Subtle variation in sepsis-III definitions markedly influences predictive performance within and across methods.

Early detection of sepsis is key to ensure timely clinical intervention. Since very few end-to-end pipelines are publicly available, fair comparisons between methodologies are difficult if not impossible. Progress is further limited by discrepancies in the reconstruction of sepsis onset time. This retrospective cohort study highlights the variation in performance of predictive models under three subtly different interpretations of sepsis onset from the sepsis-III definition and compares this against inter-model differences. The models are chosen to cover tree-based, deep learning, and survival analysis methods. Using the MIMIC-III database, between 867 and 2178 intensive care unit admissions with sepsis were identified, depending on the onset definition. We show that model performance can be more sensitive to differences in the definition of sepsis onset than to the model itself. Given a fixed sepsis definition, the best performing method had a gain of 1-5% in the area under the receiver operating characteristic (AUROC). However, the choice of onset time can cause a greater effect, with variation of 0-6% in AUROC. We illustrate that misleading conclusions can be drawn if models are compared without consideration of the sepsis definition used which emphasizes the need for a standardized definition for sepsis onset.

Interfacial Coupling Engineering Boosting Electrocatalytic Performance of CoFe Layered Double Hydroxide Assembled on N-Doped Porous Carbon Nanosheets for Water Splitting and Flexible Zinc-Air Batteries.

The disadvantages of layered double hydroxides (LDHs) such as easy stacking, poor inherent conductivity, and limited versatility hinder their application in splitting water and zinc-air batteries (ZABs). Interface engineering to regulate the electron distribution of LDHs by introducing another component is a way to compensate for the poor electron transport capacity of LDHs during catalysis. Herein, a hierarchical structure is synthesized by assembling CoFe-LDH nanosheets onto the surface of layered N-doped porous carbon (NPC), CoFe-LDH@NPC, by using an interface engineering strategy. CoFe-LDH@NPC has high catalytic activity for the oxygen/hydrogen evolution reaction (OER/HER) with overpotentials of 280/100 mV, respectively. The two-electrode water splitting catalyzed by CoFe-LDH@NPC only needs 1.61 V to drive a current density of 10 mA cm-2 for 60 h. The theoretical results show that there is an electron-deficient/electron-rich interface between the NPC substrate and the CoFe-LDH in CoFe-LDH@NPC. The electrons on the coupling interface are easily transferred, which results in a change of the adsorption behavior of the reaction intermediates and improves the catalytic activity for the OER and HER. In addition, CoFe-LDH@NPC-catalyzed rechargeable flexible ZABs have excellent performance with low charge-discharge polarization (0.87 V) and a long-term stability of 65 h.

A simple spatial extension to the extended connectivity interaction features for binding affinity prediction.

The representation of the protein-ligand complexes used in building machine learning models play an important role in the accuracy of binding affinity prediction. The Extended Connectivity Interaction Features (ECIF) is one such representation. We report that (i) including the discretized distances between protein-ligand atom pairs in the ECIF scheme improves predictive accuracy, and (ii) in an evaluation using gradient boosted trees, we found that the resampling method used in selecting the best hyperparameters has a strong effect on predictive performance, especially for benchmarking purposes.

Increased hepatic INSIG-SCAP-SREBP expression is associated with cholesterol metabolism disorder in assisted reproductive technology-conceived aged mice.

Although most children conceived by assisted reproductive technology (ART) are healthy, there are concerns regarding the potential long-term health implications of ART. It has been reported that alterations in insulin-induced gene (INSIG), sterol regulatory element binding protein (SREBP), and SREBP cleavage-activating protein (SCAP) are involved in cardiometabolic changes. Thus, ART mouse models were established via in vitro fertilization (IVF), intracytoplasmic injection (ICSI), and in vitro oocyte maturation (IVM). A significantly higher systolic blood pressure was identified in the IVM aged female mice. In addition, abnormalities in the blood lipids and liver function were identified in the IVM- or ICSI-conceived elderly mice. Furthermore, ICSI or IVM significantly affected the hepatic expression and methylation of INSIG-SCAP-SREBP from a young to old age. Our animal data indicated that ICSI or IVM result in a higher risk of cholesterol metabolism dysfunction in older mice, which may be associated with long-term alterations of INSIG-SCAP-SREBP.

Superovulation Induced Changes of Lipid Metabolism in Ovaries and Embryos and Its Probable Mechanism.

This research was intended to investigate the fetal origins of changed birth weight of the offspring born through assisted reproductive technology (ART). The association between hormone and lipid metabolism or body weight has been generally accepted, and as the basic and specific treatment in ART procedure, gonadotropin stimulation might have potential effects on intrauterine lipid metabolism. In our studies, the mice were superovulated with two doses of gonadotropin. The cholesterol metabolism in ovaries and the triglyceride metabolism in embryos were analyzed. The results showed gonadotropin probably accelerated luteinization and induced a longer time follicle development and ovulation, which resulted in histological and morphological alteration of ovary, and increased the cholesterol content and the expressions of steroidogenesis-related genes. In embryos, gonadotropin increased lipid accumulation and decreased fatty acid synthesis in a dose-dependent manner. Moreover, the changes of fatty acid composition were also shown in superovulation groups. Our studies firstly provided the evidence that the superovulation might affect the maternal and fetal lipid metabolism. These variations of lipid metabolism in our results may be associated with birth weight of ART infants.

Decreased expression of SAM68 in human testes with spermatogenic defects.

OBJECTIVE: To assess the expression patterns of SAM68 in the testes of azoospermic patients with normal and abnormal spermatogenesis. DESIGN: Retrospective study and in vitro study. SETTING: University hospital. PATIENT(S): Testicular biopsies of azoospermic men with normal spermatogenesis (OAZ; n=20), with maturation arrest at the spermatocyte stage (MA; n=20), and with Sertoli cell-only syndrome (SCOS; n=10). INTERVENTION(S): No interventions with patients. Knockdown of Sam68 was performed in the GC-2spd(ts) cell line. MAIN OUTCOME MEASURE(S): SAM68 expression was analyzed using quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot, and immunohistochemistry analysis in tissues. Moreover, Sam68 was knocked down in GC-2spd(ts) cells. Cell viability was measured using the MTT assay, and the apoptosis rate was detected using flow cytometry with the Annexin V-FITC kit. RESULT(S): Using qRT-PCR, the expression level of testicular SAM68 mRNA in MA and SCOS patients was statistically reduced compared with in OAZ patients. In addition, using qRT-PCR, Western blot, and immunohistochemistry analyses, mRNA and protein expressions of SAM68 were absent or barely detectable in testicular tissues in 45% (9 of 20) of patients with MA and in all patients with SCOS. Furthermore, decreased expression of Sam68 suppressed germ cell proliferation and induced apoptosis in transfected GC-2spd(ts) cells. CONCLUSION(S): Deficient SAM68 expression was observed in the human testis with MA at the spermatocyte stage and SCOS. These results may offer new perspectives on the molecular basis of abnormal spermatogenesis.

Human sperm devoid of germinal angiotensin-converting enzyme is responsible for total fertilization failure and lower fertilization rates by conventional in vitro fertilization.

In conventional in vitro fertilization (IVF), complete failure of fertilization occurs in 5% to 15% of treatments. Although the causes may be unclear, sperm defects appear to be the major contributor. However, a convincing test is not yet available that can predict the risk of fertilization failure. In this study, we found that germinal angiotensin-converting enzyme (gACE) (also called testicular ACE) was undetectable in sperm from patients who had total fertilization failure (TFF) and lower fertilization rates (LFRs) by IVF based on Western blot and indirect immunofluorescence analyses. Additionally, almost all of the patients without gACE on sperm (23 of 25) manifested a TT genotype of the rs4316 single-nucleotide polymorphism of ACE. Overall, our results indicate that the absence of gACE expression is responsible for TFF and LFRs by IVF. The rs4316 polymorphism of ACE might be associated with infertility in those patients. We conclude that sperm lacking gACE may be recognized before commencing IVF and that the patients may be directed instead to consider intracytoplasmic sperm injection.

Epigenetic inheritance of paternally expressed imprinted genes in the testes of ICSI mice.

Worse reproductive health in the men born through intracytoplasmic sperm injection (ICSI) or other assisted reproductive techniques (ART) has been reported in many studies. However, owing to the interference of genetic and environmental factors, it is difficult to identify whether ICSI method would affect male reproductive health. Therefore, ART mouse models were established in this study. Besides semen quality, serum testosterone and histological analysis of testes, 6 paternally expressed imprinted genes were chosen to detect their expressions and methylation levels in testes of adult F1 and F2 mice. Although the phenotypic abnormalities weren't found, Kcnq1ot1, Mest, Peg3, Plagl1 and Snrpn in ICSI group showed lower expressions than those in naturally conceived (NC) group. The expressions of Kcnq1ot1, Peg3 and Snrpn in in vitro fertilization (IVF) conceived mice was lower than those in controlled ovarian hyperstimulation (COH) conceived mice, but higher than those in ICSI mice. Most differences between NC and ICSI group and between IVF and ICSI group were also represented in F2 generations. During the methylation analysis, no matter there was significant difference between compared groups, the changing trends of methylation level were almost opposite to their corresponding gene expressions. These results indicated that the differential expressions of paternally expressed genes occurred in testes of ICSI mice, which may be mediated by methylation modification. Both ICSI procedure and mechanical stimulation can induce intergenerational transmission of the epigenetic changes. In vitro culture and mechanical stimulation were the main factors inducing the down regulation of paternally expressed imprinted genes in testes.

An overview of studies on psychological well-being in children born following assisted reproductive technologies.

Over the course of the past 35 years, assisted reproductive technologies (ARTs) have been increasingly used worldwide, while debates on their safety have been generated. Birth defects and imprinting disorders were reported in previous research. Thus, the psychological development of children born following ARTs has become a major concern nowadays. This review gives a systematic view of psychological well-being of children conceived by different types of ART, including in vitro fertilization, intracytoplasmic sperm injection (ICSI), preimplantation genetic diagnosis/screening, and in vitro maturation. The previous studies are analyzed in three sections: (1) cognitive, motor, and language developments, (2) behavior problems and socio-emotional development, and (3) parent-child relationship. We conclude that although the majority of the studies on cognitive, motor, and language developments reported comparable achievements in the ART group vs. the naturally conceived group, lower intelligence quotient (IQ) scores, worse visual-motor ability or locomotor development, and delayed receptive language competence were found in the ART group. The results on the socio-emotional development were reassuring. As for the behavior problems, a higher prevalence of behavior problems existed in ART children; moreover, ICSI children were found to be at a higher risk of autism than the general population. Meanwhile, ART parents tended to have positive parental attitudes and be more protective of their children. Some suggestions for further research are also given in this review.

Alterations in the frequency of trinucleotide repeat dynamic mutations in offspring conceived through assisted reproductive technology.

STUDY QUESTION: How does the frequency of trinucleotide repeat dynamic mutations in offspring conceived through assisted reproductive technology (ART) compare with the frequency of these mutations in control offspring conceived from spontaneous pregnancies? SUMMARY ANSWER: There is a slight increase in dynamic mutation instability in offspring conceived through ART compared with the naturally conceived offspring. WHAT IS KNOWN ALREADY: There is evidence to suggest that ART can increase the risk of birth defects and karyotypic abnormalities. However, the accumulating evidence of an association between ART and de novo genetic aberrations is controversial. STUDY DESIGN, SIZE, DURATION: A prospective clinical observational study was performed on 246 families recruited from an in vitro fertilisation (IVF) centre at a tertiary-care, university-affiliated teaching hospital from 2008 to 2012. The study included 147 ART families [75 IVF and 72 intracytoplasmic sperm injection (ICSI)] in the study group and 99 natural-conception families in the control group. PARTICIPANTS, SETTING, METHODS: Parental, umbilical cord and infant peripheral blood samples were collected, and the trinucleotide repeats of the ATN1, AR, ATXN1, ATXN3, Huntington, DMPK and FMR-1 genes were investigated between the generations; these genes were chosen due to their ability to undergo dynamic mutation. The frequencies and sizes of the mutational repeats, as well as the intergenerational instability, were measured. MAIN RESULTS AND THE ROLE OF CHANCE: In 2466 transmissions identified in the ART offspring, 2.11% (n = 52/2466) of the alleles were unstable upon transmission, while in the control group offspring, the frequency of dynamic mutation was 0.77% (n = 10/1300); this difference was statistically significant (P < 0.01). The unstable transmission alleles were detected in 32 (2.48%) of the 1288 alleles from the IVF offspring and in 20 (1.70%) of the 1178 alleles from the ICSI offspring; both of these frequencies were significantly different from that of naturally conceived offspring (0.77%) (P < 0.01 and P < 0.05, respectively). However, there were no significant differences in the sizes of the mutational repeats or in the rates of expansion or contraction among the three groups (P > 0.05). The repeat copy numbers of the examined genes were found to be within the normal ranges in all parents and infants. LIMITATIONS, REASONS FOR CAUTION: One strength of our study is the relatively large sample size; we were able to detect mutations in seven common dynamic genes, and this large sample size allowed us to detect unstable alleles. Although we observed a clear alteration in the frequency of dynamic mutation in the ART offspring compared with controls, further studies are urgently needed to confirm this observation and determine the cause of this phenomenon. WIDER IMPLICATIONS OF THE FINDINGS: DNA microsatellite analysis provides an important tool to assess genomic instability. In this study, we report an association between ART and the frequency of dynamic mutation. The instability could be a reflection of the core infertility problem, the controlled ovarian hyperstimulation and/or the in vitro culture conditions.

Persistence and intergenerational transmission of differentially expressed genes in the testes of intracytoplasmic sperm injection conceived mice.

Intracytoplasmic sperm injection (ICSI) is commonly used to solve male infertility problems. Previous studies showed that early environmental exposure of an embryo may influence postnatal development. To detect whether ICSI operations affect the reproductive health of a male or his offspring, we established assisted reproductive technologies (ART) conceived mouse models, and analyzed gene expression profiles in the testes of both ICSI and naturally conceived (NC) newborn F1 mice using micro-array analysis. Among the differentially expressed genes, we focused on the expression of eight male reproduction-related genes. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was used to analyze the expression of these genes in the testes of both adult and old F1 generation mice and adult F2 generation mice. Our results showed that down-regulated and somatic cell-expressed genes in newborn mice retained their differential expression patterns in adult and old F1 generation individuals, implying the persistence and fetal origin of the alteration in the expression of these genes. The intergenerational transmission of differential gene expression was observed, but most changes tended to be reduced in adult F2 generations. Controlled ovarian hyperstimulation (COH) and in vitro fertilization (IVF) mice models were added to explore the precise factors contributing to the differences in ICSI offspring. The data demonstrated that superovulation, in vitro culture, and mechanical stimulation involved in ICSI had a cumulative effect on the differential expression of these male reproductive genes.

In vitro fertilization alters growth and expression of Igf2/H19 and their epigenetic mechanisms in the liver and skeletal muscle of newborn and elder mice.

Epidemiological studies have reported a higher incidence of growth disorders among newborns conceived by in vitro fertilization (IVF), suggesting that IVF may be disruptive to the process of embryonic and fetal growth. However, the long-term effects of IVF on the growth and molecular mechanisms remain unclear. Therefore, we evaluated the body weight of IVF mice from birth to the age of 1.5 yr. In addition, we analyzed gene expression of insulin-like growth factor 2 (Igf2), H19, Igf2 receptor (Igf2r), and miR-483 and their DNA methylation status using real-time quantitative PCR, Western blot, and pyrosequencing. The results showed that when compared with the in vivo group, the body weight of IVF mice was significantly higher at birth, but lower at 3 wk; in addition, gene expression of Igf2 was significantly up-regulated, with down-regulated expression of H19 and miR-483 in both liver and skeletal muscle. At the same time, there were significant differences in the DNA methylation rates of Igf2/H19 differentially methylated regions (DMRs) and the IGF2 protein expression between the two groups. In the IVF treatment group, the differences in growth and expression disappeared at 10 wk. However, at 1.5 yr of age, aberrant expressions of Igf2/H19, Igf2r, and miR-483 and changes in DNA methylation rates in the liver or skeletal muscle were again observed in IVF mice. Our results indicate that IVF causes alterations in mouse growth during the postnatal periods that may be associated with alterations in Igf2/H19 expression and likely involve the regulation of miR-483 and the methylation status of Igf2/H19 DMRs.

Alteration of fatty acid metabolism in the liver, adipose tissue, and testis of male mice conceived through assisted reproductive technologies: fatty acid metabolism in ART mice.

BACKGROUND: Lipid metabolism plays important roles in the whole process of pregnancy. Previous studies have demonstrated abnormalities of lipid metabolism in the placentas of pregnancies obtained by assisted reproductive technology (ART). Therefore, we hypothesized that ART micromanipulation may affect lipid metabolism in offspring, and focused on the fatty acid metabolism in ART male offspring in this study. METHODS: The fatty acid metabolism in the liver, adipose tissue and testis was detected. The comparison between naturally conceived (NC), controlled ovarian hyperstimulation (COH), in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) mice was made to analyze the effect of ART on offspring. The mice models in this study included two age groups: adult group and old group. The fatty acid composition and the expression of lipid metabolism-related genes were analyzed by GC-MS and qRT-PCR. RESULTS: The fatty acid composition in the liver and adipose tissue were significantly altered in ART mice, but no significant difference was found in the testis. In adipose tissue, ART mice showed decreased monounsaturated fatty acids (MUFAs) and increased polyunsaturated fatty acids (PUFAs) in both adult and old mice, while the alteration of saturated fatty acids (SFAs) in the adult disappeared in the old. In liver, the changes were much complex in adult mice, while increased MUFAs and decreased PUFAs were found in ART old mice. The activities of fatty acid metabolism-related enzymes and the expression of lipogenic and lipolytic proteins changed in ART groups, with the adult mice and old mice showing inconsistent alterations. Further analysis indicated that SFAs was closely associated with the alterations of fatty acid metabolism-related enzyme activities and the expression of lipogenic and lipolytic proteins. Furthermore, we also found that the effect of separated ART treatments on fatty acid metabolism varied with different ages and tissues. CONCLUSIONS: ART treatments had effect on the fatty acid composition in adipose tissue and liver of male mice. The alteration of SFAs content was crucial for the regulation of fatty acid composition. These changes might have potential effects on the health of ART male offspring which need further investigation.

Patient-specific modeling of facial soft tissue based on radial basis functions transformations of a standard three-dimensional finite element model.

BACKGROUND: An important purpose of orthodontic treatment is to gain the harmonic soft tissue profile. This article describes a novel way to build patient-specific models of facial soft tissues by transforming a standard finite element (FE) model into one that has two stages: a first transformation and a second transformation, so as to evaluate the facial soft tissue changes after orthodontic treatment for individual patients. METHODS: The radial basis functions (RBFs) interpolation method was used to transform the standard FE model into a patient-specific one based on landmark points. A combined strategy for selecting landmark points was developed in this study: manually for the first transformation and automatically for the second transformation. Four typical patients were chosen to validate the effectiveness of this transformation method. RESULTS: The results showed good similarity between the transformed FE models and the computed tomography (CT) models. The absolute values of average deviations were in the range of 0.375 - 0.700 mm at the lip-mouth region after the first transformation, and they decreased to a range of 0.116 - 0.286 mm after the second transformation. CONCLUSIONS: The modeling results show that the second transformation resulted in enhanced accuracy compared to the first transformation. Because of these results, a third transformation is usually not necessary.

[Individualized three-dimensional finite element model of facial soft tissue and preliminary application in orthodontics].

OBJECTIVE: To get individualized facial three-dimensional finite element (FE) model from transformation of a generic one to assist orthodontic analysis and prediction of treatment-related morphological change of facial soft tissue. METHODS: A generic three-dimensional FE model of craniofacial soft and hard tissue was constructed based on a volunteer's spiral CT data. Seven pairs of main peri-oral muscles were constructed based on a combination of CT image and anatomical method. Individualized model could be obtained through transformation of the generic model based on selection of corresponding anatomical landmarks and radial basis functions (RBF) method. Validation was analyzed through superimposition of the transformed model and cone-beam CT (CBCT) reconstruction data. Pre- and post-treatment CBCT data of two patients were collected, which were superimposed to gain the amount of anterior teeth retraction and anterior alveolar surface remodeling that could be used as boundary condition. Different values of Poisson ratio ν and Young's modulus E were tested during simulation. RESULTS: Average deviation was 0.47 mm and 0.75 mm in the soft and hard tissue respectively. It could be decreased to a range of +0.29 mm and -0.21 mm after a second transformation at the lip-mouth region. The best correspondence between simulation and post-treatment result was found with elastic properties of soft tissues defined as follows. Poisson ratio ν for skin, muscle and fat being set as 0.45 while Young's modulus being set as 90.0 kPa, 6.2 kPa and 2.0 kPa respectively. CONCLUSIONS: Individualized three-dimensional facial FE model could be obtained through mathematical model transformation. With boundary condition defined according to treatment plan such FE model could be used to analyze the effect of orthodontic treatment on facial soft tissue.

Normal epigenetic inheritance in mice conceived by in vitro fertilization and embryo transfer.

An association between assisted reproductive technology (ART) and neurobehavioral imprinting disorders has been reported in many studies, and it seems that ART may interfere with imprint reprogramming. However, it has never been explored whether epigenetic errors or imprinting disease susceptibility induced by ART can be inherited transgenerationally. Hence, the aim of this study was to determine the effect of in vitro fertilization and embryo transfer (IVF-ET) on transgenerational inheritance in an inbred mouse model. Mice derived from IVF-ET were outcrossed to wild-type C57BL/6J to obtain their female and male line F2 and F3 generations. Their behavior, morphology, histology, and DNA methylation status at several important differentially methylated regions (DMRs) were analyzed by Morris water maze, hematoxylin and eosin (H&E) staining, and bisulfite genomic sequencing. No significant differences in spatial learning or phenotypic abnormality were found in adults derived from IVF (F1) and female and male line F2 and F3 generations. A borderline trend of hypomethylation was found in H19 DMR CpG island 3 in the female line-derived F3 generation (0.40±0.118, P=0.086). Methylation status in H19/Igf2 DMR island 1, Igf2 DMR, KvDMR, and Snrpn DMR displayed normal patterns. Methylation percentage did not differ significantly from that of adults conceived naturally, and the expression of the genes they regulated was not disturbed. Transgenerational integrity, such as behavior, morphology, histology, and DNA methylation status, was maintained in these generations, which indicates that exposure of female germ cells to hormonal stimulation and gamete manipulation might not affect the individuals and their descendents.

Stress area of the mandibular alveolar mucosa under complete denture with linear occlusion at lateral excursion.

BACKGROUND: The rocking and instability of a loaded complete denture (CD) during lateral excursion reduce the bearing area under the denture base, causing localized high stress concentrations. This can lead to mucosal tenderness, ulceration, and alveolar bone resorption, and the linear occlusion design was to decrease the lateral force exerted on the denture and to ensure denture stability. But it is not known how the bearing areas of linear occlusal CDs (LOCDs) and anatomic occlusal CDs (AOCDs) differ. The purpose of this study was to analyze and compare the distributions of the high and low vertical stress-bearing areas in the mandibular alveolar mucosa under LOCDs and AOCDs at lateral excursion. METHODS: Computerized tomography (CT) and finite element analysis were used to establish three-dimensional models of an edentulous maxilla and mandible with severe residual ridge resorption. These models were composed of maxillary and mandibular bone structure, mucosa, and the LOCD or AOCD. Lateral excursion movements of the mandible were simulated and the vertical stress-bearing areas in the mucosa under both mandibular CDs were analyzed using ANSYS 7.0. RESULTS: On the working side, the high stress-bearing (-0.07 to -0.1 MPa) area under the LOCD during lateral excursion was smaller than that under the AOCD, while the medium stress-bearing (-0.03 to -0.07 MPa) area under the LOCD was 1.33-fold that under the AOCD. The medium stress-bearing area on the non-working side under the LOCD was 2.4-fold that under the AOCD. Therefore, the overall medium vertical stress-bearing area under the LOCD was 20% larger than that under the AOCD. CONCLUSIONS: During lateral excursion, the medium vertical stress-bearing area under a mandibular LOCD was larger and the high vertical stress-bearing area was smaller than that under an AOCD. Thus, the vertical stress under the LOCD was distributed more evenly and over a wider area than that under the AOCD, thereby improving denture stability.

[Stress distribution in alveolar bone around implants under implant supported overdenture with linear occlusion at lateral occlusion].

OBJECTIVE: To analyze stress distribution in alveolar bone around implants of implant supported overdentures (ISO) with linear occlusion and with anatomic occlusion at lateral mandibular position, and to justify the possibility of decreased injurious force around implants in ISO with linear occlusion. METHODS: Computerized tomography scan and finite element analysis (FEA) were used to set up two 3-D FEA models of maxillae and mandible with severe residual ridge resorption. The mucosa, linear and anatomic occlusal ISO with bar attachments, and two implants inserted between mandibular foramina were also established in the models. With the condition of imitating the loading of masseter muscles, these models were loaded to simulate the stress distributions in alveolar bone around implants under ISO at lateral occlusion position. RESULTS: At lateral occlusion, the stress distributions in alveolar bone around implants under ISO with anatomic occlusion were mainly on the lingual and distal sides of the working side implants. However, stress distributions under ISO with linear occlusion were on the distal sides of bilateral implants. Both the stress peaks of ISOs with linear occlusion and with the anatomic one appeared in the working side. In anatomic occlusion model, sigma(z): -6.47 MPa and 6.81 MPa, sigma(1): -4.20 MPa and 7.20 MPa (negative value: compressive stress, positive value: tensile stress); in linear occlusion model, sigma(z): -4.86 MPa and 3.04 MPa, sigma(1): -3.48 MPa and 5.33 MPa. CONCLUSIONS: At lateral occlusion, when comparing the ISO with two different occlusion schemes, stress peak in alveolar bone around implants in the linear occlusion model was lower than that in the anatomic occlusion model at equal loading situation. Stress in the alveolar bone under ISO with linear occlusion distributed more evenly than that under ISO with anatomic occlusion.

Poor ovarian response to gonadotropin stimulation is associated with low expression of follicle-stimulating hormone receptor in granulosa cells.

OBJECTIVE: To explore the importance of follicle-stimulating hormone receptor (FSHR) in granulosa cells in the ovarian response to gonadotropin stimulation. DESIGN: Prospective study. SETTING: A women's hospital in China. PATIENT(S): One hundred infertile women undergoing ovarian stimulation with recombinant follicle-stimulating hormone (rFSH). INTERVENTION(S): These women were divided into three groups: poor, moderate, and high responders, according to the number of follicles with diameter >/=14 mm. The FSHR expression at both mRNA and protein levels was determined by either reverse transcription-polymerase chain reaction or Western blot in granulosa cells. E(2) concentrations in serum and FSH levels in serum/follicular fluid (FF) were measured by electrochemiluminescence immunoassay. MAIN OUTCOME MEASURE(S): Relative expression of mRNA and protein of FSHR in granulosa cells, serum E(2), FSH level in serum and FF, and the number of mature follicles. RESULT(S): The expression of FSHR, at both the mRNA and protein levels, was significantly different among the three groups, with the lowest expression in the poor responders. The level of FSHR protein was positively correlated with the peak level of serum E(2) and the number of mature oocytes. FSH levels in FF and the dosage of rFSH used were significantly different among the three groups, with the highest values in the poor responders. CONCLUSION(S): Different levels of FSHR expression in granulosa cells result in different ovarian response, and lower expression of FSHR may account for poor ovarian response to gonadotropin stimulation, which suggests the critical role of FSHR in the ovarian response to gonadotropin stimulation.

[Follicle-stimulating hormone receptor levels in relation to ovarian cycling response from gonadotropin hormone stimulation]

OBJECTIVE: To investigate the relationship between the ovarian response, induced by gonadotropin hormone, and levels of follicle-stimulating hormone receptor (FSHR). METHODS: The level of ovarian response was divided into three groups based on the number of follicles obtained during oocyte retrieval: poor responders (<4 follicles), normal responders (4 approximate, equals 13) and high responders(>13 follicles). FSHR mRNA was measured using reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The expression of FSHR mRNA in the poor responders was 0.54+/-0.07. This was much lower than that of the normal responders who were at 0.90+/-0.17,and the high responders who were at 1.20+/-0.45(P<0.05). CONCLUSION: Ovarian response induced by gonadotropin hormone stimulation is correlated with the level of FSHR mRNA in the granulosa cells.