Alpha/beta oscillations reveal cognitive and affective brain states associated with role taking in a dyadic cooperative game.

Social cooperation often requires taking different roles in order to reach a shared goal. By defining individual tasks, these roles dictate processing demands of the collaborators. The main aim of the present study was to examine the hypothesis that induced alpha and lower beta oscillations provide insights into affective and cognitive brain states during social cooperation. Toward this end, an experimental game was used in which participants had to navigate a Pacman figure through a maze by sending and receiving information about the correct moving direction. Supporting our hypotheses, individual roles taken by the collaborators during gameplay were associated with significant changes in alpha and lower beta power. Furthermore, effects were similar when participants played the Pacman Game with human or computer partners. Findings are discussed from the perspective of the information-via-desynchronization hypothesis proposing that alpha and lower beta power decreases reflect states of enhanced cortical information representation. Overall, experimental games are a useful tool for extending basic research on brain oscillations to the domain of naturalistic social interaction as emphasized by the second-person neuroscience perspective.

Recovery of sperm quality after COVID-19 disease in male adults under the influence of a micronutrient combination: A prospective study.

OBJECTIVE: This study aims to evaluate the safety and efficacy of a standard micronutrient preparation to improve semen parameters and seminal oxidative stress in adult male subjects after Coronavirus Disease 2019 (COVID-19) disease. METHODS: For this prospective pilot study, 30 males aged 20-50 years who had recently recovered from a symptomatic SARS-CoV-2 infection were recruited from June to October 2021 through a public call for participation. Participants of the study group (n = 30) received two semen analyses according to WHO criteria at an interval of 12 weeks, during which they daily received a micronutrient preparation (L-carnitine, L-arginine, coenzyme Q10, vitamin E, zinc, folic acid, glutathione and selenium). Changes in major semen variables and seminal oxidative stress levels before and after therapy were analyzed and compared to a control group (n = 10) adhering to the same inclusion criteria, including subjects who recently recovered from symptomatic COVID-19 disease without micronutrient supplementation within the 12 weeks between the two semen analyses. RESULTS: After 3 months of micronutrient supplementation the rate of normal semen analysis results in the study group increased significantly (p = 0.009) by 66.7%: from 50.0% before to 83.3% after therapy. There was a significant increase in progressive (p = 0.014) and overall motility (p = 0.05) as well as in the vitality (p = 0.0004) of semen cells after 12 weeks of micronutrient intake. In the control group there were no significant changes in any semen parameter or in the rate of normal semen analysis results over the 3-month observation period. In both groups, sperm density, morphology and oxidative stress did not improve significantly. CONCLUSIONS: Our data suggests that supplementation of certain micronutrients may be a safe way to support recovery of impaired semen parameters in male adults recovered from COVID-19 disease.

The effect of micronutrient supplementation on serum anti-Mullerian hormone levels: a retrospective pilot study.

BACKGROUND: The anti-Müllerian-hormone (AMH) is secreted by the granulosa cells of the oocytes and can be used as a marker of the ovarian reserve; helpful to estimate female fertility or the menopause onset. Although various factors may influence AMH levels, the correlation with nutritional factors needs more research. OBJECTIVE: To evaluate the effect of a micronutrient supplementation on female AMH levels. METHODS: This retrospective analysis includes a total of 244 women, who attended the Karl Landsteiner Institute, Korneuburg, Austria from January 2013 to June 2019 due to an unfulfilled desire for a child. All women were treated with an oral micronutrient preparation consisting the dosage of one soft capsule and one tablet per day for 3 months. The soft capsule contains omega-3 fatty acids and the tablet is a standardized combination of coenzyme Q10, vitamin E, folic acid, selenium, catechins from green tea extract, and glycyrrhizin from licorice extract. Serum AMH levels before and after 3 months were compared. In addition, available clinical data such as ovulation frequency, endometrium thickness, and luteal phase duration were analyzed. RESULTS: The mean age of the women was 37.3 ± 1.8 years, the mean body mass index of 24.3 ± 4.6 k/m2. The mean serum AMH levels and endometrial thickness values were significantly higher after micronutrient supplementation as compared to baseline (1.42 ± 0.86 versus 1.86 ± 0.82 ng/mL and 6.10 ± 1.76 versus 7.29 ± 1.65 mm, respectively). In addition, ovulation frequency and luteal phase duration significantly improved in more than 60%. CONCLUSION: Proposed micronutrient supplementation had a positive effect on serum AMH levels, endometrial thickness, ovulation frequency, and luteal phase duration. It could be a simple, risk-free therapeutic option to improve female fertility. More research is warranted to prove this effect.

[Case Report: Heterotopic Retransplantation of Cryopreserved Ovarian Tissue after Adenocarcinoma of the Uterine Cervix]. / Fallbericht: heterotope Retransplantation von kryokonserviertem Ovarialgewebe nach Adenokarzinom der Cervix uteri.

Introduction: Retransplantation of cryopreserved ovarian tissue has become an established method of restoring autologous hormone production and fertility after radiotherapy and/or chemotherapy for underlying oncological disease in women of reproductive age and has so far led to more than 170 births worldwide. Case presentation and course: In 2013, the 31-year-old patient developed adenocarcinoma of the uterine cervix, pT1b1V0L0. In January 2014, an extended hysterectomy with lymph node dissection and bilateral adnexectomy were performed. At the patient's request, ovarian tissue was cryopreserved 2 days previously. In November 2019, the retransplantation of two ovarian tissue pieces along the brachial fascia of the left forearm was performed, with no recurrence for 5 years under ongoing hormone replacement therapy (HRT). At 1 month following retransplantation, the patient stopped taking HRT, and 3 months later proper function of the retransplanted tissue could be demonstrated by checking gonadotropins and E2 levels. There was a clear swelling in the area of the retransplantation site, and three vital follicles could be visualized during an ultrasound examination in May 2020. Conclusion: This is the first successful retransplantation of cryopreserved ovarian tissue to restore autologous hormone production in a cervical cancer patient in Austria. Based on blood, ultrasound and cytological examinations, not to mention the patient's personal well-being, functionality of the retransplanted tissue could be demonstrated even at 6 months after the procedure. Finally, the authors would like to highlight the importance of informing and consulting young patients with tumor diseases on the various possibilities of fertility preservation.

Strong health messages increase audience brain coupling.

Mass media messaging is central for health communication. The success of these efforts, however, depends on whether health messages resonate with their target audiences. Here, we used electroencephalography (EEG) to capture brain responses of young adults - an important target group for alcohol prevention - while they viewed real-life video messages of varying perceived message effectiveness about risky alcohol use. We found that strong messages, which were rated to be more effective, prompted enhanced inter-subject correlation (ISC). In further analyses, we linked ISC to subsequent drinking behavior change and used time-resolved EEG-ISC to model functional neuroimaging data (fMRI) of an independent audience. The EEG measure was not only related to sensory-perceptual brain regions, but also to regions previously related to successful messaging, i.e., cortical midline regions and the insula. The findings suggest EEG-ISC as a marker for audience engagement and effectiveness of naturalistic health messages, which could quantify the impact of mass communication within the brains of small target audiences.

Impressions of HIV risk online: Brain potentials while viewing online dating profiles.

There is an increasing trend to use online dating to meet potential partners. Previous studies in off-line contexts indicate that people may judge the risk of sexually transmitted infections based on a person's appearance. Online dating profiles commonly present profile pictures and verbal self-descriptions. To examine the integration of verbal and visual risk information, the current event-related potential (ERP) study used a simulated dating platform in which verbal-descriptive information (low vs. high verbal risk) was presented, followed by a photograph (low vs. high visual risk). Results indicated main effects of verbal and visual risk. Specifically, high-risk compared with low-risk verbal profiles elicited a relative negative shift over occipitoparietal sensor sites between 260 ms and 408 ms. Furthermore, a sustained occipital negativity (132-500 ms) and central positivity (156-272 ms) was observed for high as compared with low visual risk profiles. There was also evidence for the integration of verbal and visual risk formation, as indicated by distinct positive ERP shift occurred between 272 ms and 428 ms over anterior temporal regions when a high-risk photograph was preceded by high-risk verbal information. This suggests that verbal-descriptive information is integrated with visual appearance early in the processing stream. The distinct response for high verbal and visual information extends the notion of an alarm function ascribed to risk perception by demonstrating integration about multiple sources. Simulating online dating platforms provides a useful tool to examine intuitive risk perception.

The impact of a standardized micronutrient supplementation on PCOS-typical parameters: a randomized controlled trial.

PURPOSE: To evaluate whether a micronutrient supplementation preparation that includes a high amount of omega-3 unsaturated acids, other anti-oxidants and co-enzyme Q10 would have an impact on specific serum parameters in women with polycystic ovary syndrome (PCOS). METHODS: The study was designed as a monocentral, randomized, controlled, double-blinded trial, from June 2017 to March 2018 (Clinical Trials ID: NCT03306745). Sixty women with PCOS were assigned to either the "multinutrient supplementation group" (one unlabeled soft capsule containing omega-3 fatty acids and one unlabeled tablet containing folic acid, selenium, vitamin E, catechin, glycyrrhizin, and co-enzyme Q10, for 3 months) or the "control group" (two unlabeled soft capsules containing 200 µg folic acid each, for 3 months). The main outcome parameters were anti-Mullerian hormone (AMH), total testosterone, and androstenedione. In addition, the focus was on luteinizing hormone (LH), follicle-stimulating hormone (FSH), the LH:FSH ratio, sexual hormone-binding globulin (SHBG), and estradiol. RESULTS: In the multinutrient supplementation group, the LH:FSH ratio (2.5 ± 1.1 versus 1.9 ± 0.5, p = 0.001), testosterone (0.50 ± 0.19 versus 0.43 ± 0.15, p = 0.001), and AMH (8.2 ± 4.2 versus 7.3 ± 3.6, p < 0.001) declined significantly, whereas the other parameters, namely estradiol, LH, FSH, androstenedione, and SHBG remained stable. CONCLUSION: A micronutrient supplementation that includes omega-3 fatty acids, folic acid, selenium, vitamin E, catechin, glycyrrhizin, and co-enzyme Q10, given for a minimum of 3 months, is beneficial for women with PCOS in terms of PCOS-specific parameters (LH:FSH ratio, serum testosterone and serum AMH).

Visual cues that predict intuitive risk perception in the case of HIV.

Field studies indicate that people may form impressions about potential partners' HIV risk, yet lack insight into what underlies such intuitions. The present study examined which cues may give rise to the perception of riskiness. Towards this end, portrait pictures of persons that are representative of the kinds of images found on social media were evaluated by independent raters on two sets of data: First, sixty visible cues deemed relevant to person perception, and second, perceived HIV risk and trustworthiness, health, and attractiveness. Here, we report correlations between cues and perceived HIV risk, exposing cue-criterion associations that may be used to infer intuitively HIV risk. Second, we trained a multiple cue-based model to forecast perceived HIV risk through cross-validated predictive modelling. Trained models accurately predicted how 'risky' a person was perceived (r = 0.75) in a novel sample of portraits. Findings are discussed with respect to HIV risk stereotypes and implications regarding how to foster effective protective behaviors.

Soy germ extract alleviates menopausal hot flushes: placebo-controlled double-blind trial.

BACKGROUND/OBJECTIVES: A double-blind, placebo-controlled study was performed to assess the potency of a soy germ preparation for the alleviation of menopausal hot flushes. SUBJECTS/METHODS: Caucasian women with at least seven hot flushes daily were treated with soy germ extract (100 mg isoflavone glycosides) daily or with placebo for 12 weeks, followed by 12 weeks of open treatment with soy. Outcome parameters were the number of hot flushes and the evaluation of the Greene Climacteric Scale. RESULTS: A total of 192 women were included. As the hot flush diaries from one study centre were lost, the assessment of hot flushes was based on 136 participants (soy: 54 women; placebo: 82 women). After 12 weeks, 180 women were available for the analysis of Greene Scale and safety (soy and placebo: each 90 women). Hot flushes were reduced by 43.3% (-3.5 hot flushes) with soy and by 30.8% with placebo (-2.6; p < 0.001). After the open treatment phase with soy, both original groups showed a reduction of 68% of hot flushes. A subgroup analysis showed better effects for soy when symptoms were classified as "severe" at baseline. After 12 weeks of double-blind treatment, there was an improvement from baseline values of 71 and 78% with soy with the items "hot flushes" and "sweating", compared with 24% for both items with placebo. Hormonal safety parameters remained uninfluenced. CONCLUSIONS: Soy germ extract with 100 mg of isoflavone glycosides was shown to modestly, but significantly reduce menopausal hot flushes.

How real-life health messages engage our brains: Shared processing of effective anti-alcohol videos.

Health communication via mass media is an important strategy when targeting risky drinking, but many questions remain about how health messages are processed and how they unfold their effects within receivers. Here we examine how the brains of young adults-a key target group for alcohol prevention-'tune in' to real-life health prevention messages about risky alcohol use. In a first study, a large sample of authentic public service announcements (PSAs) targeting the risks of alcohol was characterized using established measures of message effectiveness. In the main study, we used inter-subject correlation analysis of fMRI data to examine brain responses to more and less effective PSAs in a sample of young adults. We find that more effective messages command more similar responses within widespread brain regions, including the dorsomedial prefrontal cortex, insulae and precuneus. In previous research, these regions have been related to processing narratives, emotional stimuli, self-relevance and attention towards salient stimuli. The present study thus suggests that more effective health prevention messages have greater 'neural reach', i.e. they engage the brains of audience members' more widely. This work outlines a promising strategy for assessing the effects of health communication at a neural level.

The Impact of a Standardized Oral Multinutrient Supplementation on Embryo Quality in in vitro Fertilization/Intracytoplasmic Sperm Injection: A Prospective Randomized Trial.

The role of micronutrients in fertility has recently gained increased attention. We aimed to test the impact of a standardized, multinutrient supplementation on outcomes after in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in a pilot study. One hundred women undergoing IVF/ICSI were prospectively included and randomized to receive either a multinutrient supplementation named PROfertil® female that included folic acid, selenium, vitamin E, catechins, glycyrrhizin, diosgenin, damiana and omega-3-fatty acids (study group; n = 50), or 400 µg folic acid (control group; n = 50). Outcome parameters were embryo quality on day 3 after oocyte retrieval (good quality vs. poor quality) and the clinical pregnancy rate. In an intention-to-treat analyses, a higher rate of women with at least one good quality embryo (with at least 6 cells and a fragmentation rate <20%) were found for the study (29/50, 58.0%) compared to the control group (18/50, 36.0%; p = 0.045 in chi-square test; relative risk 1.611, 95% CI 1.009-2.597). In conclusion, a multinutrient supplementation that includes folic acid, selenium, vitamin E, catechins, glycyrrhizin, diosgenin, damiana and omega-3-fatty acids seems beneficial in terms of embryo quality.

Comparison of the effect of a combination of eight micronutrients versus a standard mono preparation on sperm parameters.

BACKGROUND: There are reports showing that l-carnitine alone or in combination with other micronutrients improve sperm parameters. However, comparative studies are still lacking. This study was carried out to compare the short term effects of a combination of eight micronutrients including l-carnitine vs. a mono-substance (l-carnitine alone) on sperm parameters. METHODS: This was a prospective, open-labelled, nonrandomized study that included male subjects (20 to 60 years) with at least 1 year of subfertility and at least one pathological semen analysis who received 3 months treatment with a mono-substance (500 mg l-carnitine/twice a day, n = 156) or a combined compound (440 mg l-carnitine + 250 mg l-arginine + 40 mg zinc + 120 mg vitamin E + 80 mg glutathione + 60 µg selenium + 15 mg coenzyme Q10 + 800 µg folic acid/once a day, n = 143) for the same time period. Sperm parameters were analyzed before and after treatment and groups comparisons performed. RESULTS: Baseline characteristics were similar among studied groups (age and body mass indices). Semen parameters (volume, density, overall progressive motility [including slow and fast motility]) and percentage of sperm with normal morphology improved after 3 months in both groups as compared to baseline. However, relative change (expressed as % increase of absolute values) for sperm density and overall progressive motility (including fast motility) was found to be higher for the combined micronutrient treatment group as compared to the mono-treatment using l-carnitine alone. CONCLUSION: Both analyzed groups displayed a positive short term effect on all sperm parameters; however effect on density and motility was significantly better for the combined formulation. There is need for more research in this matter that includes long term outcome data. TRIAL REGISTRATION: Retrospectively registered at ISRCTN (7th October 2016). Study ID: ISRCTN48594239.

Communicating BRCA research results to patients enrolled in international clinical trials: lessons learnt from the AGO-OVAR 16 study.

BACKGROUND: The focus on translational research in clinical trials has the potential to generate clinically relevant genetic data that could have importance to patients. This raises challenging questions about communicating relevant genetic research results to individual patients. METHODS: An exploratory pharmacogenetic analysis was conducted in the international ovarian cancer phase III trial, AGO-OVAR 16, which found that patients with clinically important germ-line BRCA1/2 mutations had improved progression-free survival prognosis. Mechanisms to communicate BRCA results were evaluated, because these findings may be beneficial to patients and their families. RESULTS: Communicating individual BRCA results was not anticipated during clinical trial design. Consequently, options were not available for patients to indicate their preference for receiving their individual results when they signed pharmacogenetic informed consent. Differences in local requirements, clinical practice, and opinion regarding the ethical aspects of how to convey genetic results to patients are all potential barriers to returning individual BRCA results to patients. Communicating the aggregate BRCA result from this study provided clinical investigators with a mechanism to disseminate the overall study finding to patients while taking individual circumstances, local guidelines and clinical practice into account. CONCLUSION: This study illustrates the importance of increasing the clarity and scope of informed consent and the need for patient engagement to ensure clinical trial participants can indicate their preference regarding receipt of potentially important individual pharmacogenetic results. TRIAL REGISTRATION: This study was registered in the NCT Clinical Trial Registry under NCT00866697 on March 19, 2009, following approval from participating ethics committees (Additional file 1).

BRCA1/2 mutations associated with progression-free survival in ovarian cancer patients in the AGO-OVAR 16 study.

OBJECTIVE: AGO-OVAR 16 demonstrated that pazopanib maintenance therapy significantly increased progression-free survival (PFS) in patients with ovarian cancer whose disease had not progressed after first-line therapy. In a sub-study, we evaluated the effect of clinically important germline BRCA1 and BRCA2 mutations on PFS. METHODS: Of 940 AGO-OVAR 16 participants, 664 had BRCA1/2 exon sequencing data (pazopanib, n=335; placebo, n=329). A Cox model was used to test the association between genetic variants and PFS. RESULTS: Ninety-seven of 664 patients (15%) carried clinically important BRCA1/2 mutations (BRCA1/2 carriers: pazopanib 14%, placebo 16%). Median PFS was longer in BRCA1/2 mutation carriers than in BRCA1/2 non-carriers in the placebo arm (30.3 vs 14.1 months, hazard ratio, 0.48; 95% confidence interval [CI]: 0.29-0.78; P=0.0031); a similar non-significant trend was noted with pazopanib (30.2 vs 17.7 months, hazard ratio, 0.64; 95% CI: 0.40-1.03; P=0.069). Among BRCA1/2 non-carriers, PFS was longer for pazopanib-treated patients than placebo-treated patients (17.7 vs 14.1 months, hazard ratio, 0.77; 95% CI: 0.62-0.97; P=0.024). Among BRCA1/2 carriers, there was no significant PFS difference between treatments, although numbers were small (pazopanib, 46; placebo, 51), resulting in a wide CI (hazard ratio, 1.36; 95% CI: 0.66-2.82). CONCLUSIONS: Patients with clinically important BRCA1/2 mutations had better prognosis. BRCA1/2 mutation status might be added as strata in future trials in primary ovarian cancer.

Red clover isoflavone metabolite bioavailability is decreased after fructooligosaccharide supplementation.

BACKGROUND: Red clover is an important source of isoflavones; which has been made commercially available as dietary supplements for the treatment of menopausal symptoms. Bioavailability and metabolism of these red clover isoflavones (RCI) have not been studied in detail. Fructooligosaccharides (FOS) stimulate the growth of intestinal bacteria and play an important role in the formation of certain isoflavone metabolites, such as equol and O-desmethylangolensin. OBJECTIVE: To determine the bioavailability of RCI metabolites and analyse whether FOS supplementation could influence their bioavailability. METHODS: Seventeen healthy adults were enrolled in the study carried out in two periods. In the first, compound bioavailability was determined after consumption of 80 mg of RCI (MF11RCE). In the second, a 6-day supplementation of 2×3000 mg/day of FOS was administered before isoflavone consumption. RESULTS: Biochanin A and formononetin were rapidly absorbed and both reached maximum concentrations at an average of 5-7h. Demethylation was a major reaction in the metabolic pathway. Daidzein serum level peaked after about 12.6h. Supplementation with FOS led to a significant decrease in the bioavailability of daidzein, dihydroformononetin, dihydrogenistein and dihydrodaidzein. An increase in equol production was also observed which did not reach statistical significance (p>0.05). CONCLUSION: This study is the first to provide detailed data on RCI bioavailability in humans and determine no influence of FOS yet a trend toward increased equol production. More research is warranted involving a greater sample size.

Implicit and Explicit Attention to Pictures and Words: An fMRI-Study of Concurrent Emotional Stimulus Processing.

The present study utilized functional magnetic resonance imaging (fMRI) to examine the neural processing of concurrently presented emotional stimuli under varying explicit and implicit attention demands. Specifically, in separate trials, participants indicated the category of either pictures or words. The words were placed over the center of the pictures and the picture-word compound-stimuli were presented for 1500 ms in a rapid event-related design. The results reveal pronounced main effects of task and emotion: the picture categorization task prompted strong activations in visual, parietal, temporal, frontal, and subcortical regions; the word categorization task evoked increased activation only in left extrastriate cortex. Furthermore, beyond replicating key findings regarding emotional picture and word processing, the results point to a dissociation of semantic-affective and sensory-perceptual processes for words: while emotional words engaged semantic-affective networks of the left hemisphere regardless of task, the increased activity in left extrastriate cortex associated with explicitly attending to words was diminished when the word was overlaid over an erotic image. Finally, we observed a significant interaction between Picture Category and Task within dorsal visual-associative regions, inferior parietal, and dorsolateral, and medial prefrontal cortices: during the word categorization task, activation was increased in these regions when the words were overlaid over erotic as compared to romantic pictures. During the picture categorization task, activity in these areas was relatively decreased when categorizing erotic as compared to romantic pictures. Thus, the emotional intensity of the pictures strongly affected brain regions devoted to the control of task-related word or picture processing. These findings are discussed with respect to the interplay of obligatory stimulus processing with task-related attentional control mechanisms.

Interaction of tumor cells with the immune system: implications for dendritic cell therapy and cancer progression.

There is a continuous demand for preclinical modeling of the interaction of dendritic cells with the immune system and cancer cells. Recent progress in gene expression profiling with nucleic acid microarrays, in silico modeling and in vivo cell and animal approaches for non-clinical proof of safety and efficacy of these immunotherapies is summarized. Immunoinformatic approaches look promising to unfold this potential, although still unstable and difficult to interpret. Animal models have progressed a great deal in recent years, finally narrowing the gap from bench to bedside. However, translation to the clinic should be done with precaution. The most significant results concerning clinical benefit might come from detailed immunologic investigations made during well designed clinical trials of dendritic-cell-based therapies, which in general prove safe.

Stability of purple membranes from Halobacterium salinarum toward surfactants: inkjet printing of a retinal protein.

Inkjet printing is a versatile technique widely applied in biological microarray technology. Because of its photochemical and photophysical properties, bacteriorhodopsin (BR) from Halobacterium salinarum holds promise for applications in nanotechnology, and inkjet printing would simplify the transfer of BR to suitable substrates. Surfactants are essential parts of inkjet formulations tuning viscosity, rheology, and spreading behavior of the solution. However, many surfactants destabilize the structure of proteins and often cause denaturation accompanied by a complete loss of function. Inkjet printing of membrane proteins is particularly challenging and special care must be taken in the choice of the surfactant. For BR, the situation is complicated by the fact that the structural integrity of BR depends on its native membrane environment, the so-called purple membrane (PM). PM contains 10 lipid molecules per BR monomer and is very sensitive toward surfactants. In this work, we identified surfactants suitable for inkjet formulations containing PM. Initially, we screened a variety of technically relevant surfactants for compatibility with PM using the UV-vis absorption of the retinal chromophore as a natural probe. Promising candidates were selected, and their impact on the structure of PM and BR was analyzed using UV-vis spectroscopy, CD spectroscopy, and small-angle X-ray scattering (SAXS). We identified two surfactants compatible with PM and suitable for inkjet formulations. An inkjet formulation containing PM as dye component was developed. We demonstrate that the photochromic properties of BR are maintained upon inkjet printing.

Structural changes in bacteriorhodopsin caused by two-photon-induced photobleaching.

Bacteriorhodopsin (BR) is the key protein of the halobacterial photosynthetic system. BR assembles into two-dimensional crystalline patches, the so-called purple membranes (PM), and acts as a light-driven proton pump converting light energy into the chemical energy of a proton gradient over the cell membrane. The two-photon absorption (TPA) of BR is so far not fully understood. Astonishingly high TPA cross sections have been reported, but the molecular mechanisms have not been elucidated. In this work, we address structural changes in BR and PM upon TPA, investigating its TPA photochemistry by spectroscopy, small-angle X-ray scattering, as well as electron and atomic force microscopy. We observe that TPA of BR leads to formation of an UV-absorbing N-retinyl-bacterioopsin state, which is accompanied by the loss of crystalline order in PM. FTIR and CD spectroscopy confirm that BR trimers as well as the secondary structure of the BR molecules are preserved. We demonstrate that excitation by TPA results in the photochemical reduction of the retinal Schiff base, which in turn causes a permanent asymmetric shape change of BR, similar to the one transiently observed during the photocycle-related opening and closing of the cytoplasmic proton half channel. This shape change causes PM sheets to merely roll up toward the extracellular side and causes the loss of crystallinity of PM. We present a model for the TPA photoresponse of BR, which also explains the irreversibility of the process in terms of a photochemical reduction of the Schiff base.

The impact of varicocelectomy on sperm parameters: a meta-analysis.

PURPOSE: We determined the impact of 3 surgical techniques (high ligation, inguinal varicocelectomy and the subinguinal approach) for varicocelectomy on sperm parameters (count and motility) and pregnancy rates. MATERIALS AND METHODS: By searching the literature using MEDLINE and the Cochrane Library with the last search performed in February 2011, focusing on the last 20 years, a total of 94 articles published between 1975 and 2011 reporting on sperm parameters before and after varicocelectomy were identified. Inclusion criteria for this meta-analysis were at least 2 semen analyses (before and 3 or more months after the procedure), patient age older than 19 years, clinical subfertility and/or abnormal semen parameters, and a clinically palpable varicocele. To rule out skewing factors a bias analysis was performed, and statistical analysis was done with RevMan5(®) and SPSS 15.0(®). RESULTS: A total of 14 articles were included in the statistical analysis. All 3 surgical approaches led to significant or highly significant postoperative improvement of both parameters with only slight numeric differences among the techniques. This difference did not reach statistical significance for sperm count (p = 0.973) or sperm motility (p = 0.372). After high ligation surgery sperm count increased by 10.85 million per ml (p = 0.006) and motility by 6.80% (p <0.00001) on the average. Inguinal varicocelectomy led to an improvement in sperm count of 7.17 million per ml (p <0.0001) while motility changed by 9.44% (p = 0.001). Subinguinal varicocelectomy provided an increase in sperm count of 9.75 million per ml (p = 0.002) and sperm motility by 12.25% (p = 0.001). Inguinal varicocelectomy showed the highest pregnancy rate of 41.48% compared to 26.90% and 26.56% after high ligation and subinguinal varicocelectomy, respectively, and the difference was statistically significant (p = 0.035). CONCLUSIONS: This meta-analysis suggests that varicocelectomy leads to significant improvements in sperm count and motility regardless of surgical technique, with the inguinal approach offering the highest pregnancy rate.