Intensive care medicine in Mongolia's 3 largest cities: outlining the needs

PURPOSE: To evaluate intensive care resources, support, and personnel available in Mongolia's 3 largest cities. MATERIALS AND METHODS: This prospective study was performed as a questionnaire-based survey evaluating intensive care units (ICUs) in Mongolia's 3 main cities. RESULTS: Twenty-one of 31 ICUs participated in the survey. The median number of beds per ICU was 7 (interquartile ranges, 6-10) with 0.7 (0.6-0.9) physicians and 1.5 (0.6-1.8) nurses per bed. A 24-hour physician service was available in 61.9% of the participating ICUs. A median number of 359 patients (250-500) with an average age of 39 (30-49) years were treated annually. Oxygen was available in all ICUs, but only for 60% (17-75) of beds. Pressurized air was available in 33% of the ICUs for 24% (0-15) of beds. Of the ICUs, 52.4% had a lung ventilator serving 20% (0-23) of beds. The most common admission diagnoses were sepsis, stroke, cardiac disease, postoperative or postpartum hemorrhage, and intoxication. Availability of medical equipment, disposables, and drugs was inadequate in all ICUs. CONCLUSIONS: Intensive care medicine in Mongolia's 3 largest cities is an under-resourced and underdeveloped medical specialty. The main problems encountered are insufficient training of staff as well as lack of medical equipment, disposables, and drugs.

Identification of small Sca-1(+), Lin(-), CD45(-) multipotential cells in the neonatal murine retina

OBJECTIVE: Bone marrow contains a subset of stem cells that give rise to nonhematopoietic lineages. These nonhematopoietic stem cells appear heterogeneous and contain cells committed to mesenchymal and endothelial lineages, as well as more primitive multipotential cells resembling progenitors of germ cells and very small embryonic/epiblast-like stem cells (VSELs). Nonhematopoietic stem cells can be mobilized from the bone marrow in response to tissue injury, and cells with similar properties have been found in cord blood and normal adult organs. However, the relationship between bone marrow cells and these adult organ stem cells is still unclear. The differentiation potential of some adult stem cells is organ-restricted, but other populations appear to retain multipotential capacity. MATERIALS AND METHODS: A population of small Sca-1(+), lineage-negative (Lin(-)), CD45(-) cells resembling VSELs were isolated from neonatal mouse retina by cell sorting. Differentiation of the cells in culture was achieved by exposure to embryonic stem cell differentiation protocols. RESULTS: VSEL-like cells comprise 1.5% of the neonatal mouse retina. They remain quiescent during retinal differentiation, and thus they do not contribute to normal retinal development. However, they display eye cell differentiation potential in culture and they are also multipotential and can give rise to cells representative of all three embryonic layers. CONCLUSIONS: The neonatal retina is an abundant postnatal source of multipotential VSEL-like cells that can differentiate in culture into a variety of lineages.

Anti-eosinophil activity and clinical efficacy of the CRTH2 antagonist OC000459 in eosinophilic esophagitis

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic, Th2-type inflammatory disease. Chemoattractant receptor-homologous molecule on Th2 cells (CRTH2) is a prostaglandin D(2) (PGD(2)) receptor, expressed by Th2 cells and other inflammatory cells, including eosinophils and basophils, that mediates chemotaxis and activation. OC000459 is a selective CRTH2 antagonist and would be expected to suppress eosinophilic tissue inflammation. The purpose of this study was to evaluate the efficacy and safety of an OC000459 monotherapy in adult patients with active, corticosteroid-dependent or corticosteroid-refractory EoE. METHODS: In this randomized, double-blind, placebo-controlled trial, 26 adult patients (m/f = 22/4; mean age 41 years, range 22-69 years) with active EoE, dependent or resistant to corticosteroids, were treated either with 100 mg OC000459 (n = 14) or placebo (n = 12) twice daily. Pre- and post-treatment disease activity was assessed clinically, endoscopically, histologically, and via biomarkers. The primary end point was the reduction in esophageal eosinophil infiltration. RESULTS: After an 8-week OC000459 treatment, the esophageal eosinophil load decreased significantly, from 114.83 to 73.26 eosinophils per high-power field [(eos/hpf), P = 0.0256], whereas no reduction was observed with placebo (102.80-99.47 eos/hpf, P = 0.870). With OC000459, the physician's global assessment of disease activity improved from 7.13 to 5.18 (P = 0.035). OC000459 likewise reduced extracellular deposits of eosinophil peroxidase and tenascin C, the effects not seen with placebo. No serious adverse events were observed. CONCLUSIONS: An 8-week treatment with the CRTH2-antagonist, OC000459, exerts modest, but significant, anti-eosinophil and beneficial clinical effects in adult patients with active, corticosteroid-dependent or corticosteroid-refractory EoE and is well tolerated.

Strategies for Artificial Insemination of Cattle at Synchronized Ovulation or Synchronized Estrus

Two synchronization protocols in lactating dairy and beef cows and in dairy heifers were tested for efficacy of breeding by artificial insemination (AI) with or without estrus detection. Controls received three prostaglandin F2a (PGF2a) injections 14 days apart before AI at observed estrus. Pregnancy rates were compared with animals on the Ovsynch protocol that combined gonadotropin releasing hormone (GnRH) and PGF2a treatments with a timed AI 16 to 20 hours after the second GnRH injection. The pregnancy rates were similar at synchronized ovulation to fixed-time AI in lactating cows, but not effective in heifers because of the lack of synchronization.

Comparison of Various Methods of Estrus Detection in Synchronized Virgin Beef Heifers

Methods of heat detection were compared in the Mid- Crest Area Cattle Evaluation Program (MACEP) heifer development program in the 1998-breeding season. A total of 189 heifers from thirteen consignors entered the program on November 10, 1997. These heifers were condition scored, hip height measured, weighed, disposition scored, booster vaccinated, and treated for parasites at the time of arrival. Determination of the heifer’s mature weight was made and a target of 65% of their mature weight at breeding was established. The ration was designed to meet this goal. The heifers were kept in a dry lot until all heifers were AI bred once. The heifers were periodically weighed and condition scored to monitor their gains and the ration was adjusted as needed. The estrus synchronization program consisted of an oral progesterone analog for 14 days; 17 days after completion of the progesterone analog treatment a single injection of prostaglandin was given and the heifers were then estrus detected. Two concurrent methods of estrus detection were utilized: 1) Ovatec â electronic breeding probe (probe), 2) HeatWatchâ estrus detection system (HW), and 3) a combination of probe and HW. Probe readings were obtained each 12 hours and the heifers were continuously monitored for estrus activity using the HW system. The probe was used as the primary estrus detection method and the HW system was used as a back-up system. Those heifers that did not demonstrate any estrus signs prior to 96 hours post prostaglandin treatment were mass inseminated at 96 hours. Post AI breeding, 151 of the heifers were placed on pasture and ran with clean-up bulls for 60 days. The remaining heifers left the program after the AI breeding was completed. Pregnancy to the AI breeding was determined by ultrasound on June 29, 1998. Results from using both probe and HW were 60% pregnant by AI, probe alone was 32% pregnant by AI, and HW alone was 27% pregnant by AI. The result of mass insemination was 20% pregnant by AI.

The Use of a Vaginal Conductivity Probe to Influence Calf Sex Ratio via Altered Insemination Time

One hundred eighty-nine mixed breed beef heifers from 13 consignors enrolled in the MACEP heifer development project were utilized in this study. Heifers were synchronized by feeding 0.5 mg melengestrol acetate (MGA) per head per day for 14 days followed by an injection of prostaglandin F2a (PGF2a; 25 mg Lutalyse®) 17 days after the last MGA feeding. Each heifer was fitted with a Heatwatch® transmitter on the morning of PGF2a administration to facilitate detection of estrus. Vaginal conductivity measurements were taken using an Ovatec® probe every 12 hours for 96 hours beginning at the time of PGF2a injection. Heifers randomly assigned to produce a female calf were inseminated near the onset of estrus (as indicated by probe values of £ 55 on the decline). Heifers randomly assigned to produce a male calf were inseminated approximately 24 hours after the onset of estrus (as indicated by probe values of ³ 60 on the incline). All heifers not inseminated by 96 hours after PGF2a were mass inseminated in an attempt to impregnate as many heifers as possible. Heifers that were diagnosed as pregnant as a result of the artificial insemination were subjected to ultrasonography for fetal sex determination. Only 70 of the 189 heifers (37.0%) exhibited estrus according to Heatwatch® and incidence of estrus was influenced by heifer average daily gain, reproductive tract score, and disposition score. Heifers receiving a disposition score of 3 (78.7) had a higher (P<.05) probe reading at AI than those receiving a disposition score of 1 or 2 (70.8 and 72.5, respectively). Heifers with probe readings at insemination of 80 - 84 and > 84 had lower (P<.05) pregnancy rates to AI (13.6 and 0.0%, respectively) than heifers with probe readings in the ranges of < 60, 60 - 64, 65 - 69, 70 - 74, and 75 - 79 (35.7, 40.9, 31.4, 35.3, and 26.9% respectively). Heifers that were bred when probe values were increasing had a lower (P<.05) percentage of male fetuses (34.4%) than those bred during a period of decreasing probe values (69.2% male fetuses). These results demonstrate that a vaginal conductivity probe may be a useful tool to determine an insemination time that could potentially alter calf sex ratio.

Superovulation of Beef Heifers with Follicle Stimulating Hormone or Human Menopausal Gonadotropin: Acute Effects on Hormone Secretion

The effects of superovulatory treatment (follicle stimulating hormone [FSH] versus human menopausal gonadotropin [HMG]) and of route of administration (intramuscular versus intravenous) of prostaglandin F2a (PGF2a) on hormonal profiles were determined in 32 Angus x Hereford heifers for breeding and subsequent embryo collection and transfer. Heifers were superstimulated either with FSH (total of 26 milligrams) or HMG (total of 1,050 international units) beginning on days 9 to 12 of an estrous cycle and PGF2a (40 milligrams) was administered at 60 and 72 hours after the beginning of superovulatory treatments. Heifers were artificially inseminated three times at 12-hour intervals beginning 48 hours after PGF2a treatment. Blood serum samples were collected immediately before treatments began and at frequent intervals until embryo collection 288 hours later. Concentrations of luteinizing hormone (LH) and FSH were not affected by hormone treatments, route of PGF2a injection, or interactions between them. Estradiol-17ß (E2-17ß) levels were higher in HMG- than in FSH-treated heifers 60 hours after gonadotropin treatment. Peak concentration of E2-17ß occurred earlier in HMGthan in FSH-treated heifers and earlier in heifers injected with PGF2a intramuscularly than those injected intravenously. Progesterone concentrations were not influenced by treatment or route of PGF2a administration. The progesterone:E2-17ß ratio was higher in FSH- than in HMG-treated heifers 24 hours after the LH peak. The high steroid hormone concentrations in superovulated beef heifers before and after ovulation may lead to asynchrony between stages of embryonic development, a situation that may interfere with the pregnancy outcome of superovulated embryos in recipient animals.

Impact of B-type natriuretic peptide on short-term clinical outcomes following transcatheter aortic valve implantation

Aims: We aimed to assess the impact of B-type natriuretic peptide (BNP) on short-term outcomes in patients undergoing transcatheter aortic valve implantation (TAVI). Methods and results: Of 500 consecutive patients with severe aortic stenosis undergoing TAVI at our institution, we studied 340 patients who had a BNP assessment prior to TAVI. Patients were divided into tertiles - low: BNP ≤201 pg/mL (n=114), mid: BNP 202-595 pg/mL (n=113) and high: BNP ≥596 pg/mL (n=113). The primary endpoint was all-cause mortality, cardiac death and major adverse cardiac and cerebrovascular events (MACCE; death, major stroke and myocardial infarction) at 30 days. Compared with low tertile, high tertile patients were at higher baseline surgical risk (STS score 5.5±3.0 vs. 7.4±4.1, p=0.002). On echocardiography, high tertile patients had smaller valve areas (0.74±0.21 vs. 0.66±0.23 cm2, p=0.008), higher left ventricular (LV) mass indices (123.40±33.66 vs. 168.22±47.96 g/m2, p<0.001) and lower LV ejection fractions (61.59±7.18 vs. 42.65±15.41%, p<0.001) as compared with low tertile patients. At 30 days, a significantly higher incidence of death (hazard ratio [HR] 7.41, p=0.001) cardiac death (HR 5.82, p=0.006) and MACCE (HR 9.04, p<0.001) was observed among high as compared to low tertile patients. Conclusions: In TAVI patients, higher BNP values at baseline are associated with an increased risk for an adverse event periprocedurally and after 30 days, respectively.

Influence of enamel matrix derivative on cells at different maturation stages of differentiation

Enamel matrix derivative (EMD), a porcine extract harvested from developing porcine teeth, has been shown to promote formation of new cementum, periodontal ligament and alveolar bone. Despite its widespread use, an incredibly large variability among in vitro studies has been observed. The aim of the present study was to determine the influence of EMD on cells at different maturation stages of osteoblast differentiation by testing 6 cell types to determine if cell phenotype plays a role in cell behaviour following treatment with EMD. Six cell types including MC3T3-E1 pre-osteoblasts, rat calvarial osteoblasts, human periodontal ligament (PDL) cells, ROS cells, MG63 cells and human alveolar osteoblasts were cultured in the presence or absence of EMD and proliferation rates were quantified by an MTS assay. Gene expression of collagen1(COL1), alkaline phosphate(ALP) and osteocalcin(OC) were investigated by real-time PCR. While EMD significantly increased cell proliferation of all cell types, its effect on osteoblast differentiation was more variable. EMD significantly up-regulated gene expression of COL1, ALP and OC in cells early in their differentiation process when compared to osteoblasts at later stages of maturation. Furthermore, the effect of cell passaging of primary human PDL cells (passage 2 to 15) was tested in response to treatment with EMD. EMD significantly increased cell proliferation and differentiation of cells at passages 2-5 however had completely lost their ability to respond to EMD by passages 10+. The results from the present study suggest that cell stimulation with EMD has a more pronounced effect on cells earlier in their differentiation process and may partially explain why treatment with EMD primarily favors regeneration of periodontal defects (where the periodontal ligament contains a higher number of undifferentiated progenitor cells) over regeneration of pure alveolar bone defects containing no periodontal ligament and a more limited number of osteoprogenitor cells.

The potential association between gingival crevicular fluid inflammatory mediators and adverse pregnancy outcomes: a systematic review

OBJECTIVES The association between periodontal disease and adverse pregnancy outcomes (APO), primarily preterm birth (PTB), is still controversially discussed in the literature. Therefore, the aim of the present systematic review was to analyze the existing literature on the potential association between inflammatory mediators detected in gingival crevicular fluid (GCF) and APO. MATERIALS AND METHODS MEDLINE (PubMed) and EMBASE databases were searched for entries up to April 2012 and studies were selected by two independent reviewers. RESULTS The majority of the eight studies included confirmed a positive association between GCF mediators, such as interleukin-1β, prostaglandin E2, and tumor necrosis factor-alpha, and APO. Due to the heterogeneity and variability of the available studies, no meta-analysis could be performed. CONCLUSIONS A positive association between GCF inflammatory mediator levels and APO/PTB might be present but the results need to be considered with great caution because of the heterogeneity and variability among the studies. Further studies with an adequate number of patients allowing for an appropriate analysis are warranted to definitely confirm this association. CLINICAL RELEVANCE The present findings suggest that an association between GCF inflammatory mediator levels and APO might exist.

Sphingosine 1-phosphate (S1P) induces COX-2 expression and PGE2 formation via S1P receptor 2 in renal mesangial cells

Understanding the mechanisms of sphingosine 1-phosphate (S1P)-induced cyclooxygenase (COX)-2 expression and prostaglandin E2 (PGE2) formation in renal mesangial cells may provide potential therapeutic targets to treat inflammatory glomerular diseases. Thus, we evaluated the S1P-dependent signaling mechanisms which are responsible for enhanced COX-2 expression and PGE2 formation in rat mesangial cells under basal conditions. Furthermore, we investigated whether these mechanisms are operative in the presence of angiotensin II (Ang II) and of the pro-inflammatory cytokine interleukin-1β (IL-1β). Treatment of rat and human mesangial cells with S1P led to concentration-dependent enhanced expression of COX-2. Pharmacological and molecular biology approaches revealed that the S1P-dependent increase of COX-2 mRNA and protein expression was mediated via activation of S1P receptor 2 (S1P2). Further, inhibition of Gi and p42/p44 MAPK signaling, both downstream of S1P2, abolished the S1P-induced COX-2 expression. In addition, S1P/S1P2-dependent upregulation of COX-2 led to significantly elevated PGE2 levels, which were further potentiated in the presence of Ang II and IL-1β. A functional consequence downstream of S1P/S1P2 signaling is mesangial cell migration that is stimulated by S1P. Interestingly, inhibition of COX-2 by celecoxib and SC-236 completely abolished the migratory response. Overall, our results demonstrate that extracellular S1P induces COX-2 expression via activation of S1P2 and subsequent Gi and p42/p44 MAPK-dependent signaling in renal mesangial cells leading to enhanced PGE2 formation and cell migration that essentially requires COX-2. Thus, targeting S1P/S1P2 signaling pathways might be a novel strategy to treat renal inflammatory diseases.

Ecological validity of virtual reality daily living activities screening for early dementia: longitudinal study

Background: Dementia is a multifaceted disorder that impairs cognitive functions, such as memory, language, and executive functions necessary to plan, organize, and prioritize tasks required for goal-directed behaviors. In most cases, individuals with dementia experience difficulties interacting with physical and social environments. The purpose of this study was to establish ecological validity and initial construct validity of a fire evacuation Virtual Reality Day-Out Task (VR-DOT) environment based on performance profiles as a screening tool for early dementia. Objective: The objectives were (1) to examine the relationships among the performances of 3 groups of participants in the VR-DOT and traditional neuropsychological tests employed to assess executive functions, and (2) to compare the performance of participants with mild Alzheimer’s-type dementia (AD) to those with amnestic single-domain mild cognitive impairment (MCI) and healthy controls in the VR-DOT and traditional neuropsychological tests used to assess executive functions. We hypothesized that the 2 cognitively impaired groups would have distinct performance profiles and show significantly impaired independent functioning in ADL compared to the healthy controls. Methods: The study population included 3 groups: 72 healthy control elderly participants, 65 amnestic MCI participants, and 68 mild AD participants. A natural user interface framework based on a fire evacuation VR-DOT environment was used for assessing physical and cognitive abilities of seniors over 3 years. VR-DOT focuses on the subtle errors and patterns in performing everyday activities and has the advantage of not depending on a subjective rating of an individual person. We further assessed functional capacity by both neuropsychological tests (including measures of attention, memory, working memory, executive functions, language, and depression). We also evaluated performance in finger tapping, grip strength, stride length, gait speed, and chair stands separately and while performing VR-DOTs in order to correlate performance in these measures with VR-DOTs because performance while navigating a virtual environment is a valid and reliable indicator of cognitive decline in elderly persons. Results: The mild AD group was more impaired than the amnestic MCI group, and both were more impaired than healthy controls. The novel VR-DOT functional index correlated strongly with standard cognitive and functional measurements, such as mini-mental state examination (MMSE; rho=0.26, P=.01) and Bristol Activities of Daily Living (ADL) scale scores (rho=0.32, P=.001). Conclusions: Functional impairment is a defining characteristic of predementia and is partly dependent on the degree of cognitive impairment. The novel virtual reality measures of functional ability seem more sensitive to functional impairment than qualitative measures in predementia, thus accurately differentiating from healthy controls. We conclude that VR-DOT is an effective tool for discriminating predementia and mild AD from controls by detecting differences in terms of errors, omissions, and perseverations while measuring ADL functional ability.