A cross-sectional study of nutritional status in healthy, young, physically-active German omnivores, vegetarians and vegans reveals adequate vitamin B12 status in supplemented vegans.

BACKGROUND/OBJECTIVE: Plant-based diets reduce the risk of cardiovascular disease but also increase the risk of certain micronutrient deficiencies, particularly, of vitamin B12 (B12). The extent to which the unsupervised use of oral nutrient supplements is sufficient to prevent these deficiencies is not well established. We analyzed nutrient intake, laboratory biomarkers, supplementation behavior, and B12 status adequacy amongst young, healthy, physically active omnivores, lacto-ovo-vegetarians and vegans from Germany. METHODS: We recruited 115 participants (n = 40 omnivores; n = 37 lacto-ovo-vegetarians, and n = 38 vegans) with comparable age, sex, marital status, physical activity and educational levels through online advertisements and local newspapers in Freiburg, Germany. RESULTS: Energy intake and macronutrient distribution were comparable across diets. Major differences included intake of fiber, cholesterol, and several vitamins. Vegans had the lowest intake of B12 from foods (0.43 (0.58) µg/d), compared to omnivores (2.14 (2.29) µg/d) and lacto-ovo-vegetarians (0.98 (1.34) µg/day). Multivariate analysis of 36 blood biomarkers revealed that three major classes of biomarkers contributed the most to the clustering of individuals by dietary group, namely, biomarkers of B12 status (B12, holoTC, Hcy), iron (iron, ferritin, transferrin) and lipid metabolism (vitamin A, HDL, LDL, total cholesterol, TAG). This suggests that nutrients that modify the metabolic pathways represented by these biomarkers have the most penetrating effect on health status across diets. Analysis of B12 status (including 4cB12) revealed adequacy in omnivores and vegans, and a poorer B12 status amongst lacto-ovo-vegetarians. Fewer lacto-ovo-vegetarians used B12 supplements compared to vegans (51% versus 90%). CONCLUSIONS: Even amongst homogeneously healthy Germans, each diet manifested with measurable differences in dietary intakes and biomarkers of health. Plant-based diets, in particular the vegan diet, exhibited the most favorable patterns of lipid metabolism and glycemic control, but the lowest food intake of B12. Supplementation of healthy vegans with B12 (median 250 µg B12/day, over 2 years) secured an adequate B12 status that was comparable to that of healthy omnivores.Clinical Trial Registry: German Clinical Trial register number: DRKS00027425.

Plant-based diets, in particular the vegan diet, exhibited the most favorable patterns of lipid metabolism and glycemic control, but the lowest food intake of B12.Analysis of B12 status (including 4cB12) revealed adequacy in omnivores and vegans, and a poorer B12 status amongst lacto-ovo-vegetarians.Supplementation with B12 (median 250 µg B12/day, over 1 year) in healthy physically-active vegans secured an adequate B12 status that was comparable to that of healthy omnivores.

Spending Time in the Forest or the Field: Investigations on Stress Perception and Psychological Well-Being-A Randomized Cross-Over Trial in Highly Sensitive Persons.

Research suggests that stays in a forest promote relaxation and reduce stress compared to spending time in a city. The aim of this study was to compare stays in a forest with another natural environment, a cultivated field. Healthy, highly sensitive persons (HSP, SV12 score > 18) aged between 18 and 70 years spent one hour in the forest and in the field at intervals of one week. The primary outcome was measured using the Change in Subjective Self-Perception (CSP-14) questionnaire. Secondary outcomes were measured using the Profile Of Mood States (POMS) questionnaire and by analyzing salivary cortisol. We randomized 43 participants. Thirty-nine were allocated and included in the intention-to-treat analysis (90% female, mean age 45 years). CSP-14 in part showed significant differences-total score (p = 0.054, Cohen's d = 0.319), item "integration" (p = 0.028, Cohen's d = 0.365)-favoring the effects of the forest. These effects were more pronounced in summer (August). In October, during rainfall, we detected no relevant differences. POMS only showed a significant difference in the subcategory "depression/anxiety" in favor of the field. The amount of cortisol in saliva was not different between the groups. A short-term stay in a forest in summer caused a greater improvement in mood and well-being in HSP than in a field. This effect was not detectable during bad weather in the fall.

Prenatal stress perturbs fetal iron homeostasis in a sex specific manner.

The adverse effects of maternal prenatal stress (PS) on child's neurodevelopment warrant the establishment of biomarkers that enable early interventional therapeutic strategies. We performed a prospective matched double cohort study screening 2000 pregnant women in third trimester with Cohen Perceived Stress Scale-10 (PSS-10) questionnaire; 164 participants were recruited and classified as stressed and control group (SG, CG). Fetal cord blood iron parameters of 107 patients were measured at birth. Transabdominal electrocardiograms-based Fetal Stress Index (FSI) was derived. We investigated sex contribution to group differences and conducted causal inference analyses to assess the total effect of PS exposure on iron homeostasis using a directed acyclic graph (DAG) approach. Differences are reported for p < 0.05 unless noted otherwise. Transferrin saturation was lower in male stressed neonates. The minimum adjustment set of the DAG to estimate the total effect of PS exposure on fetal ferritin iron biomarkers consisted of maternal age and socioeconomic status: SG revealed a 15% decrease in fetal ferritin compared with CG. Mean FSI was higher among SG than among CG. FSI-based timely detection of fetuses affected by PS can support early individualized iron supplementation and neurodevelopmental follow-up to prevent long-term sequelae due to PS-exacerbated impairment of the iron homeostasis.

Complementary medicine in orthopaedic and trauma surgery: a cross-sectional survey on usage and needs.

OBJECTIVES: Complementary and alternative medicine (CAM) is frequently used in Western countries within general medicine and internal medicine. Information on the use in orthopaedic and trauma surgery is widely lacking. The aim of this study was to investigate usage and needs regarding CAM for these patients. DESIGN: Prospective paper-based, pseudoanonymous, cross-sectional survey. SETTING: From August to December 2018, a questionnaire composed of 17 questions was distributed to all eligible patients. PARTICIPANTS: In-house patients in orthopaedic and trauma surgery at a high-volume medical centre in Germany. PRIMARY AND SECONDARY OUTCOME MEASURES: Previous or current usage of CAM, interest and requests towards CAM as well as communication about CAM. RESULTS: Overall, 457 orthopaedic and trauma surgical patients took part in the survey. They were on average 52 years old and 54% were male. Most of the patients were admitted due to bone fractures and most underwent operative therapy. Previous or current CAM usage was stated by 76% and 30% of patients, respectively. Most of the patients stated to be interested in usage of CAM and demanded for more clinical usage of CAM and reliable information about CAM. More than 90% of patients did not discuss CAM interest or usage with their treating physicians. Patients stated that physicians should have knowledge about CAM. They wish to be treated in a holistic manner and want to strengthen self-efficacy. CONCLUSIONS: Usage of CAM of patients in orthopaedic and trauma surgery appears to be high. Only a few patients discuss their interest and usage of CAM with their treating physician. Therefore, surgeons should ask their patients about CAM and should consider evidence-based CAM approaches for complementary treatment. TRIAL REGISTRATION NUMBER: DRKS0001544.

Efficacy of Carbohydrate Supplementation Compared With Bolus Insulin Dose Reduction Around Exercise in Adults With Type 1 Diabetes: A Retrospective, Controlled Analysis.

OBJECTIVES: Individuals with type 1 diabetes try to manage the risk of exercise-induced hypoglycemia by either pre-exercise/pre-meal bolus insulin dose reductions and/or consuming additional carbohydrates during exercise. Both strategies have proven to be effective in offsetting hypoglycemia, but it remains unclear which one is more beneficial. The aim of this study was to assess the efficacy of carbohydrate supplementation vs bolus insulin dose reduction in prevention of hypoglycemia during moderate-intensity exercise in those with type 1 diabetes. METHODS: This investigation was a retrospective, controlled analysis of 2 independent clinical trials. All participants performed continuous, moderate-intensity cycle ergometer exercise for ∼45 minutes. Two therapy management groups and a control group were compared. Group A was supplemented with 15 to 30 g carbohydrates at a glycemic threshold of 7.0 mmol/L during exercise, group B reduced their individual bolus insulin dose by 50% with their last meal before exercise and group C served as a control. RESULTS: No hypoglycemic events occurred in group A, whereas 4 events were recorded in groups B (p=0.02) and C (p=0.02). CONCLUSIONS: Carbohydrate supplementation was superior to bolus insulin reduction for prevention of hypoglycemia during exercise in people with type 1 diabetes.

5-Hydroxymethylfurfural and Alpha-Ketoglutaric Acid as an Ergogenic Aid During Intensified Soccer Training: A Placebo Controlled Randomized Study.

Intensified training may lead to fatigue or even a state of overreaching with temporary reductions in performance. Any aid helping to prevent these consequences and to better tolerate such a training regime would be of great importance. 5-hydroxymethylfurfural (5-HMF) and α-ketoglutaric acid (α-KG) supplementation has been suggested to support favorable training outcomes but its effectiveness to facilitate adaptations during an intensified training period has never been investigated. During an in-season competition break (2 weeks), seventeen young outfield soccer players (age:14.7 ± 0.4 yr) performed a 9-day lasting shock microcyle including 5-7 repeated sprint exercise sessions in addition to the regular training (∼6 sessions/wk) and match (1-2 matches/wk) schedule. Before the training period a treadmill test to exhaustion, a YOYO intermittent recovery level 2 (YYIR2) and a repeated sprint ability (RSA) test were performed. The treadmill test was repeated 3 days after the shock microcycle whereas the YYIR2 and the RSA test on day 10 after the training. Magnitude based inference analysis showed likely positive effects of the 5-HMF/α-KG compared to the control group for changes in the maximal running velocity (+0.3 ± 0.7 vs. -0.3 ± 0.8 km/h) and running velocity at lactate turn-point 1 (+0.2 ± 0.4 vs. -0.2 ± 0.6) and lactate turn-point 2 (+0.4 ± 0.4 vs. -0.2 ± 0.6 km/h, for the 5-HMF/α-KG and placebo group, respectively). Training improved YYIR2 performance (+180 ± 67 vs. +200 ± 168m) and RSA (mean time: -0.1 ± 0.1 vs. -0.1 ± 0.1s, for the 5-HMF/α-KG and placebo group, respectively) in both groups and to the same extent. In conclusion, an in-season shock microcyle including repeated sprint training improves YYIR2 performance and RSA in youth soccer players. Supplementation with 5-HMF/α-KG did not modify training adaptations but led to likely positive exercise performance responses shortly after the intensified training regime.

Holistic physical exercise training improves physical literacy among physically inactive adults: a pilot intervention study.

BACKGROUND: Physical literacy (PL), given as a multidimensional construct, is considered a person's capacity and commitment to a physically active lifestyle. We investigated the effect of a holistic physical exercise training on PL among physically inactive adults. METHODS: A non-randomised controlled study was conducted. Thirty-one physically inactive adults in the intervention group (IG; 81% females, 44 ± 16 years) participated in a holistic physical exercise training intervention once weekly for 15 weeks. A matched, non-exercising control group (CG) consisted of 30 physically inactive adults (80% female, 45 ± 11 years). PL, compliance and sociodemographic parameters were measured. PL was evaluated by a questionnaire, covering five domains: physical activity behaviour, attitude towards a physically active lifestyle, exercise motivation, knowledge and self-confidence/self-efficacy. Data were analysed using ANCOVA models, adjusted for age, gender and BMI at baseline. RESULTS: At post-training intervention, the IG showed significant improvements in PL (p = 0.001) and in the domains physical activity behaviour (p = 0.02) and exercise self-confidence/self-efficacy (p = 0.001), with no changes overserved for the CG regarding PL and those domains. No intervention effect were found for the other three domains, i.e. attitude, knowledge and motivation. Additionally, for the IG baseline BMI was identified to be positively correlated with physical exercise-induced improvements in PL (ß = 0.51, p = 0.01). CONCLUSIONS: The results from this study are very useful for further public health activities, which aim at helping physically inactive adults to adopt a physically active lifestyle as well as for the development of further PL intervention strategies. This pilot-study was a first attempt to measure PL in inactive adults. Yet, a validated measurement tool is still not available. Further research is necessary to determine the psychometric properties for this PL questionnaire. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00013991 , date of registration: 09.02.2018, retrospectively registered.

Prostate volume reduction following pure transurethral bipolar plasma vaporization and conventional transurethral resection of the prostate: a prospective investigation using transrectal 3D ultrasound volumetry.

PURPOSE: To evaluate and compare postoperative changes in prostate volume and clinical outcome after bipolar plasma vaporization (BPV) and conventional transurethral resection of the prostate (TURP). PATIENTS AND METHODS: Consecutive series of patients undergoing BPV or TURP were included in this prospective, nonrandomized study. Planimetric volumetry after transrectal three-dimensional ultrasound of the prostate was performed preoperatively and postoperatively after 6 weeks, 6 months and 12 months. Additionally, changes in clinical outcome parameters were assessed and compared between the groups. The reduction ratio and analysis of covariance were used to compare volume changes between BPV and TURP. Multiple regression analysis was performed to assess a possible interaction between preoperative prostate volume and effect of therapy. RESULTS: A total of 157 patients were included (BPV: n = 68, TURP: n = 89). Median preoperative prostate volume was 43.1 ml in the BPV group and 45.9 ml in the TURP group (p = 0.43). Postoperatively, the prostate volumes decreased significantly in both groups. After catheter removal, the relative residual prostate volume was significantly higher in the BPV group (66.6 vs. 60.8 %; p = 0.02). Thereafter, significant differences were not detectable anymore (12 months: 46.6 vs. 47.1 %; p = 0.82). Regression analysis revealed that tissue ablation after BPV was superior to TURP in prostates <45 ml but inferior in prostates >45 ml. All clinical outcome parameters improved significantly and were not significantly different between the groups. CONCLUSIONS: Volume reduction and short-term clinical outcome following pure BPV was excellent and comparable to conventional TURP. However, volume reduction seems to be limited in patients with larger prostates.

Absorption of irrigation fluid occurs frequently during high power 532 nm laser vaporization of the prostate.

PURPOSE: Absorption of irrigation fluid was not detected during GreenLight™ laser vaporization of the prostate using the first generation 80 W laser. However, data are lacking on intraoperative irrigation fluid absorption using the second generation 120 W high power laser. We assessed whether fluid absorption occurs during high power laser vaporization of the prostate. MATERIALS AND METHODS: We performed this prospective investigation at a tertiary referral center in patients undergoing 120 W laser vaporization for prostatic bladder outlet obstruction. Normal saline containing 1% ethanol was used for intraoperative irrigation. The expired breath ethanol concentration was measured periodically during the operation using an alcometer. The volume of saline absorption was calculated from these concentrations. Intraoperative changes in hematological and biochemical blood parameters were also recorded. RESULTS: Of 50 investigated patients 22 (44%) had a positive breath ethanol test. Median absorption volume in the absorber group was 725 ml (range 138 to 3,452). Ten patients absorbed more than 1,000 ml. Absorbers had a smaller prostate, more capsular perforation, higher bleeding intensity and more laser energy applied during the operation. Three patients (13%) had symptoms potentially related to fluid absorption. Hemoglobin, hematocrit and serum chloride were the only blood parameters that changed significantly in the absorber group. The changes were significantly different than those in nonabsorbers. CONCLUSIONS: Fluid absorption occurs frequently during high power laser vaporization of the prostate. This should be considered in patients who present with cardiopulmonary or neurological symptoms during or after the procedure.

Ablative efficiency of 532-nm laser vaporization compared to transurethral resection of the prostate: results from a prospective three-dimensional ultrasound volumetry study.

PURPOSE: To assess and compare postoperative prostate volume changes following 532-nm laser vaporization (LV) and transurethral resection of the prostate (TURP). To investigate whether differences in volume reduction are associated with differences in clinical outcome. METHODS: In this prospective, non-randomized study, 184 consecutive patients undergoing 120 W LV (n = 98) or TURP (n = 86) were included. Transrectal three-dimensional ultrasound and planimetric volumetry of the prostate were performed preoperatively, after catheter removal, 6 weeks, 6 and 12 months. Additionally, clinical outcome parameters were recorded. Mann-Whitney U test and analysis of covariance were utilized for statistical analysis. RESULTS: Postoperatively, a significant prostate volume reduction was detectable in both groups. However, the relative volume reduction was lower following LV (18.4 vs. 34.7 %, p < 0.001). After 6 weeks, prostate volumes continued to decrease in both groups, yet differences between the groups were less pronounced. Nonetheless, the relative volume reduction remained significantly lower following LV (12 months 43.3 vs. 50.3 %, p < 0.001). All clinical outcome parameters improved significantly in both groups. However, the maximum flow rate (Q max) and prostate-specific antigen (PSA) reduction were significantly lower following LV. Subgroup analyses revealed significant differences only if the initial prostate volume was >40 ml. Re-operations were necessary in three patients following LV. CONCLUSIONS: The modest but significantly lower volume reduction following LV was associated with a lower PSA reduction, a lower Q max and more re-operations. Given the lack of long-term results after LV, our results are helpful for preoperative patient counseling. Patients with large prostates and no clear indication for the laser might not benefit from the procedure.

Pure bipolar plasma vaporization of the prostate: the Zürich experience.

INTRODUCTION AND OBJECTIVES: Bipolar plasma vaporization (BPV) has been introduced as an alternative to transurethral resection of the prostate (TURP). Promising short-term results, but inferior mid-term results compared to TURP have been reported following first-generation bipolar electrovaporization. Outcome data following second-generation BPV are still scarce. The aim of this investigation was to evaluate the intra- and postoperative outcomes of contemporary BPV in a center with long-standing expertise on laser vaporization of the prostate. METHODS: A consecutive series of 83 patients undergoing BPV in a tertiary referral center was prospectively evaluated. The investigated outcome parameters included the maximum flow rate (Qmax), postvoid residual volume, International Prostate Symptom Score (IPSS)/quality of life (Qol), and prostate-specific antigen (PSA) tests. Follow-up investigations took place after 6 weeks, 6 months, and 12 months. The Wilcoxon signed-rank test was used to compare pre- and post-treatment parameters. RESULTS: The median (range) preoperative prostate volume was 41 mL (17-111 mL). The preoperative IPSS, Qol, Qmax, and residual volume were 16 (2-35), 4 (0-6), 10.1 mL/s (3-29.3 mL/s), and 87 mL (0-1000 mL), respectively. One third of the patients were undergoing platelet aggregation inhibition (PAI). No intraoperative complications occurred. Postoperatively, 13 patients (15.7%) had to be recatheterized. Three patients (3.6%) had clot retention and 28 patients (34%) reported any grade of dysuria. After 6 weeks, all outcome parameters improved significantly and remained improved over the 12-month observation period [IPSS: 3 (0-2); Qol: 1 (0-4); Qmax: 17.2 mL/s (3.2-56 mL/s); residual volume 11 mL (0-190 mL)]. The PSA reduction was 60% at study conclusion. Three patients (3.6%) developed a urethral stricture and four patients (4.8%) bladder neck sclerosis. Re-resections were not necessary. CONCLUSIONS: Contemporary BPV is a safe and efficacious treatment option even for patients undergoing PAI. Early urinary retention and temporary dysuria seem to be specific side effects of the treatment. Bleeding complications are rare. Long-term follow-up is needed to confirm these promising short-term results.

Design and evaluation of a hybrid radiofrequency applicator for magnetic resonance imaging and RF induced hyperthermia: electromagnetic field simulations up to 14.0 Tesla and proof-of-concept at 7.0 Tesla.

This work demonstrates the feasibility of a hybrid radiofrequency (RF) applicator that supports magnetic resonance (MR) imaging and MR controlled targeted RF heating at ultrahigh magnetic fields (B0≥7.0T). For this purpose a virtual and an experimental configuration of an 8-channel transmit/receive (TX/RX) hybrid RF applicator was designed. For TX/RX bow tie antenna electric dipoles were employed. Electromagnetic field simulations (EMF) were performed to study RF heating versus RF wavelength (frequency range: 64 MHz (1.5T) to 600 MHz (14.0T)). The experimental version of the applicator was implemented at B0 = 7.0T. The applicators feasibility for targeted RF heating was evaluated in EMF simulations and in phantom studies. Temperature co-simulations were conducted in phantoms and in a human voxel model. Our results demonstrate that higher frequencies afford a reduction in the size of specific absorption rate (SAR) hotspots. At 7T (298 MHz) the hybrid applicator yielded a 50% iso-contour SAR (iso-SAR-50%) hotspot with a diameter of 43 mm. At 600 MHz an iso-SAR-50% hotspot of 26 mm in diameter was observed. RF power deposition per RF input power was found to increase with B0 which makes targeted RF heating more efficient at higher frequencies. The applicator was capable of generating deep-seated temperature hotspots in phantoms. The feasibility of 2D steering of a SAR/temperature hotspot to a target location was demonstrated by the induction of a focal temperature increase (ΔT = 8.1 K) in an off-center region of the phantom. Temperature simulations in the human brain performed at 298 MHz showed a maximum temperature increase to 48.6C for a deep-seated hotspot in the brain with a size of (19×23×32)mm(3) iso-temperature-90%. The hybrid applicator provided imaging capabilities that facilitate high spatial resolution brain MRI. To conclude, this study outlines the technical underpinnings and demonstrates the basic feasibility of an 8-channel hybrid TX/RX applicator that supports MR imaging, MR thermometry and targeted RF heating in one device.

Implementation of a design of experiments to study the influence of the background electrolyte on separation and detection in non-aqueous capillary electrophoresis-mass spectrometry.

Non-aqueous capillary electrophoresis (NACE) background electrolytes are most often composed of a mixture of methanol and acetonitrile (ACN) with soluble ammonium salts added as electrolyte. In this study on NACE-MS, we used a mixture of glacial acetic acid and ACN giving rise to an acidic background electrolyte (BGE) with a very low dielectric constant. Impressive changes in selectivity and resolution were observed for structurally closely related indole alkaloids including diastereomers upon addition of ammonium formate as electrolyte and upon variation of the solvent ratio. In order to obtain best separation and MS detection conditions and to reveal the influence of the parameters of the BGE on separation and detection and vice versa of the MS parameters on separation, an optimization strategy was employed using a design of experiments in a central composite design with response surface methodology. It was proven that at high electroosmotic flow conditions capillary electrophoretic separations and thus optimization can be realized without interference from the coupling to an MS system. Several significantly interacting parameters were revealed, which are not accessible with classical univariate optimization approaches. With this optimization, alkaloid mixtures from a plant extract of Mitragyna speciosa, containing a large number of diastereomeric compounds were successfully separated.

Cardiac and gastrointestinal liabilities caused by deficiency in the immune modulatory enzyme indoleamine 2,3-dioxygenase.

Indoleamine 2,3-dioxygenase (IDO) modifies adaptive immunity, in part by determining the character of inflammatory responses in the tissue microenvironment. Small molecule inhibitors of IDO are being developed to treat cancer, chronic infections and other diseases, so the systemic effects of IDO disruption on inflammatory phenomena may influence the design and conduct of early phase clinical investigations of this new class of therapeutic agents. Here, we report cardiac and gastrointestinal phenotypes observed in IDO deficient mice that warrant consideration in planned assessments of the safety risks involved in clinical development of IDO inhibitors. Calcification of the cardiac endometrium proximal to the right ventricle was a sexually dimorphic strain-specific phenotype with ~30% penetrance in BALB/c mice lacking IDO. Administration of complete Freund's adjuvant containing Toll-like receptor ligands known to induce IDO caused acute pancreatitis in IDO deficient mice, with implications for the design of planned combination studies of IDO inhibitors with cancer vaccines. In an established model of hyperlipidemia, IDO deficiency caused a dramatic elevation in levels of serum triglycerides. In the large intestine, IDO loss only slightly increased sensitivity to induction of acute colitis, but it markedly elevated tumor incidence, multiplicity and staging during inflammatory colon carcinogenesis. Together, our findings suggest potential cardiac and gastrointestinal risks of IDO inhibitors that should be monitored in patients as this new class of drugs enter early clinical development.

Zinc protoporphyrin IX stimulates tumor immunity by disrupting the immunosuppressive enzyme indoleamine 2,3-dioxygenase.

The tryptophan catabolic enzyme indoleamine 2,3-dioxygenase (IDO) has emerged as an important driver of immune escape in a growing number of cancers and cancer-associated chronic infections. In this study, we define novel immunotherapeutic applications for the heme precursor compound zinc protoporphyrin IX (ZnPP) based on our discovery that it is a potent small-molecule inhibitor of IDO. Inhibitory activity was determined using in vitro and in-cell enzyme assays as well as a novel in vivo pharmacodynamic system. An irreversible mechanism of inhibition was documented, consistent with competition for heme binding in newly synthesized cellular protein. siRNA methodology and an IDO-deficient mouse strain were used to verify the specificity of ZnPP as an IDO inhibitor. In a preclinical model of melanoma, ZnPP displayed antitumor properties that relied on T-cell function and IDO integrity. ZnPP also phenocopied the known antitumor properties of IDO inhibitors in preclinical models of skin and breast carcinoma. Our results suggest clinical evaluation of ZnPP as an adjuvant immunochemotherapy in chronic infections and cancers in which there is emerging recognition of a pathophysiologic role for IDO dysregulation.

The effect of hyperbaric oxygen therapy on erectile function recovery in a rat cavernous nerve injury model.

INTRODUCTION: Cavernosal oxygenation appears to be important for preservation of erectile tissue health. Hyperbaric oxygen therapy (HBOT) has been shown to improve tissue oxygenation and has neuromodulatory effects. AIM: This study was designed to define the effects of HBOT on erectile function (EF) and cavernosal tissue in the rat cavernous nerve (CN) injury model. METHODS: Four groups of Sprague-Dawley rats were studied: rats with bilateral CN crush, HBOT treated (Crush+/HBOT+); bilateral CN-crush/no HBOT (C+/H-); no crush/no HBOT (C-/H-); and no crush/HBOT (C-/H+). HBOT was delivered daily for 90 minutes at three atmospheres for 10 days commencing the day of CN crush. MAIN OUTCOME MEASURES: Ten days after CN injury, the animals underwent CN stimulation measuring the maximal intracavernosal pressure/mean arterial pressure (ICP/MAP) ratios. Corporal tissue was harvested pre-sacrifice, and immunohistochemically stained for nerve growth factor (NGF), endothelial nitric oxide synthase (eNOS), and cluster of differentiation molecule (CD31). Histologic analysis was performed for Masson's trichrome to assess the smooth muscle-collagen ratio. Terminal deoxynucleotidyl transferase Biotin-dUTP Nick End Labeling assay was used to define apoptotic indices (AIs). RESULTS: The C+/H- group had significantly lower ICP/MAP ratios compared with C-/H- rats, (31% vs. 70%, P < 0.001). C+/H+ rats had significantly higher ICP/MAP ratio recovery compared with the C+/H- group (55% vs. 31%, P = 0.005). NGF and eNOS staining densities were higher in C+/H+ rats compared with C+/H- rats (P < 0.05 and P < 0.001, respectively). No difference was seen in CD31 expression. Staining density for MT displayed a trend toward higher smooth muscle preservation after HBOT. AIs were significantly increased by HBOT (P < 0.05). CONCLUSION: HBOT following a CN injury improved EF preservation in this model, supporting the cavernosal oxygenation concept as protective mechanism for EF. The effects appear to be mediated via preservation of neurotrophic and endothelial factor expression.

The impact of shock wave therapy at varied energy and dose levels on functional and structural changes in erectile tissue.

OBJECTIVES: Only minimal literature exists on consequences of shock wave therapy (SWT) on erectile function in treatment of Peyronie's disease (PD). This study was undertaken to define SWT impact at varied energy/dose levels at different time points on functional and structural changes in erectile tissue. METHODS: In 45 rats 2000 shock waves (sw) at 2 BAR were applied to the penis weekly sorted by one, two, and three sessions (high-dose/energy level, HD-1, HD-2, HD-3). Each group was followed for 1, 7, or 28 d before measuring intracavernosal pressure (ICP) and mean arterial pressure (MAP). Fifteen control animals (C1, C7, C28) underwent anesthesia alone. Another 15 animals were exposed to three SWT sessions applying 1000 sw at 1 BAR and analyzed identically (low-dose/energy level, LD-3-1, -7, -28). Terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling assay was used to define the apoptotic index (AI) and Masson's trichrome (MT) staining was prepared to evaluate smooth muscle-to-collagen ratios. RESULTS: ICP/MAP ratios for all C groups displayed a mean of 64%. All SWT groups demonstrated significantly reduced ICP/MAP ratios compared to their corresponding C groups (p<0.05). The LD-3 groups showed a trend toward improved ICP/MAP ratios. LD-3-28 demonstrated significant recovery compared to HD-3-28 (55+/-8% vs. 41+/-10%, p=0.004), but remained reduced compared to C28 (63+/-5%, p=0.03). No statistical differences were seen for MT staining in SWT groups compared to C (p>0.05). AIs for the LD-3 groups were significantly lower compared to the HD-3 groups (p<0.001), but all AIs were significantly increased compared to C groups (p<0.01). CONCLUSIONS: Overall, at both energy/dose levels, SWT resulted in a time- and treatment-dependent reduction of ICP/MAP ratios, which might be mediated partly through apoptosis and collagenization of corporal smooth muscle.

Photoselective vaporization (PVP) versus transurethral resection of the prostate (TURP): a prospective bi-centre study of perioperative morbidity and early functional outcome.

OBJECTIVES: To compare the early follow-up and perioperative morbidity of photoselective vaporization (PVP) and transurethral resection of the prostate (TURP) in patients (pts.) suffering from lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). MATERIAL AND METHOD: 101 pts. underwent PVP (n = 64) and TURP (n = 37) in a prospective, non-randomized bi-centre trial. Inclusion criteria were identical at both centres. Primary outcome parameters were maximum urinary flow rate (Q(max)), post-void residual volume (V(res)), International Prostate Symptom Score (IPSS). Secondary outcomes included intraoperative surgical parameters and perioperative and post-discharge morbidity. RESULTS: Baseline characteristics of both groups were similar. Operating time was slightly shorter in the TURP group (p = 0.047). During TURP significant more irrigation solution was used (p < 0.001). Decrease of serum haemoglobin (p = 0.027) and serum sodium (p = 0.013) was larger after TURP. Catheter drainage was removed significant earlier after PVP than after TURP (p < 0.001). Outcome of Q(max), and IPSS were similar in both groups within 6 months. The sort of perioperative complications was different in both groups, however overall cumulative perioperative morbidity was comparable (PVP 39.1% versus TURP 43.2.1%; ns). CONCLUSION: PVP provides excellent intraoperative safety, instant tissue removal, and immediate relief from obstructive voiding symptoms, similar to TURP. Early outcomes 6-months after PVP and TURP are comparable.