Life Expectancy After Treatment of Metastatic Bone Disease: An International Trend Analysis.

INTRODUCTION: The decision to treat metastatic bone disease (MBD) surgically depends in part on patient life expectancy. We are unaware of an international analysis of how life expectancy among these patients has changed over time. Therefore, we asked (1) how has the life expectancy for patients treated for MBD changed over time, and (2) which, if any, of the common primary cancer types are associated with longer survival after treatment of MBD? METHODS: We reviewed data collected from 2000 to 2022 in an international MBD database, as well as data used for survival model validation. We included 3,353 adults who underwent surgery and/or radiation. No patients were excluded. Patients were grouped by treatment date into period 1 (2000 to 2009), period 2 (2010 to 2019), and period 3 (2020 to 2022). Cumulative survival was portrayed using Kaplan-Meier curves; log-rank tests were used to determine significance at P < 0.05. Subgroup analyses by primary cancer diagnosis were performed. RESULTS: Median survival in period 2 was longer than in period 1 ( P < 0.001). Median survival (at which point 50% of patients survived) had not been reached for period 3. Median survival was longer in period 2 for all cancer types ( P < 0.001) except thyroid. Only lung cancer reached median survival in period 3, which was longer compared with periods 1 and 2 ( P < 0.001). Slow-growth, moderate-growth, and rapid-growth tumors all demonstrated longer median survival from period 1 to period 2; only rapid-growth tumors reached median survival for period 3, which was longer compared with periods 1 and 2 ( P < 0.001). DISCUSSION: Median duration of survival after treatment of MBD has increased, which was a consistent finding in nearly all cancer types. Longer survival is likely attributable to improvements in both medical and surgical treatments. As life expectancy for patients with MBD increases, surgical methods should be selected with this in mind. LEVEL OF EVIDENCE: VI.

Developing an antibiogram for empiric antibiotic prescribing for adult non-spinal orthopaedic infections in a developing world setting.

PURPOSE: Empiric antibiotic strategies in the treatment of fracture-related infections, chronic osteomyelitis, prosthetic joint infection, and septic arthritis should be based on local microbiological antibiograms. This study aims to describe the microbiology and review the antibiogram profiles of bacterial isolates from patients undergoing surgical treatment for non-spinal orthopaedic infections, to identify the most appropriate empiric antibiotic strategy. METHODS: A retrospective review was performed of all cases of non-spinal orthopaedic infections treated surgically from 1 January 2018 to 31 December 2018. The National Health Laboratory Service microbiology database was used to identify all intra-operative microbiological specimens obtained from orthopaedic patients, and data were correlated with the orthopaedic surgical database. Cases were divided into fracture-related infections, chronic osteomyelitis, prosthetic joint infection, and septic arthritis. Antibiotic susceptibility data were used to predict the efficacy of different empiric antibiotic regimens. RESULTS: A total of 107 cases were included in the study; 184 organisms were cultured. Overall, the most common organism cultured was Staphylococcus aureus (25%) followed by Acinetobacter baumannii (9%), Enterococcus faecalis (7%) and Enterobacter cloacae (5%). Across all categories the oral antibiotic combination with the highest effectiveness (81%) would have been a combination of co-trimoxazole, ciprofloxacin and amoxicillin. The most effective intravenous antibiotic combination would have been either piperacillin-tazobactam, amikacin and vancomycin or meropenem and vancomycin; 90% of tested isolates were susceptible to either of these combinations. CONCLUSION: Antibiogram profiles can serve to guide to empiric antibiotic choice in the management of different categories of non-spinal orthopaedic infections.

Lessons learned from the Cracked Tooth Registry: A 3-year clinical study in the Nation's Network.

BACKGROUND: This article reviews the most salient lessons learned from a large, multisite, 3-year observational study of posterior teeth with cracks conducted by The National Dental Practice-Based Research Network. TYPES OF STUDIES REVIEWED: Eight articles published over a 6-year period (2017-2022) describing clinical characteristics of posterior teeth with cracks and their treatment and outcomes are reviewed and discussed to answer 3 common questions faced by oral health care clinicians: Which cracked teeth will get worse? When should practitioners intervene? What is the best treatment? RESULTS: Although cracks in teeth are prevalent, few will fracture (3%) or show crack progression in 3 years (12%). Characteristics that guide the clinician to treatment include active caries, biting pain, and to a lesser degree, having a crack detectable with an explorer, connecting with a restoration, or blocking transilluminated light; the main treatment chosen is a complete crown. Of those teeth treated (36%), few (14%) will need retreatment but will still survive, despite having an internal crack as well. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Although cracked teeth often pose a dilemma to clinicians, clincians are generally good at deciding which teeth to treat and when and which to monitor.

Filling the gap: a series of 3D-printed titanium truss cages for the management of large, lower limb bone defects in a developing country setting.

INTRODUCTION: Large segmental long bone defects are notoriously difficult to manage. Treatment is resource-intensive due to the complexity, cost, and specialized skills required. Truss designs are known for their triangular shapes organized in web configurations. This allows for maximal mechanical strength, the least mass, and a lattice that can be filled with bone graft. Using a truss cage combined with contemporary internal fixation provides immediate stability for bone ingrowth and long-term potential union. The implant is designed using virtual 3D modelling of the patient's bone defect based on a CT scan. The truss cage can be used in a staged procedure combined with Masquelet's induced membrane technique. This study aims to review the outcomes of patient-specific, locally designed 3D titanium truss cages packed with cancellous autograft in treating segmental, long bone defects in the lower limb in a developing country setting. METHODS: This retrospective series reviewed cases performed at various institutions between January 2019 and March 2022. Parameters assessed included patient demographics, size and location of the defect, time to clinical and radiological union and complications. RESULTS: Nine cases were included for review, with a mean age of 36 years (range 19-52). Defects ranged from 60 to 205 mm, and eight cases were staged procedures. Eight cases used intramedullary reamings as bone graft. Contemporary intramedullary nails were used for fixation in all cases. No peri- or post-operative complications occurred. All cases progressed to functional union. CONCLUSION: 3D-printed titanium truss cages combined with bone graft appear to be an effective treatment of large bone defects in the lower limb in a developing country setting in the short term. No complications were encountered, but longer follow-up is needed before definitive recommendations can be made. LEVEL OF EVIDENCE: Level IV (retrospective case series).

Onset and resolution of pain among treated and untreated posterior teeth with a visible crack: Three-year findings from the national dental practice-based research network.

OBJECTIVE: Cracked teeth may be associated with pain, especially biting pain, and to a lesser degree cold and spontaneous pain.  Described are how commonly these pains remain constant, develop, or resolve over time, none of which have been well-described, especially among untreated cracked teeth. METHODS: Cracked teeth from the Cracked Tooth Registry (CTR) study were followed for 3 years.  Assessments of cold, biting, and spontaneous pain and treatments performed were completed at enrollment (Y0) and at each annual recall visit. RESULTS: 209 practitioners enrolled 2,858 patients, each with a visible crack on a posterior tooth; 2601 (91%) patients attended at least one recall visit. Overall, 960 (37%) were treated, primarily with crowns. Among both treated and untreated cracked teeth with biting pain or spontaneous pain at Y0, the vast majority (92-99%) had their pain resolved by the time of a recall visit and 85-93% remained pain-free after initial resolution. The observations for cold pain were similar: 68% (untreated) and 78% (treated) became free of cold pain at some point during follow-up, and 84% of these stayed free of cold pain after initial resolution. Few teeth developed biting or spontaneous pain (4-8%) and 44-67% of these had pain resolution during the follow-up period. CONCLUSION: In this study, treatment resolved a preponderance of pain associated with a cracked tooth.  Pain was also resolved for most untreated cracked teeth, especially biting pain, and to a lesser degree spontaneous and cold pain, although not to the same degree as with the treated cracked teeth.

Outcomes of treatment and monitoring of posterior teeth with cracks: three-year results from the National Dental Practice-Based Research Network.

OBJECTIVES: To describe treatment and monitoring outcomes of posterior teeth with cracks at baseline followed in the National Dental Practice-Based Research Network for up to three years. MATERIALS AND METHODS: Two hundred and nine dentists enrolled a convenience sample of 2,858 patients, each with a posterior tooth with at least one visible crack and followed them for three years. Characteristics at the patient, tooth, and crack level were recorded at baseline and at annual recall visits. Data on all teeth referred for extraction were reviewed. Data on all other teeth, treated or monitored, seen at one or more recall visits were reviewed for evidence of failure (subsequent extraction, endodontics, or recommendation for a re-treatment). RESULTS: The survival rate for teeth with cracks at baseline exceeded 98% (only 37 extractions), and the failure rate for teeth that were treated restoratively was only 14%. Also, only about 14% of teeth recommended at baseline for monitoring were later recommended to be treated, and about 6.5% of teeth recommended for monitoring at baseline were later treated without a specific recommendation. Thus, about 80% of teeth recommended at baseline for monitoring continued with a monitoring recommendation throughout the entire three years of the study. Treatment failures were associated with intracoronal restorations (vs. full or partial coverage) and male patients. CONCLUSIONS: In this large 3-year practice-based study conducted across the USA, the survival rate of posterior teeth with a visible crack exceeded 85%. Clinical relevance Dentists can effectively evaluate patient-, tooth-, and crack-level characteristics to determine which teeth with cracks warrant treatment and which only warrant monitoring.

Life or limb: an international qualitative study on decision making in sarcoma surgery during the COVID-19 pandemic.

OBJECTIVES: The COVID-19 pandemic is unprecedented as a global crisis over the last century. How do specialist surgeons make decisions about patient care in these unprecedent times? DESIGN: Between April and May 2020, we conducted an international qualitative study. Sarcoma surgeons from diverse global settings participated in 60 min interviews exploring surgical decision making during COVID-19. Interview data were analysed using an inductive thematic analysis approach. SETTING: Participants represented public and private hospitals in 14 countries, in different phases of the first wave of the pandemic: Australia, Argentina, Canada, India, Italy, Japan, Nigeria, Singapore, Spain, South Africa, Switzerland, Turkey, UK and USA. PARTICIPANTS: From 22 invited sarcoma surgeons, 18 surgeons participated. Participants had an average of 19 years experience as a sarcoma surgeon. RESULTS: 17/18 participants described a decision they had made about patient care since the start of the pandemic that was unique to them, that is, without precedence. Common to 'unique' decisions about patient care was uncertainty about what was going on and what would happen in the future (theme 1: the context of uncertainty), the impact of the pandemic on resources or threat of the pandemic to overwhelm resources (theme 2: limited resources), perceived increased risk to self (theme 3: duty of care) and least-worst decision making, in which none of the options were perceived as ideal and participants settled on the least-worst option at that point in time (theme 4: least-worst decision making). CONCLUSIONS: In the context of rapidly changing standards of justice and beneficence in patient care, traditional decision-making frameworks may no longer apply. Based on the experiences of surgeons in this study, we describe a framework of least-worst decision making. This framework gives rise to actionable strategies that can support decision making in sarcoma and other specialised fields of surgery, both during the current crisis and beyond.

Baseline characteristics as 3-year predictors of tooth fracture and crack progression: Findings from The National Dental Practice-Based Research Network.

BACKGROUND: The authors of this practice-based study estimated the risk of experiencing tooth fractures and crack progression over 3 years and correlated baseline patient-, tooth-, and crack-level characteristics with these outcomes. METHODS: Two-hundred-and-nine National Dental Practice-Based Research Network dentists enrolled a convenience sample of 2,601 participants with a cracked vital posterior tooth that had been examined for at least 1 recall visit over 3 years. Data were collected at the patient, tooth, and crack levels at baseline, annual follow-up visits, and any interim visits. Associations between these characteristics and the subsequent same-tooth fractures and crack progression were quantified. RESULTS: Of the 2,601 teeth with a crack or cracks at baseline, 78 (3.0%; 95% confidence interval, 2.4% to 3.7%) subsequently developed a fracture. Of the 1,889 patients untreated before year 1, 232 (12.3%; 95% confidence interval, 10.9% to 13.8%) had some type of crack progression. Baseline tooth-level characteristics associated with tooth fracture were the tooth was maxillary and had a wear facet through enamel and a crack was detectable with an explorer, on the facial surface, and in a horizontal direction. Crack progression was associated with males and teeth with multiple cracks at baseline; teeth with a baseline facial crack were less likely to show crack progression. There was no commonality between characteristics associated with tooth fracture and those associated with crack progression. CONCLUSIONS: Development of tooth fractures and crack progression over 3 years were rare occurrences. Specific characteristics were associated with the development of tooth fracture and crack progression, although none were common to both. PRACTICAL IMPLICATIONS: This information can aid dentists in assessing factors that place posterior cracked teeth at risk of experiencing adverse outcomes.

Total Talar Replacements Short-Medium Term Case Series, South Africa 2019.

There are few surgical options available to manage complex talar pathology that result in predictably acceptable functional and patient satisfaction scores. Recently, total talar replacement has gained popularity as a viable option. This study presents the clinical outcomes of a case series of total talar replacements in South Africa. A review of data for 8 (N = 8) consecutive patients who underwent total talus replacement between July 2014 and August 2018 was performed. The American Orthopedic Foot and Ankle Society hindfoot score was used to assess clinical function and the Short Form-36 was used to assess patient satisfaction. Patient demographics as well as data on pathology, range of motion, gait analysis, and radiological outcomes were included. The mean age was 46 (range, 23-71) years. Pathologies included trauma, avascular necrosis, and tumors. The mean duration of follow-up was 23 (range, 12-49) months. The mean American Orthopedic Foot and Ankle Society score was 79.25 (range, 69-88) and the mean Short Form-36 satisfaction score was 83.25 (range, 60-93). No revision surgeries have been performed to date. Seven patients demonstrated a mildly abnormal gait and 1 revealed a moderately abnormal gait. The patient with the longest duration of follow-up showed radiological changes of tibial wear, although he remained symptom free. Our experience with the patients described in this report leads us to believe that total talar replacement is a viable surgical option in appropriately selected patients with end-stage talar pathology in the short to medium term, without compromising future salvage options.

Symptom changes and crack progression in untreated cracked teeth: One-year findings from the National Dental Practice-Based Research Network.

OBJECTIVES: The study objective was to: (1) quantify symptom (pain) and crack changes during one year of follow-up, among teeth that had at least one visible crack at baseline but which did not receive treatment for those cracks; (2) identify any patient traits/behaviors and external tooth/crack characteristics correlated with these changes. METHODS: In this observational study, 209 National Dental Practice-Based Research Network dentists enrolled a convenience sample of 2858 subjects, each with a single, vital posterior tooth with at least one observed external crack; 1850 teeth remained untreated after one year of follow-up and were the cohort for analyses. Data were collected at the patient-, tooth-, and crack-level at baseline, one-year follow up (Y1), and interim visits. Associations between changes in symptoms and cracks were identified, as were changes in symptoms associated with baseline treatment recommendations. RESULTS: Changes in pain symptoms were observed in 32% of patients; decreases were twice as common as increases (23% vs. 10%). More changes were observed in cold pain than in biting pain and spontaneous pain combined; 2% had increases in biting pain and 2% in spontaneous pain. Only 6% had an increase in the number of cracks. Changes in pain symptoms were not associated with an increase in the number of cracks, but were associated with baseline treatment recommendations. Specifically, pain symptom changes (especially decreases) were more common when the tooth was recommended for treatment at baseline. CONCLUSIONS: Cracked teeth that have not received treatment one year after baseline do not show meaningful progression as measured by increased symptoms or number of cracks during follow-up. CLINICAL SIGNIFICANCE: Untreated cracked teeth, most of which were recommended for monitoring at baseline and some of which were recommended for treatment but did not receive treatment, remained relatively stable for one year with little progression of cracks or symptoms.

Recommended treatment of cracked teeth: Results from the National Dental Practice-Based Research Network.

STATEMENT OF PROBLEM: Despite the high prevalence of posterior cracked teeth, questions remain regarding the best course of action for managing these teeth. PURPOSE: The purpose of this clinical study was to identify and quantify the characteristics of visible cracks in posterior teeth and their association with treatment recommendations among patients in the National Dental Practice-Based Research Network. MATERIAL AND METHODS: Network dentists enrolled patients with a single, vital posterior tooth with at least 1 observable external crack. Data were collected at the patient, tooth, and crack levels, including the presence and type of pain and treatment recommendations for subject teeth. Frequencies according to treatment recommendation were obtained, and odds ratios (ORs) comparing recommendations for the tooth to be restored versus monitored were calculated. Stepwise regressions were performed using generalized models to adjust for clustering; characteristics with P<.05 were retained. RESULTS: A total of 209 dentists enrolled 2858 patients with a posterior tooth with at least 1 crack. Mean ±standard deviation patient age was 54 ±12 years; 1813 (63%) were female, 2394 (85%) were non-Hispanic white, 2213 (77%) had some dental insurance, and 2432 (86%) had some college education. Overall, 1297 (46%) teeth caused 1 or more of the following types of pain: 1055 sensitivity to cold, 459 biting, and 367 spontaneous. A total of 1040 teeth were recommended for 1 or more treatments: restoration (n=1018; 98%), endodontics (n=29; 3%), endodontic treatment and restoration (n=20; 2%), extraction (n=2; 0.2%), and noninvasive treatment, for example, occlusal device, desensitizing (n=11; 1%). The presence of caries (OR=67.3), biting pain (OR=7.3), and evidence of a crack on radiographs (OR=5.0) were associated with over 5-fold odds of recommending restoration. Spontaneous pain was associated with nearly 3-fold odds; pain to cold, having dental insurance, a crack that was detectable with an explorer or blocked transilluminated light, or connected with a restoration were each weakly associated with increased odds of recommending a restoration (OR<2.0). CONCLUSIONS: Approximately one-third of cracked teeth were recommended for restoration. The presence of caries, biting pain, and evidence of a crack on a radiograph were strong predictors of recommending a restoration, although the evidence of a crack on a radiograph only accounted for a 3% absolute difference (4% recommended treatment versus 1% recommended monitoring).

Observable characteristics coincident with internal cracks in teeth: Findings from The National Dental Practice-Based Research Network.

BACKGROUND: This study determined if there are observable patient-, tooth- and crack-level characteristics markedly associated with whether a tooth with an external crack also has an internal crack. METHODS: Two hundred nine dentists in The National Dental Practice-Based Research Network enrolled 2,858 adults with a vital permanent posterior tooth having at least 1 observed external crack. Presence and characteristics of internal cracks were recorded for 435 cracked teeth that were treated. Generalized estimating equations were used to identify significant (P < .05) independent odds ratios associated with the tooth having internal cracks. RESULTS: Overall, 389 teeth (89%) had at least 1 internal crack, with 46% of these teeth having 2 or more internal cracks. Sixty-nine percent of treated cracked teeth were associated with 1 or more types of pain assessed before treatment; 53% were associated with cold testing, 37% with bite testing, and 26% with spontaneous pain. In the final model, biting pain, having an external crack that connected with a restoration, or an external crack that extended onto the root was each associated with more than a 2-fold increased odds of having an internal crack. CONCLUSIONS: Essentially 9 of 10 teeth that had at least 1 external crack also had at least 1 internal crack. PRACTICAL IMPLICATIONS: The external cracks that a dental practitioner should be most concerned about, because they are most likely to be associated with internal cracks in the tooth, are those in which the patient experiences biting pain, is connected with a restoration of some type, or extends onto the root.

Associations of types of pain with crack-level, tooth-level and patient-level characteristics in posterior teeth with visible cracks: Findings from the National Dental Practice-Based Research Network.

OBJECTIVES: The objective of this study was to determine which patient traits, behaviors, external tooth and/or crack characteristics correlate with the types of symptoms that teeth with visible cracks exhibit, namely pain on biting, pain due to cold stimuli, or spontaneous pain. METHODS: Dentists in the National Dental Practice-Based Research Network enrolled a convenience sample of subjects each of whom had a single, vital posterior tooth with at least one observable external crack (cracked teeth); 2858 cracked teeth from 209 practitioners were enrolled. Data were collected at the patient-, tooth-, and crack-level. Generalized estimating equations were used to obtain significant (p < .05) independent odds ratios (OR) associated with teeth that were painful for 10 outcomes based on types of pain and combinations thereof. RESULTS: Overall, 45% of cracked teeth had one or more symptoms. Pain to cold was the most common symptom, which occurred in 37% of cracked teeth. Pain on biting (16%) and spontaneous pain (11%) were less common. Sixty-five percent of symptomatic cracked teeth had only one type of symptom, of these 78% were painful only to cold. No patient-, tooth- or crack-level characteristic was significantly associated with pain to cold alone. Positive associations for various combinations of pain symptoms were present with cracks that: (1) were on molars; (2) were in occlusion; (3) had a wear facet through enamel; (4) had caries; (5) were evident on a radiograph; (6) ran in more than one direction; (7) blocked transilluminated light; (8) connected with another crack; (9) extended onto the root; (10) extended in more than one direction; or (11) were on the distal surface. Persons who were <65 yo or who clench, grind, or press their teeth together also were more likely to have pain symptoms. Pain was less likely in teeth with stained cracks or exposed roots, or in non-Hispanic whites. CONCLUSIONS: Although pain to cold was the most commonly noted pain associated with symptomatic cracked teeth, no patient-, tooth- or crack-level characteristic was significantly associated with pain to cold alone. Characteristics were only associated with pain on biting and/or spontaneous pain with or without pain to cold. CLINICAL SIGNIFICANCE: Although often considered the most reliable diagnosis for a cracked tooth, pain on biting is not the most common symptom of a tooth with a visible crack, but rather pain to cold.

An Item Bank for Abuse of Prescription Pain Medication from the Patient-Reported Outcomes Measurement Information System (PROMIS®).

OBJECTIVE: There is a need to monitor patients receiving prescription opioids to detect possible signs of abuse. To address this need, we developed and calibrated an item bank for severity of abuse of prescription pain medication as part of the Patient-Reported Outcomes Measurement Information System (PROMIS ® ). METHODS: Comprehensive literature searches yielded an initial bank of 5,310 items relevant to substance use and abuse, including abuse of prescription pain medication, from over 80 unique instruments. After qualitative item analysis (i.e., focus groups, cognitive interviewing, expert review, and item revision), 25 items for abuse of prescribed pain medication were included in field testing. Items were written in a first-person, past-tense format, with a three-month time frame and five response options reflecting frequency or severity. The calibration sample included 448 respondents, 367 from the general population (ascertained through an internet panel) and 81 from community treatment programs participating in the National Drug Abuse Treatment Clinical Trials Network. RESULTS: A final bank of 22 items was calibrated using the two-parameter graded response model from item response theory. A seven-item static short form was also developed. The test information curve showed that the PROMIS ® item bank for abuse of prescription pain medication provided substantial information in a broad range of severity. CONCLUSION: The initial psychometric characteristics of the item bank support its use as a computerized adaptive test or short form, with either version providing a brief, precise, and efficient measure relevant to both clinical and community samples.

Correlation between symptoms and external characteristics of cracked teeth: Findings from The National Dental Practice-Based Research Network.

BACKGROUND: Cracked teeth are ubiquitous in the adult dentition. The objective of this study was to determine which patient traits and behaviors and external tooth and crack characteristics correlate with cracked teeth being symptomatic. METHODS: Dentists in The National Dental Practice-Based Research Network enrolled a convenience sample of patients each with a single, vital posterior tooth with at least 1 observable external crack in this observational study; they enrolled 2,975 cracked teeth from 209 practitioners. The authors collected data at the patient level, tooth level, and crack level. They used generalized estimating equations to obtain significant (P < .05) independent odds ratios (OR) associated with teeth that were symptomatic for a crack. RESULTS: Characteristics positively associated with cracked tooth symptoms, after adjusting for demographics, included patients who clenched, ground, or pressed their teeth together (OR, 1.30; 95% confidence interval [CI], 1.12-1.50), molars (OR, 1.58; 95% CI, 1.30-1.92), teeth with a wear facet through enamel (OR, 1.22; 95% CI, 1.01-1.40), carious lesions (OR, 1.31; 95% CI, 1.07-1.60), cracks that were on the distal surface of the tooth (OR, 1.31; 95% CI, 1.13-1.52), and cracks that blocked transilluminated light (OR, 1.31, 95% CI, 1.09-1.57). Teeth with stained cracks were negatively associated with having cracked tooth symptoms (OR, 0.68; 95% CI, 0.55-0.84). CONCLUSIONS: The greatest likelihood of a cracked tooth being symptomatic was found when patients reported clenching or grinding their teeth and had a molar with a distal crack that blocked transilluminated light. PRACTICAL IMPLICATIONS: This information can help inform dentists in the decision-making process regarding the prognosis for a cracked tooth.

Regulation of Dense-Core Granule Replenishment by Autocrine BMP Signalling in Drosophila Secondary Cells.

Regulated secretion by glands and neurons involves release of signalling molecules and enzymes selectively concentrated in dense-core granules (DCGs). Although we understand how many secretagogues stimulate DCG release, how DCG biogenesis is then accelerated to replenish the DCG pool remains poorly characterised. Here we demonstrate that each prostate-like secondary cell (SC) in the paired adult Drosophila melanogaster male accessory glands contains approximately ten large DCGs, which are loaded with the Bone Morphogenetic Protein (BMP) ligand Decapentaplegic (Dpp). These DCGs can be marked in living tissue by a glycophosphatidylinositol (GPI) lipid-anchored form of GFP. In virgin males, BMP signalling is sporadically activated by constitutive DCG secretion. Upon mating, approximately four DCGs are typically released immediately, increasing BMP signalling, primarily via an autocrine mechanism. Using inducible knockdown specifically in adult SCs, we show that secretion requires the Soluble NSF Attachment Protein, SNAP24. Furthermore, mating-dependent BMP signalling not only promotes cell growth, but is also necessary to accelerate biogenesis of new DCGs, restoring DCG number within 24 h. Our analysis therefore reveals an autocrine BMP-mediated feedback mechanism for matching DCG release to replenishment as secretion rates fluctuate, and might explain why in other disease-relevant systems, like pancreatic ß-cells, BMP signalling is also implicated in the control of secretion.

Polymerization stress--is it clinically meaningful?

OBJECTIVES: The objective of this article is to discuss the evidence for polymerization shrinkage and shrinkage stress of dental composite restoratives in terms of its potential relevance to the clinical situation METHODS: Articles relating to the issue of polymerization contraction stress generation in dental composite materials, and the factors that influence it, were reviewed and included. Particular attention was paid to evidence derived from clinical studies. Articles were identified through PubMed and through the bibliographies of other articles. RESULTS: There is extensive evidence for the presence of polymerization contraction stress in dental composites, as well as evidence for its deleterious effects, which include marginal leakage, gap formation, cuspal deflection, tooth cracking, reduced bond strength and lowered mechanical properties of the restorative. There is little, if any, direct evidence for the clinical effect of these contraction stresses. No study has directly established a link between these stresses and enhanced postoperative sensitivity or recurrent caries, for example. However, the concern over these stresses and the manner in which they influence the placement of current composite materials demonstrates that they are considered to be very important. CONCLUSION: Though no direct evidence exists to prove that the generation of contraction stress in dental composite restorations causes reduced clinical longevity, the indirect evidence from numerous in vitro studies and the concern over controlling their effects proves that they are clinically relevant.

The Key to Individualized Addiction Treatment is Comprehensive Assessment and Monitoring of Symptoms and Behavioral Change.

Modern health services now strive for individualized treatment. This approach has been enabled by the increase in knowledge derived from neuroscience and genomics. Substance use disorders are no exception to individualized treatment even though there are no gene-specific medications yet available. What is available is the ability to quickly and precisely assess and monitor biopsychosocial variables known to vary during addiction recovery and which place addicts at increased risk of relapse. Monitoring a broad spectrum of biopsychosocial health enables providers to address diverse genome-specific changes that might trigger withdrawal from treatment or recovery relapse in time to prevent that from occurring. This paper describes modern measurement tools contained in the NIH Patient-Reported Outcomes Measurement Information System (PROMIS) and the NIH Toolbox and suggests how they might be applied to support recovery from alcohol and other substance use disorders in both pharmacological and abstinence-oriented modalities of care.