Rationale and study design of the RESERVOIR trial: a randomized trial comparing reservoir-based polymer-free amphilimus-eluting stents versus everolimus-eluting stents with durable polymer in patients with diabetes mellitus.

BACKGROUND: Patients with diabetes mellitus (DM) remain at high risk for stent restenosis and adverse cardiovascular events in the drug-eluting stent era. The amphilimus-eluting stent (AES) is a third generation reservoir-based polymer-free drug-eluting stent that has shown promising preliminary results in patients with DM. It has been suggested that the formulation of the drug with fatty acids could not only modulate the drug release in a timely manner but also achieve convenient levels of drug concentration in diabetic cardiac cells. The aim of this trial is to assess the efficacy of the AES in patients with DM compared with the cobalt chromium everolimus-eluting stent with non-erodible polymer (EES). STUDY DESIGN: This is an investigator-initiated, multicenter, randomized clinical trial, performed in patients with DM. A total of 112 diabetic patients receiving glucose-lowering agents and requiring percutaneous revascularization of a de novo lesion will be randomized in a 1:1 fashion to receive AES or EES. The primary endpoint is the neointimal volume obstruction at 9 months, evaluated by optical coherence tomography. Secondary endpoints will include strut coverage, angiographic in-stent late loss and clinical endpoints such as target vessel revascularization or probable/definite stent thrombosis. This study completed the inclusion in October 2013. CONCLUSIONS: The RESERVOIR trial is an investigator-initiated trial that will evaluate whether the polymer-free AES is not inferior to the EES inhibiting the neointimal hyperplasia in patients with DM. These results are also expected to improve our knowledge of the neointimal healing process in this population (Clinicaltrials.gov number NCT01710748).

Developmental competence and embryo quality of small oocytes from pre-pubertal goats cultured in IVM medium supplemented with low level of hormones, insulin-transferrin-selenium and ascorbic acid.

The aim of this study was to test the effect of insulin-transferrin-selenium (ITS) and L-ascorbic acid (AA) supplementation and the hormonal level during in vitro maturation (IVM) of small oocytes from pre-pubertal goat on the blastocyst yield and quality. Concretely, we used four maturation media: conventional IVM medium (CM), growth medium (GM: CM+ITS+AA and low level of hormones), modified CM (mCM: CM with low level of hormones) and modified GM (mGM: CM+ITS+AA and normal level of hormones). Cumulus-oocyte complexes (COCs) were classified into two categories according to oocyte diameter: <125 µm and ≥ 125 µm. Large oocytes were matured 24 h in CM (Treatment A). Small oocytes were matured randomly in six experimental groups: Treatment B: 24 h in CM; Treatment C: 12 h in GM and 12 h in CM; Treatment D: 24 h in mGM; Treatment E: 12 h in mGM and 12 h in CM; Treatment F: 12 h in mCM and 12 h in CM; and Treatment G: 12 h in GM and 12 h in mGM. After IVM, oocytes were fertilized and cultured for 8 days. The blastocyst quality was assessed by the survival following vitrification/warming and the mean cell number. When different maturation media were combined, the blastocyst rate did not improve. The large oocytes produced the highest blastocysts yield. However, the culture of small oocytes in GM (53.3%) enhanced the post-warming survival of blastocysts compared to large oocytes matured in CM (35.7%). In conclusion, IVM of pre-pubertal goat small oocytes in GM would be useful to improve the quality of in vitro-produced blastocysts.

Effect of ICSI and embryo biopsy on embryo development and apoptosis according to oocyte diameter in prepubertal goats.

ICSI and embryo biopsy are routine methods used for assisted reproduction. However, their impact on embryo quality is still poor studied. Moreover, oocyte size is also a crucial factor for blastocyst production. In this study effect of oocyte size, ICSI and embryo biopsy was assessed in terms of incidence of apoptosis and blastocyst development. IVM-oocytes from prepubertal goats were fertilized by ICSI or IVF. Embryos obtained were divided depending on oocyte size, biopsied at day-4 post-insemination/injection and cultured for additional 4-5 days. Apoptotic cell number was assessed by TUNEL staining in day-4 embryos and blastocysts obtained. In each diameter group, ICSI did not affect embryo development, blastocyst cell number and embryo apoptotic grade in comparison to IVF. Embryo biopsy did not affect blastocyst rate and apoptotic cell number, but decreased blastocyst cell number (P=0.0018). Moreover, there was a negative relationship between blastocyst cell number and apoptotic grade (P<0.05). In conclusion, ICSI and embryo biopsy do not have negative effect on embryo quality and development. However, oocyte size has a positive relationship on blastocyst yield and quality.

Multivisceral transplantation for megacystis microcolon intestinal hypoperistalsis syndrome.

BACKGROUND: Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a rare autosomal recessive disorder causing a functional neonatal bowel obstruction. Its etiopathogenesis is not fully understood. The prognosis is poor in the majority of cases; most patients die before the age of 6 months. In this report, we describe our experience with three patients with MMIHS in whom multivisceral transplantation was performed. METHODS: Three patients with MMIHS underwent multivisceral transplantation. All patients were females with a history of long-term total parenteral nutrition (TPN) with TPN-related cholestatic liver disease. RESULTS: Patient 1 died 17 months after transplantation because of aspiration after revision of her feeding gastrostomy. At the time of death, the graft was functioning and the patient was completely off TPN. Patient 2 is alive 17 months after transplant. She is a fully functional, active 2-year-old and has also recently begun oral feeding after intensive rehabilitation. Patient 3 died on day 44 of multisystem failure. CONCLUSIONS: This is the first report in the literature of multivisceral transplantation for MMIHS. Although one of the three patients died 44 days after surgery from multiorgan system failure, the other two patients had long-term survival after transplant and both grew well on enteral feeding alone. One patient died 17 months from a non-transplant-related complication, while the other is living at home off of TPN, with almost complete dietary rehabilitation 17 months after transplant. Our case reports suggest that multivisceral transplantation is a valuable therapeutic option for patients affected by MMIHS with TPN-induced liver failure.

Pulmonary embolism with bone fragments following vertebral body marrow infusion for tolerance induction.

Protocols of donor bone marrow infusion for tolerance induction are receiving increasing attention in clinical trials of organ allotransplantation. We report pulmonary embolism with bone fragments following vertebral body marrow infusion in a recipient of a liver and intestinal transplant. Even though pulmonary embolism with bony microfragments has been widely described following bone marrow transplantation, the use of single, high-dose donor bone marrow infusion and/or multiple infusions currently under clinical investigation for induction of donor specific unresponsiveness, may warrant the implementation of additional steps in the vertebral body marrow processing technique to decrease or eliminate the component of bony microfragments in the final preparation.

Adrenocortical carcinoma with cerebral metastasis in a child: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: Adrenocortical carcinoma (ACC) is rare in the pediatric population, and brain metastasis seldom occurs. CLINICAL PRESENTATION: The authors report a case of metastatic ACC to the brain in a 9-year-old patient who had an adrenal cortex neoplasm removed at 4 years of age, and was free of symptoms for 5 years. Two weeks before admission she complained of blurred vision in both eyes. INTERVENTION: Examination revealed bilateral papilledema, and a Magnetic Resonance Imaging (MRI) of the brain revealed a mass in the left lateral ventricle with extensive vasogenic edema and hydrocephalus. The tumor was removed, and histopathologic examination demonstrated metastatic ACC. CONCLUSION: Although ACC is a rare neoplasm it must be considered in the differential diagnosis of cerebral lesions in patients with a history of this tumor. Periodic long-term brain imaging is suggested as part of the follow up in patients with adrenocortical neoplasms.

Oral health during pregnancy: an analysis of information collected by the pregnancy risk assessment monitoring system.

BACKGROUND: Little is known about the use of dental services during pregnancy. Yet research suggests that a pregnant woman's oral health and her pregnancy outcome may be associated. METHODS: Four states collected oral health data a part of the Pregnancy Risk Assessment Monitoring System, or PRAMS, in 1998. PRAMS is an ongoing, population-based survey designed to obtain information from mothers who recently delivered live-born infants about their experiences and behaviors before, during and immediately after pregnancy. RESULTS: Reports of dental care use during pregnancy ranged from 22.7 to 34.7 percent. In three states, 12.2 percent to 25.4 percent of respondents reported having a dental problem and of these, 44.7 percent to 54.9 percent went for care. Among mothers reporting a dental problem, prenatal care, or PNC, insurance through public funding and late PNC entry were significantly associated with their not getting dental care. CONCLUSIONS: Most mothers did not go for dental care during their pregnancy; among those who reported having problems, one-half did not get dental care. PRACTICE IMPLICATIONS: Attention toward the oral health needs of pregnant women is warranted. A coordinated effort from the dental and obstetric communities to establish guidelines could benefit maternal oral health and perinatal outcomes.

Polymer-free amphilimus-eluting stents in patients with diabetes mellitus.

Despite several improvements in drug-eluting stents design, diabetes mellitus (DM) remains an Achilles' heel for percutaneous coronary revascularization at the present time. The Cre8 stent is a third-generation drug-eluting stent devoid of polymer. The drug, which is formulated with an amphiphilic carrier, is eluted from laser-dug wells on the stent's abluminal surface. The Cre8 stent hat has shown promising preliminary results in patients with DM. This review summarizes the mechanisms of DES failure in patients with DM and the potential role of the Cre8 stent in this high-risk population.

Seroprevalence of herpes simplex virus 2 among Hispanics in the USA: National Health and Nutrition Examination Survey, 2007-2008.

To examine the seroprevalence of herpes simplex virus type 2 (HSV-2) among Hispanics in the USA, we used the cross-sectional, nationally representative National Health and Nutrition Examination Survey to compare the seroprevalence of HSV-2 between Hispanic persons of Mexican heritage and non-Mexican heritage aged 14-44 years, from survey years 2007-2008. The overall HSV-2 seroprevalence among Hispanics aged 14-44 years was 17.5% (95% confidence interval [CI], 15.2, 20.1) in the USA. HSV-2 seroprevalence was significantly lower among Mexican Americans than among other Hispanics (11.7% vs. 27.8%, P < 0.01). Prevalence of HSV-2 was also significantly associated with gender and age. The significant difference in HSV-2 seroprevalence between Hispanic persons of Mexican heritage and non-Mexican heritage suggested that targeting specific subgroups of Hispanics for preventive interventions may be a strategy to reduce the transmission of HSV-2 and HIV among Hispanics in the USA.

Prepubertal goat oocytes from large follicles result in similar blastocyst production and embryo ploidy than those from adult goats.

Developmental competence of oocytes from prepubertal females is lower than those from adult females. Oocyte development competence is positively related to follicular diameter. Most of the follicles of prepubertal goat ovaries are smaller than 3 mm. The aim of this study was to compare oocytes of two follicle sizes (< 3 mm and ≥ 3 mm) from prepubertal goats with oocytes from adult goats in relation to their in vitro production and quality of blastocysts. Oocytes from prepubertal goats were obtained from slaughterhouse ovaries and selected according to the follicle diameter whereas oocytes from adult goats were recovered in vivo by LOPU technique without prior selection of follicle size. COCs were IVM for 27 h, IVF at the conventional conditions with fresh semen and presumptive zygotes were cultured in SOF medium for 8 days. Blastocysts obtained were vitrified and after warming their blastocoele re-expansion and the ploidy by FISH technique were assessed. We found significant differences between blastocysts yield of oocytes recovered from follicles smaller than 3 mm of prepubertal goats compared to those from adult goats (5.45% vs 20. 83%, respectively) however, these differences disappear if oocytes were recovered form large follicles (18.07%). A total of 28 blastocysts were analysed and 96.43% showed mixoploidy. Age did not affect the number of embryos with abnormal ploidy or blastocyst re-expansion after warming. Furthermore, the percentage of diploid blastomeres per embryo was similar in the 3 groups studied, adult, prepubertal from follicles ≥ 3 mm and < 3 mm (68.6%, 80.8% and 73.6%, respectively). In conclusion, IVP of blastocysts coming from follicles larger than 3 mm of goats 45 days old were not different to the blastocysts produced from adult goats, both in terms of quantity and quality.

Effect of follicle diameter on oocyte apoptosis, embryo development and chromosomal ploidy in prepubertal goats.

The aim of this study was to assess the following parameters in prepubertal goat oocytes of different follicle diameter (> or =3 mm, <3 mm, control): oocyte diameter, early (Annexin-V) and late (TUNEL) apoptosis, embryo development and chromosomal ploidy of these blastocysts using Fluorescence In Situ Hybridization (FISH). Before in vitro maturation, oocytes were measured and stained with Annexin-V or TUNEL. The rest of the oocytes were matured, fertilized, and cultured in vitro for 8 days. Oocytes from follicles of > or =3 mm showed greater mean oocyte diameter (128.27 +/- 7.20 microm vs. 125.35 +/- 7.59 microm), higher percentages of TUNEL positive (42.86 vs. 24.23%), higher cleavage (47.85 +/- 3.98 vs. 23.07 +/- 2.44 %) and blastocyst rates (19.77 +/- 3.04 vs. 4.11 +/- 1.10 %) than oocytes from follicles of <3 mm.. Blastocyst mean cell numbers did not show differences between follicular groups (123.83 +/- 49.62 vs. 104.29 +/- 36.09 for follicles of > or =3 mm and <3 mm, respectively). A total of 54 blastocysts with 7084 nuclei were hybridized with specific probes to chromosomes X and Y. Ninety-eight percent (98%) of the embryos presented at least one cell carrying an abnormal number of chromosomes, but 78% of them presented less than 25% of chromosomal abnormal cells. No differences in the percentage of blastocysts with abnormal ploidy were found in embryos produced from oocytes of different follicle diameter.

Oocyte secreted factors improve embryo developmental competence of COCs from small follicles in prepubertal goats.

Oocytes secrete soluble paracrine factors called Oocyte Secreted Factors (OSFs) which regulate the cumulus cell phenotype. Follicle populations in ovaries from prepubertal females have smaller diameters than their adult counterparts. Oocytes from small follicles are less competent than those from large follicles. The aim of this study was to investigate, in prepubertal goats, the effect of OSFs secreted by denuded oocytes (DOs) from small (<3 mm) or large (>or=3 mm) follicles during IVM on embryo development and the blastocyst quality of cumulus-oocyte complexes (COCs) from small follicles and to determine if GDF9 participates in this process. Treatment groups were: (A) COCs non selected by their follicle size (control group); (B) cumulus oocytes complexes from small follicles (SFCOCs), (C) cumulus oocytes complexes from small follicles co-cultured with denuded oocytes from small follicles (SFCOCs + SFDOs), and (D) cumulus oocytes complexes from small follicles co-cultured with denuded oocytes from large follicles (SFCOCs + LFDOs). The effect of the addition of kinase inhibitor SB-431542, which antagonizes GDF9, was tested in A, C, and D treatment groups. Co-cultured SFCOCs with SFDOs or LFDOs significantly augmented the blastocyst rate in comparison to SFCOCs alone (15.77%, 17.39% vs. 10.31%, respectively). Blastocysts from SFCOCs + LFDOs group showed higher rates of tetraploid nuclei than blastocysts from SFCOCs and the control group (14.43% vs. 5.45% and 5.24%, respectively; P < 0.05). However, we did not observe differences in the hatching rate, mean cell number or embryo cryotolerance (P > 0.05) between the four treatment groups. The addition of SB-431542 during IVM did not have any effect on blastocyst rate (P > 0.05). In conclusion, in prepubertal goats, COCs with a low embryo developmental competence as a consequence of follicle size can be improved by coculturing them with denuded oocytes from both small and large follicles. GDF9 does not seem play a role in this improvement.

Effect of the apoptosis rate observed in oocytes and cumulus cells on embryo development in prepubertal goats.

Oocyte quality is the main factor that determines blastocyst yield; any factor that could affect it, such as apoptosis, could impair subsequent embryonic development. Our aim was to investigate the incidence of apoptosis in prepubertal goat oocytes and cumulus cells, assessed by Annexin-V staining and TUNEL assay, and their effect on embryo development. Oocyte-cumulus complexes (COCs) from slaughtered females were collected and classified depending on COC morphology as: Healthy (H) and Early Atretic (EA). Each one of these groups was classified depending on oocyte diameter: A: 110-125microm, B: 125-135microm and C: >135microm. The COCs were IVM for 27h, IVF with fresh semen and IVC for 8 days after insemination. Apoptosis analyses were performed before and after maturation. Annexin-positive oocytes decreased with diameter in the EA class (immature oocytes: A: 42.6%; B: 30.3%; C: 21%; IVM-oocytes: A: 17.5%; B: 4.8%; C: 0%), while TUNEL assay showed a decrease of apoptosis in the largest oocytes before and after IVM only in Healthy oocytes (immature oocytes: A: 51.5%; B: 43.3%; C: 12.1%; IVM-oocytes: A: 31.7%; B: 12%; C: 0%). Blastocyst rate increased with increasing oocyte diameter, and it was higher in H than in EA oocytes (Healthy; A: 0%; B: 5.3%; C: 14.4%; Early atretic: A: 0.3%; B: 4.1%; C: 5.1%). Oocyte diameter and COC morphology had no effect on the percentage of apoptosis in blastocyst cells. In conclusion, oocyte developmental competence in prepubertal goats is influenced by oocyte diameter and COC morphology.

Lessons learned from the first funding period of the CDC Assessment Initiative.

The Centers for Disease Control and Prevention Assessment Initiative enables state and local health departments to improve their capacity to use data for developing policy and ensuring that needed health services are provided. Using reports and comments submitted by staff from the participating states, lessons learned are summarized for the first funding period of the initiative. Although many activities were common among the participating states, the lessons learned varied for them. From a commitment to the concepts of assessment, policy development, and assurance, a vision for the national mission of public health is provided and the various roles in fulfilling the mission are defined.

Exaggerated neurogenic inflammation and substance P receptor upregulation in RSV-infected weanling rats.

Respiratory syncytial virus (RSV) infection in adult rats causes exaggerated inflammation after sensory nerve stimulation in the extrapulmonary, but not in the intrapulmonary airways. The goal of this study was to analyze neurogenic inflammation in weanling F-344 rats infected with RSV 18 +/- 2 d after birth. Five days after RSV inoculation, the extravasation of Evans blue-labeled albumin after nerve stimulation was significantly greater in the intrapulmonary airways of RSV-infected weanling rats than in pathogen-free control rats. In contrast, no difference was found in the extrapulmonary airways. The level of messenger RNA (mRNA) encoding the substance P (SP) receptor (neurokinin 1 [NK1]) increased fourfold in RSV-infected lungs, whereas mRNA encoding the VIPR1 receptor for the antiinflammatory vasoactive intestinal peptide (VIP) increased to a much lesser degree. mRNAs encoding the other neurokinin (NK2) and VIP (VIPR2) receptors were not affected by the virus. Selective inhibition of the NK1 receptor abolished neurogenic inflammation in RSV-infected intrapulmonary airways. Also, neurogenic inflammation and NK1 receptor upregulation in infected lungs were inhibited by prophylaxis with a monoclonal antibody against RSV. These data suggest that RSV lower respiratory tract infection makes the intrapulmonary airways of young rats abnormally susceptible to the proinflammatory effects of SP by selectively upregulating the expression of NK1 receptors.