Identification of pregnancies and their outcomes in healthcare claims data, 2008-2019: An algorithm.

Pregnancy is a condition of broad interest across many medical and health services research domains, but one not easily identified in healthcare claims data. Our objective was to establish an algorithm to identify pregnant women and their pregnancies in claims data. We identified pregnancy-related diagnosis, procedure, and diagnosis-related group codes, accounting for the transition to International Statistical Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) diagnosis and procedure codes, in health encounter reporting on 10/1/2015. We selected women in Merative MarketScan commercial databases aged 15-49 years with pregnancy-related claims, and their infants, during 2008-2019. Pregnancies, pregnancy outcomes, and gestational ages were assigned using the constellation of service dates, code types, pregnancy outcomes, and linkage to infant records. We describe pregnancy outcomes and gestational ages, as well as maternal age, census region, and health plan type. In a sensitivity analysis, we compared our algorithm-assigned date of last menstrual period (LMP) to fertility procedure-based LMP (date of procedure + 14 days) among women with embryo transfer or insemination procedures. Among 5,812,699 identified pregnancies, most (77.9%) were livebirths, followed by spontaneous abortions (16.2%); 3,274,353 (72.2%) livebirths could be linked to infants. Most pregnancies were among women 25-34 years (59.1%), living in the South (39.1%) and Midwest (22.4%), with large employer-sponsored insurance (52.0%). Outcome distributions were similar across ICD-9 and ICD-10 eras, with some variation in gestational age distribution observed. Sensitivity analyses supported our algorithm's framework; algorithm- and fertility procedure-derived LMP estimates were within a week of each other (mean difference: -4 days [IQR: -13 to 6 days]; n = 107,870). We have developed an algorithm to identify pregnancies, their gestational age, and outcomes, across ICD-9 and ICD-10 eras using administrative data. This algorithm may be useful to reproductive health researchers investigating a broad range of pregnancy and infant outcomes.

"They're forcing people to have children that they can't afford": a qualitative study of social support and capital among individuals receiving an abortion in Georgia.

Abortion is common but highly stigmatized in the United States, and the overturning of Roe v. Wade severely restricted abortion access in many states across the nation. Data reveal that maternal morbidity and mortality are already increasing, and research suggests existing inequities in abortion access across racial/ethnic and socioeconomic groups will be exacerbated. Research has shown that social support (perceived and received aid from one's social network) and social capital (resources accessed through those social connections) can improve access to health services and decrease barriers to care. Given the escalating barriers to abortion, including longer travel distances, it is imperative to better understand the roles of social support and social capital within abortion access, especially for people living on lower incomes and people of color. Our team conducted in-depth interviews with post-abortion patients (n = 18) from an urban abortion clinic in Georgia in 2019 and 2020, shortly after a six-week gestational age abortion limit had been passed but before it was enacted. We examined how people described their social support and social capital - or lack thereof - when making decisions about their pregnancy and their ability to access abortion. We found that social support and social capital - economic support in particular - were key facilitators of both abortion access and parenting, but participants often experienced barriers to economic support within their social networks due to poverty, unstable partnerships, structural inequality, and abortion stigma. Women experienced constraints to their reproductive autonomy, wherein they had no alternatives but abortion. Our findings suggest that increased economic support and de-stigmatization of abortion are needed to improve reproductive autonomy. Our findings also indicate that restricting and outlawing abortion services is significantly detrimental to the well-being of pregnant people, their families and networks, and their communities by perpetuating cycles of poverty and deepening socioeconomic and racial/ethnic inequities.

Bespoke 3D-Printed Polydrug Implants Created via Microstructural Control of Oligomers.

Controlling the microstructure of materials by means of phase separation is a versatile tool for optimizing material properties. Phase separation has been exploited to fabricate intricate microstructures in many fields including cell biology, tissue engineering, optics, and electronics. The aim of this study was to use phase separation to tailor the spatial location of drugs and thereby generate release profiles of drug payload over periods ranging from 1 week to months by exploiting different mechanisms: polymer degradation, polymer diluent dissolution, and control of microstructure. To achieve this, we used drop-on-demand inkjet three-dimensional (3D) printing. We predicted the microstructure resulting from phase separation using high-throughput screening combined with a model based on the Flory-Huggins interaction parameter and were able to show that drug release from 3D-printed objects can be predicted from observations based on single drops of mixtures. We demonstrated for the first time that inkjet 3D printing yields controllable phase separation using picoliter droplets of blended photoreactive oligomers/monomers. This new understanding gives us hierarchical compositional control, from droplet to device, allowing release to be "dialled up" without manipulation of device geometry. We exemplify this approach by fabricating a biodegradable, long-term, multiactive drug delivery subdermal implant ("polyimplant") for combination therapy and personalized treatment of coronary heart disease. This is an important advance for implants that need to be delivered by cannula, where the shape is highly constrained and thus the usual geometrical freedoms associated with 3D printing cannot be easily exploited, which brings a hitherto unseen level of understanding to emergent material properties of 3D printing.

Update to U.S. Selected Practice Recommendations for Contraceptive Use: Self-Administration of Subcutaneous Depot Medroxyprogesterone Acetate.

U.S. Selected Practice Recommendations for Contraceptive Use (U.S. SPR), adapted by CDC from global guidance developed by the World Health Organization (WHO), provides evidence-based guidance on contraceptive use for U.S. health care providers (1). During January-February, 2021, CDC evaluated the 2019 WHO recommendation on self-administered subcutaneous depot medroxyprogesterone acetate (DMPA-SC) (2). CDC adopted the WHO recommendation on the basis of moderate-certainty evidence that self-administered DMPA-SC is safe and effective, and has higher continuation rates compared with provider-administered DMPA. The new U.S. SPR recommendation states that self-administered DMPA-SC should be made available as an additional approach to deliver injectable contraception. Provider-administered DMPA should remain available. Self-administered DMPA-SC is a user-controlled method that has the potential to improve contraceptive access and increase reproductive autonomy. Self-administered DMPA-SC should be offered in a noncoercive manner through a shared decision-making process between patients and their health care providers, with a focus on patient preferences and equitable access to the full range of contraceptive methods.

Effects of Premedication With Midazolam on Recovery and Discharge Times After Tonsillectomy and Adenoidectomy.

Background Midazolam is commonly used preoperatively for anxiety. Adverse effects data in pediatric patients with obstructive sleep apnea (OSA) undergoing tonsillectomy and adenoidectomy (T&A) is limited. Aims We hypothesized that preoperative midazolam increases the time to emergence from anesthesia and postoperative discharge. Secondary objectives assessed if patients receiving midazolam experienced increased side effects or complications from treatment. Methods This study was a retrospective chart review of patients undergoing T&A from July 2014 to December 2015. Midazolam receiving patients (midazolam group: MG) were compared to patients who did not (non-midazolam group: NMG). Multivariable analyses were performed and adjusted for predefined potential cofounder variables. Results Emergence and discharge times were 5.2 minutes (95% CI [-7.1, 17.4]; p=0.41) and 10.1 minutes (95% CI [-6.7, 26.8]; p=0.24) longer in MG. These results were not statistically significant. Comparing by OSA status, there was no statistical difference in emergence and discharge times between mild, moderate and severe OSA groups or between MG and NMG within each OSA group. Emergence and discharge times in moderate OSA was 6.1 minutes (95% CI [-17.6, 29.8]; p=0.61) and 18.8 minutes (95% CI [-16.4, 53.9]; p=0.29) longer than mild OSA, and in the severe OSA group, 2.6 minutes (95% CI [-19.9, 25.1]; p=0.82) shorter and 2.8 minutes (95% CI [-30.3, 35.9]; p=0.87) longer. The incidence of postoperative complications was comparable between MG and NMG groups. Conclusions Premedication with midazolam was not associated with prolonged emergence or discharge time or higher incidence of complications after anesthesia for T&A in patients with OSA.

Abortion restrictions in the state of Georgia: Anticipated impact on people seeking abortion.

OBJECTIVE: To explore the impact of restrictive abortion policies in the state of Georgia on the lives of people seeking abortion and how they would manage unwanted pregnancies. STUDY DESIGN: We conducted a cross sectional study of English and Spanish-speaking people seeking abortion from three high-volume outpatient abortion clinics in Atlanta, Georgia from April 2019 through August 2019. Participants completed a multiple-choice questionnaire. We used bivariable and multivariable analysis to explore relationships between demographic characteristics and how people would manage their unwanted pregnancies if abortion were illegal in the state. Two researchers (EC and SC) conducted qualitative analysis on free response answers and coded them by key emotion. RESULTS: Of the 382 participants, 312 (81.9%) considered at least one way to end their pregnancy if abortion were illegal in Georgia: 252 (66.1%) by traveling to another state, 85 (22.3%) by self-management with medications and/or herbs, and 32 (8.4%) considered self-harm behaviors. When asked how they would feel about not being able to have a desired abortion, 94% reported negative emotions, ranging from "scared" to "enslaved." CONCLUSIONS: Limiting access to legal abortion in Georgia would negatively impact the lives of people seeking abortion and has the potential to drive individuals to seek more costly and risky alternatives to end their pregnancy. IMPLICATIONS: Restricting abortion in Georgia may cause medically unnecessary delays in care, increased travel time, cost and negative emotional responses to people seeking abortion. Mitigating strategies include legislative challenges to restrictive laws as well as harm reduction education.

Iron and Sulfur Precursors Affect Crystalline Structure, Speciation, and Reactivity of Sulfidized Nanoscale Zerovalent Iron.

The reactivity of sulfidized nanoscale zerovalent iron (SNZVI) is affected by the amount and species of sulfur in the materials. Here, we assess the impact of the Fe (Fe2+ and Fe3+) and S (S2O42-, S2-, and S62-) precursors used to synthesize both NZVI and SNZVI on the resulting physicochemical properties and reactivity and selectivity with water and trichloroethene (TCE). X-ray diffraction indicated that the Fe precursors altered the crystalline structure of both NZVI and SNZVI. The materials made from the Fe3+ precursor had an expanded lattice in the Fe0 body-centered-cubic (BCC) structure and lower electron-transfer resistance, providing higher reactivity with water (∼2-3 fold) and TCE (∼5-13 fold) than those made from an Fe2+ precursor. The choice of the S precursor controlled the S speciation in the SNZVI particles, as indicated by X-ray absorption spectroscopy. Iron disulfide (FeS2) was the main S species of SNZVI made from S2O42-, whereas iron sulfide (FeS) was the main S species of SNZVI made from S2-/S62-. The former SNZVI was more hydrophobic, reactive with, and selective for TCE compared to the latter SNZVI. These results suggest that the Fe and S precursors can be used to select the conditions of the synthesis process and provide selected physicochemical properties (e.g., S speciation, hydrophobicity, and crystalline structure), reactivity, and selectivity of the SNZVI materials.

The Relationship between Protein Intake and Source on Factors Associated with Glycemic Control in Individuals with Prediabetes and Type 2 Diabetes.

Type 2 diabetes (T2D) is a major contributor to morbidity and mortality largely due to increased cardiovascular disease risk. This study examined the relationships among protein consumption and sources on glycemic control and cardiovascular health in individuals with prediabetes and T2D. Sixty-two overweight or obese participants with prediabetes or T2D, aged 45-75 years were stratified into the following three groups based on protein intake: <0.8 g (gram)/kg (kilogram) body weight (bw), ≥0.8 but <1.0 g/kg bw, and ≥1.0 g/kg bw as below, meeting, and above the recommended levels of protein intake, respectively. Body mass, body mass index (BMI), hip circumference (HC), waist circumference (WC), lean mass, and fat mass (FM) were significantly higher in participants who consumed below the recommended level of protein intake as compared with other groups. Higher animal protein intake was associated with greater insulin secretion and lower triglycerides (TG). Total, low-density, and high-density cholesterol were significantly higher in participants who met the recommended protein intake as compared with the other groups. These data suggest that high protein consumption is associated with lower BMI, HC, WC, and FM, and can improve insulin resistance without affecting lipid profiles in this population. Furthermore, higher intake of animal protein can improve ß-cell function and lower plasma TG.

The Facial Action Coding System for Characterization of Human Affective Response to Consumer Product-Based Stimuli: A Systematic Review.

To characterize human emotions, researchers have increasingly utilized Automatic Facial Expression Analysis (AFEA), which automates the Facial Action Coding System (FACS) and translates the facial muscular positioning into the basic universal emotions. There is broad interest in the application of FACS for assessing consumer expressions as an indication of emotions to consumer product-stimuli. However, the translation of FACS to characterization of emotions is elusive in the literature. The aim of this systematic review is to give an overview of how FACS has been used to investigate human emotional behavior to consumer product-based stimuli. The search was limited to studies published in English after 1978, conducted on humans, using FACS or its action units to investigate affect, where emotional response is elicited by consumer product-based stimuli evoking at least one of the five senses. The search resulted in an initial total of 1,935 records, of which 55 studies were extracted and categorized based on the outcomes of interest including (i) method of FACS implementation; (ii) purpose of study; (iii) consumer product-based stimuli used; and (iv) measures of affect validation. Most studies implemented FACS manually (73%) to develop products and/or software (20%) and used consumer product-based stimuli that had known and/or defined capacity to evoke a particular affective response, such as films and/or movie clips (20%); minimal attention was paid to consumer products with low levels of emotional competence or with unknown affective impact. The vast majority of studies (53%) did not validate FACS-determined affect and, of the validation measures that were used, most tended to be discontinuous in nature and only captured affect as it holistically related to an experience. This review illuminated some inconsistencies in how FACS is carried out as well as how emotional response is inferred from facial muscle activation. This may prompt researchers to consider measuring the total consumer experience by employing a variety of methodologies in addition to FACS and its emotion-based interpretation guide. Such strategies may better conceptualize consumers' experience with products of low, unknown, and/or undefined capacity to evoke an affective response such as product prototypes, line extensions, etc.

Effects of Montmorency Tart Cherry Juice Consumption on Cardiometabolic Biomarkers in Adults with Metabolic Syndrome: A Randomized Controlled Pilot Trial.

Greater than one-third of adults in the United States have metabolic syndrome (MetS), a cluster of risk factors highly associated with the development of cardiovascular diseases. Premature vascular dysfunction in MetS may lead to accelerated age-related atherogenesis and arterial stiffening, thereby increasing cardiovascular risk. Montmorency tart cherries (Prunus cerasus L.) are rich in bioactive compounds, such as anthocyanins, known to exert cardiovascular protective effects. Previous research suggests that tart cherry juice consumption may improve cardiovascular health. The objective of this study was to evaluate the effects of daily consumption of tart cherry juice on hemodynamics, arterial stiffness, and blood biomarkers of cardiovascular and metabolic health in men and women with MetS. In a randomized, single-blind, placebo-controlled, parallel-arm pilot clinical trial, 19 men and women 20 to 60 years of age with MetS consumed 240 mL of tart cherry juice (Tart Cherry; n = 5 males, 4 females) or an isocaloric placebo-control drink (Control; n = 5 males, 5 females) twice daily for 12 weeks. Arterial stiffness (pulse wave velocity), brachial and aortic blood pressures, wave reflection (augmentation index), and blood biomarkers of cardiovascular and metabolic health were assessed at baseline and 6 and 12 weeks. Oxidized low-density lipoprotein and soluble vascular cell adhesion molecule-1 were significantly lower (P = .047 and P = .036, respectively) in Tart Cherry than Control at 12 weeks, but were not significantly lower than baseline values. There was a trend for total cholesterol to be lower (P = .08) in Tart Cherry than Control at 12 weeks. No significant changes were observed in hemodynamics, arterial stiffness, or other blood biomarkers assessed. These results suggest that daily tart cherry consumption may attenuate processes involved in accelerated atherogenesis without affecting hemodynamics or arterial stiffness parameters in this population. The pilot nature of this study warrants interpreting these findings with caution, and future clinical trials with a larger sample size are needed to confirm these findings.

Making tablets for delivery of poorly soluble drugs using photoinitiated 3D inkjet printing.

In this study, we investigate the viability of three-dimensional (3D) inkjet printing with UV curing to produce solid dosage forms containing a known poorly soluble drug, carvedilol. The formulation consists of 10 wt% carvedilol, Irgacure 2959, and a photocurable N-vinyl-2-pyrrolidone (NVP) and poly(ethylene glycol) diacrylate matrix, with the intention of forming an amorphous solid solution for release of carvedilol. Characterization of the printed tablets showed that the drug is an amorphous state and indicated hydrogen bonding interactions between the drug and cross-linked matrix. Several simple geometries (ring, mesh, cylinder, thin film) were printed, and the surface area to volume ratio of the prints was estimated. Over 80% carvedilol release was observed for all printed tablet geometries within ten hours. The release behaviour of carvedilol was fastest for the thin films, followed by the ring and mesh geometries, and slowest in the cylindrical forms. More rapid release was correlated to an increased surface area to volume ratio. This is the first study to implement 3D UV inkjet to make solid dispersion tablets suitable for poorly soluble drugs. Results also demonstrate that high drug-loaded tablets with a variety of release profiles can successfully be accessed with the same UV-curable inkjet formulation by varying the tablet geometry.

Egg consumption may improve factors associated with glycemic control and insulin sensitivity in adults with pre- and type II diabetes.

Without appropriate interventions, prediabetes is typically followed by type II diabetes. Eggs are a rich source of important nutrients including protein, vitamins, minerals, carotenoids and lecithin. In this 12-week, parallel, randomized controlled trial, 42 overweight or obese individuals between the ages of 40 and 75 years with pre- and type II-diabetes were included. Participants were randomly assigned to receive either one large egg per day or an equivalent amount of egg substitute for 12 weeks. Blood samples were obtained to analyze lipid profile and biomarkers associated with glycemic control at all time points. Regular egg consumption resulted in improvements of fasting blood glucose, which was significantly (P = 0.05) reduced by 4.4% at the final visit in the egg group. Participants in the egg group had significantly (P = 0.01) lower levels of homeostatic model assessment of insulin resistance (HOMA-IR) at all visits. In the egg group, ATP-binding cassette protein family A1 (ABCA1) was significantly higher at the 6-week visit (0.78 ± 0.21 vs. 0.28 ± 0.05 mg dL-1, P < 0.001) and tended to be higher at the final visit (0.62 ± 0.11 vs. 0.55 ± 0.18 mg dL-1, P = 0.1). The mean apolipoprotein A1 (apo A1) level was also significantly higher at the final visit in the egg group compared to the control (147.43 ± 5.34 vs. 142.81 ± 5.09 mg dL-1, P = 0.01). There were no significant changes in total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels. Daily consumption of one large egg may reduce the risk of diabetes without having any adverse effects on lipid profiles in individuals with pre- and type II diabetes.

Military Sexual Trauma in Female Veterans is Associated With Chronic Pain Conditions.

INTRODUCTION: Little is known about the impact of MST on chronic pain conditions among female Veterans. The primary objective of this study was to compare the prevalence of chronic pain conditions among U.S. female veterans with a history of military sexual trauma (MST) to those without a history of MST. We anticipated that female Veterans with a history of MST would have higher associations with chronic pain conditions than the female Veterans without a history of MST. MATERIALS AND METHODS: This was a large-scale, retrospective study using the Veterans' Health Administration Corporate Data Warehouse with institutional approval (15-H175). International Classification of Diseases, 9th Revision codes from the outpatient visits, outpatient problem lists, and inpatient discharge diagnoses were used to identify chronic pain diagnoses. Baseline demographic data including date of birth, self-identified race/ethnicity, and body mass index were obtained. Significant findings in the univariate analysis were then placed into a multivariable logistic regression model to adjust the effect of each predictor for the presence of others. Significance was set at p < 0.01 because of multiple comparisons made. RESULTS: For the entire cohort (516,950 women), 28.9% (149,540) were diagnosed with headaches, 18.3% (94,393) with chronic pelvic pain, 14.4% (74,216) with chronic back pain, 10.5% (54,302) with nonspecific joint pain, 9% (48,509) with fibromyalgia, 6.2% (32,037) with generalized abdominal pain, 4.2% (21,911) with irritable bowel syndrome, and 3.2% (16,309) with dyspareunia. Most women had more than one chronic pain diagnosis. At baseline, women with a history of MST were younger (63.3 ± 15.9 vs. 67.4 ± 17.9 years p < 0.001), heavier (29.5± 6.2 vs. 28.8 ± 6.1 kg/m2 p < 0.001), smokers (49.3 vs. 38.8% p < 0.001), and more likely to be non-Hispanic white (56.3 vs. 52.3% p < 0.001) than women without a history of MST. Women with a history of MST had more pain diagnoses than those without the history of MST (all p < 0.001). The adjusted odds ratio of women with history of MST presenting with any pain condition compared to a women without a history of MST was 1.26 (95% confidence interval 1.24-1.28). In the multivariable model there remained an association between MST and chronic pain conditions including irritable bowel syndrome, chronic pelvic pain, back pain, chronic joint pain, fibromyalgia, dyspareunia, chronic abdominal pain, and headaches after adjusting for baseline differences in age, body mass index, smoking, and ethnicity. Importantly, drug abuse, and overdose were also associated with MST. CONCLUSION: A history of MST is associated with chronic pain diagnoses. Weaknesses of this study are those applicable to analyses of any retrospective database study. Specifically, the data are limited by the accuracy of physician coding and reporting. The strength of this study is that it represents a comprehensive, retrospective evaluation of potential sources for chronic pain within the female veteran population. In summary, we found that female veteran survivors of MST face an increased burden of chronic pain, including a broad range of pain conditions independent of the psychological effects of MST.

3D printing of tablets using inkjet with UV photoinitiation.

Additive manufacturing (AM) offers significant potential benefits in the field of drug delivery and pharmaceutical/medical device manufacture. Of AM processes, 3D inkjet printing enables precise deposition of a formulation, whilst offering the potential for significant scale up or scale out as a manufacturing platform. This work hypothesizes that suitable solvent based ink formulations can be developed that allow the production of solid dosage forms that meet the standards required for pharmaceutical tablets, whilst offering a platform for flexible and personalized manufacture. We demonstrate this using piezo-activated inkjetting to 3D print ropinirole hydrochloride. The tablets produced consist of a cross-linked poly(ethylene glycol diacrylate) (PEGDA) hydrogel matrix containing the drug, photoinitiated in a low oxygen environment using an aqueous solution of Irgacure 2959. At a Ropinirole HCl loading of 0.41mg, drug release from the tablet is shown to be Fickian. Raman and IR spectroscopy indicate a high degree of cross-linking and formation of an amorphous solid dispersion. This is the first publication of a UV inkjet 3D printed tablet. Consequently, this work opens the possibility for the translation of scalable, high precision and bespoke ink-jet based additive manufacturing to the pharmaceutical sector.

Determination of Abraham model solute descriptors for the monomeric and dimeric forms of trans-cinnamic acid using measured solubilities from the Open Notebook Science Challenge.

BACKGROUND: Calculating Abraham descriptors from solubility values requires that the solute have the same form when dissolved in all solvents. However, carboxylic acids can form dimers when dissolved in non-polar solvents. For such compounds Abraham descriptors can be calculated for both the monomeric and dimeric forms by treating the polar and non-polar systems separately. We illustrate the method of how this can be done by calculating the Abraham descriptors for both the monomeric and dimeric forms of trans-cinnamic acid, the first time that descriptors for a carboxylic acid dimer have been obtained. RESULTS: Abraham descriptors were calculated for the monomeric form of trans-cinnamic acid using experimental solubility measurements in polar solvents from the Open Notebook Science Challenge together with a number of water-solvent partition coefficients from the literature. Similarly, experimental solubility measurements in non-polar solvents were used to determine Abraham descriptors for the trans-cinnamic acid dimer. CONCLUSION: Abraham descriptors were calculated for both the monomeric and dimeric forms of trans-cinnamic acid. This allows for the prediction of further solubilities of trans-cinnamic acid in both polar and non-polar solvents with an error of about 0.10 log units. Graphical abstractMolar concentration of trans-cinnamic acid in various polar and non-polar solvents.

Concise review: MicroRNA function in multipotent mesenchymal stromal cells.

Multipotent mesenchymal stromal cells (MSCs) are ideal candidates for different cellular therapies due to their simple isolation, extensive expansion potential, and low immunogenicity. For various therapeutic approaches, such as bone and cartilage repair, MSCs are expected to contribute by direct differentiation to replace the damaged tissue, while many other applications rely on the secretion of paracrine factors which modulate the immune response and promote angiogenesis. MicroRNAs (miRNAs), which target messenger RNA for cleavage or translational repression, have recently been shown to play critical functions in MSC to regulate differentiation, paracrine activity, and other cellular properties such as proliferation, survival, and migration. The global miRNA expression profile of MSC varies according to the tissue of origin, species, and detection methodology, while also certain miRNAs are consistently found in all types of MSC. The function in MSC of more than 60 different miRNAs has been recently described, which is the subject of this review. A special emphasis is given to miRNAs that have demonstrated a function in MSC in vivo. We also present in detail miRNAs with overlapping effects (i.e., common target genes) and discuss future directions to deepen our understanding of miRNA biology in MSC. These recent discoveries have opened the possibility of modulating miRNAs in MSC, in order to enhance their proregenerative, therapeutic potential.

Structure and function of cytidine monophosphate kinase from Yersinia pseudotuberculosis, essential for virulence but not for survival.

The need for new antibiotics has become pressing in light of the emergence of antibiotic-resistant strains of human pathogens. Yersinia pestis, the causative agent of plague, is a public health threat and also an agent of concern in biodefence. It is a recently emerged clonal derivative of the enteric pathogen Yersinia pseudotuberculosis. Previously, we developed a bioinformatic approach to identify proteins that may be suitable targets for antimicrobial therapy and in particular for the treatment of plague. One such target was cytidine monophosphate (CMP) kinase, which is an essential gene in some organisms. Previously, we had thought CMP kinase was essential for Y. pseudotuberculosis, but by modification of the mutagenesis approach, we report here the production and characterization of a Δcmk mutant. The isogenic mutant had a growth defect relative to the parental strain, and was highly attenuated in mice. We have also elucidated the structure of the CMP kinase to 2.32 Å, and identified three key residues in the active site that are essential for activity of the enzyme. These findings will have implications for the development of novel CMP kinase inhibitors for therapeutic use.

Regulation of microRNA-375 by cAMP in pancreatic ß-cells.

MicroRNA-375 (miR-375) is necessary for proper formation of pancreatic islets in vertebrates and is necessary for the development of ß-cells in mice, but regulation of miR-375 in these cells is poorly understood. Here, we show that miR-375 is transcriptionally repressed by the cAMP-protein kinase A (PKA) pathway and that this repression is mediated through a block in RNA polymerase II binding to the miR-375 promoter. cAMP analogs that are PKA selective repress miR-375, as do cAMP agonists and the glucagon-like peptide-1 receptor agonist, exendin-4. Repression of the miR-375 precursor occurs rapidly in rat insulinoma INS-1 832/13 cells, within 15 min after cAMP stimulation, although the mature microRNA declines more slowly due to the kinetics of RNA processing. Repression of miR-375 in isolated rat islets by exendin-4 also occurs slowly, after several hours of stimulation. Glucose is another reported antagonist of miR-375 expression, although we demonstrate here that glucose does not target the microRNA through the PKA pathway. As reported previously, miR-375 negatively regulates insulin secretion, and attenuation of miR-375 through the cAMP-PKA pathway may boost the insulin response in pancreatic ß-cells.