Balancing risks and rewards of alternate strategies in the seaward extent, duration and timing of fjord use in contemporary anadromy of brown trout (Salmo trutta).

BACKGROUND: Anadromy comprises a successful life-cycle adaptation for salmonids, with marine migration providing improved feeding opportunities and thus improved growth. These rewards are balanced against costs from increased energy expenditure and mortality risk. Anthropogenic-induced environmental changes that reduce benefits and/or increase costs of migration e.g., aquaculture and hydropower, may therefore result in adaptations disfavouring anadromy. We tagged brown trout (Salmo trutta) smolts (N = 175) and veteran migrants (N = 342), from five adjacent riverine populations located in Sognefjorden, the longest Norwegian fjord-system supporting anadromous brown trout populations (209 km). Over four years, 138 acoustic telemetry receivers were deployed to track migrations of tagged individuals from freshwater and throughout Sognefjorden. Detected movements were used to fit migration models and multi-state mark-recapture models of survival and movement for each life-stage. Seaward migration distance was modelled to examine the fitness consequences from alternate migration strategies, with these models used to simulate the extent of fjord-use by individuals and accompanying growth, fecundity and survival consequences. We compared these findings with mark-recapture data collected prior to aquaculture and hydropower development. RESULTS: The telemetry data revealed that the outermost-fjord region was utilised by all populations albeit by few individuals. However, historical recaptures were located at a greater distance from the river mouth (87.7 ± 70.3 km), when compared to maximum migration distances of present-day counterparts (58.6 ± 54.9 km). River of origin influenced observed migratory behaviour and differential survival was estimated for each population and life-stage. The simulations based on telemetry-data models revealed a 30% and 23% difference in survival among populations for smolts and veteran migrants, respectively. At the individual-level, a long-distance migration strategy was rewarded with enhanced fecundity. However, the main contribution to population-level fecundity was overwhelmingly derived from middle-distance migrants, due to higher mortality rates and limited numbers of long-distant migrants. CONCLUSIONS: We conclude that present-day anadromy is precarious, but potential risk varies considerably between life-stages and populations, even within a single fjord system. Our findings suggest that selection for extended migration is under pressure, we therefore stress the importance of monitoring and management actions to secure genetic variation pertinent to preserve fitness gains of anadromy.

Application of tensor fascia lata perforator flap in head and neck reconstruction.

The aim of this study was to describe the authors' experience in head and neck reconstruction with the tensor fascia lata perforator flap (TFLPF). Between April 2009 and August 2020, 16 patients underwent head and neck reconstruction with a TFLPF. The flaps were designed in a vertical or transverse fashion based on perforators traveling along the medial or lateral aspect of the posterior edge of the tensor fascia lata muscle. Clinical details and postoperative results were recorded and analyzed. The size of the flap ranged from 7 × 5 cm2 to 25 × 9 cm2. The perforators were mostly septocutaneous (11 patients), allowing a simple and straightforward dissection of the perforator and TFLPF in most patients. There were either one or two perforators in all cases. The overall flap survival rate was 100%. All of the flaps healed uneventfully with no delayed wound healing or donor site dysfunction. Follow-up ranged from 18 to 120 months, during which all patients experienced satisfactory functional and aesthetic results, without serious complications at either the recipient or donor site. The TFLPF is a pliable and reliable flap that could be a first choice in selected head and neck reconstruction cases.

Clinical comparison of superior thyroid artery perforator flap and sternocleidomastoid myocutaneous flap for intraoral reconstruction.

The aim was to evaluate the techniques and outcomes of superior thyroid artery perforator flaps (STAPF) for intraoral reconstruction and to compare them with those of the sternocleidomastoid myocutaneous flap (SCMMF). The cases of 43 patients who underwent reconstruction with either a SCMMF or STAPF for the repair of a medium-sized intraoral defect, between January 2013 and December 2020, were reviewed retrospectively. Although both flaps are based on the superior thyroid artery, their specific harvesting techniques largely differ. All SCMMF (n = 23) were superiorly-based rotational flaps with myocutaneous designs. The STAPF cases (n = 20) included 18 septocutaneous flaps and two chimeric flaps. The flap size was larger in the STAPF group (P = 0.008), while incomplete level IIB dissection (oncological safety) was more frequent in the SCMMF group (P = 0.002). The flap necrosis rate was lower in the STAPF group (STAPF 15% vs SCMMF 34.8%, though this was not statistically significant). Cox multivariate analysis showed that the postoperative flap outcome (total flap necrosis vs flap survival; hazard ratio 27, 95% confidence interval 2.149-336.05; P = 0.001) and complications (excluding fistula) (hazard ratio 14, 95% confidence interval 1.314-142.767; P = 0.029) were associated with overall patient survival. Both speech (P < 0.001) and neck mobility (P < 0.001) functions were superior with STAPF reconstruction. Compared with the traditional SCMMF, the STAPF was found to have a lower necrosis rate with uncompromised oncological safety during harvesting. The STAPF is a good alternative for the repair of medium-sized head and neck defects.

Artificial intelligence in the fertility clinic: status, pitfalls and possibilities.

In recent years, the amount of data produced in the field of ART has increased exponentially. The diversity of data is large, ranging from videos to tabular data. At the same time, artificial intelligence (AI) is progressively used in medical practice and may become a promising tool to improve success rates with ART. AI models may compensate for the lack of objectivity in several critical procedures in fertility clinics, especially embryo and sperm assessments. Various models have been developed, and even though several of them show promising performance, there are still many challenges to overcome. In this review, we present recent research on AI in the context of ART. We discuss the strengths and weaknesses of the presented methods, especially regarding clinical relevance. We also address the pitfalls hampering successful use of AI in the clinic and discuss future possibilities and important aspects to make AI truly useful for ART.

Functions of genes related to testicular germ cell tumour development.

OBJECTIVE: Testicular germ cell tumour (TGCT) is a malignancy with a high heritable component. The inherited risk is polygenic, and around 50 susceptibility genes are identified. The functional role of the gene products for TGCT development is not well understood. The focus of this review is functional studies of genetic risk factors for TGCT derived from GCNIS and the signalling pathways involved in the pathogenesis. RECENT DEVELOPMENTS: Genome-wide association studies have identified new risk loci for TGCT and confirmed previously identified susceptibility genes. Many of these risk genes are related to male germ cell development, sex determination and genomic integrity. Gain- and loss-of-function studies in animal models and TGCT cell lines, as well as gene and protein expression studies in TGCT patient samples, have contributed to the understanding of TGCT development. KITLG-KIT signalling is of crucial importance, but several other signal transduction pathways may also play a role. Many of the risk loci are in non-coding regions, and studies have revealed that non-coding RNAs may act as oncogenes or tumour suppressors in TGCT development. CONCLUSIONS: The risk of TGCT is polygenic, and the underlying molecular mechanisms are complex. Several signalling pathways are related to TGCT development, and both proteins and non-coding RNAs may act as oncogenes or tumour suppressors. Epigenetic studies are of importance to get further knowledge about how the signalling pathways are regulated.

Association between semen parameters and chance of fatherhood - a long-term follow-up study.

BACKGROUND: Evaluation of male fertility includes standard semen analysis; however, there is uncertainty about the value of sperm parameters in predicting fertility. OBJECTIVE: To evaluate the association between semen parameters and fatherhood during a long-time period. MATERIALS AND METHODS: Semen parameters (total sperm count, concentration, motility, and morphology) and sperm DNA fragmentation Index (DFI) assessed on samples collected from 195 Norwegian men from the general population in 2001/2002 were matched with information about fatherhood until 2015, obtained from the Medical Birth Register. The parameters were dichotomized as normal vs. abnormal according to the WHO reference values from 1999 and 2010. Cut-offs at 20% and 30% were used for DFI. RESULTS: Among men who had no children before 2003, those with normal progressive sperm motility had more often become fathers (WHO 1999, cut-off ≥50%, adjusted OR 2.8, 95% CI 1.3-6.1 and WHO 2010, cut-off ≥32%; aOR 4.2, 95% CI 1.1-15). Based on the WHO 1999 reference value, men with normal sperm concentration (≥20 × 106 /mL) had more often become fathers (aOR 3.1, 95% CI 1.1-8.6). Men with progressive sperm motility ≥50% and concentration ≥20 × 106 /mL did more often achieve fatherhood (aOR 8.4, 95% CI 2.1-34). For DFI, there was a borderline significance at cut-off 20% in the group of men who had ever been fathers (OR 2.7, 95% CI 1.0-7.0 p < 0.05). DISCUSSION: The results indicate that sperm progressive motility, sperm concentration, and DFI are associated with fatherhood during a longer time period, with sperm motility being most consistent. Although the sample size is relatively small and our results should be replicated in larger studies, they may be of clinical relevance. CONCLUSION: Semen parameters may have a diagnostic value not only in a short time frame but also for predicting future fertility potential.

Kinematic stride cycle asymmetry is not associated with sprint performance and injury prevalence in athletic sprinters.

The aims of this study were to (a) quantify the magnitude of kinematic stride cycle asymmetry in high-level athletic sprinters, (b) explore the association between kinematic asymmetry and maximal sprint running performance, and (c) investigate possible associations between kinematic asymmetry and injury prevalence. Twenty-two competitive sprinters (age 23 ± 3 year, height 1.81 ± 0.06 m, body mass 75.5 ± 5.6 kg, personal best 100 m 10.86 ± 0.22 seconds) performed 2-3 flying sprints over 20 m. Kinematics were recorded in 3D using a motion tracking system with 21 cameras at a 250 Hz sampling rate, allowing assessment of six consecutive steps for each athlete. Information about injuries sustained 1 year prior to and after the experiment was continuously registered (type, location, severity/duration, and time of year occurrence). The results showed that ≥11 of the 22 participating athletes displayed large or very large asymmetry for at least 11 of 14 variables, and all athletes displayed large or very large asymmetry for at least three variables. No correlations between individual magnitudes of asymmetry and sprint performance were significant (trivial to moderate). No significant changes in asymmetry between best and worst trial were observed for any of the analyzed variables. In addition, injured and non-injured athletes did not differ in asymmetry, neither for the time period 1 year prior to nor after the test. In conclusion, kinematic asymmetries in the stride cycle were not associated with neither maximal sprint running performance nor the prevalence of injury among high-level athletic sprinters.

Plerocercoids of the cestode Diphyllobothrium ditremum in brown trout Salmo trutta: substantial increase in infection after establishment of European minnow Phoxinus phoxinus.

This study focuses on plerocercoids of the cestode Diphyllobothrium ditremum in brown trout Salmo trutta from the subalpine lake Øvre Heimdalsvatn in south-central Norway. Salmo trutta was the only fish species in this lake until European minnow Phoxinus phoxinus was registered in 1969. The P. phoxinus population increased substantially in the following years. In contrast with the 1969-1972 period, when plerocercoids of D. ditremum were practically absent in S. trutta, there was a high prevalence and intensity of infection in the 2013 S. trutta samples. Because the life cycle of D. ditremum involves two larval stages, in copepods and salmonids and mature worms in piscivorous birds, such as mergansers and loons, a change in feeding ecology of S. trutta or changes in population densities of copepods, fish or birds might have influenced the infection pattern. No relationships between D. ditremum infection and muscle-tissue δ15 N signature or Hg concentration were found, indicating that infection is not a result of piscivory or cannibalism. Furthermore, consumption of copepods by S. trutta during summer and autumn was low. On the other hand, the number of piscivorous birds has increased, probably due to the presence of P. phoxinus as a new and numerous prey. An increased number of final D. ditremum hosts may have produced a higher output of cestode eggs, resulting in more infected copepods that in turn are consumed by S. trutta. Indirectly, P. phoxinus may therefore have caused the observed increased infection in S. trutta and thereby imposed further negative effects on S. trutta in high mountain areas.

Mendelian randomisation analysis provides no evidence for a relationship between adult height and testicular cancer risk.

Observational studies have suggested anthropometric traits, particularly increased height are associated with an elevated risk of testicular cancer (testicular germ cell tumour). However, there is an inconsistency between study findings, suggesting the possibility of the influence of confounding factors. To examine the association between anthropometric traits and testicular germ cell tumour using an unbiased approach, we performed a Mendelian randomisation study. We used genotype data from genome wide association studies of testicular germ cell tumour totalling 5518 cases and 19,055 controls. Externally weighted polygenic risk scores were created and used to evaluate associations with testicular germ cell tumour risk per one standard deviation (s.d) increase in genetically-defined adult height, adult BMI, adult waist hip ratio adjusted for BMI (WHRadjBMI), adult hip circumference adjusted for BMI (HIPadjBMI), adult waist circumference adjusted for BMI (WCadjBMI), birth weight (BW) and childhood obesity. Mendelian randomisation analysis did not demonstrate an association between any anthropometric trait and testicular germ cell tumour risk. In particular, despite good power, there was no global evidence for association between height and testicular germ cell tumour. However, three SNPs for adult height individually showed association with testicular germ cell tumour (rs4624820: OR = 1.47, 95% CI: 1.41-1.55, p = 2.7 × 10-57 ; rs12228415: OR = 1.17, 95% CI: 1.11-1.22, p = 3.1 × 10-10 ; rs7568069: OR = 1.13, 95% CI: 1.07-1.18, p = 1.1 × 10-6 ). This Mendelian randomisation analysis, based on the largest testicular germ cell tumour genome wide association dataset to date, does not support a causal etiological association between anthropometric traits and testicular germ cell tumour aetiology. Our findings are more compatible with confounding by shared environmental factors, possibly related to prenatal growth with exposure to these risk factors occurring in utero.

Small larvae in large rivers: observations on downstream movement of European grayling Thymallus thymallus during early life stages.

Behaviour of early life stages of the salmonid European grayling Thymallus thymallus was investigated by assessing the timing of larval downstream movement from spawning areas, the depth at which larvae moved and the distribution of juvenile fish during summer in two large connected river systems in Norway. Trapping of larvae moving downstream and electrofishing surveys revealed that T. thymallus larvae emerging from the spawning gravel moved downstream predominantly during the night, despite light levels sufficient for orientation in the high-latitude study area. Larvae moved in the water mostly at the bottom layer close to the substratum, while drifting debris was caught in all layers of the water column. Few young-of-the-year still resided close to the spawning areas in autumn, suggesting large-scale movement (several km). Together, these observations show that there may be a deliberate, active component to downstream movement of T. thymallus during early life stages. This research signifies the importance of longitudinal connectivity for T. thymallus in Nordic large river systems. Human alterations of flow regimes and the construction of reservoirs for hydropower may not only affect the movement of adult fish, but may already interfere with active movement behaviour of fish during early life stages.

Corrigendum to "Comparison of Different Strategies for Selection/Adaptation of Mixed Microbial Cultures Able to Ferment Crude Glycerol Derived from Second-Generation Biodiesel".

[This corrects the article DOI: 10.1155/2015/932934.].

Fatty acid composition of spermatozoa is associated with BMI and with semen quality.

High body mass index (BMI) is negatively associated with semen quality. In addition, the composition of fatty acids of spermatozoa has been shown to be important for their function. The aim of the study was to examine the association between BMI and the composition of spermatozoa fatty acids in men spanning a broad BMI range. We also analysed the relation between fatty acid composition of spermatozoa and semen characteristics, and the relationship between serum fatty acids and spermatozoa fatty acids. One hundred forty-four men with unknown fertility status were recruited from the general population, from couples with identified female infertility and from morbid obesity centres. Standard semen analysis (WHO) and sperm DNA integrity (DFI) analysis were performed. Fatty acid compositions were assessed by gas chromatography. When adjusted for possible confounders, BMI was negatively associated with levels of sperm docosahexaenoic acid (DHA) (p < 0.001) and palmitic acid (p < 0.001). The amount of sperm DHA correlated positively with total sperm count (r = 0.482), sperm concentration (r = 0.469), sperm vitality (r = 0.354), progressive sperm motility (r = 0.431) and normal sperm morphology (r = 0.265). A negative association was seen between DHA levels and DNA fragmentation index (r = -0.247). Levels of spermatozoa palmitic acid correlated positively with total sperm count (r = 0.227), while levels of linoleic acid correlated negatively (r = -0.254). When adjusted for possible confounders, only the levels of arachidonic acid showed positive correlation between spermatozoa and serum phospholipids (r = 0.262). Changes in the fatty acid composition of spermatozoa could be one of the mechanisms underlying the negative association between BMI and semen quality. The relationship between fatty acids of spermatozoa and serum phospholipids was minor, which indicates that BMI affects fatty acid composition of spermatozoa through regulation of fatty acid metabolism in the testis. The role of dietary intake of fatty acids on the spermatozoa fatty acid composition remains to be elucidated.

Anti-Müllerian hormone in seminal plasma and serum: association with sperm count and sperm motility.

STUDY QUESTION: Is anti-Müllerian hormone (AMH) in seminal plasma and serum associated with sperm count and sperm motility? SUMMARY ANSWER: AMH in seminal plasma is positively associated with sperm concentration, total sperm count, and progressive sperm motility, while no association was found between serum AMH levels and semen characteristics. WHAT IS KNOWN ALREADY: AMH is secreted by the Sertoli cells and is detectable in both serum and seminal plasma in adult men. It has been suggested as a marker of spermatogenesis, however, its function in the adult male is largely unknown. STUDY DESIGN, SIZE, DURATION: Participants were recruited in between 2008 and 2013, from the general population (n = 94) and from couples with female factor infertility in a fertility clinic (n = 32). AMH data were available for 126 participants. PARTICIPANTS/MATERIALS, SETTING, METHODS: Mean age of the participants was 36 years, and BMI was between 19 and 39 kg/m(2). Semen quality was evaluated by semen analysis according to the World Health Organization, and AMH levels were measured in seminal plasma. Blood samples were analyzed for AMH, total testosterone, FSH, LH, and inhibin B. AMH analysis was performed using the improved Beckman Coulter method. MAIN RESULTS AND THE ROLE OF CHANCE: The central 95% intervals of AMH concentrations were 2-2812 pmol/l in seminal plasma and 15-134 pmol/l in serum. Total AMH (pmol/ejaculate) in seminal plasma was positively associated with sperm concentration (B = 0.177, P< 0.001) and total sperm count (B = 0.212, P< 0.001) when adjusted for age, BMI, time of abstinence, and positively associated with progressive sperm motility (B = 6.762, P = 0.001) when adjusted for age, BMI, time of abstinence, and site of sample collection. No association was found between serum AMH and semen characteristics. Serum levels of inhibin B were positively correlated with total AMH in seminal plasma (B = 18.52, P< 0.001) and concentration of AMH in serum (B = 0.507, P< 0.001). LIMITATIONS, REASONS FOR CAUTION: Participants were recruited both from the general population and from a fertility clinic. This may limit the applicability to men in the general population. WIDER IMPLICATIONS OF THE FINDINGS: The AMH levels found in this study show large inter-individual variation, especially in seminal plasma. AMH in seminal plasma may serve as a marker of sperm production, however, in the lower range the predictive value is low. STUDY FUNDING/COMPETING INTERESTS: All funding for this study was received from Oslo and Akershus University College of Applied Sciences. The authors have no conflicts of interest to declare.

Comparison of Different Strategies for Selection/Adaptation of Mixed Microbial Cultures Able to Ferment Crude Glycerol Derived from Second-Generation Biodiesel.

Objective of this study was the selection and adaptation of mixed microbial cultures (MMCs), able to ferment crude glycerol generated from animal fat-based biodiesel and produce building-blocks and green chemicals. Various adaptation strategies have been investigated for the enrichment of suitable and stable MMC, trying to overcome inhibition problems and enhance substrate degradation efficiency, as well as generation of soluble fermentation products. Repeated transfers in small batches and fed-batch conditions have been applied, comparing the use of different inoculum, growth media, and Kinetic Control. The adaptation of activated sludge inoculum was performed successfully and continued unhindered for several months. The best results showed a substrate degradation efficiency of almost 100% (about 10 g/L glycerol in 21 h) and different dominant metabolic products were obtained, depending on the selection strategy (mainly 1,3-propanediol, ethanol, or butyrate). On the other hand, anaerobic sludge exhibited inactivation after a few transfers. To circumvent this problem, fed-batch mode was used as an alternative adaptation strategy, which led to effective substrate degradation and high 1,3-propanediol and butyrate production. Changes in microbial composition were monitored by means of Next Generation Sequencing, revealing a dominance of glycerol consuming species, such as Clostridium, Klebsiella, and Escherichia.

Profiling of the small RNA populations in human testicular germ cell tumors shows global loss of piRNAs.

BACKGROUND: Small non-coding RNAs play essential roles in gene regulation, however, the interplay between RNA groups, their expression levels and deregulations in tumorigenesis requires additional exploration. In particular, a comprehensive analysis of microRNA (miRNA), PIWI-interacting RNAs (piRNAs), and tRNA-derived small RNAs in human testis and testicular germ cell tumor (TGCT) is lacking. RESULTS: We performed small RNA sequencing on 22 human TGCT samples from 5 histological subtypes, 3 carcinoma in situ, and 12 normal testis samples. miRNA was the most common group among the sequences 18-24 nt in length and showed histology-specific expression. In normal samples, most sequences 25-31 nucleotides in length displayed piRNA characteristics, whereas a large proportion of the sequences 32-36 nt length was derived from tRNAs. Expression analyses of the piRNA population demonstrated global loss in all TGCT subtypes compared to normal testis. In addition, three 5' small tRNA fragments and 23 miRNAs showed significant (p < 10(-6)) differential expression in cancer vs normal samples. CONCLUSIONS: We have documented significant changes in the small RNA populations in normal adult testicular tissue and TGCT samples. Although components of the same pathways might be involved in miRNA, piRNA and tRNA-derived small RNA biogenesis, our results showed that the response to the carcinogenic process differs between these pathways, suggesting independent regulation of their biogenesis. Overall, the small RNA deregulation in TGCT provides new insight into the small RNA interplay.

No association between body mass index and sperm DNA integrity.

STUDY QUESTION: Is overweight associated with impaired sperm DNA integrity? SUMMARY ANSWER: High body mass index (BMI) is not associated with impaired sperm DNA integrity as assessed by the DNA Fragmentation Index (DFI). WHAT IS KNOWN ALREADY: Previous studies, based on fewer subjects and including mainly subfertile men, have shown conflicting results regarding the influence of overweight and obesity on sperm DNA integrity. STUDY DESIGN, SIZE, DURATION: This cross-sectional study was based on semen samples from 1503 men from the general population. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included two cohorts (cohort A and B) of military recruits (n = 275, n = 304, respectively), one group (cohort C) of fertile men and men without known fertility problems (n = 724), and one group (cohort D) of men between 19 and 40 years without known fertility problems (n = 200). In all cohorts, data were available on BMI, DFI as measured by the sperm chromatin structure assay (SCSA), standard semen characteristics, and potential confounders (age, abstinence time, smoking habits). The subjects were categorized according to BMI into four groups: underweight (<18.5 kg/m(2)), normal weight (18.5-24.9 kg/m(2)), overweight (25.0-29.9 kg/m(2)) and obese (≥30.0 kg/m(2)). Using a linear regression model, the inter-group differences in DFI were calculated. Furthermore with the normal-weight group as the reference, the odds ratios (ORs) for DFI > 20% and DFI > 30%, were calculated for the other groups. Calculations were made for the material as a whole and after exclusion of cohort C which included proven fertile men. MAIN RESULTS AND THE ROLE OF CHANCE: We found that normal-weight men had significantly higher DFI than overweight men, with a mean difference of 1.13% (95% CI: 1.05-1.22%); P = 0.001). Overweight men had a reduced risk of having DFI ≥ 20% and DFI ≥ 30%, compared with normal-weight men; adjusted odds ratio (OR) = 0.61 (95% CI: 0.42-0.88; P < 0.01) and adjusted OR = 0.48 (95% CI: 0.28-0.84; P < 0.01), respectively. When excluding cohort C, the statistical significance was lost. Regarding standard semen parameters, we found that obese men had a higher percentage of progressive motile spermatozoa than normal-weight men; mean difference 1.15% (95% CI: 1.02-1.30%, P < 0.05) but the significance was lost when excluding cohort C. All other standard semen parameters were unaffected by BMI. LIMITATIONS, REASONS FOR CAUTION: A main limitation might be the cross-sectional nature of the data. Furthermore our study included a significant proportion of men with proven fertility (75% of cohort C, n = 550), and could therefore be biased toward fertility. WIDER IMPLICATIONS OF THE FINDINGS: Our study indicates that overweight per se is not associated with a higher level of sperm DNA damage. STUDY FUNDING/COMPETING INTERESTS: This research has been given grants from the following: EU 5th and 7th framework program (Inuendo and Clear projects, [Contracts no. QLK4-CT-2001-00202 and FP7-ENV-2008-1-226217)]), the Swedish Research Council (Grants No. 2007-2590, 521-2004-6072 and 521-2002-3907); the Swedish Governmental Funding for Clinical Research, Skåne county council's research and development foundation, MAS Funds, University Hospital MAS Foundation in Malmö, Crafoordska Fund, Ove Tulefjords Fund, Foundation for Urological Research, Fundacion Federico SA, and Gunnar Nilssons Cancer Fund. The authors declare that there are no conflicts of interest.

Effect of an intense period of competition on race performance and self-reported illness in elite cross-country skiers.

The aim of this study was to determine whether participating in a cross-country skiing stage race (Tour de Ski; TDS) affects subsequent illness incidence, training, and race performance. Self-reported training and illness data from 44 male and female elite cross-country skiers were included. In total, 127 years of data were collected (2-3 seasons per athlete). Illness incidence, training load, and performance in international competitions were calculated for athletes who did and did not participate in TDS. Forty-eight percent of athletes reported becoming ill during or in the days immediately after taking part in TDS vs 16% of athletes who did not participate. In both groups, illness incidence was somewhat lower for female athletes. For male athletes, race performance was significantly worse for 6 weeks following TDS vs 6 weeks before TDS. Furthermore, while female athletes who participated in TDS performed relatively better than controls in Olympics/World Championships, male athletes who participated in TDS typically performed worse in subsequent major championships. Participating in TDS appears to result in ∼ 3-fold increase in risk of illness in this period. Male athletes appear more prone to illness and also see a drop in race performance following TDS, possibly linked to differences in training load before and after the event.

Genetic variations associated with the effect of testicular cancer treatment on gonadal hormones.

STUDY QUESTION: Do genetic variations in the testosterone pathway genes modify the effect of treatment on the levels of testosterone and LH in long-term testicular cancer (TC) survivors (TCSs)? SUMMARY ANSWER: Variations in LH receptor (LHR) and in 5α-reductase II (SRD5A2) genes may modify the effect of TC treatment on testosterone levels, whereas genetic variations in the androgen receptor (AR) may modify the effect on LH levels. WHAT IS KNOWN ALREADY: TCSs experience variable degrees of long-term reduction in gonadal function after treatment. This variability can in part be explained by treatment intensity, but may also be due to individual variations in genes involved in the function and metabolism of reproductive hormones. STUDY DESIGN, SIZE, DURATION: Cross-sectional study on testosterone and LH levels in 637 Norwegian TCSs in relation to genetic variants and TC treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS: The single nucleotide polymorphisms LHR Asn291Ser (rs12470652) and Ser312Asn (rs2293275), as well as SRD5A2 Ala49Thr (rs9282858) and Val89Leu (rs523349) were analyzed by allele-specific PCR. The insertion polymorphism LHR InsLQ (rs4539842) was analyzed by sequencing. The numbers of AR CAG and GGN repeats were determined by capillary electrophoresis. Blood samples were collected 5-21 years after diagnosis (median 11 years) and serum total testosterone and LH were analyzed by commercial immunoassays. The TCSs were divided into four groups according to their treatment; surgery only, radiotherapy and chemotherapy with ≤850 or >850 mg of cisplatin. Polymorphisms presenting P < 0.1 for the interaction term with treatment in an initial two-way analysis of covariance (ANCOVA) were investigated further in two consecutive one-way ANCOVA analyses to elucidate the interaction between treatment and genotype. MAIN RESULTS AND THE ROLE OF CHANCE: For the whole group of TCSs, there were no significant differences between the hormone levels in homozygotes for the wild type and carriers of at least one polymorphic allele for the investigated polymorphisms. Three of the polymorphisms showed signs of interaction with treatment, i.e. LHR InsLQ, SRD5A2 A49T and the AR CAG repeat. Follow-up analyses revealed three situations where only one of the genotypes of the polymorphism where associated with significantly different hormone levels after surgery compared with after additional cytotoxic treatment: For LHR InsLQ, only the wild-type allele was associated with lower testosterone levels after cisplatin > 850 mg compared with after surgery (24% lower, P < 0.001). For SRD5A2 A49T, testosterone levels were lower after radiotherapy compared with after surgery, but only for the heterozygotes for the polymorphism (39% lower, P = 0.001). In comparison, the testosterone levels were just slightly lower after radiotherapy (6% lower, P = 0.039) or cisplatin ≤ 850 mg (7% lower, P = 0.041), compared with surgery, independent of genotypes. For AR CAG, only the reference length of CAG = 21-22 had significantly higher LH levels after cisplatin ≤ 850 mg compared with after surgery (70% higher, P < 0.001). Independent of genotypes, however, LH levels after cisplatin ≤ 850 mg were only 26% higher than after surgery (P = 0.005). LIMITATIONS, REASONS FOR CAUTION: Unadjusted P-values are presented. For analysis involving genotypes, the level of statistical significance was adjusted for the total number of polymorphisms tested, n = 7, i.e. to P < 0.007 (0.5/7). The rather weak associations indicate that additional polymorphisms are involved in the modulation. WIDER IMPLICATIONS OF THE FINDINGS: To our knowledge, this is the first study supporting the notion that polymorphisms may explain at least some of the inter-individual differences in endocrine response to TC treatment. Our findings suggest that individuals with certain genotypes may be more vulnerable to certain treatments. Knowledge on genetic predisposition concerning treatment-related endocrine gonadotoxicity to different treatment regimens may help tailoring TC therapy when possible. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Research Council of Norway (Grant No. 160619). There were no competing interests.

Genetic variation in AKT1, PTEN and the 8q24 locus, and the risk of testicular germ cell tumor.

STUDY QUESTION: Is there an association between testicular germ cell tumor (TGCT) and genetic polymorphisms in AKT1, PTEN and the 8q24 locus? SUMMARY ANSWER: Our findings suggest that genetic variation in PTEN may influence the risk of TGCT. WHAT IS KNOWN ALREADY: There is strong evidence that genetic variation influences the risk of TGCT. The oncogene, AKT1, the tumor suppressor gene, PTEN and the chromosome 8q24 locus play important roles in cancer development in general. STUDY DESIGN, SIZE, DURATION: We have conducted a population-based Norwegian-Swedish case-parent study, based on cases diagnosed in 1990-2008, including 831 triads (TGCT case and both parents), 474 dyads (TGCT case and one parent) and 712 singletons (only the TGCT case). In addition we expanded the study to include 3922 unrelated male controls from the TwinGene project. PARTICIPANTS/MATERIALS, SETTING, METHODS: We genotyped 26 single nucleotide polymorphisms (SNPs) in AKT1, PTEN and the 8q24 locus. First, triads and dyads were included in a likelihood-based association test. To increase the statistical power, case singletons and controls from the TwinGene project were included in a single test for association. We examined if the allelic effect on TGCT risk differed by histological subgroup, country of origin or parent of origin. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated with Bonferroni correction (P bonf) for multiple testing. MAIN RESULTS AND THE ROLE OF CHANCE: In the case-parent analyses, none of the 26 SNPs were significantly associated with TGCT. Of the 23 SNPs investigated in the combined study, one SNP in PTEN (rs11202586) remained associated with TGCT risk after adjusting for multiple testing (OR = 1.16, 95% CI = 1.06-1.28, P bonf = 0.040). We found no difference in risk according to histological subgroup, parent of origin or between countries. LIMITATIONS, REASONS FOR CAUTION: Our study is strengthened by the population-based design and large sample size, which gives high power to detect risk alleles. The reported association was not highly significant, and although it was based on an a priori hypothesis of this tumor suppressor gene being implicated in the etiology of TGCT, replication studies, as well as functional studies of this polymorphism, are warranted. WIDER IMPLICATIONS OF THE FINDINGS: We report, to our knowledge, a novel association between TGCT and a marker in the tumor suppressor gene PTEN. Previous studies have linked PTEN to TGCT etiology, and there is also a link between PTEN and KITLG, which contains TGCT susceptibility loci revealed through recent genome-wide studies.