Effect of functional excipients on the dissolution and membrane permeation of furosemide formulated into multiple-unit pellet system (MUPS) tablets.

The effect of functional excipients (i.e. chitosan, sodium lauryl sulphate, NaHCO3, and CaCO3) formulated in multiple-unit pellet system (MUPS) tablets has been investigated on the dissolution and permeability of furosemide, a BCS class IV compound. Spherical beads were produced and compressed into MUPS tablets. MUPS tablet formulations were evaluated for hardness, disintegration, mass variation, friability, and dissolution (pH 1.2, pH 4.6, and pH 7.4). Ex vivo permeability studies were conducted across excised pig tissues (pyloric antrum and duodenal region) on selected experimental MUPS tablet formulations. Histological analysis was conducted on the tissues after exposure to selected experimental MUPS tablet formulations. Dissolution results in the 0.1 M HCl (pH 1.2) showed the highest effect of the excipients on furosemide release. Dissolution parameters showed increased dissolution of furosemide for the MUPS tablet formulations containing functional excipients: a 4.5-10-fold increase in the AUC values, the %max showed a 60-70% increase and up to a 19-fold increase in DRi was seen. Permeability results revealed a 2.5-fold higher cumulative percentage transport for selected formulations. The results proved that functional excipients incorporated into beads, compressed into MUPS tablet formulations increased furosemide release as well as permeation across excised intestinal tissues.

Impact of Magnetic Field Configuration on Heat Transport in Stellarators and Heliotrons.

We assess the magnetic field configuration in modern fusion devices by comparing experiments with the same heating power, between a stellarator and a heliotron. The key role of turbulence is evident in the optimized stellarator, while neoclassical processes largely determine the transport in the heliotron device. Gyrokinetic simulations elucidate the underlying mechanisms promoting stronger ion scale turbulence in the stellarator. Similar plasma performances in these experiments suggests that neoclassical and turbulent transport should both be optimized in next step reactor designs.

Estimating the diagnostic accuracy of the ankle-brachial pressure index for detecting peripheral arterial disease in people with diabetes: A systematic review and meta-analysis.

AIM: To systematically evaluate research investigating the accuracy of the ankle-brachial index (ABI) for diagnosing peripheral artery disease (PAD) in people with diabetes, as the accuracy is thought to be reduced in this cohort. METHODS: A database search of EBSCO Megafile Premier, Embase and The Cochrane Library was conducted to 28 February 2019. Prospective and retrospective investigations of the diagnostic accuracy of the ABI for PAD in people with diabetes using an imaging reference standard were eligible. Sensitivity and specify of the ABI and bivariate meta-analysis against reference tests, or a standard summary receiver operating curve analysis (SROC) was performed. RESULTS: Thirty-three studies met the inclusion criteria. ABI was compared with angiography in 12 studies and with colour duplex ultrasound (CDUS) in 21 studies. A SROC analysis of studies using angiography as the reference standard found a diagnostic odds ratio (DOR) of 9.06 [95% confidence interval (CI) 3.61 to 22.69], and area under the curve (AUC) of 0.76 (95% CI 0.66 to 0.86). Bivariate analysis of studies using CDUS demonstrated mean sensitivity of 0.60 (95% CI 0.48 to 0.71; P = 0.097) and mean specificity of 0.87 (95% CI 0.78 to 0.92; P < 0.001) with a DOR of 9.76 (95% CI 5.24 to 18.20; P < 0.0001) and AUC 0.72. CONCLUSIONS: These results suggest the ABI has a high specificity but lower sensitivity in detecting imaging diagnosed PAD in people with diabetes. The low probability of the testing being able to rule diagnosis in or out suggest that the ABI has limited effectiveness for early detection of PAD in this cohort.

Evidence for neuroplastic compensation in the cerebral cortex of persons with depressive illness.

We yoked anatomical brain magnetic resonance imaging to a randomized, double-blind, placebo-controlled trial (RCT) of antidepressant medication for 10-week's duration in patients with dysthymia. The RCT study design mitigated ascertainment bias by randomizing patients to receive either duloxetine or placebo, and it supported true causal inferences about treatment effects on the brain by controlling treatment assignment experimentally. We acquired 121 anatomical scans: at baseline and end point in 41 patients and once in 39 healthy controls. At baseline, patients had diffusely thicker cortices than did healthy participants, and patients who had thicker cortices had proportionately less severe symptoms. During the trial, symptoms improved significantly more in medication-compared with placebo-treated patients; concurrently, thicknesses in medication-treated patients declined toward values in healthy controls, but they increased slightly, away from control values, in placebo-treated patients. Changes in symptom severity during the trial mediated the association of treatment assignment with the change in thickness, suggesting that the beneficial effects of medication on symptom severity were at least partially responsible for normalizing cortical thickness. Together our findings suggest that baseline cortical hypertrophy in medication-free patients likely represented a compensatory, neuroplastic response that attenuated symptom severity. Medication then reduced symptoms and lessened the need for compensation, thereby normalizing thickness. This is to the best of our knowledge the first study to report within an RCT a differential change in cortical morphology during medication treatment for depressive illness and the first to provide within an RCT in vivo evidence for the presence of neuroanatomical plasticity in humans.

JNK1 controls adult hippocampal neurogenesis and imposes cell-autonomous control of anxiety behaviour from the neurogenic niche.

Promoting adult hippocampal neurogenesis is expected to induce neuroplastic changes that improve mood and alleviate anxiety. However, the underlying mechanisms remain largely unknown and the hypothesis itself is controversial. Here we show that mice lacking Jnk1, or c-Jun N-terminal kinase (JNK) inhibitor-treated mice, display increased neurogenesis in adult hippocampus characterized by enhanced cell proliferation and survival, and increased maturation in the ventral region. Correspondingly, anxiety behaviour is reduced in a battery of tests, except when neurogenesis is prevented by AraC treatment. Using engineered retroviruses, we show that exclusive inhibition of JNK in adult-born granule cells alleviates anxiety and reduces depressive-like behaviour. These data validate the neurogenesis hypothesis of anxiety. Moreover, they establish a causal role for JNK in the hippocampal neurogenic niche and anxiety behaviour, and advocate targeting of JNK as an avenue for novel therapies against affective disorders.

JNK1 controls adult hippocampal neurogenesis and imposes cell-autonomous control of anxiety behaviour from the neurogenic niche.

This corrects the article DOI: 10.1038/mp.2016.203.

Top predators induce habitat shifts in prey within marine protected areas.

Emerging conservation efforts for the world's large predators may, if successful, restore natural predator-prey interactions. Marine reserves, where large predators tend to be relatively common, offer an experimental manipulation to investigate interactions between large-bodied marine predators and their prey. We hypothesized that southern stingrays-large, long-lived and highly interactive mesopredators-would invest in anti-predator behavior in marine reserves where predatory large sharks, the primary predator of stingrays, are more abundant. Specifically, we predicted southern stingrays in marine reserves would reduce the use of deep forereef habitats in the favor of shallow flats where the risk of shark encounters is lower. Baited remote underwater video was used to survey stingrays and reef sharks in flats and forereef habitats of two reserves and two fished sites in Belize. The interaction between "protection status" and "habitat" was the most important factor determining stingray presence. As predicted, southern stingrays spent more time interacting with baited remote underwater videos in the safer flats habitats, were more likely to have predator-inflicted damage inside reserves, and were less abundant in marine reserves but only in the forereef habitat. These results are consistent with a predation-sensitive habitat shift rather than southern stingray populations being reduced by direct predation from reef sharks. Our study provides evidence that roving predators can induce pronounced habitat shifts in prey that rely on crypsis and refuging, rather than active escape, in high-visibility, heterogeneous marine habitats. Given documented impacts of stingrays on benthic communities it is possible restoration of reef shark populations with reserves could induce reef ecosystem changes through behavior-mediated trophic cascades.

A pilot investigation on impact of participation in a long-term follow-up clinic (LTFU) on breast cancer and cardiovascular screening among women who received chest radiation for Hodgkin lymphoma.

BACKGROUND: Women treated with chest radiation for Hodgkin lymphoma (HL) are at significantly increased risk of breast cancer and cardiovascular disease. HL survivors are recommended to have annual dual screening with mammogram (MMG) and breast magnetic resonance imaging (MRI). They are also recommended to undergo echocardiogram (echo) 5 years after completion of radiation. We performed a pilot study to characterize the women who are and are not receiving proper dual screening for breast cancer and baseline echo, and to examine the impact of a LTFU clinic consultation on screening. METHODS: A retrospective chart review of 114 women treated for HL at University of Minnesota (UMN) between 1993 and 2009 was performed. Demographics, disease and treatment history (age at diagnosis, stage, radiation dose and field, chemotherapy, recurrence) were assessed, as well as screening practices (MMG, MRI, both and echo), participation in LTFU clinic, and recommendations from providers. Data was summated in yes/no (y/n) format; statistical analysis was performed using chi-squared and Fisher's exact tests. Breast cancer and cardiovascular screening outcomes were compared by participation in the LTFU clinic (y/n) using Fisher's exact tests. P values < 0.05 were considered statistically significant. RESULTS: Forty-one of 114 women met inclusion criteria and had follow-up data for analysis. Median age at diagnosis was 29 years; 67.6% were diagnosed at stage IIa. Median dose of radiation was 3570 cGy. 56.1% participated in the LTFU clinic at the UMN. 36.6% had dual screening with both MMG and MRI, 41.5% had screening with only MMG, and 19.5% had no screening performed. Women were more likely to have dual screening if they were seen in LTFU clinic vs not seen in LTFU clinic (52.2 vs 16.7%, p = 0.02). 67.5% of women were screened with echo; women were also more likely to have screening with echo if seen in LTFU clinic vs not seen (86.4 vs 44.4%, p = 0.007). CONCLUSION: Many women are not getting the proper dual screening for breast cancer despite their increased risk, with only 36.6% of our study sample getting dual screening. Having a consultation in a LTFU clinic increases dual screening for breast cancer and echo screening for cardiovascular disease. Proper screening allows for detection of secondary breast cancer at earlier stages where treatment can be local therapy. Diagnosing CV disease early could allow for proper preventative treatment or intervention.

Safety and efficacy of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with critical limb ischemia.

VM202, a plasmid DNA that expresses two isoforms of hepatocyte growth factor, may elicit angiogenic effects that could benefit patients with critical limb ischemia (CLI). In a phase 2, double-blind trial in 52 CLI patients, we examined the safety and potential efficacy of intramuscular injections of low-dose (n=21) or high-dose (n=20) VM202 or placebo (n=11) in the affected limb (days 0, 14, 28 and 42). Adverse events and serious adverse events were similar among the groups; no malignancy or proliferative retinopathy was seen. In exploratory efficacy analyses, we found no differences in ankle or toe-brachial index, VAS, VascuQuol or amputation rate among the groups. Complete ulcer healing was significantly better in high-dose (8/13 ulcers; P<0.01) versus placebo (1/9) patients. Clinically meaningful reductions (>50%) in ulcer area occurred in high-dose (9/13 ulcers) and low-dose (19/27) groups versus placebo (1/9; P<0.05 and P<0.005, respectively). At 12 months, significant differences were seen in TcPO2 between the high-dose and placebo groups (47.5 ± 17.8 versus 36.6 ± 24.0 mm Hg, respectively; P<0.05) and in the change from baseline among the groups (P<0.05). These data suggest that VM202 is safe and may provide therapeutic bioactivity in CLI patients.

Knowledge, attitudes, and intentions toward fertility awareness and oocyte cryopreservation among obstetrics and gynecology resident physicians.

STUDY QUESTION: What knowledge, attitudes and intentions do US obstetrics and gynecology (OB/GYN) residents have toward discussing age-related fertility decline and oocyte cryopreservation with their patients? SUMMARY ANSWER: Most OB/GYN residents believe that age-related fertility decline, but not oocyte cryopreservation, should be discussed during well-woman annual exams; furthermore, nearly half of residents overestimated the age at which female fertility markedly declines. WHAT IS KNOWN ALREADY: Oocyte cryopreservation can be utilized to preserve fertility potential. Currently, no studies of US OB/GYN residents exist that question their knowledge, attitudes, and intentions toward discussing age-related fertility decline and oocyte cryopreservation with patients. STUDY DESIGN, SIZE, DURATION: A cross-sectional online survey was conducted during the fall of 2014 among residents in American Council for Graduate (ACOG) Medical Education-approved OB/GYN residency programs. Program directors were emailed via the ACOG Council on Resident Education in Obstetrics and Gynecology server listing and asked to solicit resident participation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants included 238 residents evenly distributed between post-graduate years 1-4 with varied post-residency plans; 90% of residents were women and 75% were 26-30 years old. The survey was divided into three sections: demographics, fertility awareness, and attitudes toward discussing fertility preservation options with patients. Descriptive and inferential statistics were conducted. MAIN RESULTS AND THE ROLE OF CHANCE: A strong majority of residents (83%) believed an OB/GYN should initiate discussions about age-related fertility decline with patients (mean patient age 31.8), and 73% percent believed these discussions should be part of an annual exam. One third of residents overestimated the age at which there is a slight decline in female fertility, while nearly half of residents overestimated the age at which female fertility markedly declines. Over three-quarters of residents (78.4%) also overestimated the likelihood of success using assisted reproductive treatments (ARTs). Residents were likely to support oocyte cryopreservation in cancer patients irrespective of the woman's age, but much less likely to support elective oocyte cryopreservation. For elective oocyte cryopreservation, 40% believed OB/GYNs should initiate discussions with patients (mean age 31.1), while only 20% believed this topic should be part of an annual exam. LIMITATIONS, REASONS FOR CAUTION: Because the study invitation was sent through US OB/GYN residency program directors rather than directly to residents, it is possible that some residents did not receive the invitation to participate. This limits the generalizability of the findings. WIDER IMPLICATIONS OF THE FINDINGS: Within the USA, there appears to be a critical need for improved education on fertility decline in OB/GYN residency programs. To promote informed reproductive decision-making among patients, efforts should be made to help OB/GYNs provide comprehensive fertility education to all women, while also respecting patient choices. STUDY FUNDING/COMPETING INTERESTS: None.

Intentions and attitudes towards parenthood and fertility awareness among Chinese university students in Hong Kong: a comparison with Western samples.

STUDY QUESTION: What are the levels of awareness regarding female fertility and the intentions and attitudes towards parenthood among Chinese university students in Hong Kong compared with their counterparts in the West? SUMMARY ANSWER: Chinese university students in Hong Kong were similarly over-optimistic about the age-related fertility decline, although they were less inclined to have children and undergo fertility treatment compared with their Western counterparts. WHAT IS KNOWN ALREADY: Past studies of highly educated young adults in Europe and the USA have found that they are not sufficiently aware of the age-related decline in female fertility, and falsely believe that advanced reproductive treatments such as IVF will overcome fertility problems associated with age. Little is known about the perceptions of Chinese students in Hong Kong, a modernized Chinese city where the fertility rate is among the lowest in the world. STUDY DESIGN, SIZE, DURATION: An online cross-sectional survey of Chinese university students in Hong Kong was conducted in 2013. Results were compared with two similar studies in Sweden and the USA. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 367 university students in Hong Kong (275 female, 92 male; mean age 23) responded to an e-mail invitation to participate in an online survey. Intentions and attitudes towards parenthood and awareness regarding female fertility were assessed using the Swedish Fertility Awareness Questionnaire. MAIN RESULTS AND THE ROLE OF CHANCE: Like their Western counterparts, a large proportion of Chinese university students underestimated the age-related fertility decline (92%) and overestimated the fertility treatment success rate (66%). However, they were less inclined to have children, were more aware of and less concerned with infertility and were less motivated to seek solutions in the event of a fertility problem. These comparisons were significant at P < 0.05. LIMITATIONS, REASONS FOR CAUTION: Self-selection bias was inevitable in the questionnaire survey, and the anonymous nature of the survey did not permit the collection of characteristics of non-responders. International comparisons warrant caution because the Hong Kong sample was older than the US sample (mean age 20), but not older than the Sweden sample (mean age 24). WIDER IMPLICATION OF FINDINGS: While this study was consistent with past Western studies on the lack of fertility awareness among highly educated young people, the findings reveal significant cultural differences in family planning and responses to infertility between Asia and the West.

Limacina helicina shell dissolution as an indicator of declining habitat suitability owing to ocean acidification in the California Current Ecosystem.

Few studies to date have demonstrated widespread biological impacts of ocean acidification (OA) under conditions currently found in the natural environment. From a combined survey of physical and chemical water properties and biological sampling along the Washington-Oregon-California coast in August 2011, we show that large portions of the shelf waters are corrosive to pteropods in the natural environment. We show a strong positive correlation between the proportion of pteropod individuals with severe shell dissolution damage and the percentage of undersaturated water in the top 100 m with respect to aragonite. We found 53% of onshore individuals and 24% of offshore individuals on average to have severe dissolution damage. Relative to pre-industrial CO2 concentrations, the extent of undersaturated waters in the top 100 m of the water column has increased over sixfold along the California Current Ecosystem (CCE). We estimate that the incidence of severe pteropod shell dissolution owing to anthropogenic OA has doubled in near shore habitats since pre-industrial conditions across this region and is on track to triple by 2050. These results demonstrate that habitat suitability for pteropods in the coastal CCE is declining. The observed impacts represent a baseline for future observations towards understanding broader scale OA effects.

Dyadic dynamics of perceived social support in couples facing infertility.

STUDY QUESTION: Is perceived social support from partner, family, and friends associated with increased infertility-related stress? SUMMARY ANSWER: While men's perceived support did not seem to influence their partners' stress, women's perceptions of spousal and familial support can affect the way men deal with the challenge of infertility. WHAT IS KNOWN ALREADY: Previous studies showed that low levels of social support are associated with poor psychosocial adjustment and treatment termination in women and men. Studies examining the impact of social support using the couple as unit of analysis are lacking. STUDY DESIGN, SIZE, DURATION: A cross-sectional sample of 613 Portuguese patients participated in the research, online over a 3-month period, and in a public fertility clinic over 11 months. PARTICIPANTS/MATERIALS, SETTING, METHODS: The final sample comprised 213 married or cohabiting couples (191 from the fertility clinic) who were actively attempting to have a child, were seeking infertility treatment and had not undergone previous preimplantation genetic diagnosis. Perceived social support was assessed through the Multidimensional Scale of Perceived Social Support and infertility-related stress was assessed with the fertility problem inventory. Hypotheses were tested by applying the actor-partner interdependence model using structural equation modeling. MAIN RESULTS AND THE ROLE OF CHANCE: Couples had been living together for an average (±SD) of 6 ± 3.5 years, and attempting a pregnancy for 3.8 ± 2.6 years. Nearly half of the couples had undergone infertility treatment (41.3%). Infertility stress was found to be associated with low family support for women (ß = -0.27, P = .003), and low partner support for both men (ß = -0.29, P = .001) and women (ß = -0.45, P = .006). Both women and men's perceived friend support were not significantly related to male or female infertility stress. Men infertility stress was also associated with their partners low levels of partner (ß = -0.24, P = .049) and family support (ß = -0.23, P < .001). No significant partner effects were observed for women. Despite being related to actor effects alone (female partner and family support), the explained variance of the model in women's fertility stress was greater (R(2) = 21%) than that (R(2) = 15.6%) for the combined actor and partner effects in men's fertility stress (male partner support, female partner and family support). LIMITATIONS, REASONS FOR CAUTION: The study data are cross-sectional and the generalizability of results is limited by self-selection. The characteristics of non-participants in both the clinical and online samples were not available, the perception of infertility-specific supportive behaviors was not assessed and differential analyses according to infertility diagnosis were not included in this study. WIDER IMPLICATIONS OF THE FINDINGS: Our data underline the importance of partner support in alleviating the burden of infertility. Men may experience infertility indirectly through the impact that it has on their partners. Our findings reinforce the need to involve the male partner throughout the whole treatment process and for couple-based interventions when providing infertility counseling. Further prospective research should be aimed at investigating the male experience of infertility. STUDY FUNDING/COMPETING INTEREST: This research was supported by a PhD scholarship from the Portuguese Foundation for Science and Technology granted to M.M. (FCT, SFRH/BD/44232/2008). The authors have no conflicts of interest to declare.

Antimicrobial penetration in a dual-species oral biofilm after noncontact brushing: an in vitro study.

OBJECTIVES: Oral biofilm is inevitably left behind, even after powered brushing. As a special feature, powered brushing removes biofilm in a noncontact mode. When the brushing distance becomes too large, biofilm is left behind. We hypothesize that biofilm left behind after brushing has different viscoelastic properties than before brushing, impacting antimicrobial penetration. MATERIALS AND METHODS: In vitro grown dual-species biofilms were subjected to 20 % mechanical deformation before and after powered brushing at 4-mm brushing distance. Biofilm thickness and stress relaxation were measured for unbrushed and brushed biofilms. Stress relaxation was analyzed with a three-element Maxwell model. Antimicrobial penetration from five mouthrinses was microscopically evaluated for unbrushed and brushed biofilms. RESULTS: Thicknesses of unbrushed and brushed biofilms were similar. Brushing decreased the prevalence of fast and increased the prevalence of slow relaxation elements, which was accompanied by deeper penetration of chlorhexidine and cetylpyridinium chloride. Penetration of antimicrobials from other mouthrinses was relatively low in unbrushed and brushed biofilms. CONCLUSIONS: This confirmation of our hypothesis points to an additional advantage of powered toothbrushing in a noncontact mode, changing the viscoelastic properties of biofilm in a direction that increases antimicrobial penetration of chlorhexidine and cetylpyridinium. CLINICAL RELEVANCE: The biofilm left behind after noncontact powered toothbrushing may have less recalcitrance toward penetration of chlorhexidine and cetylpyridinium chloride than prior to brushing.

A phase I multi-institutional study of systemic sorafenib in conjunction with regional melphalan for in-transit melanoma of the extremity.

BACKGROUND: Isolated limb infusion with melphalan (ILI-M) corrected for ideal body weight (IBW) is a well-tolerated treatment for patients with in-transit extremity melanoma with an approximate 29 % complete response (CR) rate. Sorafenib, a multi-kinase inhibitor, has been shown to augment tumor response to chemotherapy in preclinical studies. METHODS: A multi-institutional, dose-escalation, phase I study was performed to evaluate the safety and antitumor activity of sorafenib in combination with ILI-M. Patients with AJCC stage IIIB/IIIC/IV melanoma were treated with sorafenib starting at 400 mg daily for 7 days before and 7 days after ILI-M corrected for IBW. Toxicity, drug pharmacokinetics, and tumor protein expression changes were measured and correlated with clinical response at 3 months. RESULTS: A total of 20 patients were enrolled at two institutions. The maximum tolerated dose (MTD) of sorafenib in combination with ILI-M was 400 mg. Four dose-limiting toxicities occurred, including soft tissue ulcerations and compartment syndrome. There were three CRs (15 %) and four partial responses (20 %). Of patients with the Braf mutation, 83 % (n = 6) progressed compared with only 33 % without (n = 12). Short-term sorafenib treatment did alter protein expression as measured with reverse phase protein array (RPPA) analysis, but did not inhibit protein expression in the MAP kinase pathway. Sorafenib did not alter melphalan pharmacokinetics. CONCLUSION: This trial defined the MTD of systemically administered sorafenib in combination with ILI-M. Although some responses were seen, the addition of sorafenib to ILI-M did not appear to augment the effects of melphalan but did increase regional toxicity.

A novel explosive process is required for the gamma-ray burst GRB 060614.

Over the past decade, our physical understanding of gamma-ray bursts (GRBs) has progressed rapidly, thanks to the discovery and observation of their long-lived afterglow emission. Long-duration (> 2 s) GRBs are associated with the explosive deaths of massive stars ('collapsars', ref. 1), which produce accompanying supernovae; the short-duration (< or = 2 s) GRBs have a different origin, which has been argued to be the merger of two compact objects. Here we report optical observations of GRB 060614 (duration approximately 100 s, ref. 10) that rule out the presence of an associated supernova. This would seem to require a new explosive process: either a massive collapsar that powers a GRB without any associated supernova, or a new type of 'engine', as long-lived as the collapsar but without a massive star. We also show that the properties of the host galaxy (redshift z = 0.125) distinguish it from other long-duration GRB hosts and suggest that an entirely new type of GRB progenitor may be required.

Fertility awareness and parenting intentions among Mexican undergraduate and graduate university students.

An online, cross-sectional survey was carried out between November 2017 and January 2018 to assess fertility awareness among students attending the National Autonomous University of Mexico (UNAM) in Mexico City. A total of 371 students participated in the survey (n = 228 females, 143 males). 75% of females and 74% of males believed a woman's fertility begins to decline markedly after age 40. Over 75% of all participants overestimated the probability of couples having a live birth after undergoing one cycle of IVF. With regard to parenting intentions, only 48% of females wished to have children compared to 59% of males (p = 0.037) and men were more likely to have their first child at age 30 or later (71% men vs 55% women). In the event of infertility, participants had a higher preference not to have children or to pursue adoption rather than use in vitro fertilisation (IVF). In summary, university students in Mexico City demonstrated low levels of fertility awareness and a smaller proportion indicated a wish to have children than has been reported by young people elsewhere in the world.

Identification of disease-associated DNA methylation in intestinal tissues from patients with inflammatory bowel disease.

Overwhelming evidence supports the theory that inflammatory bowel disease (IBD) is caused by a complex interplay between genetic predispositions of multiple genes, combined with an abnormal interaction with environmental factors. It is becoming apparent that epigenetic factors can have a significant contribution in the pathogenesis of disease. Changes in the methylation state of IBD-associated genes could significantly alter levels of gene expression, potentially contributing to disease onset and progression. We have explored the role of DNA methylation in IBD pathogenesis. DNA methylation profiles (1505 CpG sites of 807 genes) of matched diseased (n = 26) and non-diseased (n = 26) intestinal tissues from 26 patients with IBD [Crohn's disease (CD) n = 9, ulcerative colitis (UC) n = 17] were profiled using the GoldenGate™ methylation assay. After an initial identification of a panel of 50 differentially methylated CpG sites from a training set (14 non-diseased and 14 diseased tissues) and subsequent validation with a testing set (12 non-diseased and 12 diseased tissues), we identified seven CpG sites that are differentially methylated in intestinal tissues of IBD patients. We have also identified changes in DNA methylation associated with the two major IBD subtypes, CD and UC. This study reports IBD-associated changes in DNA methylation in intestinal tissue, which may be disease subtype-specific.

Post-transplant lymphoproliferative disorders in lung transplant recipients: 20-yr experience at the University of Minnesota.

Post-transplant lymphoproliferative disorders (PTLD) are potentially fatal complications of solid organ transplantation. The natural history of PTLD varies considerably among the different types of organs transplanted. While lung transplant recipients are highly susceptible to PTLD, there are only a few small studies that detail PTLD in this setting. We undertook this study to better describe the characteristics and treatment response in PTLD after lung transplantation. We conducted a retrospective chart review of lung and heart/lung-transplant recipients between 1985 and 2008. A total of 32 cases (5%) of PTLD were identified in 639 patients. The median interval after transplantation to the diagnosis was 40 (3-242) months. Eight patients (25%) were diagnosed within one yr of transplantation and had PTLD predominantly within the thorax and allograft. Twenty-four patients (75%) were diagnosed more than one yr after transplantation and their tumors mainly affected the gastrointestinal tract. Monomorphic PTLD, diffuse large B-cell lymphoma, was diagnosed in 91%. Treatment of PTLD varied according to stage and clinical circumstances. Twenty-four patients (75%) have died. The median overall survival was 10 (0-108) months. PTLD after lung transplantation remains a challenge as a result of its frequency, complexity and disappointing outcome.