Maternal, infant and childhood risks associated with advanced paternal age: The need for comprehensive counseling for men.

The increasing maternal age at first birth is well recognized, but much less discussed are the fact that the prevalence of advanced paternal age (APA) is also increasing and the societal implications of this trend. Over the past 40 years in the United States, the proportion of infants born to fathers of APA, which has been variably defined as above 35 or above 45, increased from ˜4% to 10% (Khandwala et al., 2017, 2018) While there has been extensive research regarding infertility and comorbidities in the aging mother, relatively few studies have explored similar reproductive factors in aging men. However, evidence does suggest a decrease in fertility and an increase in pregnancy complications such as gestational diabetes, intrauterine growth restriction and preterm birth. Additionally, the offspring of fathers of APA have increased risks of chromosomal and non-chromosomal birth defects and an increased incidence of childhood autism and cancers. This review explores the data, with the intent that key counseling points, including the suggestion of sperm banking, can be highlighted when advising the midlife and older man who is considering paternity.

Contraceptive challenges and the transgender individual.

In recent years public awareness of healthcare disparities experienced by transgender individuals throughout the world have garnered increasing attention within the media and from health advocates. Despite this increasing awareness, a paucity of research data and clinical protocols of care for clinicians continues to exist, especially in regard to the transgender individual's family planning needs. Clinicians should be on the forefront of promoting strategies that forge a meaningful and collaborative relationship with the transgender man, including as he transitions through to the menopause and his sexual and reproductive healthcare needs. Unfortunately, despite best efforts to address the health concerns of transgender men in midlife, including their contraceptive needs and pregnancy desires, there is currently a paucity of research. Although hormonal contraceptives are not an option for this group of individuals, especially those on masculinizing hormones, IUD's, both copper containing and progestin containing, should be considered for those with intact pelvic organs. For this group of transgender men with potential for pregnancy who have either completed their family or choose not to give birth, sterilization can be offered. Regardless of where they identify along the gender spectrum, these midlife individuals with potential reproductive potential should have equitable access to and up to date counseling on their contraceptive options. This commentary addresses the contraceptive challenges of the midlife transgender man. (Note: Pronouns used in this article are he/him for cis and transgender men and she/her for cis and transgender women).

Male sexual enhancement after methoprene treatment in Anastrepha fraterculus (Diptera: Tephritidae): A sustained response that does not fade away after sexual maturation.

The juvenile hormone (JH) of insects triggers physiological changes related to reproduction in adults of both sexes. Methoprene is a sesquiterpene with some effects that are analogous to those of JH. Treatments with methoprene accelerate sexual maturation in males of the South American fruit fly Anastrepha fraterculus, giving young males a mating advantage over non-treated males of the same age. Here, we evaluated the effects of methoprene treatment on A. fraterculus males after the sexual maturation phase and tested whether this compound provides a long-term mating advantage. Moreover, we took the first step to unravel the mechanisms that underlie male sexual enhancement. We treated males 1day or 8days after adult emergence and compared mate choice between recently matured (young) females and females that had been mature for ca. 10days (aged females). We also addressed methoprene treatment effects on male sexual signalling. We found that methoprene treatment enhanced male sexual competitiveness even after the sexual maturation phase, and the effect did not decrease until males were older than 20days. However, when methoprene treatment was carried out close to sexual maturity, the mating enhancement was no longer observed, suggesting a non-immediate effect and excluding the possibility that methoprene acts as a pheromonal compound. Young and aged females tended to mate more frequently with treated-males. This might indicate that in a context of sexual selection, the potential benefits associated with reproductive success would be similar for females of both ages. Treated males released larger amounts of pheromonal compounds than non-treated males, but their courtship behaviour was not altered to the same extent, suggesting that methoprene treatment may accelerate differently the components of male courtship. We discuss potential benefits of using methoprene to increase the efficiency of the sterile insect technique, which is an environmentally safe method to control this important South American fruit pest.

Effects of superparasitism on immature and adult stages of Diachasmimorpha longicaudata Ashmead (Hymenoptera: Braconidae) reared on Ceratitis capitata Wiedemann (Diptera: Tephritidae).

The optimal use of available host by parasitoid insects should be favoured by natural selection. For solitary parasitoids, superparasitism (i.e. the egg-laying of several eggs/host) may represent a detrimental phenomenon both in a biological and an applied sense, but under certain circumstances it may be adaptive. Here, we studied the effects of increasing levels of superparasitism (LSPs, number of parasitoid larvae/host) on fitness-related parameters of the immature and adult stages of Diachasmimorpha longicaudata, a solitary endoparasitoid parasitizing Ceratitis capitata. We investigated the moment when supernumerary parasitoid larvae are eliminated and the effects produced by this process, together with its repercussion on female fecundity, parasitism rate, sex ratio, adult survival, flight ability and body size. Complete elimination of competitors occurred soon after larval hatching, before reaching the second larval stage. Elimination process took longer at higher LSPs, although a normal developmental (egg-adult) time was achieved. For LSPs 1, 2, 3 and 5 the effects on parasitoid emergence were mild, but LSP 10 led to the death of all developing parasitoids. Aside from this, to develop in superparasitized hosts did not significantly affect any of the evaluated parameters, and only a female-biased sex ratio was observed at higher LSPs. However, the effects of superparasitism on the adults may have a different outcome under more variable conditions in the field, once they are released for biological control purposes.

Ospemifene 12-month safety and efficacy in postmenopausal women with vulvar and vaginal atrophy.

OBJECTIVE: Assessment of 12-month safety of ospemifene 60 mg/day for treatment of postmenopausal women with vulvar and vaginal atrophy (VVA). METHODS: In this 52-week, randomized, double-blind, placebo-controlled, parallel-group study, women 40-80 years with VVA and an intact uterus were randomized 6 : 1 to ospemifene 60 mg/day or placebo. The primary objective was 12-month safety, particularly endometrial; 12-week efficacy was assessed. Safety assessments included endometrial histology and thickness, and breast and gynecological examinations. Efficacy evaluations included changes from baseline to week 12 in percentage of superficial and parabasal cells and vaginal pH. RESULTS: Of 426 randomized subjects, 81.9% (n = 349) completed the study with adverse events the most common reason for discontinuation (ospemifene 9.5%; placebo 3.9%). Most (88%) treatment-emergent adverse events with ospemifene were considered mild or moderate. Three cases (1.0%) of active proliferation were observed in the ospemifene group. For one, active proliferation was seen at end of study week 52, and diagnosed as simple hyperplasia without atypia on follow-up biopsy 3 months after the last dose. This subsequently resolved with progestogen treatment and dilatation and curettage. In six subjects (five ospemifene (1.4%), one placebo (1.6%)) endometrial polyps were found (histopathology); however, only one (ospemifene) was confirmed as a true polyp during additional expert review. Endometrial histology showed no evidence of carcinoma. Statistically significant improvements were seen for all primary and secondary efficacy measures and were sustained through week 52 with ospemifene vs. placebo. CONCLUSIONS: The findings of this 52-week study confirm the tolerance and efficacy of oral ospemifene previously reported in short- and long-term studies.

Precocious sexual signalling and mating in Anastrepha fraterculus (Diptera: Tephritidae) sterile males achieved through juvenile hormone treatment and protein supplements.

Sexual maturation of Anastrepha fraterculus is a long process. Methoprene (a mimic of juvenile hormone) considerably reduces the time for sexual maturation in males. However, in other Anastrepha species, this effect depends on protein intake at the adult stage. Here, we evaluated the mating competitiveness of sterile laboratory males and females that were treated with methoprene (either the pupal or adult stage) and were kept under different regimes of adult food, which varied in the protein source and the sugar:protein ratio. Experiments were carried out under semi-natural conditions, where laboratory flies competed over copulations with sexually mature wild flies. Sterile, methoprene-treated males that reached sexual maturity earlier (six days old), displayed the same lekking behaviour, attractiveness to females and mating competitiveness as mature wild males. This effect depended on protein intake. Diets containing sugar and hydrolyzed yeast allowed sterile males to compete with wild males (even at a low concentration of protein), while brewer´s yeast failed to do so even at a higher concentration. Sugar only fed males were unable to achieve significant numbers of copulations. Methoprene did not increase the readiness to mate of six-day-old sterile females. Long pre-copulatory periods create an additional cost to the management of fruit fly pests through the sterile insect technique (SIT). Our findings suggest that methoprene treatment will increase SIT effectiveness against A. fraterculus when coupled with a diet fortified with protein. Additionally, methoprene acts as a physiological sexing method, allowing the release of mature males and immature females and hence increasing SIT efficiency.

Structural brain abnormalities in patients with Parkinson disease: a comparative voxel-based analysis using T1-weighted MR imaging and magnetization transfer imaging.

BACKGROUND AND PURPOSE: In PD, tissue damage occurs in specific cortical and subcortical regions. Conventional MR images have only limited capacity to depict these structural changes. The purpose of the current study was to investigate whether voxel-based MT imaging could indicate structural abnormalities beyond atrophy measurable with T1-weighted MR imaging. MATERIALS AND METHODS: Thirty-six patients with PD without dementia (9 in H&Y stage 1, thirteen in H&Y 2, eleven in H&Y 3, three in H&Y 4) and 23 age-matched control subjects were studied with T1-weighted MR imaging and MT imaging. Voxel-based analyses of T1-weighted MR imaging was performed to investigate brain atrophy, while MT imaging was used to study abnormalities within existing tissue. Modulated GM and WM probability maps, sensitive to volume, and nonmodulated maps, indicative of tissue density, were obtained from T1-weighted MR imaging. Effects seen on MTR images, but absent on density maps, were attributed to damage of existing tissue. RESULTS: Contrary to T1-weighted MR imaging, MT imaging was sensitive to the progression of brain pathology of the neocortex and paraventricular WM. MTR images and T1-based volume images, but not density images, showed a progression of disease in the olfactory cortex, indicating the occurrence of atrophy as well as damage to existing tissue in this region. MTR images revealed bilateral damage to the SN, while T1-weighted MR imaging only showed left-sided abnormalities. CONCLUSIONS: The findings suggest that voxel-based MT imaging permits a whole-brain unbiased investigation of CNS structural integrity in PD and may be a valuable tool for identifying structural damage occurring without or before measurable atrophy.

[Tibial pain and unilateral knee arthritis: Precursors of paraneoplastic arthropathy]. / Prätibiale Schmerzen und unilaterale Gonitis: Vorboten paraneoplastischer Gelenkbeschwerden.

Various rheumatic symptoms can occur in association with malignancies and are termed the so-called paraneoplastic arthropathy. The clinical picture is often similar to primary inflammatory rheumatic diseases. At present there exist no epidemiological data on this disease entity. The case of a patient with tibial pain and unilateral knee arthritis as precursors of a paraneoplastic syndrome is presented. The patient presented with the clinical manifestation of small cell lung cancer 2 years after the first presentation in the rheumatology clinic.

Effects of bazedoxifene/conjugated estrogens on quality of life in postmenopausal women with symptoms of vulvar/vaginal atrophy.

OBJECTIVE: To evaluate the effects of the tissue selective estrogen complex (TSEC) pairing bazedoxifene (BZA) with conjugated estrogens (CE) on sexual function and quality of life in postmenopausal women. METHODS: In this 12-week, double-blind, placebo-controlled study, postmenopausal, non-hysterectomized women (n = 652) with symptoms of moderate to severe vulvar/vaginal atrophy were randomized to once-daily treatment with BZA 20 mg/CE 0.45 or 0.625 mg, BZA 20 mg, or placebo. The Arizona Sexual Experiences (ASEX) Scale, Menopause-Specific Quality of Life (MENQOL) questionnaire, and Menopause Symptoms Treatment Satisfaction Questionnaire (MS-TSQ) were secondary measures used to assess the effects of BZA/CE on sexual function, menopausal symptoms, and satisfaction with treatment, respectively. RESULTS: At week 12, both BZA/CE doses were associated with significant improvement in ease of lubrication score from baseline compared with placebo (p < 0.05) on the ASEX scale, although there was no difference in the change in total score. The MENQOL questionnaire results at week 12 showed significant improvements in vasomotor function, sexual function and total scores with both BZA/CE doses vs. placebo or BZA 20 mg (p < 0.001). The MS-TSQ results showed that BZA/CE-treated subjects reported significantly greater overall satisfaction with treatment, as well as satisfaction with control of hot flushes during the day and night, effect on quality of sleep, and effect on mood or emotions, compared with subjects treated with placebo or BZA 20 mg (all p < 0.05). CONCLUSION: Treatment with BZA/CE for 12 weeks was shown to significantly improve sexual function and quality-of-life measures in symptomatic postmenopausal women.

LPS-induced endotoxic shock does not cause early brain edema formation - an MRI study in rats.

OBJECTIVE AND DESIGN: Early microcirculatory failure is assumed as a key factor in the development of a septic encephalopathy. However, brain edema is also a common finding in sepsis syndromes possibly interfering with the vasoregulative mechanisms of the brain. We assessed the occurrence of brain edema in a rat model of endotoxic shock. MATERIAL AND SUBJECTS: Eleven mechanically ventilated male CD-rats. TREATMENT: Intravenous application of 5 mg/kg LPS (n = 8) or vehicle (n = 3). METHODS: Apparent diffusion coefficient (ADC) and T2-relaxation time (T2RT) were quantified on cerebral MRI at baseline and repeatedly for up to 3.5 h after LPS-injection. Change in blood pressure was compensated with norepinephrine. Brain water content was quantified using the wet/dry method. RESULTS: All LPS-treated rats developed endotoxic shock. No significant difference in T2RT or ADC was detectable before and after LPS-injection (T2RT: baseline 60.33 +/- 1.21; after 3.5 h 60.15 +/- 0.59; ADC: baseline 6.86 +/- 0.51; after 3.5 h 6.75 +/- 0.33). Post-mortem analysis did not indicate a difference in brain water content between septic and non-septic animals. CONCLUSIONS: Reports of early microcirculatory failure seem not to be related to the occurrence of early (< or =3.5 h) brain edema.

Pulmonary perfusion in acute pulmonary embolism: agreement of MRI and SPECT for lobar, segmental and subsegmental perfusion defects.

PURPOSE: To assess prospectively the agreement of magnetic resonance (MR) pulmonary perfusion with single-photon emission computed tomography (SPECT) perfusion for perfusion defects down to the subsegmental level in patients with suspected pulmonary embolism (PE). MATERIAL AND METHODS: In 41 patients with suspected PE, contrast-enhanced MR pulmonary perfusion (3D-FLASH, TR/TE 1.6/0.6 ms) was compared to SPECT perfusion on a per-examination basis as well as at the lobar, segmental, and subsegmental level. RESULTS: The MRI protocol was completed in all patients, and mean examination time was 3 min 56 s. MR perfusion showed a very high agreement with SPECT (kappa value per examination 0.98, and 0.98, 0.83, and 0.69 for lobar, segmental, and subsegmental perfusion defects, respectively). Of 15 patients with PE, MR perfusion detected 14 cases. CONCLUSION: The very high agreement of MR perfusion with SPECT perfusion enables the detection of subtle findings in suspected PE.

Experimental stroke: ischaemic lesion volume and oedema formation differ among rat strains (a comparison between Wistar and Sprague-Dawley rats using MRI).

Investigating focal cerebral ischaemia requires animal models that are relevant to human stroke. This study was designed to evaluate the influence of early reperfusion and choice of rat strains on infarct volume and oedema formation. Thirty-six Wistar and Sprague-Dawley rats were subjected to temporary middle cerebral artery occlusion (MCAO) for 90 min (groups I and II) or to permanent MCAO (groups III and IV) using the suture technique. Ischaemic lesion volume and oedema formation were quantified 24 h after MCAO using 7T-magnetic resonance imaging (MRI). Impact of rat strains: Reperfusion led to significant larger ischaemic lesion volumes in Wistar rats as compared to Sprague-Dawley rats (P<0.0005). Oedema formation was similar in both rat strains. Permanent MCAO led to significantly larger ischaemic lesion volumes in Sprague-Dawley rats (P<0.05). Oedema formation, however, was significantly more accentuated in Wistar rats (P<0.005). Impact of reperfusion: Reperfusion did not cause any changes in ischaemic lesion volume in Wistar rats. Oedema formation, however, was significantly reduced (P<0.0005). In Sprague-Dawley rats, reperfusion caused a significant reduction of ischaemic lesion volume (P<0.00005), but did not modify oedema formation. These findings emphasize the critical importance of rat strain differences in experimental stroke research.

[Thoracic real-time MRI: experience from 2200 examinations in acute and ill-defined thoracic diseases]. / Thorakale Echtzeit-MRT: Erfahrungen aus 2200 Untersuchungen bei akuten und unklaren thorakalen Erkrankungen.

PURPOSE: To retrospectively assess the indication for thoracic real-time MRI, demonstrate typical findings, analyze the diagnostic potential in subgroups with suspected pulmonary embolism (PE) and aortic dissection (AD), and describe the influence of real-time MRI on the role of MRI in acute thoracic diseases. MATERIALS AND METHODS: From July 2001 to February 2005, real-time MRI was applied in 2,256 examinations in 1,714 patients. MRI was the primary diagnostic modality for these thoracic diseases as computed tomography has been available only since 2003. Characteristics of the TrueFISP sequence applied were: TR/TE/flip angle 3.1 ms/1.6 ms/59 degrees , respectively. FOV 340 - 360 mm, matrix size 156 to 192 x 256 pixels, slice thickness 3 to 4 mm, slices overlapped by 50 %. Acquisition time was 0.4 to 0.5 s per image. Three hundred and twenty transverse, coronal and sagittal images were acquired in three minutes. No breath holding, and only minimal patient cooperation, was required. Turbo-spin-echo sequences as well as ECG-gated and contrast-enhanced sequences were added depending on the indication. RESULTS: Most common indications were: acute thoracic nonspecified disease (n = 276, 12.24 %), PE (n = 573, 25.4 %), bleeding (n = 154, 6.8 %), AD (n = 222, 9.8 %), topographic information in complex findings (n = 654, 29.0 %). Real-time MRI was the sole MRI technique applied in 180 examinations (8.0 %), ECG-gated real-time MRI was applied in 87 examinations and breath hold was used in 107 examinations. PE was diagnosed in 181 examinations; reference techniques (MRI, computed tomography, single photon emission computed tomography) confirmed 170 of these and detected 19 more cases (sensitivity 90.0 %, specificity 97.1 %). Real-time MRI detected 141 suspected AD and 53 more nonsuspected AD. Of these, 191 were confirmed by other MRI techniques, surgery or clinical course (98.5 %). Real-time MRI coincidentally detected 56 pulmonary tumors, all were confirmed with computed tomography. Thus, especially vascular diseases could be easily assessed with real-time MRI, while computed tomography had advantages in the evaluation of the lung parenchyma. CONCLUSION: Real-time MRI both enables emergency MRI examinations for thoracic diseases in clinical patients in unstable condition and allows an explorative style of working in patients with nondefined acute thoracic diseases.

Screening women with menorrhagia for underlying bleeding disorders: the utility of the platelet function analyser and bleeding time.

Menorrhagia is a very common clinical problem among women of reproductive age and recent studies have suggested that underlying bleeding disorders, particularly von Willebrand's deficiency and platelet function defects, are prevalent in women presenting with menorrhagia. The objective of this study was to determine the utility of the platelet function analyser (PFA-100) and bleeding time (BT) as initial screening tests for underlying bleeding disorders in women with menorrhagia. In this study, 81 women with a physician diagnosis of menorrhagia underwent PFA-100 testing, BT and comprehensive haemostatic testing. The effectiveness of the PFA-100 and BT as screening tools in women with menorrhagia was assessed using results of haemostatic testing for von Willebrand's disease (VWD) and platelet dysfunction. In women presenting with menorrhagia, the PFA-100 had a sensitivity 80%, specificity 89%, positive predictive value (PPV) 33%, negative predictive value (NPV) 98% and efficiency 88% for VWD. For platelet aggregation defects, the PFA-100 closure time had a sensitivity 23%, specificity 92%, PPV of 75%, NPV of 52% and efficiency 55%. The data suggest that the PFA-100 may be useful in stratifying women with menorrhagia for further von Willebrand testing; however, neither the PFA-100 nor the BT tests are effective for purposes of classifying women for standard platelet aggregometry testing in women presenting with menorrhagia.

Ankylosing spondylitis and bone mineral density--what is the ideal tool for measurement?

Ankylosing spondylitis (AS) is characterised by chronic inflammation and partial ossification, yet vertebral fractures due to osteoporosis, although common, are frequently unrecognised. The aim of this study was to (1) show the frequency of changes in the progress of osteopenia/osteoporosis in AS depending on duration and stage of the disease and (2) assess the ranking of two different methods of bone density measurement in this clinical pattern. We measured bone density in 84 male and female patients with both dual X-ray absorptiometry (DXA) and single energy quantitative computed tomography (SE-QCT). In the initial and advanced stages of the disease, a high decrease in axial bone density could be verified (DXA: osteopenia in 5% and osteoporosis in 9.2%; SE-QCT: osteopenia in 11.8% and osteoporosis in 30.3%). Peripheral bone density decrease as in osteopenia could be proven in 17.6% by DXA measurement. With SE-QCT, a decrease in vertebral trabecular bone density could already be observed in the initial stage and continued steadily during the course of the disease; cortical bone displayed the same trend up to stages of ankylosis. With DXA, valid conclusions are more likely to be expected in less marked ankylosing stages of AS. In stages of advanced ankyloses in the vertebral region (substantial syndesmophytes), priority should be given to SE-QCT, due to the selective measurement of trabecular and cortical bone. The DXA method often yields values that are too high, and the replacement of vertebral trabecular bone by fatty bone marrow is not usually recorded as standard. There may already be an increased risk of bone fracture in AS in osteopenia on DXA along with an osteoporosis already established on SE-QCT.

Pre- and postoperative assessment of left ventricular function by magnetic resonance imaging and 2-D-echocardiography in patients undergoing left ventricular aneurysmectomy.

BACKGROUND: Left ventricular (LV) aneurysms may complicate myocardial infarctions. Reliable quantification of LV functional parameters is mandatory to predict clinical outcome in patients undergoing LV aneurysmectomy. We compared global LV function measured by magnetic resonance (MR) and 2-D-echocardiography in patients before and after aneurysmectomy. METHODS: 31 patients (23 male), mean age 64 (range 35 - 85) years with an LV aneurysm (25/31 anterior MI, 5/31 inferior MI, 1/31 both) were enrolled. MR and echocardiography were performed directly before and 3 - 65 (median 8) days after surgery. MR studies were performed on a 1.5 Tesla scanner. End-diastolic and end-systolic volumes and diameters (EDV/ESV, EDD/ESD), ejection fraction (EF) and stroke volume (SV) were determined. Echocardiography was performed to determine EF, EDD and ESD. NYHA class was assessed before and 3 months after surgery. RESULTS: After aneurysmectomy MR analysis showed a decrease in EDV (255 +/- 68 ml to 202 +/- 59 ml) ( p < 0.001) and ESV (186 +/- 71 ml to 134 +/- 53 ml; p < 0.001); EF increased (28 +/- 10 % to 35 +/- 12 %; p < 0.001); EDD/ESD decreased ( p < 0.01). Compared to echocardiography, a low correlation was found in EF before/after surgery r = 0.76/r = 0.69 and ESD r = 0.43/r = 0.60, respectively. In EDD a good correlation was found before surgery (r = 0.81), and a lower correlation after surgery (r = 0.72). NYHA class improved from 3.0 +/- 0.5 before to 1.8 +/- 0.8 after operation ( p < 0.001). CONCLUSION: Resection of an LV aneurysm results in a mean improvement of 25 % in LV function, and improved clinical outcome. In asymmetric ventricles with aneurysms MR proved to be superior as a sensitive and non-invasive tool compared to conventional 2-D-echocardiography.