Biomedical subjects

Stephen M Downs

Publications and source records attributed to Stephen M Downs.

At least 19 recordsLinked to original sources

PubMed2006

AMPK regulation of mouse oocyte meiotic resumption in vitro.

We have previously shown that the adenosine analog 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR), an activator of AMP-activated protein kinase (AMPK), stimulates an increase in AMPK activity and induces meiotic resumption in mouse oocytes [Downs, S.M., Hudson, E.R., Hardie, D.G., 2002. A potential role for AMP-activated protein kinase in meiotic induction in mouse oocytes. Dev. Biol, 245, 200-212]. The present study was carried out to better define a causative role for AMPK in oocyte meiotic maturation. When microinjected with a constitutively active AMPK, about 20% of mouse oocytes maintained in meiotic arrest with dibutyryl cAMP (dbcAMP) were stimulated to undergo germinal vesicle breakdown (GVB), while there was no effect of catalytically dead kinase. Western blot analysis revealed that germinal vesicle (GV)-stage oocytes cultured in dbcAMP-containing medium plus AICAR possessed elevated levels of active AMPK, and this was confirmed by AMPK assays using a peptide substrate of AMPK to directly measure AMPK activity. AICAR-induced meiotic resumption and AMPK activation were blocked by compound C or adenine 9-beta-d-arabinofuranoside (araA, a precursor of araATP), both inhibitors of AMPK. Compound C failed to suppress adenosine uptake and phosphorylation, indicating that it did not block AICAR action by preventing its metabolism to the AMP analog, ZMP. 2'-deoxycoformycin (DCF), a potent adenosine deaminase inhibitor, reversed the inhibitory effect of adenosine on oocyte maturation by modulating intracellular AMP levels and activating AMPK. Rosiglitazone, an anti-diabetic agent, stimulated AMPK activation in oocytes and triggered meiotic resumption. In spontaneously maturing oocytes, GVB was preceded by AMPK activation and blocked by compound C. Collectively, these results support the proposition that active AMPK within mouse oocytes provides a potent meiosis-inducing signal in vitro.

AMP-Activated Protein Kinases↗

PubMed2006

Simulating cost-effectiveness of fluoride varnish during well-child visits for Medicaid-enrolled children.

OBJECTIVE: To examine the cost-effectiveness of fluoride varnish application by medical providers when implemented within a well-child periodicity schedule for Medicaid-enrolled children. DESIGN: Cost-effectiveness was analyzed using published probabilities and costs. Input parameters included the effectiveness of fluoride varnish (35.4%) applied according to the well-child periodicity schedule up to 3 years of age at $16.00 per application, annual caries increment (14%), age-specific dental care usage rates (0.2% at 9 months to 19% at 42 months), and age-related nonhospital treatment costs ($292.00-$503.00) and hospital treatment costs ($2191.00-$2940.00). Sensitivity analysis was conducted to assess the effects for varying input parameters. SETTING: Well-child visits during primary care. PARTICIPANTS: Children aged 9 to 42 months. INTERVENTION: Application of universal fluoride varnish (fluoride varnish-all) at 9, 18, 24, and 36 months vs no intervention (fluoride varnish-none) was compared. MAIN OUTCOME MEASURES: Cost per month without cavities and treatment averted during the first 42 months of life from a Medicaid payer's perspective. RESULTS: Fluoride varnish improved clinical outcomes by 1.52 cavity-free months but at a cost of $7.18 for each cavity-free month gained per child and $203 for each treatment averted. Considerable uncertainty existed for some parameters. Fluoride varnish was cost saving when dental services and nonhospital treatment costs were 1.5 to 2 times greater, respectively, than our base case estimate. CONCLUSIONS: Based on these assumptions, fluoride varnish use in the medical setting is effective in reducing early childhood caries in low-income populations but is not cost saving in the first 42 months of life. Potential total cost reductions with varying parameters suggest that evaluations using a longitudinal cohort are needed.

Cariostatic Agents↗

PubMed2006

Differential response of cumulus cell-enclosed and denuded mouse oocytes in a meiotic induction model system.

In this study we have examined the effects of denuded oocyte coculture with dissociated cumulus cells (CC) or intact oocyte-CC complexes on meiotic resumption. When denuded oocytes (DO) or cumulus cell-enclosed oocytes (CEO) were cultured in 40-microl drops of medium under oil, and held in meiotic arrest with 4 mM hypoxanthine plus 25 microM dbcAMP, they underwent germinal vesicle breakdown (GVB) at similar frequencies (34%-35%). Coculture of DO with complexes or dissociated CCs stimulated maturation (50% and 61% GVB, respectively), with no effect of DO on maturation of cocultured CEO (32% GVB). This coculture effect was increased with the number of CCs added to the culture drop. When either glucose or glutamine was eliminated from the medium, no meiotic induction resulted from cocultured CCs. When CEO were cultured alone in microdrops, increasing their number from 10 to 50 significantly lowered the percentage resuming maturation, an effect also reduced by removing glucose and/or glutamine from the medium. This effect was not observed with DO. When inhibitory medium was conditioned overnight with complexes, subsequent culture with DO led to higher maturation percentages than culture in unconditioned medium; however, when CEO were cultured in conditioned medium, there was either no effect or increased inhibition of maturation. Assay of glucose and pyruvate in spent medium showed that DO cultured alone consumed glucose and pyruvate, but under CC coculture conditions more glucose was consumed and significant amounts of pyruvate accumulated in the medium, changes that led to an increase in the maturation of DO. Further experiments showed that DO were more sensitive than CEO to the meiosis-inducing effect of pyruvate. These results demonstrate different responsiveness of DO and CEO to coculture conditions and question the physiological relevance of denuded oocyte/CC coculture to study meiotic induction.

Animals↗

PubMed2006

Induction of meiotic maturation in mouse oocytes by adenosine analogs.

In this study we have examined the meiosis-inducing influence of adenosine analogs in mouse oocytes. When a varied group of nucleosides and nucleotides were tested on overnight cultures of hypoxanthine-arrested, cumulus cell-enclosed oocytes (CEO), halogenated adenosine nucleosides, but not native adenosine, exhibited a significant meiosis-inducing capability. When tested under a variety of conditions, meiotic induction by 8-bromo-adenosine (8-Br-Ado) and a second adenosine analog, methylmercaptopurine riboside (MMPR), was especially potent in denuded oocytes (DO) compared to CEO and was not dependent on the type of inhibitor chosen to maintain meiotic arrest. Germinal vesicle breakdown (GVB) was stimulated with rapid kinetics and was preceded by an increase in AMP-activated protein kinase (AMPK) activity. Moreover, compound C, an inhibitor of AMPK, blocked the meiosis-inducing activities of both adenosine analogs. When tested for an effect on meiotic progression to metaphase II (MII) in spontaneously maturing CEO, 8-Br-Ado and the AMPK activator, 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside (AICAR), increased the percentage of MII-stage oocytes, but MMPR decreased this number. Adenosine and inhibitors of de novo purine synthesis had no effect on the completion of maturation, while compound C suppressed this process. These results support the proposition that oocyte AMPK mediates the positive influence of AICAR and 8-Br-Ado on both the initiation and completion of meiotic maturation. The role of AMPK in MMPR action is less clear.

AMP-Activated Protein Kinases↗

PubMed2006

The Indiana Chronic Disease Management Program.

The Indiana Chronic Disease Management Program (ICDMP) is intended to improve the quality and cost-effectiveness of care for Medicaid members with congestive heart failure (chronic heart failure), diabetes, asthma, and other conditions. The ICDMP is being assembled by Indiana Medicaid primarily from state and local resources and has seven components: (1) identification of eligible participants to create regional registries, (2) risk stratification of eligible participants, (3) nurse care management for high-risk participants, (4) telephonic intervention for all participants, (5) an Internet-based information system, (6) quality improvement collaboratives for primary care practices, and (7) program evaluation. The evaluation involves a randomized controlled trial in two inner-city group practices, as well as a statewide observational design. This article describes the ICDMP, highlights challenges, and discusses approaches to its evaluation.

Chronic Disease↗

PubMed2006

Shortcomings in infant iron deficiency screening methods.

BACKGROUND: Screening for iron deficiency anemia is a well-established practice in pediatrics, but numerous challenges surrounding current recommendations raise questions about the effectiveness of this strategy. OBJECTIVE: To evaluate iron deficiency anemia screening approaches, by assessing rates of follow-up testing and resolution among patients meeting screening criteria in a primary care setting. METHODS: A retrospective cohort study was performed. We extracted electronic medical record data on complete blood counts for infants who received primary care in our clinics in the past 10 years. We calculated rates of positive screening results with 9 different measurement criteria and determined rates of follow-up testing and of documented correction of iron deficiency among those who screened positive. RESULTS: Our cohort consisted of 4984 children who were screened at 9 to 15 months of age, between 1994 and 2004. There was a wide distribution of positive detection rates (range: 1.5-14.5%) among the 9 screening criteria. Follow-up testing rates were low. No more than 25% of infants who screened positive by any criterion underwent a repeat complete blood count within 6 months. Moreover, no more than 11.6% (range: 4.4-11.6%) had documented correction of their laboratory abnormalities. CONCLUSIONS: Significant shortcomings exist in current iron deficiency anemia screening practices. A widely agreed-on, specific, and inexpensive screening criterion, with increased emphasis on systems-based approaches to iron deficiency screening, is needed.

Anemia, Iron-Deficiency↗

PubMed2006

The role of parental preferences in the management of fever without source among 3- to 36-month-old children: a decision analysis.

OBJECTIVES: Recent analyses assessing the impact of the conjugate pneumococcal vaccine on the care of febrile children do not reflect the role parental preferences play in physicians' decisions. The objective of this study was to identify the management strategy that would best suit parents, on the basis of their values for possible outcomes of fever of > or =39 degrees C without source among well-appearing, 3- to 36-month-old children. METHODS: A decision analysis was performed to compare the benefits and outcomes of 3 management options (treat: blood culture and antibiotics for all children; test: blood culture and complete blood count for all children, with antibiotics for selected children; observe: no immediate intervention). A hypothetical cohort of 100,000 children with fever of > or =39 degrees C with no obvious source of infection was modeled for each strategy. Using this model, we identified the treatment option that would best suit each parent's preferences, on the basis of parental utilities (from a prior study) for various interventions and outcomes at vaccine efficacies of 0% (ie, no vaccine) and 95%. In addition, we performed survival analyses to assess the morbidity and mortality rates associated with each treatment strategy at various vaccine efficacies. RESULTS: At a vaccine efficacy of 0%, the majority of parents' preferences suggested the treat option, the strategy with the lowest mortality rate. At a vaccine efficacy of 95%, mortality rates were similar for all 3 management options (approximately 1 in 100,000), but parental preferences were still aligned with different options; 50% suggested observe, 42% suggested test, and 8% suggested treat. CONCLUSIONS: Like physicians, parents have different approaches to risk. With the conjugate pneumococcal vaccine, risks of complications from fever without source are low regardless of treatment strategy. Rather than having a "one size fits all" approach, it is reasonable to incorporate parental preferences into the treatment decision.

Anti-Bacterial Agents↗

PubMed2006

Screening for celiac disease in asymptomatic children with Down syndrome: cost-effectiveness of preventing lymphoma.

BACKGROUND: Studies demonstrate an increased prevalence of celiac disease in persons with Down syndrome, leading some organizations and authors to recommend universal screening of children with Down syndrome. However, many children with Down syndrome are asymptomatic, and the long-term implications of screening are unknown. The complication of celiac disease that leads to mortality in the general population is non-Hodgkin's lymphomas. OBJECTIVES: The purpose of this research in asymptomatic children with Down syndrome was to (1) calculate the number needed to screen to prevent a single case of lymphoma and (2) present a cost-effectiveness study of screening. METHODS: We constructed a decision tree using probabilities derived from the published literature for Down syndrome or from the general population where Down syndrome-specific data were not available. Celiac disease was determined by serologic screening and confirmation with intestinal biopsy. Sensitivity analysis was used to alter probability estimates affecting the cost of preventing lymphoma. RESULTS: Using our baseline values, the no-screen strategy is dominant; that is, screening not only costs more but also results in fewer quality-adjusted life-years. A screening strategy costs more than $500,000 per life-year gained. Screening all asymptomatic children with Down syndrome for celiac disease costs almost $5 million to prevent a single case of lymphoma. CONCLUSION: These analyses do not support the cost-effectiveness of screening, and more data are needed before recommendations to screen asymptomatic children with Down syndrome for celiac disease can be made.

Celiac Disease↗

PubMed2006

Comprehensive cost-utility analysis of newborn screening strategies.

BACKGROUND: Inborn errors of metabolism are a significant cause of morbidity and death among children. Inconsistencies in how individual states arrive at screening strategies, however, lead to marked variations in testing between states. OBJECTIVE: To determine the cost-effectiveness of each component test of a multitest newborn screening program, including screening for phenylketonuria, congenital adrenal hyperplasia, congenital hypothyroidism, biotinidase deficiency, maple syrup urine disease, galactosemia, homocystinuria, and medium-chain acyl-CoA dehydrogenase deficiency. METHODS: A decision model was used, with cohort studies, government reports, secondary analyses, and other sources. Discounted costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios were measured. RESULTS: All except 2 screening tests dominated the "no-test" strategy. The 2 exceptions were screening for congenital adrenal hyperplasia, which cost slightly more than $20,000 per QALY gained, and screening for galactosemia, which cost $94,000 per QALY gained. The screening test with the lowest expected cost was tandem mass spectrometry. The results found in our base-case analysis were stable across variations in nearly all variables. In instances in which changes in risks, sequelae, costs, or utilities did affect our results, the variation from base-case estimates was quite large. CONCLUSIONS: Newborn screening seems to be one of the rare health care interventions that is beneficial to patients and, in many cases, cost saving. Over the long term, funding comprehensive newborn screening programs is likely to save money for society.

Cost-Benefit Analysis↗

PubMed2005

Stress stimulates AMP-activated protein kinase and meiotic resumption in mouse oocytes.

This study examined the effects of three different cellular stresses on oocyte maturation in meiotically arrested mouse oocytes. Cumulus-cell enclosed oocytes (CEO) or denuded oocytes (DO) from immature, eCG-primed mice were cultured for 17-18 h in dbcAMP-containing medium plus increasing concentrations of the metabolic poison, sodium arsenite, or the free radical-generating agent, menadione. Alternatively, oocytes were exposed to osmotic stress by pulsing with sorbitol and returned to control inhibitory conditions for the duration of culture. Arsenite and menadione each dose-dependently induced germinal vesicle breakdown (GVB) in both DO and CEO. DO, but not CEO, pulsed for 60 min with 500 mM sorbitol were stimulated to resume maturation. The lack of effect in CEO suggests that the cumulus cells may be playing a protective role in osmotic stress-induced GVB. The AMP-activated protein kinase (PRKA; formerly known as AMPK) inhibitors, compound C and araA, completely blocked the meiosis-stimulating effects of all the tested stresses. Western blots showed that acetyl-CoA carboxylase, an important substrate of PRKA, was phosphorylated before GVB, supporting a role for PRKA in stress-induced maturation. Together, these data show that a variety of stresses stimulate GVB in meiotically arrested mouse oocytes in vitro and suggest that this effect is mediated through activation of PRKA.

Acetyl-CoA Carboxylase↗

PubMed2005

MEK inhibitors block AICAR-induced maturation in mouse oocytes by a MAPK-independent mechanism.

The present study was carried out to assess the possible role of mitogen-activated protein kinase (MAPK) in the meiosis-inducing action of the AMP-activated protein kinase (AMPK) activator, 5-aminoimidazole-4-carboxamide 1-beta-ribofuranoside (AICAR). Cumulus cell-enclosed oocytes (CEO) or denuded oocytes (DO) from immature, eCG-primed mice were cultured 4 hr in Eagle's minimum essential medium containing dbcAMP plus increasing concentrations of AICAR or okadaic acid (OA). OA is a phosphatase inhibitor known to stimulate both meiotic maturation and MAPK activation and served as a positive control. Both OA and AICAR were potent inducers of meiotic resumption in mouse oocytes and brought about the phosphorylation (and thus, activation) of MAPK, but by different kinetics: MAPK phosphorylation preceded GVB in OA-treated oocytes, while that resulting from AICAR treatment appeared only after GVB. The MEK inhibitors, PD98059 and U0126, blocked the meiotic resumption induced by AICAR but not that induced by OA. Although the MEK inhibitors suppressed MAPK phosphorylation in both OA- and AICAR-treated oocytes, meiotic resumption was not causally linked to MAPK phosphorylation in either group. Furthermore, AICAR-induced meiotic resumption in Mos-null oocytes (which are unable to stimulate MAPK) was also abrogated by PD98059 treatment. A non-specific effect of the MEK inhibitors on AICAR accessibility to the oocyte was discounted by showing that they failed to suppress either nucleoside uptake or AICAR-stimulated phosphorylation of acetyl CoA carboxylase (ACC), a substrate of AMPK. The suppression of AICAR-induced maturation by MEK inhibitors must, therefore, be occurring by actions unrelated to MEK stimulation of MAPK; consequently, it would be prudent to consider this possible non-specific action of the inhibitors when they are used to block MAPK activation in mouse oocytes.

AMP-Activated Protein Kinases↗

PubMed2005

Indiana chronic disease management program risk stratification analysis.

OBJECTIVE: The objective of this study was to compare the ability of risk stratification models derived from administrative data to classify groups of patients for enrollment in a tailored chronic disease management program. SUBJECTS: This study included 19,548 Medicaid patients with chronic heart failure or diabetes in the Indiana Medicaid data warehouse during 2001 and 2002. MEASURES: To predict costs (total claims paid) in FY 2002, we considered candidate predictor variables available in FY 2001, including patient characteristics, the number and type of prescription medications, laboratory tests, pharmacy charges, and utilization of primary, specialty, inpatient, emergency department, nursing home, and home health care. METHODS: We built prospective models to identify patients with different levels of expenditure. Model fit was assessed using R statistics, whereas discrimination was assessed using the weighted kappa statistic, predictive ratios, and the area under the receiver operating characteristic curve. RESULTS: We found a simple least-squares regression model in which logged total charges in FY 2002 were regressed on the log of total charges in FY 2001, the number of prescriptions filled in FY 2001, and the FY 2001 eligibility category, performed as well as more complex models. This simple 3-parameter model had an R of 0.30 and, in terms in classification efficiency, had a sensitivity of 0.57, a specificity of 0.90, an area under the receiver operator curve of 0.80, and a weighted kappa statistic of 0.51. CONCLUSION: This simple model based on readily available administrative data stratified Medicaid members according to predicted future utilization as well as more complicated models.

Adult↗

PubMed2005

Assessing cost-effectiveness of sealant placement in children.

OBJECTIVE: The lack of cost-effectiveness information regarding sealant placement strategies is thought to have influenced reimbursement policies and subsequent sealant utilization in dental practice. This study compared three strategies for managing the occlusal surfaces of first permanent molars: seal all (SA), risk-based (RBS), and seal none (SN). METHODS: A decision tree was developed for various possible outcomes following each of the above strategies. Due to the complexity of the decision tree, a Markov model was used to allow for the construction of a chain of events representing the natural history of sealant retention, caries formation, and their associated health states. The outcome measures were the incremental cost per month gained in a cavity-free state over a ten-year period. RESULTS: Our theoretical model showed that RBS strategy improved clinical outcomes, in the form of cavity-free months, and saved money over SN. The strategy of sealing both high and low risk teeth (SA) further improved outcomes but at an additional cost compared to RBS. However, the cost was small, .08 dollars for each additional cavity-free month gained per tooth. Further, minor changes in the baseline assumptions resulted in the SA strategy being the dominant strategy. CONCLUSION: This study provides evidence that sealing children's first permanent molars can improve outcomes and save money by delaying or avoiding invasive treatment and the destructive cycle of caries. In a time of limited funds for dental services, these results can assist payers in establishing more rational sealant reimbursement policies.

Child↗

PubMed2005

Automating the recognition and prioritization of needed preventive services: early results from the CHICA system.

An ever-growing plethora of preventive services guidelines threatens to overwhelm primary care providers who are expected to recognize and prioritize these needed services for each patient. The Child Health Improvement through Computer Automation (CHICA) system was designed to facilitate this process through a workflow-sensitive interface that gathers and distills the most relevant patient data within pediatric settings. We evaluated family responses to 21 CHICA questions that assess risk factors and health behaviors over a three month period. 3005 patients provided 15,434 responses to these questions, and 1756 or 11.3% of these suggest risk factors which merit attention. This preliminary analysis suggests that, using CHICA, families identify significant risk factors that our clinicians acknowledge are often overlooked given the realities of practicing within this setting.

Adolescent↗

PubMed2005

Human and system errors, using adaptive turnaround documents to capture data in a busy practice.

Capturing coded clinical data for clinical decision support can improve care, but cost and disruption of clinic workflow present barriers to implementation. Previous work has shown that tailored, scannable paper forms (adaptive turnaround documents, ATDs) can achieve the benefits of computer-based clinical decision support at low cost and minimal disruption of workflow. ATDs are highly accurate under controlled circumstances, but accuracy in the setting of busy clinics with untrained physician users is untested. We recently developed and implemented such a system and studied rates of errors attributable to physician users and errors in the system. Prompts were used in 63% of encounters. Errors resulting from incorrectly marking forms occurred in 1.8% of prompts. System errors occurred in 7.2% of prompts. Most system errors were failures to capture data and may represent human errors in the scanning process. ATDs are an effective way to collect coded data from physicians. Further automation of the scanning process may reduce system errors.

Ambulatory Care Information Systems↗

PubMed2004

Potential role for the sorbitol pathway in the meiotic dysfunction exhibited by oocytes from diabetic mice.

Complications common to type I diabetes, such as cataracts and cardiovascular disorders, have been associated with activation of the polyol pathway, which converts glucose to fructose via the intermediate, sorbitol. Under normal glycemic conditions, glucose is typically targeted for glycolysis or the pentose phosphate pathway through phosphorylation by hexokinase. When glucose levels are elevated under diabetic conditions, hexokinase becomes saturated, and the excess glucose is then shunted to aldose reductase, which converts glucose to sorbitol. In the present study, we examined the potential effects of this pathway on the maturation process in mouse oocytes. Increasing concentrations of sorbitol suppressed FSH-induced maturation in oocytes from control mice. Culturing oocytes from diabetic mice in the presence of inhibitors of aldose reductase reversed the suppression of FSH-induced meiotic maturation. When oocytes from control mice were cultured with activators of aldose reductase, FSH-induced maturation was compromised. In addition, treatment with sorbitol or activators of the polyol pathway led to reduced cell-cell communication between the oocyte and the cumulus cells, as well as compromised FSH-mediated cAMP production and de novo purine synthesis. These data indicate that the suppression of FSH-induced meiotic maturation observed in oocytes from diabetic mice may result from a shunting of glucose through the polyol pathway.

Aldehyde Reductase↗

PubMed2004

Child Health Improvement through Computer Automation: the CHICA system.

Clinical guidelines are prevalent but frequently not used. Computer reminder systems can improve adherence to guidelines but have not been widely adopted. We present a computer-based decision support system that combines these elements: 1) pediatric preventive care guidelines encoded in Arden Syntax; 2) a dynamic, scannable paper user interface; and 3) a HL7-compliant interface to existing electronic medical record systems. The result is a system that both delivers "just in time" patient-relevant guidelines to physicians during the clinical encounter and accurately captures structured data from all who interact with the system. The system performs these tasks while remaining sensitive to the workflow constraints of a busy outpatient pediatric practice.

Algorithms↗

PubMed2003

Physiological changes in oocyte-cumulus cell complexes from diabetic mice that potentially influence meiotic regulation.

We have previously shown that the type I diabetic condition significantly alters meiotic regulation in mouse oocytes. In the present study, possible physiological deficiencies underlying such meiotic dysfunction were examined in oocyte-cumulus cell complexes (OCC) from type I diabetic mice. Whereas the diabetic condition did not affect glycolysis or the tricarboxylic acid cycle, the increased flux of glucose through the pentose phosphate pathway in response to FSH treatment was suppressed. De novo purine synthesis was also compromised, and ATP levels were reduced in freshly isolated OCC. Additionally, diabetes resulted in a reduction in FSH-mediated cAMP synthesis. The responsiveness of the oocyte to cAMP was also affected; fewer oocytes were induced to resume maturation after a stimulatory pulse with cAMP analogs. Meiotic induction triggered by FSH was significantly reduced, but that stimulated by phorbol ester or epidermal growth factor was affected to a much lesser extent. In addition to metabolic deficiencies, the cell-cell communication between the oocyte and the cumulus cells was reduced in diabetic mice as determined by coupling assays. Thus, numerous physiological parameters are affected by type I diabetes, and these changes may collectively contribute to altered meiotic regulation.

Animals↗