Associations of smoking and alcohol consumption with the development of open angle glaucoma: a retrospective cohort study.

OBJECTIVES: To investigate the associations of alcohol consumption and smoking with the development of perimetric glaucoma in patients with suspected glaucoma. DESIGN: A retrospective cohort study of patients suspected to have glaucoma enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES). SETTING: Three tertiary glaucoma centres in the USA. PARTICIPANTS: 825 eyes of 610 patients with glaucoma suspect eyes with normal visual fields (VF) at baseline were followed over an average of 9 years from the DIGS and ADAGES studies. OUTCOME MEASURES: Development of glaucoma was defined as occurrence of three consecutive abnormal VF tests during follow-up. Univariable and multivariable Cox regression models were used to investigate lifestyle-related factors associated with development of VF loss over time. RESULTS: VF tests were abnormal three times in a row in 235 (28.5%) eyes. Alcohol consumption was associated with a higher risk of developing glaucoma (HR 1.57, 95% CI 1.03 to 2.38, p=0.037). In men, the risk of developing glaucoma in alcohol drinkers (HR 1.92, 95% CI 1.00 to 3.68, p=0.048) was greater than non-alcohol drinkers. In individuals of African descent, the risk of developing glaucoma in alcohol drinkers (HR 1.79, 95% CI 1.02 to 3.15, p=0.043) was greater than non-alcohol drinkers. Age was a modifier of the relationship between smoking and glaucomatous VF defects (p=0.048). The risk of developing glaucoma in smokers (HR 1.73, 95% CI 1.10 to 2.72, p=0.019) was greater than never smokers after adjustment for confounding factors in older patients (age >61 years). CONCLUSION: Alcohol consumption was associated with an increased risk of developing glaucoma, particularly in men and individuals of African descent. The risk of developing glaucoma among smokers suspected of having glaucoma was influenced by age, with older individuals having a higher risk than younger people. TRIAL REGISTRATION NUMBER: NCT00221897 and NCT00221923.

Long-term reproducibility of optical coherence tomography angiography in healthy and stable glaucomatous eyes.

BACKGROUND/AIMS: To assess and compare long-term reproducibility of optic nerve head (ONH) and macula optical coherence tomography angiography (OCTA) vascular parameters and optical coherence tomography (OCT) thickness parameters in stable primary open-angle glaucoma (POAG), glaucoma suspect and healthy eyes. METHODS: Eighty-eight eyes (15 healthy, 38 glaucoma suspect and 35 non-progressing POAG) of 68 subjects who had at least three visits within 1-1.5 years with OCTA and OCT imaging (Angiovue; Optovue, Fremont, California, USA) on the same day were included. A series of vascular and thickness parameters were measured including macular parafoveal vessel density (pfVD), ONH circumpapillary capillary density (cpCD), macular parafoveal ganglion cell complex (pfGCC) and ONH circumpapillary retinal nerve fibre layer (cpRNFL). A random effects analysis of variance model was used to estimate intraclass correlation (ICC) coefficients and long-term variability estimates. RESULTS: ICC was lower for OCTA (pfVD 0.823 (95% CI 0.736 to 0.888) and cpCD 0.871 (0.818 to 0.912)) compared with OCT (pfGCC 0.995 (0.993 to 0.997) and cpRNFL 0.975 (0.964 to 0.984)). Within-subject test-retest SD was 1.17% and 1.22% for pfVD and cpCD, and 0.57 and 1.22 µm for pfGCC and cpRNFL. Older age and lower signal strength index were associated with decreasing long-term variability of vessel densities. CONCLUSIONS: OCTA-measured macula and ONH vascular parameters have good long-term reproducibility, supporting the use of this instrument for longitudinal analysis. OCTA long-term reproducibility is less than OCT-measured thickness reproducibility. This needs to be taken into consideration when serial OCTA images are evaluated for change. TRIAL REGISTRATION NUMBER: NCT00221897.

Association of Intraocular Pressure With Retinal Nerve Fiber Layer Thinning in Patients With Glaucoma.

Importance: Higher intraocular pressure variability may be associated with faster structural changes in patients with glaucoma. Objectives: To investigate the association of mean intraocular pressure and intraocular pressure variability (defined as the SD of intraocular pressure and the intraocular pressure range) with the rate of retinal nerve fiber layer thinning over time in patients with glaucoma. Design, Setting, and Participants: In this retrospective analysis of a longitudinal cohort, patients were enrolled from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation study. A total of 815 eyes (564 with perimetric glaucoma and 251 with preperimetric glaucoma) from 508 patients with imaging follow-up for a mean of 6.3 years from December 2008 to October 2020 were studied. Data were analyzed from November 2021 to March 2022. Main Outcomes and Measures: In this longitudinal study, eyes with at least 4 visits and 2 years of follow-up optical coherence tomography and intraocular pressure measurement were included. A linear mixed-effect model was used to investigate the association of intraocular pressure parameters with the rates of retinal nerve fiber layer thinning. Dominance analysis was performed to determine the relative importance of the intraocular pressure parameters. Results: Of 508 included patients, 280 (55.1%) were female, 195 (38.4%) were African American, 24 (4.7%) were Asian, 281 (55.3%) were White, and 8 (1.6%) were another race or ethnicity; the mean (SD) age was 65.5 (11.0) years. The mean rate of retinal nerve fiber layer change was -0.67 (95% CI, -0.73 to -0.60) µm per year. In multivariable models adjusted for mean intraocular pressure and other confounding factors, faster annual rate of retinal nerve fiber layer thinning was associated with a higher SD of intraocular pressure (-0.20[ 95% CI, -0.26 to -0.15] µm per 1-mm Hg higher; P < .001) or higher intraocular pressure range (-0.05 [95% CI, -0.06 to -0.03] µm per 1-mm Hg higher; P < .001). Conclusions and Relevance: In this study, intraocular pressure variability was independently associated with structural change in patients with glaucoma, even after adjustment for mean intraocular pressure, supporting its potential value in clinical management.

Polymorphous low-grade adenocarcinoma with cavernous sinus involvement presenting as third nerve palsy.

Purpose: Polymorphous low-grade adenocarcinoma is a tumor of the salivary glands that typically localizes within the oral cavity. We present a case of isolated third cranial nerve palsy as the initial presentation of polymorphous low-grade adenocarcinoma involving the left cavernous sinus in a patient status post glaucoma surgery. Observations: A 68-year-old woman status post glaucoma drainage device implantation in her left eye presented with an isolated left third nerve palsy ten weeks postoperatively. Differential diagnoses included microvascular ischemic neuropathy, postoperative ptosis, and compressive mass. MRI revealed a left cavernous sinus mass, and subsequent excisional biopsy revealed a diagnosis of polymorphous low-grade adenocarcinoma. Conclusions: There are few cases reporting polymorphous low-grade adenocarcinoma originating from and extending beyond the nasopharynx. This report emphasizes an unexpected neuro-ophthalmic manifestation of this salivary gland tumor.

Association of Initial Optical Coherence Tomography Angiography Vessel Density Loss With Faster Visual Field Loss in Glaucoma.

IMPORTANCE: Rapid vessel density loss during an initial follow-up period may be associated with the rates of visual field loss over time. OBJECTIVES: To evaluate the association between the rate of vessel density loss during initial follow-up and the rate of visual field loss during an extended follow-up period in patients suspected of having glaucoma and patients with primary open-angle glaucoma. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study assessed 124 eyes (86 with primary open-angle glaucoma and 38 suspected of having glaucoma) of 82 patients who were followed up at a tertiary glaucoma center for a mean of 4.0 years (95% CI, 3.9-4.1 years) from January 1, 2015, to February 29, 2020. Data analysis for the current study was undertaken in March 2021. MAIN OUTCOMES AND MEASURES: The rate of vessel density loss was derived from macular whole-image vessel density values from 3 optical coherence tomography angiography scans early during the study. The rate of visual field loss was calculated from visual field mean deviation during the entire follow-up period after the first optical coherence tomography angiography visit. Linear mixed-effects models were used to estimate rates of change. RESULTS: A total of 124 eyes from 82 patients (mean [SD] age, 69.2 [10.9] years; 41 female [50.0%] and 41 male [50.0%]; and 20 African American [24.4%], 10 Asian [12.2%], 50 White [61.0%], and 2 other race or ethnicity [2.4%]) were assessed. The annual rate of vessel density change was -0.80% (95% CI, -0.88% to -0.72%) during a mean initial follow-up of 2.1 years (95% CI, 1.9-2.3 years). Eyes with annual rates of vessel density loss of -0.75% or greater (n = 62) were categorized as fast progressors, and eyes with annual rates of less than -0.75% (n = 62) were categorized as slow progressors. The annual rate of visual field loss was -0.15 dB (95% CI, -0.29 to -0.01 dB) for the slow optical coherence tomography angiography progressors and -0.43 dB (95% CI, -0.58 to -0.29 dB) for the fast optical coherence tomography angiography progressors (difference, -0.28 dB; 95% CI, -0.48 to -0.08 dB; P = .006). The fast optical coherence tomography angiography progressor group was associated with the faster overall rate of visual field loss in a multivariable model after adjusting to include concurrent visual field mean deviation rate (-0.17 dB; 95% CI, -0.33 to -0.01 dB; P = .04). CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that faster vessel density loss during an initial follow-up period was associated with faster concurrent and subsequent rates of visual field loss during an extended period.

Rates of Circumpapillary Retinal Nerve Fiber Layer Thinning and Capillary Density Loss in Glaucomatous Eyes with Disc Hemorrhage.

PURPOSE: To investigate longitudinal changes in rates of optic nerve head circumpapillary retinal nerve fiber layer (cpRNFL) thinning and vessel density loss in patients with primary open-angle glaucoma with or without a history of disc hemorrhage (DH). DESIGN: Observational cohort. METHODS: In this longitudinal study, 34 eyes with DH and 134 eyes without DH that had ≥1.5 years of follow-up and 3 optical coherence tomography and optical coherence tomography angiography follow-up scans were enrolled. A linear mixed-effects model was used to compare the rates of cpRNFL thinning and vessel density loss between DH and non-DH eyes. RESULTS: Rates of whole image capillary density loss were faster in the DH group compared with the non-DH group (mean difference [95% confidence interval] -0.32% [-0.59% to -0.04%] per year; P = .027). Faster mean rates of vessel density loss were found in the inferotemporal, inferonasal, and nasal sectors in eyes with DH than without DH (P < .05). There was no statistically significant difference in the global rate of cpRNFL thinning between the 2 groups (P = .679). The mean rate of cpRNFL thinning was faster in the DH group compared with the non-DH group only in the inferotemporal sector (mean difference [95% confidence interval] -1.01 µm (-1.62 µm to -0.40 µm) per year; P = .001). CONCLUSIONS: Mean rates of vessel density loss between DH and non-DH eyes were different not only in the affected area but also in the other regions. In contrast, a significant difference in cpRNFL thinning between the 2 groups was detected only in the inferotemporal sector. Disc hemorrhage is an independent predictor of faster vessel density loss in glaucoma suspects and patients with primary open-angle glaucoma.

Association of Visual Field Pattern Reversal with Paracentral Visual Field Loss.

PURPOSE: Visual field (VF) results that show more test points outside normal limits on the pattern deviation map than on the total deviation map have been assumed to be evidence of unreliable VF results. We propose the term pattern reversal to describe this VF finding and explore its association with paracentral loss. DESIGN: Retrospective cohort and case-control studies. PARTICIPANTS: Glaucoma and glaucoma suspect patients who completed VF testing in Veteran's Affairs ophthalmology or optometry clinics. METHODS: In the cohort study, VF results were included that demonstrated pattern reversal. The area of pattern reversal was categorized as peripheral, paracentral, or mixed (both peripheral and paracentral). In the case-control study, a group of patients with paracentral loss confirmed on 10-2 VF tests were compared with a control group whose VF results were without paracentral loss. MAIN OUTCOME MEASURES: In the cohort study, the calculated false-positive (FP) error rates were compared among groups categorized by area of pattern reversal. In the case-control study, the rates of pattern reversal were compared between patients with and without paracentral loss. RESULTS: Two hundred seventeen eyes of 145 patients were included in the cohort study. Visual field results with pattern reversal and mixed loss had significantly higher FP rates compared with those with paracentral or peripheral loss only (16.25% vs. 6.26% and 8.15%, respectively; P < 0.001). Fifty-five eyes of 41 patients were included in the case group and 55 eyes of 41 patients were included in the control group. Patients with paracentral loss were more likely to have history of pattern reversal compared with those without paracentral loss (58.2% vs. 29.1%; P = 0.004). Twelve eyes with paracentral loss had 24-2 VF results that showed defects on the pattern deviation map, but not on the total deviation map. CONCLUSIONS: Pattern reversal may be associated with paracentral VF loss and is not always associated with elevated FP rates.

Full-Length 16S rRNA and ITS Gene Sequencing Revealed Rich Microbial Flora in Roots of Cycas spp. in China.

Cycads have developed a complex root system categorized either as normal or coralloid roots. Past literatures revealed that a great diversity of key microbes is associated with these roots. This recent study aims to comprehensively determine the diversity and community structure of bacteria and fungi associated with the roots of two Cycas spp. endemic to China, Cycas debaoensis Zhong & Chen and Cycas fairylakea D.Y. Wang using high-throughput amplicon sequencing of the full-length 16S rRNA (V1-V9 hypervariable) and short fragment ITS region. The total DNA from 12 root samples were extracted, amplified, sequenced, and analyzed. Resulting sequences were clustered into 61 bacteria and 2128 fungal OTUs. Analysis of community structure revealed that the coralloid roots were dominated mostly by the nitrogen-fixer Nostocaceae but also contain other non-diazotrophic bacteria. The sequencing of entire 16S rRNA gene identified four different strains of cyanobacteria under the heterocystous genera Nostoc and Desmonostoc. Meanwhile, the top bacterial families in normal roots were Xanthobacteraceae, Burkholderiaceae, and Bacillaceae. Moreover, a diverse fungal community was also found in the roots of cycads and the predominating families were Ophiocordycipitaceae, Nectriaceae, Bionectriaceae, and Trichocomaceae. Our results demonstrated that bacterial diversity in normal roots of C. fairylakea is higher in richness and abundance than C. debaoensis. On the other hand, a slight difference, albeit insignificant, was noted for the diversity of fungi among root types and host species as the number of shared taxa is relatively high (67%). Our results suggested that diverse microbes are present in roots of cycads which potentially interact together to support cycads survival. Our study provided additional knowledge on the microbial diversity and composition in cycads and thus expanding our current knowledge on cycad-microbe association. Our study also considered the possible impact of ex situ conservation on cyanobiont community of cycads.

The complete chloroplast genome of Microcycas calocoma (Miq.) A. DC. (Zamiaceae, Cycadales) and evolution in Cycadales.

Cycadales is an extant group of seed plants occurring in subtropical and tropical regions comprising putatively three families and 10 genera. At least one complete plastid genome sequence has been reported for all of the 10 genera except Microcycas, making it an ideal plant group to conduct comprehensive plastome comparisons at the genus level. This article reports for the first time the plastid genome of Microcycas calocoma. The plastid genome has a length of 165,688 bp with 134 annotated genes including 86 protein-coding genes, 47 non-coding RNA genes (39 tRNA and eight rRNA) and one pseudogene. Using global sequence variation analysis, the results showed that all cycad genomes share highly similar genomic profiles indicating significant slow evolution and little variation. However, identity matrices coinciding with the inverted repeat regions showed fewer similarities indicating that higher polymorphic events occur at those sites. Conserved non-coding regions also appear to be more divergent whereas variations in the exons were less discernible indicating that the latter comprises more conserved sequences. Phylogenetic analysis using 81 concatenated protein-coding genes of chloroplast (cp) genomes, obtained using maximum likelihood and Bayesian inference with high support values (>70% ML and = 1.0 BPP), confirms that Microcycas is closest to Zamia and forms a monophyletic clade with Ceratozamia and Stangeria. While Stangeria joined the Neotropical cycads Ceratozamia, Zamia and Microcyas, Bowenia grouped with the Southern Hemisphere cycads Encephalartos, Lepidozamia and Macrozamia. All Cycas species formed a distinct clade separated from the other genera. Dioon, on the other hand, was outlying from the rest of Zamiaceae encompassing two major clades-the Southern Hemisphere cycads and the Neotropical cycads. Analysis of the whole cp genomes in phylogeny also supports that the previously recognized family-Stangeriaceae-which contained Bowenia and Stangeria, is not monophyletic. Thus, the cp genome topology obtained in our study is congruent with other molecular phylogenies recognizing only a two-family classification (Cycadaceae and Zamiaceae) within extant Cycadales.

Plastome structure and phylogeny of Gnetum luofuense C.Y. Cheng (Gnetaceae, Gnetales).

This article describes the complete chloroplast genome of Gnetum luofuense. The G. luofense plastome was 114,795 bp in length, containing a large single copy region (66,103 bp) and a small single copy region (9438 bp), separated by two inverted repeat regions (19,627 bp). The genome lost all ndh genes and contained 116 genes, including 68 protein-coding genes, 40 tRNA genes, and eight rRNA genes. The GC content was 33.3%, 12 genes all contained an intron, ycf3 gene contained two introns while rps12 was a transpliced gene. Phylogenetic analysis using 61 concatenated protein-coding genes suggests that G. luofuense with the rest of other gnetophytes were sister to or nested within all conifers.

Perspectives on Endosymbiosis in Coralloid Roots: Association of Cycads and Cyanobacteria.

Past endosymbiotic events allowed photosynthetic organisms to flourish and evolve in terrestrial areas. The precursor of chloroplasts was an ancient photosynthetic cyanobacterium. Presently, cyanobacteria are still capable of establishing successful symbioses in a wide range of hosts. One particular host plant among the gymnosperms is cycads (Order Cycadales) in which a special type of root system, referred to as coralloid roots, develops to house symbiotic cyanobacteria. A number of studies have explained coralloid root formation and cyanobiont invasion but the questions on mechanisms of this host-microbe association remains vague. Most researches focus on diversity of symbionts in coralloid roots but equally important is to explore the underlying mechanisms of cycads-Nostoc symbiosis as well. Besides providing an overview of relevant areas presently known about this association and citing putative genes involved in cycad-cyanobacteria symbioses, this paper aims to identify the limitations that hamper attempts to get to the root of the matter and suggests future research directions that may prove useful.

RELATIONSHIP BETWEEN OBSTRUCTIVE SLEEP APNEA AND THE PRESENCE AND SEVERITY OF DIABETIC RETINOPATHY.

PURPOSE: To evaluate the relationship between obstructive sleep apnea (OSA) and the presence and severity of diabetic retinopathy (DR). METHODS: Three hundred seventeen patients with International Classification of Diseases diagnoses of both DR and OSA were evaluated retrospectively. Diabetic retinopathy severity and diabetic macular edema status were determined by diagnostic coding and medical records. Obstructive sleep apnea severity and additional sleep measures were obtained from overnight polysomnography. Analysis was performed using multivariable logistic regression. RESULTS: After adjustment, an association was seen between DR and severe OSA (odds ratio [OR]: 2.18, 95% confidence interval [CI]: 1.14-4.18, P = 0.019). Proliferative DR was associated with severe OSA versus no DR (OR: 2.40, 95% CI: 1.12-5.14, P = 0.024) and mild nonproliferative DR (OR: 2.87, 95% CI: 1.26-6.55, P = 0.012). Comparing all nonproliferative DR with proliferative DR, proliferative DR and severe OSA were associated (OR: 2.20, 95% CI: 1.03-4.70, P = 0.043), as well as diabetic macular edema and severe OSA (OR: 2.89, 95% CI: 1.58-5.27, P = 0.001). No association was seen between DR/diabetic macular edema and secondary sleep measures. CONCLUSION: The findings suggest an increased risk of DR, proliferative DR, and diabetic macular edema in patients with severe OSA. Ophthalmologists following these patients should be aware of this association to better manage ocular sequelae of diabetes.

Association Between Eyelid Laxity and Obstructive Sleep Apnea.

Importance: While much has been reported on the relationship between floppy eyelid syndrome and obstructive sleep apnea (OSA), the diagnostic criteria of floppy eyelid syndrome are often subjective and vague. Objective: To evaluate the association between OSA and quantitative markers of eyelid laxity or secondary ocular surface disease in a sleep clinic population. Design, Setting, and Participants: This investigation was a cross-sectional observational study at the Center for Sleep Medicine at Icahn School of Medicine at Mount Sinai. Participants were individuals referred for overnight polysomnography from March 1 to August 30, 2015. Main Outcomes and Measures: Eyelid laxity and ocular surface disease were assessed on bedside ophthalmologic examination. The presence and severity of OSA were determined from polysomnography results. Initial correlation between OSA and ocular surface and eyelid markers was calculated through bivariate linear regression analysis, and the association between ocular symptoms was obtained through bivariate ordered logistic regression. Analysis was repeated adjusting for known associations between OSA and sex, age, body mass index, and medical comorbidities through multivariable analysis. Results: In total, 201 individuals (402 eyes) were enrolled in the study. Their mean (SD) age was 53.2 (13.5) years, 43.3% (n = 87) were female, 56.7% (n = 114) were of white race/ethnicity, 26.9% (n = 54) were black/African American, 4.0% (n = 8) were Asian, 8.0% (n = 16) were multiracial or other, and 4.5% (n = 9) were of unknown race/ethnicity, with 21.9% (n = 44) of all individuals self-identifying as Hispanic and 75.1% (n = 151) self-identifying as non-Hispanic. After adjustment, no association was observed between OSA severity and an eyelid laxity score (regression coefficient, 0.85; 95% CI, -0.33 to 0.62; P = .40) or an ocular surface score (regression coefficient, 1.09; 95% CI, -0.32 to 0.29; P = .93). Through subset analysis, male sex was associated with a higher ocular surface score, while older age and diabetes were associated with a higher eyelid laxity score. Only one patient (0.5%) exhibited findings of floppy eyelid syndrome. Conclusions and Relevance: Among individuals referred for overnight polysomnography, quantitative markers of eyelid laxity were not associated with the presence or severity of OSA. Subset analysis suggests that prior studies may have been limited by confounding variables or the technique of identifying eyelid laxity.

A prospective, randomized, double-blinded study of assisted hatching in women younger than 38 years undergoing in vitro fertilization.

OBJECTIVE: To determine whether assisted hatching is beneficial to IVF patients younger than 38 years whose embryos have a thickened zona pellucida (ZP). DESIGN: Prospective, randomized, double-blinded, crossover study. SETTING: University-based infertility center. PATIENT(S): One hundred twenty-one women less than 38 years of age, undergoing IVF at Washington University between April 2004 and February 2007, with ZP thickness > or =13 microm for any embryos. INTERVENTION(S): Measurement of ZP thickness in embryos undergoing IVF; randomization of women with embryos with ZP thickness > or =13 microm to no procedure or assisted hatching performed by acidic Tyrode's solution. MAIN OUTCOME MEASURE(S): Clinical intrauterine pregnancy rate, implantation rate, spontaneous pregnancy loss, and live birth rate. RESULT(S): Baseline characteristics and ZP thickness were not significantly different between the two study arms (hatched and unhatched). No significant differences were observed between hatched and unhatched patients in the rates of clinical pregnancy (47% vs. 50% respectively) or live birth (46% vs. 45% respectively). Further, no significant differences were noted between hatched and unhatched groups in rates of spontaneous abortions, monozygotic twinning, dizygotic twinning, chromosomal abnormalities, or ectopic gestations. In addition, mean ZP thickness did not have a significant effect on pregnancy. CONCLUSION(S): In patients younger than 38 years with embryos with ZP thickness of > or =13 microm, assisted hatching does not improve the rates of implantation, clinical pregnancy, or live birth, and thus does not appear to offer any benefit to patients in this age group undergoing IVF.

Estrogens regulate posttranslational modification of neural cell adhesion molecule during the estrogen-induced gonadotropin surge.

Estrogen-induced synaptic plasticity (EISP) in the periventricular area (PVA) of the hypothalamus is necessary for the preovulatory gonadotropin surge. Because in situ enzymatic desialization of hypothalamic polysialylated (PSA) neural cell adhesion molecule (NCAM) blocked EISP, we examined the presence and amount of NCAM isotopes, PSA-NCAM, and sialylation enzymes in microdissected mouse hypothalamus tissues from proestrous afternoon [peak of estrogens and nadir of arcuate nucleus (AN) synapses] and metestrous morning (nadir of estrogens and highest AN synapses). Immunohistochemistry confirmed immunoreactive (ir) PSA-NCAM staining in the perineural spaces of the PVA. The extent of staining was cycle dependent, with more dense and complete profiles of individual neurons limned by the ir-PSA-NCAM staining on proestrus and less on metestrus. Western blots showed that high levels of ir-PSA-NCAM on proestrus are accompanied by diminished ir-NCAM-140 and -180 but not ir-NCAM-120 and the reverse on metestrus (P < 0.05). To evaluate the increase of sialylated NCAM at the expense of desialylated protein, expression of the responsible polysialyltransferase enzymes polysialyltransferase (ST8Sia IV) and sialyltransferase (ST8Sia II) mRNA levels were measured using RT-PCR. Both polysialyltransferase and sialyltransferase mRNA are more abundant on proestrus than metestrus (P < 0.05), indicating that these enzymes are regulated by estrogens. These results support estrogen-regulated formation and extrusion of hydrophilic PSA-NCAM into perineural spaces in the PVA as part of the mechanism of EISP.

Morbid obesity is associated with lower clinical pregnancy rates after in vitro fertilization in women with polycystic ovary syndrome.

OBJECTIVE: To determine whether morbid obesity is associated with decreased pregnancy and live birth rates after IVF in women with polycystic ovary syndrome (PCOS). DESIGN: Retrospective cohort study. SETTING: University-based fertility center. PATIENT(S): Seventy-two women with PCOS who completed their first IVF cycle between 2001 and 2006. INTERVENTION(S): Outcomes of IVF were compared between women with a body mass index (BMI) of <40 kg/m(2) vs. those with a BMI of > or =40 kg/m(2). MAIN OUTCOME MEASURE(S): Clinical pregnancy rate, live birth rate. RESULT(S): Morbidly obese women with PCOS (n = 19) had significantly lower clinical pregnancy rates after IVF than patients with PCOS who were not morbidly obese (n = 53) (32% vs. 72%, relative risk 0.44, 95% confidence interval 0.22-0.87). Their live birth rates were lower too, although this difference was not statistically significant (32% vs. 60%, relative risk 0.52, 95% confidence interval 0.26-1.05). CONCLUSION(S): Morbid obesity is associated with lower pregnancy rates in women with PCOS after IVF, raising the question of whether weight loss may improve IVF success rates for morbidly obese PCOS patients.

Encouraging patient-driven single-embryo transfer.

Single-embryo transfer (SET) removes the risk of multiples in in vitro fertilization (IVF), but women with unfavorable IVF prognosis have been dissuaded from SET despite their desire to avoid multiples. In our clinic, 54% of the women who requested SET delivered healthy singletons, even though only two of them had met the American Society for Reproductive Medicine's SET guidelines. This demonstrates the value of encouraging patient-driven SET.

Maternal diabetes adversely affects AMP-activated protein kinase activity and cellular metabolism in murine oocytes.

Maternal diabetes is associated with an increased risk of miscarriages and congenital anomalies. Preovulatory oocytes in murine models also experience maturational delay and greater granulosa cell apoptosis. The objective of this study was to examine whether maternal diabetes influences preovulatory oocyte metabolism and impacts meiotic maturation. Streptozotocin-induced diabetic B6SJLF1 mice were superovulated, and oocytes were collected at 0, 2, and 6 h after human chorionic gonadotropin (hCG) injection. Individual oocyte concentrations of ATP, 5'-AMP, glycogen, and fructose-1,6-phosphate (FBP) and enzyme activities of glucose-6-phosphate dehydrogenase (G6PDH), adenylate kinase, hydroxyacyl-CoA dehydrogenase (Hadh2), and glutamic pyruvate transaminase (Gpt2) were measured. Protein levels of phosphorylated AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) were also measured. ATP levels were significantly lower in oocytes from diabetic mice, and the percent change in the AMP-to-ATP ratio was significantly higher in these oocytes. In contrast, activities of Hadh2 and Gpt2, two enzymes activated by AMPK, were significantly less in these oocytes. Additionally, glycogen and FBP levels, both endogenous inhibitors of AMPK, were elevated. Phosphorylated ACC, a downstream target of AMPK, and phosphorylated AMPK were both decreased in diabetic oocytes, thus confirming decreased AMPK activity. Finally, addition of the activator AICAR to the in vitro maturation assay restored AMPK activity and corrected the maturation defect experienced by the oocytes from diabetic mice. In conclusion, maternal diabetes adversely alters cellular metabolism leading to abnormal AMPK activity in murine oocytes. Increasing AMPK activity in these oocytes during the preovulatory phase reverses the metabolic changes and corrects delays in meiotic maturation.