Bigger testes increase paternity in a simultaneous hermaphrodite, independently of the sperm competition level.

Hermaphroditic animals face the fundamental evolutionary optimization problem of allocating their resources to their male vs. female reproductive function (e.g. testes and sperm vs. ovaries and eggs), and this optimal sex allocation can be affected by both pre- and post-copulatory sexual selection. For example, local sperm competition (LSC) - the competition between related sperm for the fertilization of a partner's ova - occurs in small mating groups and can favour a female-biased sex allocation, because, under LSC, investment into sperm production is predicted to show diminishing fitness returns. Here, we test whether higher testis investment increases an individual's paternity success under sperm competition, and whether the strength of this effect diminishes when LSC is stronger, as predicted by sex allocation theory. We created two subsets of individuals of the simultaneously hermaphroditic flatworm Macrostomum lignano - by sampling worms from either the highest or lowest quartile of the testis investment distribution - and estimated their paternity success in group sizes of either three (strong LSC) or eight individuals (weak LSC). Specifically, using transgenic focal individuals expressing a dominant green-fluorescent protein marker, we showed that worms with high testis investment sired 22% more offspring relative to those with low investment, corroborating previous findings in M. lignano and other species. However, the strength of this effect was not significantly modulated by the experienced group size, contrasting theoretical expectations of more strongly diminishing fitness returns under strong LSC. We discuss the possible implications for the evolutionary maintenance of hermaphroditism in M. lignano.

Experimentally evolved and phenotypically plastic responses to enforced monogamy in a hermaphroditic flatworm.

Sexual selection is considered a potent evolutionary force in all sexually reproducing organisms, but direct tests in terms of experimental evolution of sexual traits are still lacking for simultaneously hermaphroditic animals. Here, we tested how evolution under enforced monogamy affected a suite of reproductive traits (including testis area, sex allocation, genital morphology, sperm morphology and mating behaviour) in the outcrossing hermaphroditic flatworm Macrostomum lignano, using an assay that also allowed the assessment of phenotypically plastic responses to group size. The experiment comprised 32 independent selection lines that evolved under either monogamy or polygamy for 20 generations. While we did not observe an evolutionary shift in sex allocation, we detected effects of the selection regime for two male morphological traits. Specifically, worms evolving under enforced monogamy had a distinct shape of the male copulatory organ and produced sperm with shorter appendages. Many traits that did not evolve under enforced monogamy showed phenotypic plasticity in response to group size. Notably, individuals that grew up in larger groups had a more male-biased sex allocation and produced slightly longer sperm than individuals raised in pairs. We conclude that, in this flatworm, enforced monogamy induced moderate evolutionary but substantial phenotypically plastic responses.

Fumarate hydratase immunohistochemical staining may help to identify patients with multiple cutaneous and uterine leiomyomatosis (MCUL) and hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome.

AIMS: Multiple cutaneous and uterine leiomyomatosis (MCUL) also named as hereditary leiomyomatosis and renal cancer syndrome (HLRCC) is an autosomal dominant disorder caused by heterozygotic germline mutations in fumarate hydratase (FH) with incomplete penetrance and clinically challenging to diagnose. To test immunohistochemistry for FH as a potential marker for the detection of FH-deficiency. METHODS AND RESULTS: We have tested 42 smooth muscle neoplasms, 13 lesions of patients with suspicious or confirmed HLRCC, 20 sporadic piloleiomyomas, two angioleiomyomas and 7 leiomyosarcomas. FH staining grades from 1 to 3. Ten of the 13 lesions from the patients with HLRCC syndrome showed negative FH staining. Most sporadic piloleiomyomas presented grade 3 FH staining although five cases presented grade 1 FH staining. Sensitivity of FH staining in our series is 83.3% but specificity is 75%. CONCLUSIONS: This staining could indicate a high risk of HLRCC in most of the confirmed cases but it could also suggest the presence of a syndrome in up to 25% of sporadic cases. HLRCC syndrome should be rule out in FH negative piloleiomyomas after complete anamnesis if multiple lesions or positive familiar history is found.

Occurrence, costs and heritability of delayed selfing in a free-living flatworm.

Evolutionary theory predicts that in the absence of outcrossing opportunities, simultaneously hermaphroditic organisms should eventually switch to self-fertilization as a form of reproductive assurance. Here, we report the existence of facultative self-fertilization in the free-living flatworm Macrostomum hystrix, a species in which outcrossing occurs via hypodermic insemination of sperm into the parenchyma of the mating partner. First, we show that isolated individuals significantly delay the onset of reproduction compared with individuals with outcrossing opportunities ('delayed selfing') as predicted by theory. Second, consistent with the idea of M. hystrix being a preferential outcrosser under natural conditions, we report likely costs of selfing manifested via reduced hatchling production and offspring survival. Third, we demonstrate that selfing propensity has a genetic basis in this species, with a heritability estimated at 0.43 ± 0.11. Variation in selfing propensity could arise due to differing costs of inbreeding among families; despite marked inter-family variation in apparent costs of inbreeding, we found no evidence for such a link. Alternatively, selfing propensity might differ across families because of heritable variation in reproductive traits that determine the likelihood of selfing. We speculate that adaptations to hypodermic insemination under outcrossing, most notably a highly modified copulatory stylet (male copulatory organ) and reduced sperm complexity, could also facilitate facultative selfing in this species.

Detection of Merkel cell polyomavirus in epidermodysplasia-verruciformis-associated skin neoplasms.

BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare genodermatosis that is characterized by susceptibility to infection with specific human papillomavirus (HPV) genotypes. Among polyomaviruses, the novel Merkel cell polyomavirus (MCPyV) has been found in different epithelial skin neoplasias. OBJECTIVE: To examine whether EV is associated with cutaneous MCPyV infection. METHODS: We used MCPyV-specific PCR to study skin neoplasms of 6 congenital EV patients and of 1 patient with acquired EV. RESULTS: In all congenital EV patients, MCPyV DNA was found in carcinomas in situ, in invasive squamous cell carcinomas and in common warts. In 4 of these patients, the MCPyV-positive skin lesions were from different anatomic locations. In addition, 1 immunosuppressed patient suffering from acquired EV harbored MCPyV DNA in 2 common warts. In contrast, 7 normal skin samples tested negative for MCPyV DNA. Only 2 out of 24 carcinomas in situ (8.3%) and 2 out of 30 common warts (6.7%) from immunocompetent individuals were positive for MCPyV DNA. CONCLUSIONS: The strong association of EV-associated skin neoplasms with MCPyV suggests a unique susceptibility of EV patients to infections with MCPyV. Both MCPyV and EV-HPV may act as synergistic oncogenic cofactors in the development of EV-associated skin neoplasms.

Incidence of bullous pemphigoid and pemphigus in Switzerland: a 2-year prospective study.

BACKGROUND: Bullous pemphigoid (BP), pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune bullous diseases characterized by the presence of tissue-bound and circulating autoantibodies directed against disease-specific target antigens of the skin. Although rare, these diseases run a chronic course and are associated with significant morbidity and mortality. There are few prospective data on gender- and age-specific incidence of these disorders. OBJECTIVES: Our aims were: (i) to evaluate the incidence of BP and PV/PF in Swiss patients, as the primary endpoint; and (ii) to assess the profile of the patients, particularly for comorbidities and medications, as the secondary endpoint. METHODS: The protocol of the study was distributed to all dermatology clinics, immunopathology laboratories and practising dermatologists in Switzerland. All newly diagnosed cases of BP and pemphigus occurring between 1 January 2001 and 31 December 2002 were collected. In total, 168 patients (73 men and 95 women) with these autoimmune bullous diseases, with a diagnosis based on clinical, histological and immunopathological criteria, were finally included. RESULTS: BP showed a mean incidence of 12.1 new cases per million people per year. Its incidence increased significantly after the age of 70 years, with a maximal value after the age of 90 years. The female/male ratio was 1.3. The age-standardized incidence of BP using the European population as reference was, however, lower, with 6.8 new cases per million people per year, reflecting the ageing of the Swiss population. In contrast, both PV and PF were less frequent. Their combined mean incidence was 0.6 new cases per million people per year. CONCLUSIONS; This is the first comprehensive prospective study analysing the incidence of autoimmune bullous diseases in an entire country. Our patient cohort is large enough to establish BP as the most frequent autoimmune bullous disease. Its incidence rate appears higher compared with other previous studies, most likely because of the demographic characteristics of the Swiss population. Nevertheless, based on its potentially misleading presentations, it is possible that the real incidence rate of BP is still underestimated. Based on its significant incidence in the elderly population, BP should deserve more public health concern.

Determinants of mating and sperm-transfer success in a simultaneous hermaphrodite.

The number of mating partners an individual has within a population is a crucial parameter in sex allocation theory for simultaneous hermaphrodites because it is predicted to be one of the main parameters influencing sex allocation. However, little is known about the factors that determine the number of mates in simultaneous hermaphrodites. Furthermore, in order to understand the benefits obtained by resource allocation into the male function it is important to identify the factors that predict sperm-transfer success, i.e. the number of sperm a donor manages to store in a mate. In this study we experimentally tested how social group size (i.e. the number of all potential mates within a population) and density affect the number of mates and sperm-transfer success in the outcrossing hermaphroditic flatworm Macrostomum lignano. In addition, we assessed whether these parameters covary with morphological traits, such as body size, testis size and genital morphology. For this we used a method, which allows tracking sperm of a labelled donor in an unlabelled mate. We found considerable variation in the number of mates and sperm-transfer success between individuals. The number of mates increased with social group size, and was higher in worms with larger testes, but there was no effect of density. Similarly, sperm-transfer success was affected by social group size and testis size, but in addition this parameter was influenced by genital morphology. Our study demonstrates for the first time that the social context and the morphology of sperm donors are important predictors of the number of mates and sperm-transfer success in a simultaneous hermaphrodite. Based on these findings, we hypothesize that sex allocation influences the mating behaviour and outcome of sperm competition.

[Melanocytic nevi at special anatomical sites]. / Melanozytäre Nävi in speziellen anatomischen Lokalisationen.

Melanocytic nevi at special anatomical sites can evoke a histological picture easily leading to the false diagnosis of a highly atypical, dysplastic nevus or even malignant melanoma. It is therefore most important to recognize these lesions in order to differentiate them from "true" dysplastic nevi or malignant melanomas. The anatomical regions recognized as "special sites" are the head and neck, especially the ear, the milk line (axilla, mamae, mamillae, umbilicus, groin), acral regions (palms and soles, knee, dorsum of the foot) and flexural sites. The specific histological picture of these nevi is described as well as differential diagnostic considerations to differentiate these lesions from malignant melanomas.

[Epithelioid and hyperpigmented melanocytic tumors. An overview]. / Epitheloidzellige und hyperpigmentierte melanozytäre Tumoren : Eine Ubersicht.

Spindle cell and epithelioid cell differentiation occur in both benign and malignant hyperpigmented melanocytic lesions. Reed nevus is characterized by compact, sharply circumscribed junctional cellular nests composed of slender hyperpigmented melanocytes shaped like spindle cells. Deep penetrating nevus is characterized by a diffuse dermal proliferation composed of small nests and fascicles of pale ovoid and epithelioid melanocytes. Cellular blue nevi often have a characteristic hourglass or dumbbell shape, with sharply circumscribed elongated nests and fascicles of pale, densely layered ovoid melanocytes and adjacent melanophages. Epithelioid blue nevus is characterized by large epithelioid melanocytes with abundant cytoplasm and melanin often concentrated to some degree in the cell membrane. Animal-type melanoma is a particularly hyperpigmented variant of melanoma in which large melanophages predominate and there are varying proportions of melamin-rich spindle-shaped and large atypical epithelioid melanocytes. Morphologically, pigmented epithelioid melanocytoma combines characteristics of both animal-type melanoma and pigmented epithelioid nevus. Malignant melanoma may occur in conjunction with a preexistent blue nevus. Malignant blue nevus is now regarded as a malignant melanoma mimicking a blue nevus in structure and pattern. It is therefore of paramount importance to view multiple mitoses within a cellular blue nevus-like proliferation as an alarm signal as they are usually indicators of a malignant melanoma.

[Optimizing dermatopathologic diagnosis with digital photography and internet. The significance of clinicopathologic correlation]. / Optimierung der dermatopathologischen Diagnostik durch digitale Fotografie und Internet. Bedeutung der klinisch-pathologischen Korrelation.

Clinicopathologic correlation is the basis of a precise diagnosis. Especially in dermatopathology, the precision of a microscopic diagnosis may significantly be increased by thorough knowledge of the clinical picture. The advent of digital photography, the internet and moderately priced CDs and USB-sticks have made it possible to establish and maintain a time-saving, low-cost picture data transfer between dermatologist and dermatopathologist which is optimally suited for clinicopathologic correlation.

Resource-dependent sex-allocation in a simultaneous hermaphrodite.

Most sex allocation theory is based on the relationship between the resource investment into male and female reproduction and the consequent fitness returns (often called fitness-gain curves). Here we investigate the effects of resource availability on the sex allocation of a simultaneously hermaphroditic animal, the free-living flatworm Macrostomum lignano. We kept the worms under different resource levels and determined the size of their testes and ovaries over a period of time. At higher resource levels, worms allocated relatively more into the female function, suggesting a saturating male fitness-gain curve for this species. A large part of the observed effect was due to a correlated increase in body size, showing size-dependent sex allocation in M. lignano. However, a significant part of the overall effect was independent of body size, and therefore likely due to the differences in resource availability. Moreover, in accordance with a saturating male fitness-gain curve, the worms developed the male gonads first. As the group size was kept constant, our results contrast with expectations from sex allocation models that deal with local mate competition alone, and with previous experiments that test these models.

[Psychotropic drug-induced change of weight: a review]. / Gewichtsveränderungen unter Therapie mit Psychopharmaka.

OBJECTIVE: The purpose of this study is to give a systematic review of change of weight associated with commonly used psychotropic drugs. METHODS: Mainly based on a MEDLINE-supported review until April 2005, data from clinical studies with antidepressants, anticonvulsants, mood stabilizers and neuroleptics were scanned for change of weight during treatment. RESULTS: Among antidepressants amitryptiline and nortriptyline have the highest incidence of weight gain followed by imipramine. Maprotiline and mirtazapine have an intermediate weight increasing potential. SSRI (except paroxetine) and MAOI had no or only slight weight inducing effects. In contrary, bupropion was associated with weight reduction. Regarding mood stabilizers and anticonvulsants, a marked gain in weight with lithium and sodium valproate was reported frequently. With gabapentin and vigabatrin a slight to moderate gain in weight was found. Minor changes of weight were found with carbamazepine and lamotrigine. Treatment with topiramate and felbamate reportedly lead to weight loss. The atypical neuroleptics clozapine and olanzapine were frequently related to a strong gain in weight followed by risperidone. Quetiapine has intermediate effects. Stable weight was found with aripiprazole and ziprasidone. A gain in weight is less frequent with older/typical neuroleptics. CONCLUSION: Beside some methodological restrictions like inconsistent information of weight changes (e. g. percent vs. mass) and the small sample of available long term studies, this review specifies the incidence of weight changes for commonly used psychotropic drugs and might be helpful to look for alternatives.

The Inventory of Depressive Symptomatology: German translation and psychometric validation.

The Inventory of Depressive Symptomatology (IDS) is a rating scale for depression, widely used in international multicentre studies. There are two corresponding versions: a self-rated (IDS-SR) and a clinician-rated (IDS-C) scale. The aim of this study was to evaluate the reliability and validity of the German versions of the IDS-SR and IDS-C in comparison to the Hamilton Rating Scale for Depression (HRSD) and to the Beck Depression Inventory (BDI). The sample consisted of 59 inpatients and outpatients treated for unipolar or bipolar disorders. Internal consistency of the IDS-SR and IDS-C was found highly acceptable (alpha = 0.94 and alpha = 0.93). Item-total-correlations of the IDS-SR revealed that 68% of the items were strongly correlated with the sum score (> or =0.50). This was in the same range with the IDS-C (54%), the HRSD (53%) and the BDI (76%). Furthermore, there is a high concurrent validity (r > or = 0.88) of the IDS-SR with the IDS-C, the BDI and the HRSD. Substantial score-differences between inpatients and outpatients indicate a good discriminant validity. It is concluded that the German version of the IDS is a useful instrument for the assessment of depressive symptoms and that it has the same highly acceptable psychometric properties as the original English version.

[Corneal and conjunctival findings in systemic silver intoxication]. / Corneale und conjunctivale Befunde bei systemischer Argyrose.

BACKGROUND: Chronic silver intoxication is a rare disease and therefore the typical ocular findings may be missed. Based on a case with severe intoxication, the clinical and histological findings as well as the prognosis in argyria are presented. HISTORY: A 33-years-old-employee of a battery production plant developed a biopsy proven systemic argyria. On slit lamp examination the conjunctiva showed a dark, blue-grey discoloration in the areas of the tear flow and the small conjunctival arteries. Diffuse silver deposits were noticed on the level of Descemet's membrane without endothelial damage. Silver deposits were also visible in the trabecular meshwork. Chemical reaction of the silver particles upon exposure to UV light results in irreversible tissue discoloration. Without options for an effective treatment, early diagnosis and prevention of overexposure are most important. CONCLUSIONS: The typical ocular findings in systemic argyria are helpful in occupational medicine for establishing the correct diagnosis.

Trade-off between male and female allocation in the simultaneously hermaphroditic flatworm Macrostomum sp.

Sex allocation theory for simultaneous hermaphrodites assumes a direct trade-off between the allocation of resources to the male and female reproductive functions. Empirical support for this basic assumption is scarce, possibly because studies rarely control for variation in individual reproductive resource budgets. Such variation, which can have environmental or genetic sources, can generate a positive relationship between male and female investment and can thus obscure the trade-off. In this study on the hermaphroditic flatworm Macrostomum sp. we tried to control for budget effects by restricting food availability in a standardized way and by using an inbred line. We then manipulated mating group size in a two-way design (two group sizes x two enclosure sizes) in order to induce phenotypic variation in male allocation, and expected to find an opposing correlated response in female allocation. The results suggest that we only managed to control the budget effects under some conditions. Under these the sex allocation trade-off emerged. Under the other conditions we found a strongly positive correlation between male and female allocation. We discuss possible causes for the observed differences.

Photodynamic therapy--a new treatment option for epithelial malignancies of the skin.

Photodynamic therapy (PDT) is based on the activation of a photosensitizer by illumination with visible light, leading to photochemical tissue destruction or immunomodulation. The greatest disadvantage of systemic administration of photosensitizers is cutaneous photosensitization of the patients, which lasts for some months. An alternative approach for epithelial precancerous lesions, such as actinic keratoses and Bowen's disease, as well as for superficial skin tumors, such as basal cell carcinomas, is the topical application of sensitizers, especially 5-aminolevulinic acid. Topical PDT causes selective tissue necrosis and tumor destruction and produces excellent cosmetic results. The following article summarizes the main principles of PDT and provides a synopsis of the present status of the use of PDT for epithelial skin malignancies.

Comparison of long-term monitoring methods for bipolar affective disorder.

Long-term monitoring is a clinical necessity in bipolar affective disorder. The most important requirements are usability and value for clinical decisions. Four methods of long-term monitoring - (1) the Adjective Mood Scale by von Zerssen, (2) Kraepelin's early life charts, (3) the NIMH Life Chart Method by Leverich and Post and (4) the Social Rhythm Metric by Monk - were compared regarding the acceptance by patients, the time commitment needed for documentation and training as well as the usability for the clinician regarding psychotherapy and decision support in pharmacotherapy. The Adjective Mood Scale is easiest to learn, Kraepelin's life chart offers the best graphical presentation, the NIMH life charts offer the best clinical decision support and the Social Rhythm Metric integrates a psychotherapeutic approach.

The Stanley Foundation Bipolar Network: results of the naturalistic follow-up study after 2.5 years of follow-up in the German centres.

The Stanley Foundation Bipolar Network (SFBN) is an international, multisite network investigating the characteristics and course of bipolar disorder. Methods (history, ratings and longitudinal follow-up) are standardized and equally applied in all 7 centres. This article describes demographics and illness characteristics of the first 152 German patients enrolled in the SFBN as well as the results of 2.5 years of follow-up. Patients in Germany were usually enrolled after hospitalisation. More than 72% of the study population suffered from bipolar I disorder and 25% from bipolar II disorder. The mean +/- SD age of the study participants was 42.08 +/- 13.5 years, and the mean +/- SD age of onset 24.44 +/- 10.9 years. More than 40% of the sample reported a rapid-cycling course in history, and even more a cycle acceleration over time. 37% attempted suicide at least once. 36% had an additional Axis I disorder, with alcohol abuse being the most common one, followed by anxiety disorders. During the follow-up period, only 27% remained stable, 56% had a recurrence, 12.8% perceived subsyndromal symptoms despite treatment and regular visits. 27% suffered from a rapid-cycling course during the follow-up period. Recurrences were significantly associated with bipolar I disorder, an additional comorbid Axis I disorder, rapid cycling in history, a higher number of mood stabilizers and the long-term use of typical antipsychotics. Rapid cycling during follow-up was only associated with a rapid-cycling course in history, a higher number of mood stabilizers and at least one suicide attempt in history.

Electronic diary for bipolar patients.

Long-term monitoring methods providing an overview of the course of bipolar disorder of individual patients are a clinical necessity at least for patients who require a combination therapy with drugs that have only proven their efficacy for monotherapy. The Life Chart Method (LCM) of the NIMH is an adequate method for this purpose. Unfortunately, due to data entry and management requirements, it is too expensive for everyday clinical use. The 'electronic diary for patients with bipolar disorder' is meant to provide a method to minimize the effort for detailed long-term monitoring of patients with bipolar affective disorder and thus make it available for the everyday clinical use for every bipolar patient.