Accumulation of embryos over 3 natural modified IVF (ICSI) cycles followed by transfer to improve the outcome of poor responders.

BACKGROUND: Alternatives to improve treatment outcomes in poor responders are needed. For this we studied whether multiple (x3) Natural Modified (NM)-IVF(ICSI) cycles followed by an embryo transfer (ET) from the accumulated embryos can improve the treatment outcomes in poor responders. METHOD: A retrospective analysis was applied to a pool of participants qualifying as poor responders according to the Bologna criteria. This was performed over a 2-year IVF center database with a Study Group including women with a minimum of 3 cycles of NM-IVF (ICSI) and subsequent vitrified-thawed ET. As a control, 1 NM-IVF (ICSI) cycle with fresh ET was used. The primary outcome accounted was the livebirth rate (LBRs) following one ET; the secondary outcome was clinical pregnancy rates (CPRs), miscarriage and cycle cancellation rates. Comparisons were held over mean numbers by t-test, over median by Mann-Whitney, and categorical data were treated by Chi-square. RESULTS: The prognosis for livebirth in the study (n=125) and control (n=208) group was equally poor (mean age: 40.2 ± 3.0 vs 40.0 ± 3.3; median AMH: 2.1 vs 2.2 (pmol/L), AFC 4.0 vs 4.0). The LBR was significantly higher with the study protocol (30.6% vs 13.3%; p=0.002), particularly in women aged 35-39 years (31% vs 10.8%; p=0.05) and 40-44 years (26% vs 10.3%; p=0.02). Lower LBR in women aged ≥35 years in the control-group was mainly attributable to the higher miscarriage rate. With significantly more oocytes (mean: 6.5 ± 3.8 vs 2.0 ± 1.4; p <0.0001) and embryos available (mean: 3.6 ± 2.3 vs 0.9 ± 0.7; p<0.0001), only a minority ended up with no ET in the study-group (7.2% vs 35.6%; p<0.0001). None dropped-out while undergoing 3 cycles, whereas no patient opted for further attempts after one standalone cycle. CONCLUSION: Accumulation of embryos through 3 NM-IVF cycles before transfer improves livebirth rates and reduces the risk of lacking an embryo for transfer in poor responders aged ≥35 years.

B CHROMOSOMES IN ANGIOSPERM--A REVIEW.

A review article on B chromosomes (Bs) in angiosperms is documented considering occurrence, morphology, polymorphic B forms, divisional phase heterogeneity, chromatin organization and gene content, sequence composition, origin, evolutionary aspects and significant role on host with an objective to foresee the evolutionary perspectives as it still remains an enigma. Irrespective of the origin of Bs, it seems that they have attained the following modifications, namely, insertion of centromeric and telomeric sequences, structural reorganization and procuring mitotic and meiotic drives but shows genetic inertness and present in the host as selfish DNA. In the context, few questions are raised. Further, scientific quest may unravel the unexplored information about Bs to ascertain its evolutionary perspectives, if any.

Add-ons in IVF programme - Hype or Hope?

A series of new technologies and adjuvant therapies have been advocated in order to improve the success of IVF treatment. Dehydro-epiandrostenedione, growth hormones, Coenzyme Q 10, calcium ionosphores, immune therapy, heparin, low-dose aspirin, and vasodilators are among commonly prescribed pharmacological adjuvants. New technologies that are proposed to improve IVF outcomes include advanced sperm selection procedures, time- lapse embryo monitoring, preimplantation genetic screening, assisted hatching endometrial injury or embryo-glue. This review looked into current evidence to justify the use of these co-interventions and whether some of them can still be offered while awaiting more robust evidence to con rm or refute their role.

Organophosphate poisoning in pregnancy.

Organophosphate poisoning during pregnancy is rarely reported in the literature. In our retrospective study, we report the outcome of 21 cases of organophosphate poisoning during pregnancy. All patients received atropine injection until the tracheobronchial tree is cleared of the secretions and most secretions were dried. In addition, ventilatory care was needed in five women. Two patients (9.52%) died of the organophosphorus poisoning during the acute stage of poisoning and three patients were lost to follow-up. One woman had a spontaneous abortion. The remaining 15 women had no significant complication during pregnancy or labour and delivery. There was no congenital abnormality and no neurological deficit in any baby. However, long-term follow-up of neonates was lacking in our study population.

Synchronous occurrence of anaplastic, follicular and papillary carcinomas with follicular adenoma in thyroid gland.

Various combinations of thyroid carcinomas have been reported including those between different cancers of follicular cell origin and those between follicular and C-cell histogenesis. Accordingly, anaplastic carcinomas have been seen to coincide with simultaneous papillary and follicular cancers. We report a case of composite anaplastic and papillary cancer on one thyroid lobe with a follicular carcinoma in the other lobe in a female patient aged 64 years. The patient also had a separate and independent follicular adenoma in the same lobe as the composite anaplastic and papillary carcinoma. The papillary carcinoma was continuous with the anaplastic carcinoma. The findings were supported by immunohistochemistry. The patient was managed by a total thyroidectomy with bilateral modified radical neck dissection followed by chemotherapy. However, she died two months after surgery. The common follicular cell origin will explain the concurrent presence of all these cancers. This could result from the dedifferentiation of a pre-existing differentiated carcinoma.

Variation in relation of cords of brachial plexus and their branches with axillary and brachial arteries--a case report.

Anatomical variations in the formation, course and distribution of brachial plexus are well documented. The present report describes some rare variations with regard to relation of cords of brachial plexus, median and ulnar nerves with the third part of axillary artery and brachial artery in the left upper limb of an adult male cadaver. All three cords of brachial plexus were noted to be lateral to all three parts of axillary artery. Median nerve was lateral to brachial artery and ulnar nerve was between the brachial artery and median nerve. Further distribution of median and ulnar nerves was normal. The arterial pattern in left arm (axillary and brachial arteries) was also normal. The findings were noted after thorough and meticulous dissection of both the upper limbs (axilla, arm, cubital fossa, forearm and palm) of the same cadaver in the Department of Anatomy, College of Medical Sciences, Bharatpur, Nepal. The right upper limb revealed no abnormality. It is important to be aware of such variations while planning a surgery in the region of axilla and arm as these nerves are more liable to be injured during surgical procedures. Possible embryological explanations and clinical significance have been discussed.

Development of equine upper airway fluid mechanics model for Thoroughbred racehorses.

REASON FOR PERFORMING STUDY: Computational fluid dynamics (CFD) models provide the means to evaluate airflow in the upper airways without requiring in vivo experiments. HYPOTHESIS: The physiological conditions of a Thoroughbred racehorse's upper airway during exercise could be simulated. METHODS: Computed tomography scanned images of a 3-year-old intact male Thoroughbred racehorse cadaver were used to simulate in vivo geometry. Airway pressure traces from a live Thoroughbred horse, during exercise was used to set the boundary condition. Fluid-flow equations were solved for turbulent flow in the airway during inspiratory and expiratory phases. The wall pressure turbulent kinetic energy and velocity distributions were studied at different cross-sections along the airway. This provided insight into the general flow pattern and helped identify regions susceptible to dynamic collapse. RESULTS: The airflow velocity and static tracheal pressure were comparable to data of horses exercising on a high-speed treadmill reported in recent literature. The cross-sectional area of the fully dilated rima glottidis was 7% greater than the trachea. During inspiration, the area of highest turbulence (i.e. kinetic energy) was in the larynx, the rostral aspect of the nasopharynx was subjected to the most negative wall pressure and the highest airflow velocity is more caudal on the ventral aspect of the nasopharynx (i.e. the soft palate). During exhalation, the area of highest turbulence was in the rostral and mid-nasopharynx, the maximum positive pressure was observed at the caudal aspect of the soft palate and the highest airflow velocity at the front of the nasopharynx. CONCLUSIONS AND CLINICAL RELEVANCE: In the equine upper airway collapsible area, the floor of the rostral aspect of the nasopharynx is subjected to the most significant collapsing pressure with high average turbulent kinetic during inhalation, which may lead to palatal instability and explain the high prevalence of dorsal displacement of the soft palate (DDSP) in racehorses. Maximal abduction of the arytenoid cartilage may not be needed for optimal performance, since the trachea cross-sectional area is 7% smaller than the rima glottidis.

Miller Fisher syndrome--an uncommon clinical presentation.

Miller Fisher syndrome is an uncommon disease and it is a variant of Guillain-Barre syndrome. Miller Fisher syndrome also has rarer variants. Combined features of classic Guillain-Barre syndrome and Miller Fisher syndrome are uncommon. Here we are reporting a case of Miller Fisher variant with Guillain-Barre syndrome overlap in which ataxia, are flexia, oculomotor disturbance and limb weakness occurred within few days.

Implications of different degrees of arytenoid cartilage abduction on equine upper airway characteristics.

REASON FOR PERFORMING STUDY: The necessary degree of arytenoid cartilage abduction (ACA) to restore airway patency at maximal exercise has not been determined. OBJECTIVES: Use computational fluid dynamics modelling to measure the effects of different degrees of ACA on upper airway characteristics of horses during exercise. HYPOTHESIS: Maximal ACA by laryngoplasty is necessary to restore normal peak airflow and pressure in Thoroughbred racehorses with laryngeal hemiplegia. METHODS: The upper airway was modeled with the left arytenoid in 3 different positions: maximal abduction; 88% cross-sectional area of the rima glottis; and 75% cross-sectional area of the rima glottis. The right arytenoid cartilage was maximally abducted. Two models were assumed: Model 1: no compensation of airway pressures; and Model 2: airway pressure compensation occurs to maintain peak airflow. The cross-sectional pressure and velocity distributions for turbulent flow were studied at peak flow and at different positions along the airway. RESULTS: Model 1: In the absence of a change in driving pressure, 12 and 25% reductions in cross-sectional area of the larynx resulted in 4.11 and 5.65% reductions in peak airflow and 3.68 and 5.64% in tidal volume, respectively, with mild changes in wall pressure. Model 2: To maintain peak flow, a 6.27% increase in driving tracheal pressure was required to compensate for a cross-sectional reduction of 12% and a 13.63% increase in driving tracheal pressure was needed for a cross-sectional area reduction of 25%. This increase in negative driving pressure resulted in regions with low intraluminal and wall pressures, depending on the degree of airway diameter reduction. CONCLUSION: Assuming no increase in driving pressure, the decrease in left ACA reduced airflow and tidal volume. With increasing driving pressure, a decrease in left ACA changed the wall pressure profile, subjecting the submaximally abducted arytenoid cartilage and adjacent areas to airway collapse. CLINICAL RELEVANCE: The surgical target of ACA resulting in 88 % of maximal cross-sectional area seems to be appropriate.

Uncertainty in thermal process calculations due to variability in first-order and Weibull kinetic parameters.

Alternatives to first-order model of death kinetics of microorganisms have been proposed as improvements in the calculation of lethality for a thermal process. Although such models can potentially improve predictions for many situations, this article tries to answer the question of whether the added complexities of these models are a worthwhile investment once we include the effect of uncertainties in various microbiological and process parameters. Monte Carlo technique is used to include variability in kinetic parameters in lethality calculation for a number of heating processes, for both first-order and Weibull kinetics models. It is shown that uncertainties represented by coefficient of variation in kinetic parameters lead to a wide range of final log-reduction prediction. With the same percent variability in kinetic parameters, uncertainty in the final log reduction for Weibull kinetics was smaller or equal to that for first-order kinetics. Due to the large effect of variability in the input parameters on the final log reduction, the effort to move toward more accurate kinetic models needs to be weighed against inclusion of variability.

How does cooking time scale with size? A numerical modeling approach.

A mathematical model for a spatially distributed mechanical property such as Young's modulus and texture inside solid food during the cooking process was developed by combining a numerical conduction heat transfer model with the kinetics of property changes. Using the distributed mechanical property obtained from the thermokinetic model, linear elastic stress analysis was performed to determine the effective material property and how it changes during cooking. Spatial variation in the mechanical property is found to be significant for commonly used food sizes in potato. When property varies spatially, volume average property, which is easier to compute than an effective property obtained from mechanical stress analysis, can be a substitute for the effective property. Cooking time based on volume average Young's modulus varies less strongly with size than how temperature varies with size. When activation energy for the property change kinetics is lower, cooking time varies less with size. The scaling of cooking time with size and kinetics and the extent of property variation in a sample during cooking should provide useful guidelines in automating cooking processes.

Transplacental transfer of cobalt and chromium in patients with metal-on-metal hip arthroplasty: a controlled study.

Metal-on-metal bearings are being increasingly used in young patients. The potential adverse effects of systemic metal ion elevation are the subject of ongoing investigation. The purpose of this study was to investigate whether cobalt and chromium ions cross the placenta of pregnant women with a metal-on-metal hip resurfacing and reach the developing fetus. Whole blood levels were estimated using high-resolution inductively-coupled plasma mass spectrometry. Our findings showed that cobalt and chromium are able to cross the placenta in the study patients with metal-on-metal hip resurfacings and in control subjects without any metal implants. In the study group the mean concentrations of cobalt and chromium in the maternal blood were 1.39 microg/l (0.55 to 2.55) and 1.28 microg/l (0.52 to 2.39), respectively. The mean umbilical cord blood concentrations of cobalt and chromium were comparatively lower, at 0.839 microg/l (0.42 to 1.75) and 0.378 microg/l (0.14 to 1.03), respectively, and this difference was significant with respect to chromium (p < 0.05). In the control group, the mean concentrations of cobalt and chromium in the maternal blood were 0.341 microg/l (0.18 to 0.54) and 0.199 microg/l (0.12 to 0.33), and in the umbilical cord blood they were 0.336 microg/l (0.17 to 0.5) and 0.194 microg/l (0.11 to 0.56), respectively. The differences between the maternal and umbilical cord blood levels in the controls were marginal, and not statistically significant (p > 0.05). The mean cord blood level of cobalt in the study patients was significantly greater than that in the control group (p < 0.01). Although the mean umbilical cord blood chromium level was nearly twice as high in the study patients (0.378 microg/l) as in the controls (0.1934 microg/l), this difference was not statistically significant. (p > 0.05) The transplacental transfer rate was in excess of 95% in the controls for both metals, but only 29% for chromium and 60% for cobalt in study patients, suggesting that the placenta exerts a modulatory effect on the rate of metal ion transfer.

Characteristics of young foster children in the urban slums of Bangladesh.

AIM: To identify the reasons for the fostering of children, and to describe their feeding practices and assess their health and nutritional status. METHODS: Forty-six pairs of mothers and their young foster children (up to 24 mo of age) were interviewed in a cross-sectional study in the urban slums of Dhaka, Bangladesh. Another 82 pairs of mothers and their biological children of a similar age group were interviewed for comparison. RESULTS: Sixty-five percent of the children were fostered because of the death of their biological mothers. Eighty-three percent of the biological mothers died because of complications during delivery or the immediate postpartum period and the remainder died after the postpartum period of diseases unrelated to their pregnancies. More than half (52%) of the foster mothers were childless and a quarter (24%) fostered children for reasons of gender preference. Almost a quarter (24%) of the children were placed in foster homes because of extreme parental poverty. Divorce or separation of the biological parents accounted for only 7% of children fostered. Approximately 90% of the foster children were given animal and/or formula milk in their first month of life while all children in the comparison group were given breast milk. Among the foster children, 58% were given semisolid or solid food before completion of 4 mo compared with 14% in the comparison group. Significantly more children in the foster group suffered from diarrhoea and acute respiratory infection than in the comparison group. CONCLUSION: Maternal death, poverty and childlessness and child gender preference of foster mothers were important factors in fostering of children in the study group. Inappropriate feeding practices compounded by diseases may have contributed to the poor nutritional status of the foster children.

Lack of abundance of cytoplasmic cyclosporin A-binding protein renders free-living Leishmania donovani resistant to cyclosporin A.

The majority of the effects of cyclosporin A (CsA) on cells is caused by the inhibition of phosphatase activity of calcineurin (CN) by the cyclophilin A (CyPA)-CsA complex formed in the cytoplasm. Although CsA inhibits the proliferation of a large number of parasites, not all are susceptible. The presence of structurally altered CyPA with lower affinity for CsA had been suggested to be the cause of resistance. We report here the identification and cloning of a high affinity CsA-binding protein (LdCyP) from Leishmania donovani, a trypanosomatid parasite that is naturally resistant to CsA. The translated LdCyP consists of 187 amino acids with a cleavable 21-amino acid hydrophobic NH(2)-terminal extension. Modeling studies confirmed that all the residues of human CyPs responsible for interaction with CsA are sequentially and conformationally conserved in LdCyP. The purified recombinant protein displayed biochemical parameters comparable to human CyPs. Reverse transcription-polymerase chain reaction analysis confirmed that LdCyP was abundantly expressed. Immunoblot experiments and direct CsA binding studies revealed that LdCyP located in the subcellular organelles constituted the bulk of the CsA binding activity present in L. donovani, whereas the level of binding activity in the cytosol was conspicuously low. CsA selectively facilitated the secretion of LdCyP in the culture medium. Based on these results, it is concluded that the insensitivity of L. donovani to CsA is probably due to the paucity of CsA binding activity in the cytoplasm of the parasite. We suggest that LdCyP, located in the secretory pathway, may function as a chaperone by binding to membrane proteins rather than as the mediator of CN inhibition.

Conserved cysteines in the sialyltransferase sialylmotifs form an essential disulfide bond.

The sialyltransferase gene family is comprised of 16 cloned enzymes. All members contain two conserved protein domains, termed the S- and L-sialylmotifs, that participate in substrate binding. Of only six invariant amino acids, two are cysteines, with one found in each sialylmotif. Although the recombinant soluble form of ST6Gal I has six cysteines, quantitative analysis indicated the presence of only one disulfide linkage, and thiol reducing agents dithiothreitol and beta-mercaptoethanol inactivated the enzyme. Analysis of site-directed mutants showed that alanine or serine mutants of invariant Cys(181) or Cys(332) exhibit no detectable activity, either by direct assay or by staining of the transfected cells with Sambucus nigra agglutinin, which recognizes the product NeuAcalpha2,6Galbeta1,4GlcNAc on glycoproteins. In contrast, alanine mutations of charged residues adjacent to either cysteine showed little or no effect on enzyme activity. Immunofluorescence microscopy showed that although the wild type sialyltransferase is properly localized in the Golgi apparatus, the inactive cysteine mutants are retained in the endoplasmic reticulum. The results suggest that the invariant cysteine residues in the L- and S-sialylmotifs participate in the formation of an intradisulfide linkage that is essential for proper conformation and activity of ST6Gal I.

Neuroendocrine cell type-specific and inducible expression of the chromogranin B gene: crucial role of the proximal promoter.

Chromogranin B, a soluble acidic secretory protein, is widely distributed in neuroendocrine and neuronal cells, although not in other cell types. To identify the elements governing such widespread, yet selective, expression of the gene, we characterized the isolated mouse chromogranin B promoter. 5'-Promoter deletions localized neuroendocrine cell type-specific expression to the proximal chromogranin B promoter (from -216 to -91 bp); this region contains an E box (at [-206 bp]CACCTG[-201 bp]), four G/C-rich regions (at [-196 bp]CCCCGC[-191 bp], [-134 bp]CCGCCCGC[-127 bp], [-125 bp]GGCGCCGCC[-117 bp], and [-115 bp]CGGGGC[-110 bp]), and a cAMP response element (CRE; at [-102 bp]TGACGTCA[-95 bp]). A 60-bp core promoter region, defined by an internal deletion from - 134 to -74 bp upstream of the cap site and spanning the CRE and three G/C-rich regions, directed tissue-specific expression of the gene. The CRE motif directed cell type-specific expression of the chromogranin B gene in neurons, whereas three of the G/C-rich regions played a crucial role in neuroendocrine cells. Both the endogenous chromogranin B gene and the transfected chromogranin B promoter were induced by preganglionic secretory stimuli (pituitary adenylyl cyclase-activating polypeptide, vasoactive intestinal peptide, or a nicotinic cholinergic agonist), establishing stimulus-transcription coupling for this promoter. The adenylyl cyclase activator forskolin, nerve growth factor, and retinoic acid also activated the chromogranin B gene. Secretagogue-inducible expression of chromogranin B also mapped onto the proximal promoter; inducible expression was entirely lost upon internal deletion of the 60-bp core (from 134 to -74 bp). We conclude that CRE and G/C-rich domains are crucial determinants of both cell type-specific and secretagogue-inducible expression of the chromogranin B gene.

Coupled electromagnetic and thermal modeling of microwave oven heating of foods.

Temperature distributions from heating in a domestic microwave oven were studied by considering the coupling between the electromagnetics and heat transfer through changes in dielectric properties during heating. Maxwell's equations for electromagnetics and the thermal energy equations are solved numerically using two separate finite-element softwares. The coupling between the softwares was developed by writing special modules that interfaced these softwares at the system level. Experimentally measured temperature profiles were compared with the numerical predictions. The importance of coupling was evident when the properties changed significantly with temperature for low and high dielectric loss materials and more so for the high loss materials. For moderate loss materials, when the properties do not change as much with temperature, coupled solutions lead to results very close to the results for the uncoupled solution.