Male body size and breeding tubercles are both linked to intra-sexual dominance and reproductive success in the minnow

Male dominance hierarchies are usually linked to relative body size and to weapon size, that is, to determinants of fighting ability. Secondary sexual characters that are not directly used as weapons could still be linked to dominance if they reveal determination or overall health and vigour and hence, indirectly, fighting ability. We studied the mating behaviour of the minnow, Phoxinus phoxinus, a cyprinid fish in which males develop breeding tubercles during the spawning season. The function of these breeding tubercles is still not clear. Using microsatellite markers, we determined male reproductive success under controlled conditions. The minnows were territorial and quickly established a dominance hierarchy at the beginning of the spawning season. Dominance was strongly and positively linked to fertilization success. Although body size and number of breeding tubercles were not significantly correlated in our sample, both large males and males with many breeding tubercles were more dominant and achieved higher fertilization success than small males or males with few tubercles. We found multimale fertilization in most clutches, suggesting that sperm competition is important in this species. Females showed behaviour that may be linked to spawning decision, that is, male dominance might not be the only determinant of male reproductive success in minnows

Unusual fatal petrositis presenting as myofascial pain and dysfunction of the temporal muscle.

Petrositis is a rare and severe complication of acute otitis media and mastoiditis. Although the extension of the inflammatory process from the petrous apex to the adjacent Meckel cave can lead to trigeminal pain, an irritation of the trigeminal nerve roots resulting in acute or chronic hyperactivity of masticatory muscles has never been reported. We report here the unusual case of an 86-year-old man who presented with a handicapping myofascial pain and dysfunction syndrome of the right temporal muscle as a heralding manifestation of an unusual form of petrositis. The patient progressively developed a retropharyngeal abscess, a right sphenoid sinusitis, and fatal meningitis. This case demonstrated that (1) myofascial pain and dysfunction syndrome that does not respond to conventional treatments may suggest an unusual etiology and warrant further medical investigations and a detailed medical history and that (2) petrositis can manifest itself with atypical clinical symptoms and radiologic signs. (Quintessence Int 2011;42:419-422).

Postoperative Cognitive Dysfunction (POCD) and Inflammatory Markers in Elderly Patients

Introduction: Particularly in elderly patients, the brain responds to a systemic inflammatory response with an increased production of inflammatory mediators. This has hypothetically been linked to the development of postoperative cognitive dysfunction (POCD). Methods: We investigated 31 patients aged >65 yrs undergoing elective major surgery under standardized general anaesthesia (thiopental, sevoflurane, fentanyl, atracurium). Cognitive function was measured preoperatively and 7 days postoperatively using the extended version of the Consortium to Establish a Registry for Alzheimer's Disease - Neuropsychological Assessment Battery (CERAD-NAB, validated German version) for which we developed a diagnostic cut-off in healthy elderly volunteers. Systemic C-reactive protein (CRP) and interleukin 6 (IL-6) were measured preoperatively, 2 days postoperatively, and 7 days postoperatively. Values for CRP, IL-6, operative characteristics and hospital length of stay in patients with POCD and without POCD were compared using the Mann- Whitney U test and are shown as median [range]. Results: Fourteen patients (45%) developed POCD. Values for CRP were not statistically different in patients with POCD and without POCD but tended to be higher in patients with POCD 2 days postoperatively. Patients with POCD had significantly higher IL-6 values on postoperative days 2 and 7 (table 1). These patients also had a significantly longer duration of anaesthesia (305 [195-620] vs.190 [150-560] min, p = 0.034), larger intraoperative blood loss (425 [0-1600] vs. 100 [0-1500] ml, p = 0.018) and longer hospital stays (15 [8-45] vs. 8 [4-40] days, p = 0.008). Table 1 POCD (n = 14) No POCD (n = 17) p value CRP (mg/dl) preop. 4.0 [1.0-245] 4.2 [0.3-36.2] 0.6 2 days postop. 223 [20-318] 98 [4.5-384] 0.07 7 days postop. 58 [15-147] 44 [11-148] 0.2 IL-6 (U/ml) preop. 2[2-28.1] 2 [2-7.3] 0.8 2 days postop. 56 [17-315] 20 [2-123] 0.009 7 days postop. 9[2-77] 4 [2-16] 0.03 Interpretation: In this small group of patients, high IL-6 values postoperatively were associated with POCD supporting a role for systemic inflammation in the development of POCD. In patients with POCD, duration of anaesthesia was significantly longer, and intraoperative blood losses were larger. These risk factors will need to be confirmed in a larger group of patients. The difference in length of stay may be indicative of postoperative complications, which have been linked to POCD earlier.

Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits.

Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5×10(-8)), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.

Sexual selection in genetic colour-polymorphic species: a review of experimental studies and perspectives

Sexual selection theory has primarily focussed on the role of mating preferences for the best individuals in the evolution of condition-dependent ornaments, traits that signal absolute quality. Because the most suitable mate for one individual is not always the best for others, however, we argue that non-directional mate choice can promote the evolution of alternative morphs that are not condition-dependent in their expression (i.e. genetic polymorphism). We list the different mate-choice rules (i.e. all individuals have the same preference; preference depends on the chooser's morph; individuals mate preferentially with conspecifics displaying an uncommon or the most frequent morph) and review experimental studies that investigated mate choice in natural populations of colour-polymorphic animals. Our review emphasises that although the experimental data support the idea that sexual selection plays an important role in the evolution of genetic colour polymorphism in many different ways, little is known about the adaptive value of each mate-choice strategy and about their implication in the evolutionary stability of colour polymorphism. One way of solving this problem is to determine the adaptive function of colour morphs, a worthwhile objective, because better understanding of mate-choice rules in polymorphic species should provide important insights into sexual-selection processes and, in turn, into the maintenance of genetic variation.

The cyclophilin inhibitor alisporivir prevents hepatitis C virus-mediated mitochondrial dysfunction.

Alisporivir (Debio-025) is an analogue of cyclosporine A and represents the prototype of a new class of non-immunosuppressive cyclophilin inhibitors. In vitro and in vivo studies have shown that alisporivir inhibits hepatitis C virus (HCV) replication, and ongoing clinical trials are exploring its therapeutic potential in patients with chronic hepatitis C. Recent data suggest that the antiviral effect is mediated by inhibition of cyclophilin A, which is an essential host factor in the HCV life cycle. However, alisporivir also inhibits mitochondrial permeability transition by binding to cyclophilin D. Because HCV is known to affect mitochondrial function, we explored the effect of alisporivir on HCV protein-mediated mitochondrial dysfunction. Through the use of inducible cell lines, which allow to investigate the effects of HCV polyprotein expression independent from viral RNA replication and which recapitulate the major alterations of mitochondrial bioenergetics observed in infectious cell systems, we show that alisporivir prevents HCV protein-mediated decrease of cell respiration, collapse of mitochondrial membrane potential, overproduction of reactive oxygen species and mitochondrial calcium overload. Strikingly, some of the HCV-mediated mitochondrial dysfunctions could even be rescued by alisporivir. Conclusion: These observations provide new insights into the pathogenesis of HCV-related liver disease and reveal an additional mechanism of action of alisporivir that is likely beneficial in the treatment of chronic hepatitis C. (HEPATOLOGY 2012).

Male cognitive performance declines in the absence of sexual selection.

Sexual selection is responsible for the evolution of male ornaments and armaments, but its role in the evolution of cognition--the ability to process, retain and use information--is largely unexplored. Because successful courtship is likely to involve processing information in complex, competitive sexual environments, we hypothesized that sexual selection contributes to the evolution and maintenance of cognitive abilities in males. To test this, we removed mate choice and mate competition from experimental populations of Drosophila melanogaster by enforcing monogamy for over 100 generations. Males evolved under monogamy became less proficient than polygamous control males at relatively complex cognitive tasks. When faced with one receptive and several unreceptive females, polygamous males quickly focused on receptive females, whereas monogamous males continued to direct substantial courtship effort towards unreceptive females. As a result, monogamous males were less successful in this complex setting, despite being as quick to mate as their polygamous counterparts with only one receptive female. This diminished ability to use past information was not limited to the courtship context: monogamous males (but not females) also showed reduced aversive olfactory learning ability. Our results provide direct experimental evidence that the intensity of sexual selection is an important factor in the evolution of male cognitive ability.

Pulmonary and systemic vascular dysfunction in young offspring of mothers with preeclampsia.

BACKGROUND: Adverse events in utero may predispose to cardiovascular disease in adulthood. The underlying mechanisms are unknown. During preeclampsia, vasculotoxic factors are released into the maternal circulation by the diseased placenta. We speculated that these factors pass the placental barrier and leave a defect in the circulation of the offspring that predisposes to a pathological response later in life. The hypoxia associated with high-altitude exposure is expected to facilitate the detection of this problem. METHODS AND RESULTS: We assessed pulmonary artery pressure (by Doppler echocardiography) and flow-mediated dilation of the brachial artery in 48 offspring of women with preeclampsia and 90 offspring of women with normal pregnancies born and permanently living at the same high-altitude location (3600 m). Pulmonary artery pressure was roughly 30% higher (mean+/-SD, 32.1+/-5.6 versus 25.3+/-4.7 mm Hg; P<0.001) and flow-mediated dilation was 30% smaller (6.3+/-1.2% versus 8.3+/-1.4%; P<0.0001) in offspring of mothers with preeclampsia than in control subjects. A strong inverse relationship existed between flow-mediated dilation and pulmonary artery pressure (r=-0.61, P<0.001). The vascular dysfunction was related to preeclampsia itself because siblings of offspring of mothers with preeclampsia who were born after a normal pregnancy had normal vascular function. Augmented oxidative stress may represent an underlying mechanism because thiobarbituric acid-reactive substances plasma concentration was increased in offspring of mothers with preeclampsia. CONCLUSIONS: Preeclampsia leaves a persistent defect in the systemic and the pulmonary circulation of the offspring. This defect predisposes to exaggerated hypoxic pulmonary hypertension already during childhood and may contribute to premature cardiovascular disease in the systemic circulation later in life.

Beneficial effect of insulin-like growth factor-1 on hypoxemic renal dysfunction in the newborn rabbit.

Acute normocapnic hypoxemia can cause functional renal insufficiency by increasing renal vascular resistance (RVR), leading to renal hypoperfusion and decreased glomerular filtration rate (GFR). Insulin-like growth factor 1 (IGF-1) activity is low in fetuses and newborns and further decreases during hypoxia. IGF-1 administration to humans and adult animals induces pre- and postglomerular vasodilation, thereby increasing GFR and renal blood flow (RBF). A potential protective effect of IGF-1 on renal function was evaluated in newborn rabbits with hypoxemia-induced renal insufficiency. Renal function and hemodynamic parameters were assessed in 17 anesthetized and mechanically ventilated newborn rabbits. After hypoxemia stabilization, saline solution (time control) or IGF-1 (1 mg/kg) was given as an intravenous (i.v.) bolus, and renal function was determined for six 30-min periods. Normocapnic hypoxemia significantly increased RVR (+16%), leading to decreased GFR (-14%), RBF (-19%) and diuresis (-12%), with an increased filtration fraction (FF). Saline solution resulted in a worsening of parameters affected by hypoxemia. Contrarily, although mean blood pressure decreased slightly but significantly, IGF-1 prevented a further increase in RVR, with subsequent improvement of GFR, RBF and diuresis. FF indicated relative postglomerular vasodilation. Although hypoxemia-induced acute renal failure was not completely prevented, IGF-1 elicited efferent vasodilation, thereby precluding a further decline in renal function.

Les dysthyroïdies en médecine de premier recours [Thyroid dysfunction in primary care medicine].

Thyroid function tests include the measuring of the thyroid stimulating hormone (TSH) and free thyroxine (T4) in the case of abnormal TSH. These tests are frequently performed in primary care medicine since many clinical situations can be suggestive of dysthyroidism, as for example fatigue, depressive states or cardiac arthmia. In the case of subclinical thyroid dysfunction, the indications for treatment are controversial there being a lack of significant randomised studies. For primary care physicians faced with abnormal thyroid function tests we propose a diagnostic approach, clinical recommendations, and indications for referral to the specialist.

Systemic vascular dysfunction in patients with chronic mountain sickness.

ABSTRACT BACKGROUND: Chronic mountain sickness (CMS) is a major public health problem characterized by exaggerated hypoxemia and erythrocytosis. In more advanced stages, these patients often present functional and structural changes of the pulmonary circulation, but there is little information on the systemic circulation. In patients suffering from diseases associated with chronic hypoxemia at low altitude, systemic vascular function is altered. We hypothesized that patients with CMS display systemic vascular dysfunction that may predispose them to increased systemic cardiovascular morbidity. METHODS: To test this hypothesis, we assessed systemic endothelial function (by flow- mediated dilation, FMD), arterial stiffness and carotid intima-media thickness and arterial oxygenation (SaO(2)) in 23 patients with CMS without additional classical cardiovascular risk factors and 27 age-matched healthy mountain dwellers born and permanently living at 3600 m. For some analyses subjects were classified according to baseline SaO(2) quartiles; FMD of the highest quartile subgroup (SaO(2) ≥90%) was used as reference value for post-hoc comparisons. RESULTS: Patients with CMS displayed marked systemic vascular dysfunction, as evidenced by impaired FMD (4.6±1.2 vs. 7.6±1.9%, CMS vs. controls, P<0.0001), greater pulse wave velocity (10.6±2.1 vs. 8.4±1.0 m/s, P<0.001) and carotid intima-media thickness (690±120 vs. 570±110 μm, P=0.001). A positive relationship existed between SaO(2) and FMD (r=0.62, P<0.0001). Oxygen inhalation improved (P<0.001), but did not normalize FMD in patients with CMS; whereas it normalized FMD in hypoxemic controls (SaO(2) <90%) and had no detectable effect in normoxemic (SaO(2) ≥90%) control subjects. CONCLUSIONS: Patients with CMS display marked systemic vascular dysfunction. Structural and functional alterations contribute to this problem that may predispose these patients to premature cardiovascular disease. Clinical Trials Gov Registration # NCT01182792.

Increased prevalence of bladder and intestinal dysfunction in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is predominantly characterized by a progressive loss of motor function. While autonomic dysfunction has been described in ALS, little is known about the prevalence of lower urinary tract symptoms (LUTS) and intestinal dysfunction. We investigated disease severity, LUTS and intestinal dysfunction in 43 patients with ALS attending our outpatient department applying the ALS functional rating scale, the International Consultation on Incontinence Modular Questionnaire, the Urinary Distress Inventory and the Cleveland Clinic Incontinence Score. Results were compared to the German population of a cross-sectional study assessing LUTS in the healthy population, the EPIC study. Results showed that urinary incontinence was increased in patients with ALS aged ≥ 60 years compared to the EPIC cohort (female: 50%/19% (ALS/EPIC), p = 0.026; male: 36%/11% (ALS/EPIC), p = 0.002). No difference was seen at 40-59 years of age. Urge incontinence was the predominant presentation (73% of symptoms). A high symptom burden was stated (ICIQ-SF quality of life subscore 5.5/10). Intake of muscle relaxants and anticholinergics was associated with both urinary incontinence and severity of symptoms. Furthermore, a high prevalence of constipation (46%), but not stool incontinence (9%), was noted. In conclusion, the increased prevalence of urge incontinence and high symptom burden imply that in patients with ALS, LUTS should be increasingly investigated for.

Muscarinic receptor M1 and phosphodiesterase 1 are key determinants in pulmonary vascular dysfunction following perinatal hypoxia in mice.

Perinatal adverse events such as limitation of nutrients or oxygen supply are associated with the occurrence of diseases in adulthood, like cardiovascular diseases and diabetes. We investigated the long-term effects of perinatal hypoxia on the lung circulation, with particular attention to the nitric oxide (NO)/cGMP pathway. Mice were placed under hypoxia in utero 5 days before delivery and for 5 days after birth. Pups were then bred in normoxia until adulthood. Adults born in hypoxia displayed an altered regulation of pulmonary vascular tone with higher right ventricular pressure in normoxia and increased sensitivity to acute hypoxia compared with controls. Perinatal hypoxia dramatically decreased endothelium-dependent relaxation induced by ACh in adult pulmonary arteries (PAs) but did not influence NO-mediated endothelium-independent relaxation. The M(3) muscarinic receptor was implicated in the relaxing action of ACh and M(1) muscarinic receptor (M(1)AChR) in its vasoconstrictive effects. Pirenzepine or telenzepine, two preferential inhibitors of M(1)AChR, abolished the adverse effects of perinatal hypoxia on ACh-induced relaxation. M(1)AChR mRNA expression was increased in lungs and PAs of mice born in hypoxia. The phosphodiesterase 1 (PDE1) inhibitor vinpocetine also reversed the decrease in ACh-induced relaxation following perinatal hypoxia, suggesting that M(1)AChR-mediated alteration of ACh-induced relaxation is due to the activation of calcium-dependent PDE1. Therefore, perinatal hypoxia leads to an altered pulmonary circulation in adulthood with vascular dysfunction characterized by impaired endothelium-dependent relaxation and M(1)AChR plays a predominant role. This raises the possibility that muscarinic receptors could be key determinants in pulmonary vascular diseases in relation to "perinatal imprinting."