an acculturation index using English-language use, childhood interaction, and preservation of cultural values. Participants reported years of education. Contrary to expectations, findings showed that higher levels of all three forms of psychosocial stress, perceived stress, neighborhood stress, and perceived discrimination, predicted lower 10-year CVD risk. Acculturation and education did not moderate the effects of psychosocial stress on 10-year CVD risk. Contextualized within the biopsychosocial and reserve capacity framework, we interpret our findings such that participants who accurately reported their stressors may have turned to their social networks to handle the stress, thereby reducing their risk for CVD. We highlight the importance of examining strengths within the sociocultural environment when considering cardiovascular inequities among Latinos.

Colorectal cancer screening and surveillance strategy for patients with Diamond Blackfan anemia: Preliminary recommendations from the Diamond Blackfan Anemia Registry.

Diamond Blackfan anemia (DBA) is a rare inherited bone marrow failure syndrome characterized by red cell failure, congenital anomalies, poor linear growth, and cancer predisposition. Two previous analyses from the Diamond Blackfan Anemia Registry have quantified DBA as a cancer predisposition syndrome of moderate cancer penetrance. Patients with DBA have a 4.8-fold higher relative risk of developing cancer with an overall cumulative incidence of 13.7% by age 45 years. The two most prevalent solid tumors are colorectal cancer (CRC) and osteogenic sarcoma. Current and evolving data support the institution of cancer screening and surveillance strategies for CRC in DBA.

Characterization of Recombinant Adeno-Associated Viruses (rAAVs) for Gene Therapy Using Orthogonal Techniques.

Viruses are increasingly used as vectors for delivery of genetic material for gene therapy and vaccine applications. Recombinant adeno-associated viruses (rAAVs) are a class of viral vector that is being investigated intensively in the development of gene therapies. To develop efficient rAAV therapies produced through controlled and economical manufacturing processes, multiple challenges need to be addressed starting from viral capsid design through identification of optimal process and formulation conditions to comprehensive quality control. Addressing these challenges requires fit-for-purpose analytics for extensive characterization of rAAV samples including measurements of capsid or particle titer, percentage of full rAAV particles, particle size, aggregate formation, thermal stability, genome release, and capsid charge, all of which may impact critical quality attributes of the final product. Importantly, there is a need for rapid analytical solutions not relying on the use of dedicated reagents and costly reference standards. In this study, we evaluate the capabilities of dynamic light scattering, multiangle dynamic light scattering, and SEC-MALS for analyses of rAAV5 samples in a broad range of viral concentrations (titers) at different levels of genome loading, sample heterogeneity, and sample conditions. The study shows that DLS and MADLS® can be used to determine the size of full and empty rAAV5 (27 ± 0.3 and 33 ± 0.4 nm, respectively). A linear range for rAAV5 size and titer determination with MADLS was established to be 4.4 × 1011-8.7 × 1013 cp/mL for the nominally full rAAV5 samples and 3.4 × 1011-7 × 1013 cp/mL for the nominally empty rAAV5 samples with 3-8% and 10-37% CV for the full and empty rAAV5 samples, respectively. The structural stability and viral load release were also inferred from a combination of DLS, SEC-MALS, and DSC. The structural characteristics of the rAAV5 start to change from 40 °C onward, with increasing aggregation observed. With this study, we explored and demonstrated the applicability and value of orthogonal and complementary label-free technologies for enhanced serotype-independent characterization of key properties and stability profiles of rAAV5 samples.

The Impact of Postoperative Complications on Long-Term Oncological Outcomes Following Curative Resection of Colorectal Cancer (Stage I-III): A Systematic Review and Meta-Analysis.

Background and objective The incidence of post-surgical complications (PSCs) after curative resection of non-metastatic colorectal cancer (CRC) is very widespread and evident. Some studies suggest that PSCs often predict poor long-term oncological outcomes. However, the available data on the topic is often controversial. The aim of this systematic review and meta-analysis was to study the effect of postoperative complications (POCs) on long-term oncological outcomes following curative resection of non-metastatic (stage I-III) CRC. Methods A comprehensive search of MEDLINE® and Excerpta Medica dataBASE (EMBASE) databases was performed via the Ovid platform, by using controlled vocabulary as well as natural language terms for POCs, outcomes, and CRC. Two authors independently screened the studies and extracted data. Conflicts were resolved by discussion among authors and also independently with the help of a third author. Meta-analysis was performed using a random-effects model (REM) to calculate pooled estimates for overall survival (OS), disease-free survival (DFS), and overall recurrence. Results Overall, 3,836 studies were initially screened, and 16 studies involving 37,192 patients were ultimately selected for final inclusion in the analysis. Meta-analysis of these studies showed that PSCs following non-metastatic CRC surgery predicted worse OS rates [hazard ratio (HR): 1.36; 95% CI: 1.15-1.61; p<0.00001], DFS (HR: 1.41; 95% CI: 1.11-1.80; p<0.00001), and overall recurrence (HR: 1.19; 95% CI: 1.04-1.37; p=0.01). Conclusion Based on our findings, PSCs predict poor OS rates, DFS, and overall recurrence following curative resection of non-metastatic CRC.

The effects of ß1 and ß1+2 adrenergic receptor blockade on the exercise-induced mobilization and ex vivo expansion of virus-specific T cells: implications for cellular therapy and the anti-viral immune effects of exercise.

The adoptive transfer of donor-derived virus-specific T cells (VSTs) is an effective treatment for infections following allogeneic hematopoietic cell transplantation. Acute exercise mobilizes effector lymphocytes and VSTs to the circulation and augments the ex vivo manufacture of VSTs. This study determined if ß2 adrenergic receptor (AR) signaling precipitated the VST response to acute exercise. Healthy participants (n = 12) completed 30 min of steady-state cycling exercise after ingesting a placebo, a ß1 + 2 AR antagonist (nadolol) or a ß1 AR antagonist (bisoprolol). Circulating VSTs to cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus (AdV) antigens were enumerated before and after exercise, and peripheral blood mononuclear cells were cultured with viral peptides for 8 days to expand multi-VSTs. Compared with placebo, nadolol blunted the exercise-induced mobilization of CMV-VSTs (Δ VSTs/100,000 CD3+ T cells = 93 ± 104 vs. 22 ± 91 for placebo and nadolol, respectively; p = 0.036), while bisoprolol did not, despite both drugs evoking similar reductions in exercising heart rate and blood pressure. Circulating AdV and EBV VSTs (VSTs/mL blood) only increased after exercise with placebo. Although not significant, nadolol partially mitigated exercise-induced increases in multi-VST expansion, particularly in participants that demonstrated an exercise-induced increase in VST expansion. We conclude that exercise-induced enhancements in VST mobilization and expansion are at least partially ß2 AR mediated, thus highlighting a role for the ß2 AR in targeted therapy for the augmentation of VST immune cell therapeutics in the allogeneic adoptive transfer setting. Moreover, long-term regular exercise may provide additional viral protection in the host through frequent ß2 AR-dependent mobilization and redistribution of VSTs cumulated with each bout of exercise.

A Comprehensive Assessment of Vascular and Nonvascular Risk Factors Associated with Migraine.

INTRODUCTION:  Migraine is a chronic disabling neurological disease, with an estimated expense of $15-20 million/year. Several studies with a small number of patients have studied risk factors for migraine such as cardiovascular disorders, stroke, smoking, demographic, and genetic factors but this is the first comprehensive study for evaluation of vascular and nonvascular risk factors. It is important to evaluate all the risk factors that help to prevent the healthcare burden related to migraine.  Methodology: We performed a retrospective cross-sectional analysis of the Nationwide Inpatient Sample (NIS) (years 2013-2014) in adult (>18-years old) hospitalizations in the United States. Migraine patients were identified using ICD-9-CM code to determine the demographic characteristics, vascular, and nonvascular risk factors. Univariate analysis was performed using the chi-square test and a multivariate survey logistic regression analysis was performed to identify the prevalence of the risk factors and evaluate the odds of prevalence of risk factors amongst migraine patients compared to nonmigraine patients, respectively. RESULTS:  On weighted analysis, after removing missing data of age, gender and race, from years 2013 to 2014, of the total 983,065 (1.74%) migraine patients were identified. We found that younger (median age 48-years vs. 60-years), female (82.1% vs. 58.5%; p<0.0001), white population (76.8% vs. 70.5%; p<0.0001), and privately insured (41.1% vs. 27.4%; p<0.0001) patients were more likely to have migraine than others. Cerebral atherosclerosis, diabetes mellitus, ischemic heart disease, atrial fibrillation, and alcohol abuse were not significantly associated with migraine. Migraineurs had higher odds of having hypertension [odds ratio (OR): 1.44; 95% confidence interval (CI): 1.43-1.46; 44.49% vs. 52.84%], recent transient ischemic attack (TIA) (OR: 3.13; 95%CI: 3.02-3.25; 1.74% vs. 0.67%), ischemic stroke (OR: 1.40; 95%CI: 1.35-1.45; 2.06% vs. 1.97%), hemorrhagic stroke (OR: 1.11; 95%CI: 1.04-1.19; 0.49% vs. 0.46%), obesity (OR: 1.46; 95%CI: 1.44-1.48; 19.20% vs. 13.56%), hypercholesterolemia (OR: 1.33; 95%CI: 1.30-1.36; 5.75% vs. 5.54%), substance abuse (OR: 1.51; 95%CI: 1.48-1.54; 7.88% vs. 4.88%), past or current consumption of tobacco (OR: 1.40; 95%CI: 1.38-1.41; 31.02% vs. 27.39%), AIDS (OR: 1.13; 95%CI: 1.04-1.24; 0.33% vs. 0.41%), hypocalcemia (OR: 1.09; 95%CI: 1.03-1.14; 0.77% vs. 0.89%), and vitamin D deficiency (OR: 1.93; 95%CI: 1.88-1.99; 2.47% vs. 1.37%) than patients without migraine. Female patients were at a higher risk of migraine (OR: 3.02; 95%CI: 2.98-3.05) than male. CONCLUSION:  In this study, we have identified significant risk factors for migraine hospitalizations. Early identification of these risk factors may improve the risk stratification in migraine patients.

Cognitive disability in adult patients with brain tumors.

Cognitive dysfunction is common among patients with intracranial tumors. Most cognitive deficits are subtle, lack specificity, may mimic depression or other neurological disorders and may be recognized in retrospect by the physician. In certain cases, distinguishing between tumor recurrence and cognitive deficits that arise as a consequence of the treatment becomes challenging. Late treatment effects have also become an area of focus as the overall survival and prognosis of patients with brain tumors increases. New data has highlighted the importance of less toxic adjuvant therapies owing to their positive impact on prognosis and quality of life. Various experimental therapies and genetic influences on individual sensitivity towards injury are promising steps towards a better management strategy for cognitive dysfunction. In this literature review, we discuss cognitive dysfunction as a manifestation of intracranial tumors, treatment modalities such as radiotherapy, chemotherapy, surgery and their impact on cognition and patients' quality of life. We also discuss management options for cognitive dysfunction and emerging therapies.

Assessment and Improvement of Quality of Life in Patients Undergoing Treatment for Head and Neck Cancer.

INTRODUCTION: We compared the pre and post-treatment quality of life in head and neck cancer (HNC) patients and identified factors that could improve the quality of life in such patients.   Methods: The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) questionnaire was administered to 84 patients' pre and post-treatment. Patients who had non-metastatic, measurable, and untreated HNCs were invited, provided that their age was below 80 years. We did not discriminate based on treatment modality, stage of cancer, or co-morbidities. Patients who were mentally incapacitated, with secondary or recurrent HNC, distant metastasis, skin cancer, congenital anomaly of the head and neck, chronic illness, or any previous or current psychiatric illness were excluded from the study. A high mean score on the functional scale and a low score on symptom scale signify a better quality of life. We used the dependent t-test to compare pre and post-treatment scores. RESULTS: We found no statistically significant differences in any variables, except the four symptom scales of diarrhoea, constipation, nausea/vomiting, and financial difficulty. All of these variables had increased mean scores with p values of < 0.001. Also, we found no statistical significance (p = 0.250) when comparing the pre-treatment (59.4 ± 18.3) and post-treatment (61.2 ± 16.2) scores for the global health status. CONCLUSION: We found no improvement in the quality of life in HNC patients despite intervention. In fact, diarrhoea, constipation, nausea/vomiting, and financial difficulty of these patients worsened post-treatment.

Estrone Sulfate Transport and Steroid Sulfatase Activity in Colorectal Cancer: Implications for Hormone Replacement Therapy.

Hormone replacement therapy (HRT) affects the incidence and potential progression of colorectal cancer (CRC). As HRT primarily consists of estrone sulfate (E1S), understanding whether this conjugated estrogen is transported and metabolized in CRC will define its potential effect in this malignancy. Here, we show that a panel of CRC cell lines (Colo205, Caco2, HCT116, HT-29) have steroid sulfatase (STS) activity, and thus can hydrolyze E1S. STS activity is significantly higher in CRC cell lysate, suggesting the importance of E1S transport in intracellular STS substrate availability. As E1S transport is regulated by the expression pattern of certain solute carrier organic anion transporter polypeptides, we show that in CRC OATP4A1 is the most abundantly expressed transporter. All four CRC cell lines rapidly transported E1S into cells, with this effect significantly inhibited by the competitive OATP inhibitor BSP. Transient knockdown of OATP4A1 significantly disrupted E1S uptake. Examination of estrogen receptor status showed ERα was present in Colo205 and Caco2 cells. None of the cells expressed ERß. Intriguingly, HCT116 and HT29 cells strongly expressed the G protein coupled estrogen receptor (GPER), and that stimulation of this receptor with estradiol (E2) and G1, a GPER agonist, significantly (p < 0.01) increased STS activity. Furthermore, tamoxifen and fulvestrant, known GPER agonist, also increased CRC STS activity, with this effect inhibited by the GPER antagonist G15. These results suggest that CRC can take up and hydrolyze E1S, and that subsequent GPER stimulation increases STS activity in a potentially novel positive feedback loop. As elevated STS expression is associated with poor prognosis in CRC, these results suggest HRT, tamoxifen and fulvestrant may negatively impact CRC patient outcomes.

Dose-response effects of water supplementation on cognitive performance and mood in children and adults.

Water supplementation has been found to facilitate visual attention and short-term memory, but the dose required to improve performance is not yet known. We assessed the dose response effect of water on thirst, mood and cognitive performance in both adults and children. Participants were offered either no water, 25 ml or 300 ml water to drink. Study 1 assessed 96 adults and in Study 2, data are presented from 60 children aged 7-9 years. In both studies, performance was assessed at baseline and 20 min after drinking (or no drink); on thirst and mood scales, letter cancellation and a digit span test. For both children and adults, a large drink (300 ml) was necessary to reduce thirst, while a small drink (25 ml) was sufficient to improve visual attention (letter cancellation). In adults, a large drink improved digit span, but there was no such effect in children. In children, but not adults, a small drink resulted in increased thirst ratings. Both children and adults show dose-response effects of drinking on visual attention. Visual attention is enhanced by small amounts of fluid and appears not to be contingent on thirst reduction. Memory performance may be related to thirst, but differently for children and adults. These contrasting dose-response characteristics could imply cognitive enhancement by different mechanisms for these two domains.

Novel insights in the dysfunction of human blood-brain barrier after glycation.

The blood-brain barrier (BBB) provides a dynamic and complex interface consisting of endothelial cells, pericytes and astrocytes, which are embedded in a collagen and fibronectin-rich basement membrane. This complex structure restricts the diffusion of small hydrophilic solutes and macromolecules as well as the transmigration of leukocytes into the brain. It has been shown that carbonyl stress followed by the formation of advanced glycation endproducts (AGE=glycation) interfere with the BBB integrity and function. Here, we present data that carbonyl stress induced by methylglyoxal leads to glycation of endothelial cells and the basement membrane, which interferes with the barrier-function and with the expression of RAGE, occludin and ZO-1. Furthermore, methylglyoxal induced carbonyl stress promotes the expression of the pro-inflammatory interleukins IL-6 and IL-8. In summary, this study provides new insights into the relationship between AGE formation by carbonyl stress and brain microvascular endothelial barrier dysfunction.