Six year effectiveness of a population based two tier infant hearing screening programme

Aims: To determine whether a two tier universal infant hearing screening programme (population based risk factor ascertainment and universal distraction testing) lowered median age of diagnosis of bilateral congenital hearing impairment (CHI) >40 dB HL in Victoria, Australia. Methods: Comparison of whole population birth cohorts pre and post introduction of the Victorian Infant Hearing Screening Program (VIHSP). All babies surviving the neonatal period born in Victoria in 1989 (pre-VIHSP) and 1993 (post-VIHSP) were studied. (1) Pre-1992: distraction test at 7–9 months. (2) Post-1992: infants with risk factors for CHI referred for auditory brain stem evoked response (ABR) assessment; all others screened by modified distraction test at 7–9 months. Results: Of the 1989 cohort (n = 63 454), 1.65/1000 were fitted with hearing aids for CHI by end 1995, compared with 2.09/1000 of the 1993 cohort (n = 64 116) by end 1999. Of these, 79 cases from the 1989 cohort (1.24/1000) and 72 cases from the 1993 cohort (1.12/1000) had CHI >40 dB HL. Median age at diagnosis of CHI >40 dB HL for the 1989 birth cohort was 20.3 months, and for the 1993 cohort was 14.2 months. Median age at diagnosis fell significantly for severe CHI but not for moderate or profound CHI. Significantly more babies with CHI >40 dB HL were diagnosed by 6 months of age in 1993 than in 1989 (21.7% v 6.3%). Compared to the six years pre-VIHSP, numbers aided by six months were consistently higher in the six years post-VIHSP (1.05 per 100 000 births versus 13.4 per 100 000 births per year). Conclusions: VIHSP resulted in very early diagnosis for more infants and lowered median age of diagnosis of severe CHI. However, overall results were disappointing.     

Voluntary exercise induces neurogenesis in the hypothalamus and ependymal lining of the third ventricle

In the adult hypothalamus and ependymal lining of the third ventricle, tanycytes function as multipotential progenitor cells that enable continuous neurogenesis, suggesting that tanycytes may be able to mediate the restoration of homeostatic function after stroke. Voluntary wheel running has been shown to alter neurochemistry and neuronal function and to increase neurogenesis in rodents. In the present study, we found that voluntary exercise improved the survival rate and energy balance of stroke-prone spontaneously hypertensive rats (SHRSP/Kpo). We also investigated the effect of exercise on the proliferation and differentiation of hypothalamic cells using immunoreactivity for tanycytes and neural markers. The proliferation of elongated cells, which may be the tanycytes, was enhanced in exercising SHRSP compared to sedentary rats before and after stroke. In addition, the proliferation of cells was correlated with the induction of fibroblast growth factor-2 in the subependymal cells of the third ventricle and in the cerebrospinal fluid. Some of the newborn cells of exercising SHRSP showed differentiation into mature neurons after stroke. Our results suggest that voluntary exercise correlates with hypothalamic neurogenesis, leading to recovery of homeostatic functions in the adult brain after stroke.     

Multivariate analysis of the factors associated with live births during in vitro fertilisation in Southeast Asia: a cross-sectional study of 104,015 in vitro fertilisation records in Taiwan

Purpose

To investigate the factors associated with live births and the interaction between age and the number of embryos transferred after in vitro fertilisation (IVF) treatment.

Methods

This study analyses data from a population-based-assisted reproductive database of all registered artificial reproduction institutions (n = 80) from 2010 to 2016 in Taiwan. The probability of a live birth in correlation with the treatment parameters was measured with multivariate logistic regression analyses using the generalised additive model (GAM) and Pearson’s chi-square exact test.

Results

A total of 104,015 IVF treatments performed between 2010 and 2016 were included in our analysis. From these treatments, 31,467 (30.3%) were successfully delivered, and 40,565 test-tube babies were born. Pearson’s chi-square exact test indicated that parents’ age, cause of infertility, type of ovarian stimulation, additional assisted reproductive technology techniques, donated egg or sperm, fresh or frozen embryo, presence or absence of ovarian hyperstimulation syndrome, and day of embryo transfer were significantly associated with live births after an IVF cycle (p < 0.05). Multiple logistic regression analysis with the GAM revealed that the odds of a live birth with IVF treatment in patients < 34 years of age were 2.55 times higher than that in patients ≥ 45 years of age (odds ratio = 2.55, 95% confidence interval = 1.69–2.90) for patients who underwent a single-embryo transfer (SET); a similar pattern was observed when two or more embryos were transferred. Egg donation, the assisted hatching technique, oral ovarian stimulation agents, and implantation of frozen embryos during SET were shown to improve the chance of a live birth by 29–90%. Implantation of the embryo after the 5th day of culture yielded the highest odds of a live birth. The interaction plot revealed that maternal age, especially < 40 years, was associated with the probability of a live birth. SET and double-embryo transfer showed similar associations with the probability of a live birth across age groups. Transferring more than two embryos might reduce the probability of a live birth during IVF treatment for women ≥ 40 years of age.

Conclusions

Implanting a greater number of embryos did not improve the age-related decrease in fertility for patients undergoing IVF. Therefore, we suggested that ≤ 2 blastocysts could be transferred during IVF treatments for women ≥ 40 years. Transferring a blastocyst on day 5 of culture was associated with a significant increase in the odds of a live birth resulting from IVF.

     

New CR system with pixel size of 50 microm for digital mammography: physical imaging properties and detection of subtle microcalcifications

PURPOSE: To investigate the physical imaging properties and detection of simulated microcalcifications of a new computed radiography (CR) system with a pixel size of 50 microm for digital mammography. MATERIALS AND METHODS: New and conventional CR were employed in this study. The new CR system included a high-resolution imaging plate coupled with the FCR5000MA (50 microm pixel pitch) including transparent support and a dual-sided reader. The conventional CR system was coupled with the FCR9000 (100 microm pixel pitch). Modulation transfer functions (MTFs) and Wiener spectra (WS) of the new and conventional CR systems were measured. Observer performance tests were conducted to compare the effects of pixel size (50 microm vs. 100 microm) on the diagnostic accuracy of CR systems in the detection of simulated microcalcifications. RESULTS: The presampling MTF of the new CR system was higher at high frequencies than the conventional CR system. The WS of the new CR system was comparable to that of the conventional CR system at all frequencies. The area under the receiver operating characteristic (ROC) curve (Az) obtained with the new CR and the conventional CR systems were 0.84 and 0.79, respectively. Results showed that the detection of simulated clustered microcalcifications was significantly improved by use of the new CR system compared with the conventional CR system (p<0.05). CONCLUSION: The new CR mammography system improved physical imaging properties and detection of simulated microcalcifications over conventional CR mammography.     

Early biomechanical changes in lower extremity vein grafts--distinct temporal phases of remodeling and wall stiffness

BACKGROUND: The geometric and biomechanical changes that contribute to vein graft remodeling are not well established. We sought to measure patterns of adaptation in lower extremity vein grafts and assess their correlation with clinical outcomes. METHODS: We conducted a prospective, longitudinal study of patients undergoing infrainguinal reconstruction with autogenous conduit. In addition to standard duplex surveillance, lumen diameter (of a defined index segment of the conduit) and pulse wave velocity (PWV) were assessed by ultrasound imaging at surgery and at 1, 3, and 6 months postoperatively. Graft dimensions and wall stiffness were correlated with clinical outcomes. RESULTS: There were 92 patients and 96 limbs in this study. On average, vein graft lumen diameter increased during the first month of implantation from 0.37 +/- .01 cm to 0.45 +/- 0.02 cm (mean +/- SEM; P = .002), representing a relative change of +21.6% (median +/- 14%; range, -31 to +67%) during this period. Of the entire cohort, 72% of grafts demonstrated appreciable dilation of the index segment during the first month. Index segment lumen diameter did not change appreciably beyond 1 month, with the notable exception of arm vein conduits, which showed continued tendency to dilate. PWV increased during the first 6 months (17.2 +/- 1.2 m/s to 23.2 +/- 2.4 m/s; P = .008), reflecting a nearly 40% increase in conduit stiffness (2.0 +/- .6 Mdynes/cm to 3.3 +/- .8 Mdynes/cm, P = .01). The greatest relative increase (25%) in PWV occurred from months 1 to 3. Loss of primary patency occurred in 24 cases (19 revisions, 5 occlusions), with a mean reintervention time of 7.6 months. Grafts that demonstrated early positive remodeling (lumen dilatation) had a trend of increased primary patency (P = .08, log rank). Among the grafts that failed, a trend was noted toward greater wall stiffness at 1 month, 2.7 vs 1.5 Mdynes (P = .08). CONCLUSION: Vein graft remodeling appears to involve at least two distinct temporal phases. Outward remodeling of the lumen occurs early, and wall stiffness changes occur in a more delayed fashion. Early outward remodeling may be important for successful vein graft adaptation.     

Regeneration of hair and other skin appendages: A microenvironment‐centric view

Advances in skin regeneration have resulted in techniques and products that have allowed regeneration of both the dermis and epidermis. Yet complete skin regeneration requires the adnexal skin structures. Thus it is crucial to understand the regenerative potential of hair follicles where genetic, nutritional, and hormonal influences have important effects and are critical for skin regeneration. The follicular stem cell niche serves as an anatomical compartment, a structural unit, a functional integrator, and a dynamic regulator necessary to sustain internal homeostasis and respond to outside stimuli. In particular, mechanics such as pressure, compression, friction, traction, stretch, shear, and mechanical wounding can influence hair loss or growth. Relevant niche signaling pathways such as Wnt, bone morphogenetic protein, fibroblast growth factor, Shh, and Notch may yield potential targets for therapeutic interventions.     

Platelet-derived growth factor stimulates glucose transport in skeletal muscles of transgenic mice specifically expressing platelet-derived growth factor receptor in the muscle, but it does not affect blood glucose levels

Insulin stimulates the disposal of blood glucose into skeletal muscle and adipose tissues by the translocation of GLUT4 from intracellular pools to the plasma membrane, and consequently the concentration of blood glucose levels decreases rapidly in vivo. Phosphatidylinositol (PI) 3-kinase and Akt play a pivotal role in the stimulation of glucose transport by insulin, but detailed mechanisms are unknown. We and others reported that not only insulin but also platelet-derived growth factor (PDGF) and epidermal growth factor facilitate glucose uptake through GLUT4 translocation by activation of PI 3-kinase and Akt in cultured cells. However, opposite results were also reported. We generated transgenic mice that specifically express the PDGF receptor in skeletal muscle. In these mice, PDGF stimulated glucose transport into skeletal muscle in vitro and in vivo. Thus, PDGF apparently shares with insulin some of the signaling molecules needed for the stimulation of glucose transport. The degree of glucose uptake in vivo reached approximately 60% of that by insulin injection in skeletal muscle, but blood glucose levels were not decreased by PDGF in these mice. Therefore, PDGF-induced disposal of blood glucose into skeletal muscle is insufficient for rapid decrease of blood glucose levels.     

Suppressed complement activation in human decay accelerating factor transgenic porcine liver cross-circulated with nonhuman primates

BACKGROUND: We developed an extracorporeal liver perfusion (ECLP) system as a liver-assist device. In this study, we evaluated the safety of the ECLP using human decay accelerating factor (hDAF) transgenic porcine livers in healthy baboons. METHODS: Livers were isolated from five hDAF transgenic pigs and five nontransgenic pigs for the ECLP. Ten cross-circulations between the ECLP and healthy baboons were performed without immunosuppressive agents. Cross-circulation was discontinued in any of the following circumstances: elevated hepatic arterial (>200 mm Hg) or portal (>60 mm Hg) perfusion pressure, massive exudate from the graft liver, mild macroscopic hemolysis, thrombocytopenia, or 24-hr well-conditioned cross-circulation. RESULTS: The cross-circulations with nontransgenic porcine livers were discontinued at 4.4+/-1.2 hr (mean+/-standard deviation) because of high perfusion pressure (n=2) or hemolysis (n=3). Three cross-circulations with hDAF transgenic porcine livers were performed for 24 hr; the other two cross-circulations were discontinued at 13 and 17 hr because of massive exudate and thrombocytopenia, respectively. The duration was 20.4+/-5.1 hr. Deposition of membrane attack complex in the hDAF transgenic porcine liver was less than that in the nontransgenic liver, although immunoglobulin-M deposition was comparable. The porcine livers showed no apparent interlobular bleeding or lobular necrosis. All porcine livers maintained bile production during the cross-circulation. No baboons showed any serious complications after the cross-circulation. CONCLUSION: The hDAF transgenic porcine liver reduced complement activation in xenoperfusion with healthy nonhuman primate blood and led to extended duration of cross-circulation.     

Serum levels of IgE anti-BP180 and anti-BP230 autoantibodies in patients with bullous pemphigoid

BACKGROUND: Bullous pemphigoid (BP) is a subepidermal blistering disease characterized by autoantibodies against the hemidesmosomal proteins, BP180 and BP230. NC16A, a non-collagenous stretch of the BP180 ectodomain is the primary target of pathogenic IgG antibodies. Whereas IgG anti-BP180 autoantibodies play a primary role in the pathogenesis, there is a growing number of data regarding the potential pathogenic roles of IgE class autoantibodies in BP. OBJECTIVES: To examine the levels of IgG and IgE autoantibodies against BP180 and BP230, and to investigate mutual association and clinical relevance. METHODS: Sera obtained from 67BP patients and 36 healthy donors were subjected to ELISA assays to measure serum IgG and IgE levels of anti-BP180 and anti-BP230 antibodies. RESULTS: IgG anti-BP180 antibodies were positive in 63 (94%) of 67BP patients. IgG anti-BP230, IgE anti-BP180, and IgE anti-BP230 antibodies were found in 48 (72%), 20 (30%) and 45 (67%), respectively. IgG anti-BP180 levels were correlated with the affected areas. IgG anti-BP230 antibodies tended to increase in proportion to elongation of disease duration. IgE anti-BP230 levels showed a strong association with local eosinophil accumulation, while the levels were reversely related with the affected areas in BP. CONCLUSIONS: IgE autoantibodies to BP180 and BP230 are detected at high frequencies in BP. IgE anti-BP230 antibodies may have a role in attracting eosinophils to the skin lesions.