Development of a core minimum data set to advance real-world evidence generation for uterine fibroids treatment technologies.

Objectives: The accumulation of data through a prospective, multicenter coordinated registry network (CRN) is a robust and cost-effective way to gather real-world evidence on the performance of uterine fibroids treatment technologies for device-based and intervention-based studies. To develop the CRN, a group of uterine fibroids experts, consisting of representatives from professional societies, the US Food and Drug Administration, academia, industry, and the patient community, was convened to discuss the role and feasibility of the CRN and to identify the core data elements needed to assess uterine fibroid treatment technologies. Design: A Delphi method approach was employed to achieve consensus on a core minimum data set for the CRN. A series of surveys were sent to the panel and answered by each expert anonymously and individually. Results from the surveys were collected, collated, and analyzed by a study design team from Weill Cornell Medicine. Questions for the next round were based on the analysis process and discussed with group members via a conference call. This process was repeated twice over a 3-month time period until consensus was achieved. Results: Twenty-nine experts participated in the Delphi surveys, which began with an initial list of 200 data elements. The working group reached final consensus on 97 data elements capturing patient medical history, imaging data, procedure-related data, post-procedure data, and long-term follow-up data. Conclusions: The CRN successfully convened an expert panel on uterine fibroids treatment technologies and used the Delphi method to produce a consensus-based core set of data elements. These identified data elements include important outcomes related to efficacy and safety and thus, influence patient, provider, and regulatory decision-making about treatments for uterine fibroids. Finally, the core data elements provide the foundation of the infrastructure needed for the CRN that will allow for the comparative study of uterine fibroid treatment devices and technologies.

Depth of thermal dispersion of monopolar radiofrequency heating in the vaginal wall.

The use of energy-based devices to treat genitourinary syndrome of menopause, termed vaginal thermotherapy (VTT), has gained significant interest in recent years. Among the primary safety concerns of this relatively new procedure is the possibility of unintentionally heating tissues adjacent to the vaginal wall, i.e., heating too deeply. Herein we use numerical simulations to evaluate monopolar radiofrequency-based (RF) VTT specifically focusing on the resultant depth of heating through a range of input parameters. Varying RF power, exposure time, and the simulated rate of blood perfusion, we map the parameter space identifying which combinations of input parameters are likely to heat past the depth of the vaginal wall and affect adjacent tissue. We found that the device parameters commonly used in the literature are likely to heat past the vaginal wall and merit further investigation. In addition, we found that the parameter typically used to describe VTT devices, total energy delivered, does not reliably indicate the resultant depth of heat dispersion.

Exploring the Role of Sex and Sexual Experience in Predicting American Indian Adolescent Condom Use Intention Using Protection Motivation Theory.

Introduction: American Indian (AI) youth experience poor sexual health outcomes. Research indicates the Protection Motivation Theory (PMT) is a robust model for understanding how sexual risk and protective behaviors are associated with condom use intention (CUI). Studies indicate the constructs of the PMT which influence CUI vary by sex and sexual experience. This analysis explores associations between PMT constructs and CUI by sex and sexual experience among AI youth who participated in the Respecting the Circle of Life (RCL) trial, a sexual and reproductive health intervention. Methods: We analyzed baseline data from the sample of 267 AIs, ages 13-19, who participated in the evaluation. We examined CUI and PMT construct scores by sex and sexual experience utilizing generalized estimated equations and multiple regression models to test which PMT constructs were associated with CUI across sex and sexual experience. Results: Twenty-two percentage of participants were sexually experienced; 56.8% reported CUI at baseline. We found several differences in scores in PMT constructs by sex and sexual experience including self-efficacy, response efficacy, vulnerability, severity, and extrinsic rewards. We also found constructs varied that were associated with CUI varied across sex and sexual experience. No PMT constructs were associated with CUI among sexually experienced youth. Conclusion: Results provide support for developing, selecting and delivering sexual health programs by sex and sexual experience in American Indian communities. Girls programs should focus on internal satisfaction and self-worth while boys should focus on negative impacts of not using condoms. Programs for youth who are not sexually active should focus on negative impacts of not using condoms. Programs for sexually inactive youth should work to change peer norms around condom use and improve knowledge about the efficacy of condom use.

Parents know best in infant hip screening programme.

The importance of early identification of developmental dysplasia of the hip (DDH) is well documented, and there has been a national screening programme since the early 1960s. Until 2008, infants were checked at birth, then at six weeks and eight months; the check at eight months has since been discontinued.

Combination flap surgery with resin-modified glass ionomer for the treatment of radicular lesions: a long-term follow-up.

This retrospective study evaluated the long-term clinical success of combination therapy using resin-modified glass ionomer (RMGI) with flap surgery in treating subgingival radicular defects. The study population consisted of 142 patients with 188 radicular defects. Clinical parameters (pocket depth, recession, clinical attachment level [CAL], and bleeding on probing) were evaluated. Statistically significant CAL gain was observed from baseline to follow-up in successful cases (4.3 ± 0.1 mm to 4.1 ± 0.1 mm, respectively; P < .01). RMGI with flap surgery demonstrated an overall success rate of 86.7% (77.7% with open flap debridement and 94.4% with coronally advanced flap with or without connective tissue graft), with favorable and stable clinical results over a mean period of 4.2 years (longest follow-up, 13 years).

Bacterial and salivary biomarkers predict the gingival inflammatory profile.

BACKGROUND: The aim of this human investigation is to explore the relationship of gingivitis with salivary biomarkers, periodontal pathogens, and interleukin (IL)-1 polymorphism after a transient inflammatory burden. METHODS: Thirty healthy human participants were randomized by IL-1 genotype status to control for potential influences of this particular single nucleotide polymorphism on the inflammatory profile. Oral hygiene practices ceased for 21 days to induce gingivitis (induction), after which home care was reinstated until 35 days (resolution). Clinical parameters included plaque (PI) and gingival (GI) indices and papillary bleeding score (PBS). Levels and proportions of 40 subgingival bacteria were determined using checkerboard DNA-DNA hybridization. Saliva was analyzed using a multiplex protein array for 30 biomarkers associated with host defense, inflammation, tissue destruction, and angiogenesis. RESULTS: Mean PI, GI, and PBS values were significantly increased during induction and decreased during resolution as measured at 35 days (P <0.01), although no differences were observed between IL-1 groups. Participants were stratified as either "high" or "low" responders based on inflammatory response (high: GI >1.5; low: GI ≤1.5). Baseline levels of salivary IL-6 and IL-8 demonstrated the highest ability to discriminate between high and low responders (area under the curve [AUC] of 0.81 and 0.72, respectively). Salivary biomarkers, matrix metalloproteinases (MMPs), and bacterial biofilm were combined to generate receiver operating characteristic curves. High levels of IL-6 and MMP-1 at baseline demonstrated the strongest ability to predict high responders (AUC of 0.89; odds ratio of 17.0; 95% confidence interval, 1.7 to 171.7). CONCLUSION: In this proof-of-concept investigation, we identified specific biomarker and microbial signatures that are associated with gingival inflammation (ClinicalTrials.gov number NCT00980525).

Examination of adverse events following black widow antivenom use in California.

OBJECTIVES: Following widow spider (Latrodectus sp.) envenomation, local pain, erythema, abdominal pain, rigidity, hypertension, and diaphoresis can be seen. While an effective specific antivenom (AV) is available, its use is limited due to concern of possible severe allergic reaction. We performed the current study to determine rate of adverse effects and the efficacy of AV in patients treated for widow spider envenomation. METHODS: Observational case series of the California Poison Control System electronic database from January 1999 to December 2009. All cases of widow spider envenomation treated with AV were included. Age, gender, signs, and symptoms, adjunctive therapy, number of vials of AV given, and adverse reaction to AV were recorded. Descriptive statistical methods were used. RESULTS: Ninety-six patients received AV, mean age 26 years (0.12-74 years), 76% male. Following widow spider envenomation generalized pain was reported in 91%, erythema at site in 57%, hypertension (≥ 140/90 mmHg) in 43%, muscle rigidity/cramping in 43%, abdominal pain in 41%, tachycardia (≥ 100 bpm) in 23% and diaphoresis in 21%. No patient required more than one vial of AV. One patient developed urticaria to AV halfway through infusion which was immediately discontinued. Another patient developed generalized flushing following completion of infusion but had no other effects. Two other patients reported myalgia and paresthesia. There were no deaths in any patients receiving AV. There was no shortness of breath or respiratory distress, no hypotension or chest pain following AV administration. All patients reported pain relief with AV and did not require additional AV doses. CONCLUSIONS: Our results suggest that Black Widow Spider Antivenin® (Merck) administration is relatively safe with mild to moderate adverse effects seen in only a small percentage of patients. There were no deaths, or severe allergic reactions identified. The retrospective use of poison control system data is a limitation of our study. Further prospective studies are needed to validate our findings and elucidate the full safety profile on this antivenom.

Influence of tissue biotype on implant esthetics.

Implant dentistry has come a long way since 1981, with great improvements made to achieve primary implant stability and improve bone-to-implant contact. The focus has since shifted toward creating an esthetic restoration that is indistinguishable from natural teeth and is stable over time. This paper proposes a management triad that enhances soft tissue thickness around implant-supported restorations while discussing distinct differences between thin and thick tissue biotypes. In addition, the effect of tissue biotype on implant esthetics is highlighted.

Soft tissue biotype affects implant success.

The influence of tissue biotype in natural dentition is already well demonstrated in the literature, with numerous articles showing that thicker tissue is a preferred biotype for optimal surgical and prosthetic outcomes. In this same line of thought, current studies are directed to explore whether mucosal thickness would have similar implications around dental implants. The purpose of this review was to investigate the effects of soft tissue biotype in relation to success of implant therapy. The influence of tissue biotype was divided into 3 main categories: its relationship with periimplant mucosa and the underlying bone, immediate implant placement, and restorative outcomes. Soft tissue biotype is an important parameter to consider in achieving esthetic implant restoration, improving immediate implant success, and preventing future mucosal recession.

Biofilm related to dental implants.

Oral biofilm-related diseases such as periodontal and peri-implant diseases are unique infections in that they develop from the resident indigenous microflora. As more implants are nowadays being placed, clinicians may encounter more complications. Therefore, understanding the etiology is warranted to establish adequate diagnosis and provide proper treatment. This article focuses on understanding peri-implant microbiology and its roles in peri-implant diseases.

Screw- versus cement-retained implant restorations: current concepts.

The debate between screw- versus cement-retained implant prostheses has long been discussed but the best type of implant prosthesis remains controversial among practitioners. An understanding of their properties will help the clinician in selecting the ideal prosthesis for each clinical case while promoting final esthetic outcomes. With the evolving technology and knowledge, an update of the current trends is necessary. This article provides an overview of the different characteristics of screw- and cement-retained implant restorations, and how they may influence the esthetics, retrievability, retention, passivity, occlusion, accessibility, cost, and provisional restorations. Problems and complications frequently encountered are discussed and treatment solutions are proposed.

An open-flower mutant of Melilotus alba: Potential for floral-dip transformation of a papilionoid legume with a short life cycle?

This paper describes an open-flower mutant, designated opf, that we discovered in a genetic screen of fast neutron bombardment mutants in an attempt at floral-dip transformation of Melilotus alba (Fabaceae; white sweetclover), an alternative papilionoid legume host for Sinorhizobium meliloti. The opf mutant developed flowers with reflexed sepals and petals, thereby exposing the stamens and carpel, whereas wild-type sweetclover inflorescences developed closed flowers where the young stamens and carpel remain covered during the early stages of flower development. Based on crosses with the wild type, the mutant segregated as a single, Mendelian recessive. Crosses were successful only when the opf mutant served as the female parent, suggesting that the mutant was male sterile. However, no obvious differences from wild-type stamen development were observed in the opf mutant. The anther defect was due to indehiscence. However, as the plants approached the end of their life cycle, the frequency of selfing increased. We also investigated whether the opf mutant could be transformed via Agrobacterium tumefaciens floral-dip infiltration because open flowers like those of Arabidopsis appear to be more readily transformable. However, similar to wild-type M. alba, the opf mutant is refractory to floral-dip transformation by Agrobacterium tumefaciens.

Pro-inflammatory biomarkers during experimental gingivitis in patients with type 1 diabetes mellitus: a proof-of-concept study.

AIM: To compare gingival crevicular fluid (GCF) biomarker levels and microbial distribution in plaque biofilm (SP) samples for subjects with type 1 diabetes (T1DM) versus healthy subjects without diabetes during experimental gingivitis (EG). MATERIALS AND METHODS: A total of nine T1DM patients and nine healthy controls of age and gender similar to the T1DM patients were monitored for 35 days during EG. Hygiene practices were stopped for 3 weeks, and GCF, SP, plaque index (PI) and gingival index were determined. IL-1beta, IL-8, MMP-8 and MMP-9 were quantified by enzyme-linked immunosorbent assay, and SP samples were assessed by DNA-DNA hybridization for a panel of 40 subgingival microbial species. RESULTS: IL-1beta levels in T1DM patients were elevated compared with healthy individuals, and showed differences between groups at 7-21 days while healthy patients showed IL-1beta increases from baseline to 14-21 days (p<0.05). Differences were observed in MMP-9 levels between patients with and without T1DM at 7-14 days (p<0.05). Orange complex species and PI measurements displayed a superior correlation with biomarker levels when compared with other complexes or clinical measurements during EG. CONCLUSIONS: The mean GCF biomarker levels for IL-1beta and MMP-8 were most significantly elevated in T1DM subjects compared with healthy individuals during EG, not resulting from differences in the mean PI or microbial composition.

Sandwich bone augmentation for predictable horizontal bone augmentation.

There is much evidence in the literature to support the success and predictability of guided bone regeneration. Multiple techniques have been introduced using various types of membranes and bone grafting materials. The clinician is now faced with having to select the most predictable guided bone regeneration technique put forth within this extensive literature. Within this context and in addition to its demonstrated success, the "sandwich" bone augmentation technique creates an environment that mimics native bone and promotes regeneration. Its concept is based on a sound biologic rationale while providing flexibility in the selection of biomaterials. This article discusses the principles, the complications, and a step-by-step protocol of sandwich bone augmentation.

Cytokinin induces expansin gene expression in Melilotus alba Desr. wild-type and the non-nodulating, non-mycorrhizal (NodMyc) mutant Masym3.

We previously showed that applying 10(-6) M of the cytokinin 6-benzylaminopurine (BAP) to uninoculated roots of Masym3, a Nod(-)Myc(-)Melilotus alba (Desr.) mutant, resulted in the accumulation of MaENOD40 transcripts to levels similar to BAP-treated wild-type roots. In contrast, inoculation with a Nod(-)S. meliloti mutant expressing the trans-zeatin synthase gene of Agrobacterium tumefaciens (Nod(-)/pTZS(+)) did not induce MaENOD40 transcript accumulation in either wild-type or Masym3 roots. However, Masym3 root hairs became swollen at their tips following inoculation with wild-type or Nod(-)/pTZS(+) rhizobia. Because root hair distention and elongation are often correlated with increased expansin activity, we investigated whether BAP treatment or inoculation with Nod(-)/pTZS(+)S. meliloti upregulated the expression of expansin mRNAs. We first determined that treating wild-type roots with 10(-5) or 10(-6) M BAP resulted in greater MaEXPA1 transcript accumulation than treating roots with comparable concentrations of the auxin NAA. When Masym3 roots were treated with 10(-6) M BAP, MaEXPA mRNAs accumulated to levels comparable to wild-type roots. We then showed that MaEXPA1 mRNAs accumulated in wild-type M. alba roots in response to the Nod(-)/pTZS(+)S. meliloti strain. Masym3 mutant roots inoculated with Nod(-)/pTZS(+) rhizobia were also upregulated for MaEXPA1 expression.

ENOD40 Gene Expression and Cytokinin Responses in the Nonnodulating, Nonmycorrhizal (NodMyc) Mutant, Masym3, of Melilotus alba Desr.

Several nonnodulating, nonmycorrhizal (Nod(-)Myc(-)) mutants of Melilotus alba Desr. (white sweetclover) have been described. However, the details of their responses to Sinorhizobium meliloti have not been fully elucidated. We investigated rhizobial entry and colonization using Confocal Scanning Laser Microscopy on the Masym1-5 mutants and isolated an early nodulin (ENOD40) gene from wild-type M. alba. We focused on Masym3, the least responsive of the mutants to S. meliloti and VA-fungi, to determine its response to cytokinin. Cytokinin appears to be a downstream signal in the nodule developmental pathway based not only on our previous observations whereby Nod(-)Myc(-) alfalfa roots treated with cytokinin accumulated several ENOD gene transcripts, but also on recent reports showing the importance of cytokinin receptors for nodulation. Here we show that applying 10(-6) M 6-benzylaminopurine to uninoculated Masym3 roots elicited ENOD40 transcript accumulation. In addition, Masym3 root hairs inoculated with either wild-type S. meliloti or Nod(-)S. meliloti expressing the trans-zeatin synthase gene of Agrobacterium tumefaciens exhibited tip swelling, suggesting that cytokinin mediated this response. However, Masym3 root hair tips swelled following inoculation with Nod(-)S. meliloti or after mock-inoculation, a response resembling the phenotype of root hairs, after handling, of the Medicago truncatula mutant, dmi2. Mtdmi2 is Nod(-)Myc(-) due to a defect in a gene encoding a Nodule Receptor Kinase (NORK). Like Mtdmi2, the root hair swelling response appears in part to be mediated by touch because Masym3 root hairs not contacted by either bacteria or drops of water or buffer remain elongated and do not exhibit tip swelling.

Signals and Responses: Choreographing the Complex Interaction between Legumes and alpha- and beta-Rhizobia.

The nitrogen-fixing symbiosis between bacteria in the family Rhizobiaceae and members of the legume family (Fabaceae) has been well studied, particularly from the perspective of the early signaling and recognition events. Recent studies of non-nodulating legume mutants have resulted in the identification of a number of genes that are responsive to signal molecules from the bacteria. However, a second group of nodule-forming bacteria, completely unrelated to the Rhizobiaceae, which are alpha-Proteobacteria, has been discovered. These bacteria belong to the beta-Proteobacteria and have been designated beta-rhizobia to distinguish them from the better-known alpha-rhizobia. Here, we review what is known in this economically important symbiosis about the interaction between legumes and alpha-rhizobia, and we incorporate information, where known, about the beta-rhizobia.