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Introduction: Temporomandibular disorders (TMDs) are common musculoskeletal pain conditions that can significantly impact daily activities such as eating, talking, breathing, intimacy, and expressing emotion. TMDs are often complex and multifactorial, and many patients experience overlapping pain conditions, sleep difficulties, and mental health challenges. The National Academies of Sciences, Engineering and Medicine (NASEM) has called for improved TMD education and training for health professionals, as current training opportunities are limited., Methods: To prepare health professionals to care for patients who have a TMD, we designed a 5-hour, interactive, module-based curriculum aligned with the 2020 NASEM recommendations. The four-part module set addresses TMD physiology and pathophysiology, assessment, diagnosis, and management. Instructional methods are founded on the Cognitive Theory of Multimedia Learning and include engaging videos, clinical evaluation and education tools, and interactive digital simulation scenarios., Results: Thirty learners from diverse health professional backgrounds (medicine, dentistry, physician assistant, nursing, physical therapy) participated. Multiple-choice question assessments and pre/post retrospective survey scores demonstrated enhanced knowledge ( M = 2.9 vs. M = 4.2, p < .001) and perceived competence ( M = 1.9 vs. M = 3.4, p < .001), respectively. Encouragingly, all participants indicated applicability to their clinical practice., Discussion: Our modules offer educators and clinicians a valuable resource to improve TMD knowledge and facilitate best practices. Supplementary resources included in the curriculum are conducive to clinical implementation, fostering improved clinician assessment and patient education., (US Government work in the public domain.)

Purpose: To clarify the causal relationship between factors contributing to the postoperative survival of patients with esophageal cancer., Methods: A cohort of 195 patients who underwent surgery for esophageal cancer between 2008 and 2021 was used in the study. All patients had preoperative chest computed tomography (CT) and positron emission tomography-CT (PET-CT) scans prior to receiving any treatment. From these images, high throughput and quantitative radiomic features, tumor features, and various body composition features were automatically extracted. Causal relationships among these image features, patient demographics, and other clinicopathological variables were analyzed and visualized using a novel score-based directed graph called "Grouped Greedy Equivalence Search" (GGES) while taking prior knowledge into consideration. After supplementing and screening the causal variables, the intervention do-calculus adjustment (IDA) scores were calculated to determine the degree of impact of each variable on survival. Based on this IDA score, a GGES prediction formula was generated. Ten-fold cross-validation was used to assess the performance of the models. The prediction results were evaluated using the R-Squared Score (R 2 score)., Results: The final causal graphical model was formed by two PET-based image variables, ten body composition variables, four pathological variables, four demographic variables, two tumor variables, and one radiological variable (Percentile 10). Intramuscular fat mass was found to have the most impact on overall survival month. Percentile 10 and overall TNM (T: tumor, N: nodes, M: metastasis) stage were identified as direct causes of overall survival (month). The GGES casual model outperformed GES in regression prediction (R 2  = 0.251) (p < 0.05) and was able to avoid unreasonable causality that may contradict common sense., Conclusion: The GGES causal model can provide a reliable and straightforward representation of the intricate causal relationships among the variables that impact the postoperative survival of patients with esophageal cancer., (© 2023 American Association of Physicists in Medicine.)

Competing Interests: Competing interests: We declared the following interests based on NICE’s policy on conflicts of interests (https://www.nice.org.uk/Media/Default/About/Who-we-are/Policies-and-procedures/declaration-of-interests-policy.pdf):

Orofacial pain is a category of complex disorders, including musculoskeletal, neuropathic and neurovascular disorders, that greatly affect the quality of life of the patient. These disorders are within the fields of dentistry and medicine and management can be challenging, requiring a referral to an orofacial pain specialist, essential for adequate evaluation, diagnosis, and care. Management is specific to the diagnosis and a treatment plan is developed with diverse pharmacological and non-pharmacological modalities. The pharmacological management of orofacial pain encompasses a vast array of medication classes and approaches. This includes anti-inflammatory drugs, muscle relaxants, anticonvulsants, antidepressants, and anesthetics. In addition, as adjunct therapy, different injections can be integrated into the management plan depending on the diagnosis and needs. These include trigger point injections, temporomandibular joint (TMJ) injections, and neurotoxin injections with botulinum toxin and nerve blocks. Multidisciplinary management is key for optimal care. New and safer therapeutic targets exclusively for the management of orofacial pain disorders are needed to offer better care for this patient population., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The medical imaging community has embraced Machine Learning (ML) as evidenced by the rapid increase in the number of ML models being developed, but validating and deploying these models in the clinic remains a challenge. The engineering involved in integrating and assessing the efficacy of ML models within the clinical workflow is complex. This paper presents a general-purpose, end-to-end, clinically integrated ML model deployment and validation system implemented at UCSF. Engineering and usability challenges and results from 3 use cases are presented. A generalized validation system based on free, open-source software (OSS) was implemented, connecting clinical imaging modalities, the Picture Archiving and Communication System (PACS), and an ML inference server. ML pipelines were implemented in NVIDIA's Clara Deploy framework with results and clinician feedback stored in a customized XNAT instance, separate from the clinical record but linked from within PACS. Prospective clinical validation studies of 3 ML models were conducted, with data routed from multiple clinical imaging modalities and PACS. Completed validation studies provided expert clinical feedback on model performance and usability, plus system reliability and performance metrics. Clinical validation of ML models entails assessing model performance, impact on clinical infrastructure, robustness, and usability. Study results must be easily accessible to participating clinicians but remain outside the clinical record. Building a system that generalizes and scales across multiple ML models takes the concerted effort of software engineers, clinicians, data scientists, and system administrators, and benefits from the use of modular OSS. The present work provides a template for institutions looking to translate and clinically validate ML models in the clinic, together with required resources and expected challenges., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: NVIDIA provided 4 T4 cards as a grant to UCSF., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Tanzania's dairy sector is poorly developed, creating reliance on imports for processed, value-added dairy products and threatening food security, particularly when supply chains are disrupted due to market volatility or armed conflicts. The Tanzanian Dairy Development Roadmap is a domestic development initiative that aims to achieve dairy self-sufficiency by 2030. Here, we model different outcomes of the roadmap, finding that adoption of high-yield cattle breeds is essential for reducing dairy import dependency. Avoided land use change resulting from fewer, higher yielding dairy cattle would lead to lower greenhouse gas emissions. Dairy producers' average incomes could increase despite capital expenditure and land allocation required for the adoption of high-yield breeds. Our findings demonstrate the importance of bottom-up development policies for sustainable food system transformations, which also support food sovereignty, increase incomes for smallholder farmers and contribute towards Tanzania's commitments to reduce greenhouse gas emissions., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Botulinum toxin type A (BoNTA) injection into the masticatory muscles has been widely used to treat a number of painful and nonpainful conditions; however, no systematic reviews have been performed on the long-term effect to the mandibular bone., Objective: Our systematic review aimed to evaluate the impact of botulinum toxin injection into the masticatory muscles on mandibular bone based., Methods: PubMed, Embase, Ovid, CINAHL and Web of Science were searched for human studies assessing mandibular bone after injection of BoNTA using computed tomography (CT) and cone beam CT (CBCT)., Results: Seven studies were eligible for review; five reported significant bony changes to one or more areas of the mandible. Most frequently affected were the condylar head, coronoid process and ramus. The most frequent changes were decreased bone volume, cortical thickness and cortical and trabecular density., Conclusions: This is the first systematic review to examine an association between BoNTA injection into the masticatory muscles and mandibular bone quality. Data were analysed from a limited number of studies with a small sample size, and the quality of the included studies was very low. While the majority of available evidence suggests BoNTA injection results in bony change, further study is required to confirm a dose-dependence effect and the impact of gender and age. High-quality trials should utilise a combination of software analysis and radiologist review, with longer-term follow-up to monitor for persistence of bony effect and clinical significance., (© Published 2022. This article is a U.S. Government work and is in the public domain in the USA.)

Background and Overview: First bite syndrome (FBS) is an orofacial pain condition characterized by moderate to severe unilateral facial pain associated with the first bite or taste of food. It is important that dentists and physicians be aware of patient history and examination findings commonly associated with FBS, as well as treatment options available for managing this condition., Case Description: Described here is a case of FBS arising in a 43-year-old man after partial parotidectomy for the treatment of a mucoepidermoid carcinoma. His orofacial pain was being successfully treated by injection of onabotulinumtoxin A into the residual parotid tissue., Conclusions and Practical Implications: Onabotulinumtoxin A is a promising therapeutic option for FBS owing to its profound relief of pain and minimal reported adverse effects. Therefore, oral health care providers treating FBS should be aware of this option., (Copyright © 2022 American Dental Association. Published by Elsevier Inc. All rights reserved.)

We use an attributional life cycle assessment (LCA) and simulation modelling to assess the effect of improved feeding practices and increased yields of feed crops on milk productivity and GHG emissions from the dairy sector of Tanzania's southern highlands region. We calculated direct non-CO 2 emissions from dairy production and the CO 2 emissions resulting from the demand for croplands and grasslands using a land footprint indicator. Baseline GHG emissions intensities ranged between 19.8 and 27.8 and 5.8-5.9 kg CO 2 eq kg -1 fat and protein corrected milk for the Traditional (local cattle) and Modern (improved cattle) sectors. Land use change contributed 45.8-65.8% of the total carbon footprint of dairy. Better feeding increased milk yields by up to 60.1% and reduced emissions intensities by up to 52.4 and 38.0% for the Traditional and Modern sectors, respectively. Avoided land use change was the predominant cause of reductions in GHG emissions under all the scenarios. Reducing yield gaps of concentrate feed crops lowered emissions further by 11.4-34.9% despite increasing N 2 O and CO 2 emissions from soils management and input use. This study demonstrates that feed intensification has potential to increase LUC emissions from dairy production, but that fertilizer-dependent yield gains can offset this increase in emissions through avoided emissions from land use change.

Background: Induced abortion is a common procedure. However, there is marked variation in accessibility of services across England. Accessing abortion services may be difficult, particularly for women who live in remote areas, are in the second trimester of pregnancy, have complex pre-existing conditions or have difficult social circumstances., Objective and Rationale: This article presents a two-part review undertaken for a new National Institute of Health and Care Excellence guideline on abortion care, and aiming to determine: the factors that help or hinder accessibility and sustainability of abortion services in England (qualitative review), and strategies that improve these factors, and/or other factors identified by stakeholders (quantitative review). Economic modelling was undertaken to estimate cost savings associated with reducing waiting times., Search Methods: Ovid Embase Classic and Embase, Ovid MEDLINE(R) Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R), PsycINFO, Cochrane Library via Wiley Online, Cinahl Plus and Web of Science Core Collection were searched for articles published up to November 2018. Studies were included if they were published in English after 2001, conducted in Organization for Economic Co-operation and Development (OECD) countries and were: qualitative studies reporting views of patients and/or staff on factors that help or hinder the accessibility and sustainability of a safe abortion service, or randomized or non-randomized studies that compared strategies to improve factors identified by the qualitative review and/or stakeholders. Studies were excluded if they were conducted in OECD countries where abortion is prohibited altogether or only performed to save the woman's life. One author assessed risk of bias of included studies using the following checklists: Critical Appraisal Skills Programme checklist for qualitative studies, Cochrane Collaboration quality checklist for randomized controlled trials, Newcastle-Ottawa scale for cohort studies, and Effective Practice and Organization of Care risk of bias tool for before-and-after studies.Qualitative evidence was combined using thematic analysis and overall quality of the evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) Confidence in the Evidence from Reviews of Qualitative Research (CERQual). Quantitative evidence was analysed in Review Manager 5.3 and overall quality of evidence was assessed using GRADE., Outcomes: Eight themes (service level barriers; financial barriers; logistical barriers; personal barriers; legal and policy barriers; privacy and confidentiality concerns; training and education; community prescribing and telemedicine introduce greater flexibility) and 18 subthemes were identified from 23 papers (n = 1016) included in the qualitative review. The quality of evidence ranged from very low to high, with evidence for one theme and seven subthemes rated as high quality. Nine studies (n = 7061) were included in the quantitative review which showed that satisfaction was better (low to high quality evidence) and women were seen sooner (very low quality evidence) when care was led by nurses or midwives compared with physician-led services, women were seen sooner when they could self-refer (very low quality evidence), and clinicians were more likely to provide abortions if training used an opt-out model (very low quality evidence). Economic modelling showed that even small reductions in waiting times could result in large cost savings for services., Wider Implications: Self-referral, funding for travel and accommodation, reducing waiting times, remote assessment, community services, maximizing the role of nurses and midwives and including practical experience of performing abortion in core curriculums, unless the trainee opts out, should improve access to and sustainability of abortion services., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Temporal tendonitis (TT) is an orofacial pain disorder that can refer pain to the maxillary and mandibular molars, temporomandibular joint, masticatory muscles, eye, or ear. Patients often present to a dentist or physician with complaints reflecting these referral patterns, yet many healthcare providers are unfamiliar with TT because of the scarcity of literature published on this clinical entity. This may lead to diagnostic confusion, iatrogenic harm, and prolonged patient suffering., Methods and Results: This case report describes TT that presented as maxillary and mandibular posterior tooth pain, preauricular pain, and decreased mandibular range of motion. Patient history and examination were suggestive of TT. Local anesthetic injection adjacent to the tendon eliminated all pain complaints and improved range of motion. The patient was given education on the condition and self-care instructions. At 1-week follow-up, the patient reported resolution of her pain complaint., Conclusions: As healthcare providers familiarize themselves with appropriate diagnostic and treatment options for TT, delayed or unnecessary care can be avoided, and proper management strategies can be implemented., (Published by Elsevier Inc.)

Trigeminal neuralgia is a pain condition that is frequently misdiagnosed and challenging to manage. We present the case of a patient with trigeminal neuralgia with multiple misdiagnoses and poorly managed pain. Despite the presence of trigger zones both inside and outside her mouth, complete symptom resolution was ultimately achieved through onabotulinumtoxinA injections, delivered solely intraorally.

Entrustable professional activities (EPAs) are a curriculum development and learner assessment tool that ensure a trainee is able to safely translate the skills they have learned during residency into unsupervised clinical practice. Although EPAs are used extensively across various health professions worldwide, dentistry is just beginning to call for their development at both the predoctoral and postgraduate levels. Given the complex, multifactorial nature of orofacial pain disorders and the need for an interdisciplinary approach to management, the specialty of orofacial pain is well suited to embracing EPAs to ensure program graduates are prepared for practice. Therefore, 10 EPAs have been developed in a combined effort from program directors from every CODA-accredited postgraduate orofacial pain residency program.

Background: Long-acting reversible contraceptives (LARCs) are safe, effective and convenient post-abortal methods. However, there is concern that some LARCs may reduce the effectiveness of abortifacient drugs or result in other adverse outcomes., Objective and Rationale: We undertook two systematic reviews to examine the early administration of LARCs in women undergoing medical abortion with mifepristone and misoprostol. (i) For women who are having a medical abortion and who plan to use a progestogen-only contraceptive implant or injectable, does administration of the contraception at the same time as mifepristone influence the efficacy of the abortion? (Implant/injectable review). (ii) For women who have had a medical abortion, how soon after expulsion of the products of conception is it safe to insert an intrauterine contraceptive device/system? (LNG-IUS/Cu-IUD review)., Search Methods: On 19 November 2018, we searched Embase Classic, Embase; Ovid MEDLINE(R) including Daily and Epub Ahead-of-Print, In-Process and Other Non-Indexed Citations; the Cochrane Library; Cinahl Plus; and Web of Science Core Collection. Eligible studies were randomised controlled trials (RCTs), in English from 1985 (Implant/injectable review) or 2007 (LNG-IUS/Cu-IUD review) onwards, conducted in women undergoing medical abortion with mifepristone and misoprostol and studying either (i) simultaneous administration of mifepristone and a progestogen-only contraceptive implant or injectable compared to administration >24 h after mifepristone, or (ii) immediate insertion of intrauterine contraception after expulsion of the products of conception compared to early insertion (≤7 days) or to delayed insertion (>7 days) or early compared to delayed insertion. One author assessed the risk of bias in the studies using the Cochrane Collaboration checklist for RCTs. All the outcomes were analysed as risk ratios and meta-analysed in Review Manager 5.3 using the Mantel-Haenszel statistical method and a fixed-effect model. The overall quality of the evidence was assessed using GRADE., Outcomes: Two RCTs (n = 1027) showed lower 'subsequent unintended pregnancy' rates and higher 'patient satisfaction' rates, and no other differences, after simultaneous administration of mifepristone and the implant compared to delayed administration. One RCT (n = 461) showed higher 'patient satisfaction' rates after simultaneous administration than after delayed administration of mifepristone and the injectable, but no other differences between these interventions. Three RCTs (n = 536) found no differences other than higher copper IUC uptake after early compared to delayed insertion at ≤9 weeks of gestation and higher rates of IUC expulsion, continuation and uptake after immediate compared to delayed insertion at 9+1-12+0 weeks of gestation and higher IUC continuation rates after immediate compared to delayed insertion at 12+1-20+0 weeks of gestation. The quality of this evidence ranged from very low to high and was mainly compromised by low event rates, high attrition and no blinding., Wider Implications: The contraceptive implant or injectable should be offered on the day of taking mifepristone. Intrauterine methods of contraception should be offered as soon as possible after expulsion of the pregnancy., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In order to develop the 2019 National Institute for Health and Care Excellence (NICE) national guideline on abortion care for the National Health Service1 we undertook a systematic review comparing anti-D prophylaxis to no prophylaxis in rhesus D (RhD)-negative women undergoing medical or surgical abortion of pregnancy at ≤13 +6 weeks' gestation METHODS: We searched Embase, Medline and the Cochrane Library on 19 October 2018. We also consulted experts and checked reference lists for any missed trials. Eligible studies were randomised controlled trials and non-randomised comparative studies, published in English from 1985 onwards, comparing anti-D prophylaxis to no anti-D prophylaxis in RhD-negative women undergoing medical or surgical abortion at ≤13 +6 weeks' gestation, and reporting subsequent anti-D isoimmunisation/sensitisation or subsequent affected pregnancy. These outcomes were to be analysed as risk ratios in Review Manager 5.3 using the Mantel-Haenszel statistical method and a fixed or random effect model. The overall quality of the evidence was planned to be assessed using GRADE., Results: The search identified 426 potentially relevant studies of which none met the inclusion criteria. Recommendations for practice were therefore based on the clinical expertise of the guideline committee., Conclusions: (1) Offer anti-D prophylaxis to women who are Rhesus D negative who are having an abortion after 10 +0 weeks' gestation. (2) Do not offer anti-D prophylaxis to women who are having a medical abortion up to and including 10 +0 weeks' gestation. (3) Consider anti-D prophylaxis for women who are rhesus D negative and are having a surgical abortion up to and including 10 +0 weeks' gestation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

To enable standardisation of care of pancreatic cancer patients and facilitate improvement in outcome, the United Kingdom's National Institute for Health and Care Excellence (NICE) developed a clinical guideline for the diagnosis and management of pancreatic cancer in adults. Systematic literature searches, systematic review and meta-analyses were undertaken. Recommendations were drafted on the basis of the group's interpretation of the best available evidence of clinical and cost effectiveness. There was patient involvement and public consultation. Recommendations were made on: diagnosis; staging; monitoring of inherited high risk; psychological support; pain; nutrition management; and the specific management of people with resectable-, borderline-resectable- and unresectable-pancreatic cancer. The guideline committee also made recommendations for future research into neoadjuvant therapy, cachexia interventions, minimally invasive pancreatectomy, pain management and psychological support needs. These NICE guidelines aim to promote best current practice and support and stimulate research and innovation in pancreatic cancer., (Copyright © 2018. Published by Elsevier B.V.)

Haematological malignancies are a diverse group of cancers that affect the blood, bone marrow and lymphatic systems. Laboratory diagnosis of haematological malignancies is dependent on combining several technologies, including morphology, immunophenotyping, cytogenetics and molecular genetics correlated clinical details and classification according to the current WHO guidelines. The concept of the Specialised Integrated Haematological Malignancy Diagnostic Services (SIHMDS) has evolved since the UK National Institute for Health and Care Excellence (NICE) Improving Outcomes Guidance (IOG) in 2003 and subsequently various models of delivery have been established. As part of the 2016 update to the NICE IOG, these models were systematically evaluated and recommendations produced to form the basis for quality standards for future development of SIHMDS. We provide a summary of the systematic review and recommendations. Although the recommendations pertain to the UK National Health Service (NHS), they have relevance to the modern delivery of diagnostic services internationally., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Purpose: Posterior fossa ependymoma comprises two distinct molecular variants termed EPN&#95;PFA and EPN&#95;PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known., Methods: Four independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses., Results: Molecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN&#95;PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN&#95;PFA, a substantial proportion of patients with EPN&#95;PFB can be cured with surgery alone, and patients with relapsed EPN&#95;PFB can often be treated successfully with delayed external-beam irradiation., Conclusion: The most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN&#95;PFA and EPN&#95;PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN&#95;PFA, even with adjuvant radiation therapy. Patients with EPN&#95;PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence., (© 2016 by American Society of Clinical Oncology.)

Objective: . Patients with complaints of orofacial pain (OFP) often have other body pain, yet many do not report these to their providers. Uncontrolled pain at any location may impact the successful management of an OFP complaint. The objective of this study was to determine the number of pain regions throughout the body, and the underreporting of pain, in patients who presented to a tertiary military OFP clinic., Design: A retrospective chart review was conducted on 423 consecutive new patients. Patients were given three assessment opportunities to report their pain on a whole-body pain map: 1) prior to evaluation (Pt1), 2) following an explanatory statement by their provider on the relationship between pain and prognosis (Pt2), and 3) during directed pain inquiry of specific body regions (Pro). The pain map was divided into nine anatomical regions that were assessed for the presence of pain after Pt1, Pt2, and Pro., Results: Initially, 60.5% of patients did not report all pain locations (Pt1). Following the explanatory statement (Pt2), 30.5% still did not report all pain. Following the completion of all assessment methods, the most commonly reported number of pain regions was five (17.0%), and 91.5% of patients reported multiple pain regions., Conclusions: Most patients had multiple pain complaints outside the chief complaint, yet the majority did not report these until multiple forms of assessment were utilized. These data encourage the use of a pain map, a verbal pain explanation, and directed pain questioning to more accurately capture pain location and facilitate multidisciplinary care., (Published by Oxford University Press on behalf of the American Academy of Pain Medicine 2016. This work is written by US Government employees and is in the public domain in the US.)

Maximal sustained energy intake (SusEI) appears limited, but the factors imposing the limit are disputed. We studied reproductive performance in two lines of mice selected for high and low food intake (MH and ML, respectively), and known to have large differences in thermal conductance (29% higher in the MH line at 21°C). When these mice raised their natural litters, their metabolisable energy intake significantly increased over the first 13 days of lactation and then reached a plateau. At peak lactation, MH mice assimilated on average 45.3% more energy than ML mice (222.9±7.1 and 153.4±12.5 kJ day(-1), N=49 and 24, respectively). Moreover, MH mice exported on average 62.3 kJ day(-1) more energy as milk than ML mice (118.9±5.3 and 56.6±5.4 kJ day(-1), N=subset of 32 and 21, respectively). The elevated milk production of MH mice enabled them to wean litters (65.2±2.1 g) that were on average 50.2% heavier than litters produced by ML mothers (43.4±3.0 g), and pups that were on average 27.2% heavier (9.9±0.2 and 7.8±0.2 g, respectively). Lactating mice in both lines had significantly longer and heavier guts compared with non-reproductive mice. However, inconsistent with the 'central limit hypothesis', the ML mice had significantly longer and heavier intestines than MH mice. An experiment where the mice raised litters of the opposing line demonstrated that lactation performance was not limited by the growth capacity of offspring. Our findings are consistent with the idea that the SusEI at peak lactation is constrained by the capacity of the mothers to dissipate body heat., (© 2014. Published by The Company of Biologists Ltd.)

Adapting ways to functionalize polymer materials is becoming increasingly important to their implementation in translational biomedical sciences. By tuning the mechanical, chemical, and biological qualities of these materials, their applications can be broadened, opening the door for more advanced integration into modern medical techniques. Here, we report on a method to integrate chemical functionalizations into discrete, microscale polymer structures, which are used for tissue engineering applications, for in vivo localization, and three-dimensional manipulation. Iron oxide nanoparticles were incorporated into the polymer matrix using common photolithographic techniques to create stably functional microstructures with magnetic potential. Using magnetic resonance imaging (MRI), we can promote visualization of microstructures contained in small collections, as well as facilitate the manipulation and alignment of microtopographical cues in a realistic tissue environment. Using similar polymer functionalization techniques, fluorine-containing compounds were also embedded in the polymer matrix of photolithographically fabricated microstructures. The incorporation of fluorine-containing compounds enabled highly sensitive and specific detection of microstructures in physiologic settings using fluorine MRI techniques ((19)F MRI). These functionalization strategies will facilitate more reliable noninvasive tracking and characterization of microstructured polymer implants as well as have implications for remote microstructural scaffolding alignment for three-dimensional tissue engineering applications.

Background: Identification of causes of dementia soon after symptom onset is important, because appropriate treatment of some causes of dementia can slow or halt its progression or enable symptomatic treatment where appropriate. The accuracy of MRI and CT, and whether MRI is superior to CT, in detecting a vascular component to dementia in autopsy confirmed and clinical cohorts of patients with VaD, combined AD and VaD ("mixed dementia"), and AD remain unclear. We conducted a systematic review and meta-analysis to investigate this question., Methods: We searched eight databases and screened reference lists to identify studies addressing the review question. We assessed study quality using QUADAS. We estimated summary diagnostic accuracy according to imaging finding, and ratios of diagnostic odds ratios (RDORs) for MRI versus CT and high versus low risk of bias., Results: We included 7 autopsy and 31 non-autopsy studies. There was little evidence that selective patient enrolment and risk of incorporation bias impacted on diagnostic accuracy (p = 0.12 to 0.95). The most widely reported imaging finding was white matter hyperintensities. For CT (11 studies) summary sensitivity and specificity were 71% (95% CI 53%-85%) and 55% (44%-66%). Corresponding figures for MRI (6 studies) were 95% (87%-98%) and 26% (12%-50%). General infarcts was the most specific imaging finding on MRI (96%; 95% CI 94%-97%) and CT (96%; 93%-98%). However, sensitivity was low for both MRI (53%; 36%-70%) and CT (52%; 22% to 80%). No imaging finding had consistently high sensitivity. Based on non-autopsy studies, MRI was more accurate than CT for six of seven imaging findings, but confidence intervals were wide., Conclusion: There is insufficient evidence to suggest that MRI is superior to CT with respect to identifying cerebrovascular changes in autopsy-confirmed and clinical cohorts of VaD, AD, and 'mixed dementia'.

Nursing faculty practice groups can play a vital role in tobacco cessation in academic medical centers. Outcomes from the Georgia Health Sciences University Nursing Faculty Practice Group Tobacco Cessation Program revealed 64% abstinence outcomes at the end of treatment (N = 160) over a 2-year period from the campus-wide tobacco-free policy initiation. A nurse-led, evidence-based, interdisciplinary approach can be an effective strategy to make a difference in the lives of tobacco-dependent individuals, while at the same time integrating practice with education and research., (Copyright © 2012. Published by Elsevier Inc.)

Introduction: School-based smoking prevention programmes can be effective, but evidence on cost-effectiveness is lacking. We conducted a cost-effectiveness analysis of a school-based "peer-led" intervention., Methods: We evaluated the ASSIST (A Stop Smoking In Schools Trial) programme in a cluster randomized controlled trial. The ASSIST programme trained students to act as peer supporters during informal interactions to encourage their peers not to smoke. Fifty-nine secondary schools in England and Wales were randomized to receive the ASSIST programme or usual smoking education. Ten thousand seven hundred and thirty students aged 12-13 years attended participating schools. Previous work has demonstrated that the ASSIST programme achieved a 2.1% (95% CI = 0%-4.2%) reduction in smoking prevalence. We evaluated the public sector cost, prevalence of weekly smoking, and cost per additional student not smoking at 24 months., Results: The ASSIST programme cost of £32 (95% CI = £29.70-£33.80) per student. The incremental cost per student not smoking at 2 years was £1,500 (95% CI = £669-£9,947). Students in intervention schools were less likely to believe that they would be a smoker at age 16 years (odds ratio [OR] = 0.80; 95% CI = 0.66-0.96)., Conclusions: A peer-led intervention reduced smoking among adolescents at a modest cost. The intervention is cost-effective under realistic assumptions regarding the extent to which reductions in adolescent smoking lead to lower smoking prevalence and/or earlier smoking cessation in adulthood. The annual cost of extending the intervention to Year 8 students in all U.K. schools would be in the region of £38 million and could result in 20,400 fewer adolescent smokers.

Background & Aims: Although proteases control inflammation and pain, the identity, cellular origin, mechanism of action, and causative role of proteases that are activated during disease are not defined. We investigated the activation and function of cysteine cathepsins (Cat) in colitis., Methods: Because protease activity, rather than expression, is regulated, we treated mice with fluorescent activity-based probes that covalently modify activated cathepsins. Activated proteases were localized by tomographic imaging of intact mice and confocal imaging of tissues, and were identified by electrophoresis and immunoprecipitation. We examined the effects of activated cathepsins on excitability of colonic nociceptors and on colonic pain, and determined their role in colonic inflammatory pain by gene deletion., Results: Tomography and magnetic resonance imaging localized activated cathepsins to the inflamed colon of piroxicam-treated il10(-/-) mice. Confocal imaging detected activated cathepsins in colonic macrophages and spinal neurons and microglial cells of mice with colitis. Gel electrophoresis and immunoprecipitation identified activated Cat-B, Cat-L, and Cat-S in colon and spinal cord, and Cat-S was preferentially secreted into the colonic lumen. Intraluminal Cat-S amplified visceromotor responses to colorectal distension and induced hyperexcitability of colonic nociceptors, which required expression of protease-activated receptor-2. Cat-S deletion attenuated colonic inflammatory pain induced with trinitrobenzene sulfonic acid., Conclusions: Activity-based probes enable noninvasive detection, cellular localization, and proteomic identification of proteases activated during colitis and are potential diagnostic tools for detection of predictive disease biomarkers. Macrophage cathepsins are activated during colitis, and Cat-S activates nociceptors to induce visceral pain via protease-activated receptor-2. Cat-S mediates colitis pain and is a potential therapeutic target., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: There is limited population-based evidence on long-term smoking relapse rates after 1 year of abstinence. We estimate the incidence of relapse and evaluate demographic, health, socioeconomic characteristics, and episodic events associated with an increased probability of relapse., Methods: Smoking relapse is studied using a subsample of individuals in the annual British Household Panel Survey, between 1991 and 2006, who reported not being a smoker for at least 1 year (two consecutive surveys) after previously reporting smoking (n = 1,578). A random-effects panel logit regression was used to examine the association between smoking relapse and length of abstinence, demographic, socioeconomic, and health variables., Results: Data were available on individuals for a mean of 5.2 years after the initial 1-year smoking abstinence. We estimated that 37.1% (34.0%-40.5%; 95% CI) of the sample would relapse within 10 years. Increased length of abstinence, increased age, being married, being educated to degree level, and a high frequency of General Practitioner (GP) visits were significantly associated with a lower risk of relapse. Conversely, higher relapse rates were significantly associated with mental health problems and having a partner who started smoking., Conclusions: A significant proportion of smokers relapse after more than 1 year of abstinence. This study sheds light on factors associated with long-term relapse. This can form the basis for designing public health interventions to prolong abstinence and targeting interventions at former smokers at the highest risk of relapse.

Objective: To determine the long-term response to serial sacroiliac joint (SIJ) corticosteroid injections. Design. Retrospective practice audit., Setting and Patients: Tertiary care spine center. Review of charts of all patients in a single practice who underwent diagnostic and therapeutic fluoroscopically guided SIJ injections with combined local anesthetic, long-acting corticosteroid, and contrast., Measures: Response was evaluated at 1 hour and again at follow-up clinic visits. Response to injection was graded as positive if there was > or =50% relief of the targeted pain during the local anesthetic phase and at least 2 weeks of > or =50% relief afterward. If pain recurred, patients had to have been sufficiently satisfied with the relief to request repeat injection., Results: There were 164 patients; 5 had incomplete records, 4 had <2 year follow-up. Of the 155 patients, 120 (77%) were positive responders; 45 were men and 75 were women; and the mean age was 48 (27-91) years. Sixty-nine had prior lumbar surgery. Mean duration of follow-up was 44 months (26-101). Two were lost to follow-up. The 118 positive responders received a mean of 2.7 injections per patient. Forty patients required 1 injection only, 29 required two, 22 required three, and 27 required four or more. The mean duration of response for those receiving >1 injection was 9.3 months per injection (1-58). There were no adverse events., Conclusions: SIJ corticosteroid injections appear to be an effective palliative treatment for selected patients with SIJ pain. Most patients whose pain is responsive to SIJ steroid injections improved sufficiently and remained well after 1 to 3 injections, but some required frequent injections on a long-term basis.

Because stresses associated with long-term care settings may exacerbate distress and aggression related to past trauma, we investigated self-report and staff reports of posttraumatic stress disorder symptoms and staff observations of verbal and physical aggression in 32 elderly males who were patients in a long-term care unit for veterans. Feelings of anger and irritability were reported by 47% of patients; levels of anger and irritability were significantly correlated with observed aggressive behaviors (r = 0.43, P < .02); and observed aggressive behaviors were significantly more frequent among those reporting past traumatic stressors (t = 2.84, P < .008). Patient-reported posttraumatic stress disorder symptoms were significantly correlated with the frequency of past traumatic stressors (r = 0.48, P < .006). Observer-reported posttraumatic stress disorder symptoms and patient reports of anger were strongly correlated (r = 0.73, P < .001). No patient or staff reports were related to level of cognitive function. These findings are consistent with the hypothesis that posttraumatic symptoms can contribute to aggressive behaviors in elderly, medically ill, and cognitively impaired patients.

There is paucity of medical literature on the use of lamotrigine in elderly patients who have behavior problems and diverse psychiatric syndromes. This article is a retrospective case series summarizing the authors' experience with this medication. In a 20-patient case series from an institutional review board-approved retrospective chart review, the tolerability and efficacy of lamotrigine was evaluated for the management of agitated and aggressive behaviors in nursing home patients with a range of psychiatric and medical diagnoses. Nineteen of the elderly nursing home patients tolerated lamotrigine treatment, and 18 showed modest clinical improvement. These results support the authors' belief that controlled clinical investigations of this medication should be performed.

Trichospirura leptostoma is a spirurid nematode that inhabits the pancreatic ducts of the common marmoset, Callithrix jacchus, and other New World primates. This parasite was diagnosed in members of this species at the Marmoset Research Center in Oak Ridge, Tennessee colony after their importation from multiple colonies outside the United States. Animals with few parasites in the pancreas had few tissue changes, whereas those with many parasites had moderate to severe fibrosis replacing exocrine tissue. Trichospirura leptostoma can cause chronic pancreatitis, resulting in subclinical to clinical pancreatic insufficiency and secondary malnutrition. Clinical signs of pancreatic insufficiency in affected marmosets included weight loss (despite good appetite) and increased fecal volume. Because earlier reports did not mention treatments, experimental therapeutic regimens were attempted to eliminate infections from the marmosets. In the clinical studies, different doses and treatment periods with ivermectin and fenbendazole were evaluated for therapeutic efficacy. Fenbendazole given daily at a dosage of 50 mg/kg of body weight by gavage for 14 days was the most effective treatment (PI 0.052). Control of the cockroach vector, as well as treatment of infected animals, is needed to prevent Trichospirura leptostoma-induced disease.