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Distribution and abundance of common parasitic nematodes in marine fishes is not well documented in many geographic regions. Understanding the influence of large-scale environmental changes on infection rates of fish by nematodes requires quantitative assessments of parasite abundance for multiple host species. We collected samples of two species of cod and eight species of rockfish (total of 232 specimens) from waters near Kodiak Island, Alaska, USA during Spring and Summer of 2015, and dissected and recorded all internal nematode parasites. We quantified the prevalence and intensity of nematode parasites in the ten host species, and tested for differences in prevalence among host species. We found three species of nematode: Anisakis simplex, sensu lato (Van Thiel), Pseudoterranova decipiens, sensu lato (Krabbe), and Hysterothylacium sp. (Ward and Magath). Eighty-two percent of the examined fish were infected with at least one parasitic nematode. The overall prevalence of P. decipiens, A. simplex, and Hysterothylacium sp. was 56%, 62%, and 2%, respectively. Anisakis simplex and P. decipiens were abundant and present in all ten species of host fish examined, whereas Hysterothylacium sp. was rare and found in only five of the host fish species. Prevalence and mean intensity of P. decipiens and A. simplex varied across the ten host species, and the number of parasites varied substantially among individual hosts within host species. The mean intensity of P. terranova and A. simplex in our study was substantially higher than the mean intensity for these same species from multiple other locations in a recent meta-analysis. This study provides a baseline of nematode parasite abundance in long-lived fish in waters near Kodiak Island, AK, and fills an important gap in our quantitative understanding of patterns of occurrence and abundance of these common and widespread parasites of marine fish. [ABSTRACT FROM AUTHOR]

Introduction: Total knee arthroplasty (TKA) is one of the most performed surgical operations in the United States. Managing postoperative pain after TKA is of vital importance, as it is positively associated with outcome measures related to recovery of function and quality of life. Two commonly used methods to control postoperative pain are regional anesthesia (RA), consisting of a single or a combination of peripheral nerve and epidural blocks, and pain medication, such as opioids. Our retrospective analysis sought to better understand whether revision versus primary TKA impacted previously discovered disparities in perioperative pain management and use of RA at the Atlanta Veterans Affairs Health Care System (AVAHCS). Before data collection, we hypothesized that revision TKA would have a higher proportion of Black and older patients and that revision TKA patients would have lower postoperative pain scores., Materials and Methods: This was a retrospective analysis of AVAHCS patients who underwent elective unilateral primary or revision TKA surgery between 2014 and 2020. After application of our exclusion criteria, data from 562 patients were analyzed. Data collected included demographics information, type of RA used, and pain scores. Statistical analyses included chi-square test, t-tests, multiple logistic regression, and multiple linear regression, as appropriate to the outcomes of interest., Results: Revision TKA patients were more likely to be Black (P = .018) and younger (P = .023 for <50 years of age group, P = .006 for 50 to 64 years of age compared to the >65 years group). Black patients, compared to White patients, had significantly higher pain scores at baseline (P = .0086) and at 24 hours postsurgery (P = .0037). Older patients (≥50 years old) had significantly higher baseline pain scores (P = .021 for the 50 to 64 years group, P < .01 for the >65 years group) and significantly lower first postanesthesia care unit pain scores (P < .05). Black race (P < .01) and age > 65 years (P < .01) were associated with a significant decrease in total oral morphine equivalents (OME) prescribed at discharge. None of the predictor variables-race, age, type of surgery (primary versus revision), baseline, and first postanesthesia care unit pain scores-were significantly associated with the use of RA in our cohort., Conclusions: Sociodemographic disparities in pain management have been reported in all healthcare systems, including the VAHCS. This moderately sized retrospective study, conducted at a single veterans affairs site, yielded several noteworthy findings. One finding of particular interest was that, despite Black patients reporting higher baseline and 24-hour postoperative pain scores, they were prescribed fewer opioids at discharge. Our results highlight the presence of clinically significant disparities in perioperative TKA pain management, emphasizing the need for continuous investigation and focused mitigation efforts among Veterans., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Objective: Conduct systematic proactive pharmacovigilance screening for symptoms patients experienced after starting new medications using an electronic patient portal. We aimed to design and test the feasibility of the system, measure patient response rates, provide any needed support for patients experiencing potentially drug-related problems, and describe types of symptoms and problems patients report., Methods: We created an automated daily report of all new prescriptions, excluding likely non-new and various over-the-counter meds, and sent invitations via patient portal inviting patients to inquire if they had started the medication, and if "yes," inquire if they had they experienced any new symptoms that could be potential adverse drug effects. Reported symptoms were classified by clinical pharmacists using SOC MeDra taxonomy, and patients were offered follow-up and support as desired and needed., Results: Of 11,724 included prescriptions for 9360 unique patients, 2758 (29.4%) patients responded. Of 2616 unique medication starts, patients reported at least 1 new symptom that represented a potential adverse drug reaction (ADR) in 678/2616 (25.9%). Nearly one-third of those experiencing new symptoms (30.3%) reported 2 or more new symptoms after initiating the drug. GI disorders accounted for 30% of the total reported ADRs., Conclusions: Systematic portal-based surveillance for potential adverse drug reactions was feasible, had higher response rates than other methods (such as automated interactive phone calling), and uncovered rates of potential ADRs (roughly 1 in 4 patients) consistent with other methods/studies., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Bone metabolism is a process in which osteoclasts continuously clear old bone and osteoblasts form osteoid and mineralization within basic multicellular units, which are in a dynamic balance. The process of bone metabolism is affected by many factors, including diet. Reasonable dietary patterns play a vital role in the prevention and treatment of bone-related diseases. In recent years, dietary patterns have changed dramatically. With the continuous improvement in the quality of life, high amounts of sugar, fat and protein have become a part of people's daily diets. However, people have gradually realized the importance of a healthy diet, intermittent fasting, calorie restriction, a vegetarian diet, and moderate exercise. Although these dietary patterns have traditionally been considered healthy, their true impact on bone health are still unclear. Studies have found that caloric restriction and a vegetarian diet can reduce bone mass, the negative impact of a high-sugar and high-fat dietary (HSFD) pattern on bone health is far greater than the positive impact of the mechanical load, and the relationship between a high-protein diet (HPD) and bone health remains controversial. Calcium, vitamin D, and dairy products play an important role in preventing bone loss. In this article, we further explore the relationship between different dietary patterns and bone health, and provide a reference for how to choose the appropriate dietary pattern in the future and for how to prevent bone loss caused by long-term poor dietary patterns in children, adolescents, and the elderly. In addition, this review provides dietary references for the clinical treatment of bone-related diseases and suggests that health policy makers should consider dietary measures to prevent and treat bone loss.

The field of exercise physiology has undergone significant technological advancements since the pioneering works of exercise physiologists in the early to mid-20th century. Historically, the ability to detect metabolites in biofluids from exercising participants was limited to single-metabolite analyses. However, the rise of metabolomics, a discipline focused on the comprehensive analysis of metabolites within a biological system, has facilitated a more intricate understanding of metabolic pathways and networks in exercise. This review explores some of the pivotal technological and bioinformatic advancements that have propelled metabolomics to the forefront of exercise physiology research. Metabolomics offers a unique 'fingerprint' of cellular activity, offering a broader spectrum than traditional single-metabolite assays. Techniques, including mass spectrometry and nuclear magnetic resonance spectroscopy, have significantly improved the speed and sensitivity of metabolite analysis. Nonetheless, challenges persist, including study design and data interpretation issues. This review aims to serve as a guide for exercise physiologists to facilitate better research design, data analysis and interpretation within metabolomics. The potential of metabolomics in bridging the gap between genotype and phenotype is emphasised, underscoring the critical importance of careful study design and the selection of appropriate metabolomics techniques. Furthermore, the paper highlights the need to deeply understand the broader scientific context to discern meaningful metabolic changes. The emerging field of fluxomics, which seeks to quantify metabolic reaction rates, is also introduced as a promising avenue for future research., (© 2024 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Inducing a heat-acclimated phenotype via repeated heat stress improves exercise capacity and reduces athletes̓ risk of hyperthermia and heat illness. Given the increased number of international sporting events hosted in countries with warmer climates, heat acclimation strategies are increasingly popular among endurance athletes to optimize performance in hot environments. At the tissue level, completing endurance exercise under heat stress may augment endurance training adaptation, including mitochondrial and cardiovascular remodeling due to increased perturbations to cellular homeostasis as a consequence of metabolic and cardiovascular load, and this may improve endurance training adaptation and subsequent performance. This review provides an up-to-date overview of the metabolic impact of heat stress during endurance exercise, including proposed underlying mechanisms of altered substrate utilization. Against this metabolic backdrop, the current literature highlighting the role of heat stress in augmenting training adaptation and subsequent endurance performance will be presented with practical implications and opportunities for future research., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Although the effects of counterstereotypic individuating information (i.e., information specific to individual members of stereotyped groups that disconfirms the group stereotype) on biases in explicit person perception are well-established, research shows mixed effects of such information on implicit person perception. The present research tested the overarching hypothesis that, when social group membership is perceived to be under an individual's control, diagnostic individuating information would have lesser effects on implicit person perception than it would when social group membership is perceived not to be under an individual's control. This hypothesis was tested in the domain of implicit attitudinal and stereotype-relevant judgments of individuals who belonged to existing social groups and individuals who belonged to novel social groups. We found that individuating information consistently shifted scores on implicit measures among targets belonging to existing social groups, but not in a theoretically predicted direction among targets belonging to novel social groups. Controllability of group membership did not moderate such effects. Results of implicit and explicit measures were mostly consistent when targets belonged to existing social groups, but mostly inconsistent when targets belonged to novel social groups., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rubinstein, Jussim, Mangracina, Shaw, Yanovsky and Bennett.)

During high-intensity (HI) exercise, metabolic acidosis significantly impairs exercise performance. Increasing the body's buffering capacity through training and exogenous intake of alkalizing supplements may improve high-intensity performance. Manipulating water and diet intake may influence the acid-base balance. The aim of this study was to determine the effects of mineral water rich in bicarbonate ions (STY) or placebo water (PLA) on circulating biomarkers and anaerobic performance and to verify whether alkalizing (ALK) or acidizing (ACI) diet would modulate these effects. Twenty-four athletes, assigned either to ALK (n = 12) or ACI (n = 12) diet for four weeks, completed a 1-min rowing Wingate Test in a double-blind and randomized trial after one week of daily hydration (1.5 to 2L/d) with either STY or PLA. Blood samples were taken before and after each test, and urine samples were collected each week. Chronic consumption of bicarbonate-rich water significantly impacted resting urinary pH irrespective of alkalizing or acidizing dietary intake. STY induced a significant increase in blood pH, lactate, and HCO 3 - ion concentration post-exercise compared to PLA. Similar changes were observed when STY was associated with the ALK diet. In contrast, STY combined with the ACI diet only significantly affected urine pH and peak blood lactate compared to PLA (p < 0.05). No effect of bicarbonate-rich water was reported on anaerobic performance (p > 0.05). Our results suggest that consumption of bicarbonate-rich water alters acid-base balance during a warm-up and after HI exercise, could potentiate beneficial effects of an alkalizing diet on the acid-base balance after HI exercise, and reduces the acid load induced by an acidifying diet., Competing Interests: The authors declare no conflicts of interest, financial or otherwise. The results are presented honestly without fabrications, falsifications, or inappropriate data manipulation., (Copyright: © Academy of Physical Education in Katowice.)

Alleviating bone loss is an essential way to prevent osteoporotic fractures. Proper exercise improves bone density without the side effects of long-term medications, but the mechanism is unclear. Our study explored the role of Antxr1/LncRNA H19/Wnt/β-catenin axis in the process of exercise-mediated alleviation of bone loss. Here we discovered that moderate-intensity treadmill exercise alleviates bone loss caused by ovariectomy and ameliorates bone strength accompanied by an increased lncRNA H19 expression. Concomitantly, Antxr1, a mechanosensitive protein was found downregulated by exercise but upregulated by ovariectomy. Interestingly, knockdown expression of Antxr1 increased lncRNA H19 expression and Wnt/β-catenin signaling pathway in bone marrow mesenchymal stem cells, whereas overexpression of Antxr1 decreased lncRNA H19 expression and Wnt/β-catenin signaling pathway. Hence, our study demonstrates the regulation of Antxr1/LncRNA H19/Wnt/β-catenin axis in the process of mechanical strain-induced osteogenic differentiation, which provides further mechanistic insight into the role of mechanical regulation in bone metabolism., (© 2024 Wiley Periodicals LLC.)

Cryptococcal species are the most common fungal pathogens to cause meningitis worldwide. The majority of cases are caused by Cryptococcus neoformans and occur in immunocompromised hosts, while Cryptococcus gattii causes most fungal meningitis in immunocompetent hosts. To date, non- neoformans , non- gattii species of Cryptococcus remain rare causes of human disease, and their clinical courses and preferred treatment regimens remain poorly characterized. We present the case of an otherwise immunocompetent woman with subacute meningoencephalitis diagnosed with Papiliotrema laurentii ( formerly Cryptococcus laurentii) meningitis, who, despite successful fungal eradication, developed hydrocephalus. To our knowledge, this represents the first case of P. laurentii meningitis in an immunocompetent host leading to hydrocephalus, illustrating the diagnostic and therapeutic challenges that remain for atypical fungal meningitis., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Promoting healthy aging is contingent on understanding the underlying mechanisms for the age-associated decline in metabolic physiology. Through developing a novel concept of "metabolic elasticity" to evaluate metabolic adaptability in response to cyclical changes in energy balance, Zhou et al. present an impactful gauge of metabolic health that is particularly relevant to aging., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Carbohydrate (CHO) intake periodization via the sleep low train low (SL-TL) diet-exercise model increases fat oxidation during exercise and may enhance endurance-training adaptation and performance. Conversely, training under environmental heat stress increases CHO oxidation, but the potential of combined SL-TL and heat stress to enhance metabolic and performance outcomes is unknown., Methods: Twenty-three endurance-trained males were randomly assigned to either control (n = 7, CON), SL-TL (n = 8, SL Temp ) or SL-TL + heat stress (n = 8, SL Heat ) groups and prescribed identical 2-week cycling training interventions. CON and SL Temp completed all sessions at 20°C, but SL Heat at 35°C. All groups consumed matched CHO intake (6 g·kg -1 ·day -1 ) but timed differently to promote low CHO availability overnight and during morning exercise in both SL groups. Submaximal substrate utilization was assessed (at 20°C), and 30-min performance tests (at 20 and 35°C) were performed Pre-, Post-, and 1-week post-intervention (Post+1)., Results: SL Temp improved fat oxidation rates at 60% MAP (~66% VO 2peak ) at Post+1 compared with CON (p < 0.01). Compared with SL Temp , fat oxidation rates were significantly lower in SL Heat at Post (p = 0.02) and Post+1 (p < 0.05). Compared with CON, performance was improved at Post in SL Temp in temperate conditions. Performance was not different between any groups or time points in hot conditions., Conclusion: SL-TL enhanced metabolic adaptation and performance compared with CON and combined SL-TL and heat stress. Additional environmental heat stress may impair positive adaptations associated with SL-TL., (© 2023 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

Objective: Dragon's Blood resin (DBR) is a traditional medicinal substance renowned for its diverse pharmacological effects, which consists of potent anti-inflammatory, antioxidant and angiogenic properties. This study aimed to elucidate its therapeutic mechanism in alleviating steroid-induced osteonecrosis of the femoral head (SIONFH). Methods: Techniques such as SPR and LC-MS were employed to identify and analyze the target proteins of DBR in bone marrow macrophages (BMMs). In vitro , BMMs were treated with RANKL and DBR, and TRAcP staining and actin belt staining were utilized to assess osteoclast activity. The inhibitory effects and underlying mechanisms of DBR on osteoclastogenesis and reactive oxygen species (ROS) generation were determined using real-time PCR, western blotting and immunofluorescence staining. An in vivo SIONFH rat model was set up to assess the curative impacts of DBR using micro-CT scanning and pathological staining. Results: Bioinformatic tools revealed a pivotal role of osteoclast differentiation in SIONFH. Proteomic analysis identified 164 proteins binding in BMMs. In vitro assessments demonstrated that DBR hindered osteoclastogenesis by modulating the expression of specific genes and proteins, along with antioxidant proteins including TRX1 and Glutathione Reductase. Notably, the resin effectively inhibited the expression of crucial proteins, such as the phosphorylation of JNK and the nuclear localization of p65 within the TRAF6/JNK and NFκB signaling pathways. In vivo experiments further confirmed that DBR mitigated the onset of SIONFH in rats by curbing osteoclast and ROS activities. Conclusion: These findings underscore the potential of Dragon's Blood as an effective administration for early-stage SIONFH, shedding light on its therapeutic influence on ROS-mediated osteoclastic signaling pathways., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Mo, Lu, Wei, Zhang, Bennett, Xu, Zhou, Fang and Chen.)

Parthenolide (PTL or PAR) was first isolated from Magnolia grandiflora and identified as a small molecule cancer inhibitor. PTL has the chemical structure of C15H20O3 with characteristics of sesquiterpene lactones and exhibits the biological property of inhibiting DNA biosynthesis of cancer cells. In this review, we summarise the recent research progress of medicinal PTL, including the therapeutic effects on skeletal diseases, cancers, and inflammation-induced cytokine storm. Mechanistic investigations reveal that PTL predominantly inhibits NF-κB activation and other signalling pathways, such as reactive oxygen species. As an inhibitor of NF-κB, PTL appears to inhibit several cytokines, including RANKL, TNF-α, IL-1β, together with LPS induced activation of NF-κB and NF-κB -mediated specific gene expression such as IL-1β, TNF-α, COX-2, iNOS, IL-8, MCP-1, RANTES, ICAM-1, VCAM-1. It is also proposed that PTL could inhibit cytokine storms or hypercytokinemia triggered by COVID-19 via blocking the activation of NF-κB signalling. Understanding the pharmacologic properties of PTL will assist us in developing its therapeutic application for medical conditions, including arthritis, osteolysis, periodontal disease, cancers, and COVID-19-related disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhu, Sun, Bennett, Charlesworth, Tan, Peng, Gu, Kujan and Xu.)

Physical activity represents a potent, non-pharmacological intervention delaying the onset of over 40 chronic metabolic and cardiovascular diseases, including type 2 diabetes, coronary heart disease, and reducing all-cause mortality. Acute exercise improves glucose homeostasis, with regular participation in physical activity promoting long-term improvements in insulin sensitivity spanning healthy and disease population groups. At the skeletal muscle level, exercise promotes significant cellular reprogramming of metabolic pathways through the activation of mechano- and metabolic sensors, which coordinate downstream activation of transcription factors, augmenting target gene transcription associated with substrate metabolism and mitochondrial biogenesis. It is well established that frequency, intensity, duration, and modality of exercise play a critical role in the type and magnitude of adaptation; albeit, exercise is increasingly considered a vital lifestyle factor with a critical role in the entrainment of the biological clock. Recent research efforts revealed the time-of-day-dependent impact of exercise on metabolism, adaptation, performance, and subsequent health outcomes. The synchrony between external environmental and behavioural cues with internal molecular circadian clock activity is a crucial regulator of circadian homeostasis in physiology and metabolism, defining distinct metabolic and physiological responses to exercise unique to the time of day. Optimising exercise outcomes following when to exercise would be essential to establishing personalised exercise medicine depending on exercise objectives linked to disease states. We aim to provide an overview of the bimodal impact of exercise timing, i.e. the role of exercise as a time-giver ( zeitgeber ) to improve circadian clock alignment and the underpinning clock control of metabolism and the temporal impact of exercise timing on the metabolic and functional outcomes associated with exercise. We will propose research opportunities that may further our understanding of the metabolic rewiring induced by specific exercise timing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bennett and Sato.)

Purpose of Review: The risks of cerebrovascular manifestations due to SARS-CoV-2 infection are significantly increased within the first 6 months of the infection. Our work aims to give an update on current clinical aspects of diagnosis and treatment of cerebrovascular manifestations during acute and long-term SARS-CoV-2 infection., Recent Findings: The incidence of acute ischemic stroke and haemorrhagic stroke during acute SARS-CoV-2 patients is estimated at 0.9 to 4.6% and 0.5-0.9%, respectively, and were associated with increased mortality. The majority presented with hemiparesis, dysarthria, sensory deficits, and a NIHSS score within 5-15. In addition, beyond the first 30 days of infection people with COVID-19 exhibited increased risk of stroke. During acute phase, age, hypertension, diabetes, and medical history of vascular disease were increased in patients with COVID-19 with new onset of cerebrovascular manifestations, while during long-COVID-19, the risk of cerebrovascular manifestations were found increased regardless of these factors. The management of patients with large-vessel ischemic stroke fulfilling the intravenous thrombolysis criteria are successfully treated according to the guidelines, while hyperosmolar therapy is typically administered in 4- to 6-h intervals. In addition, prophylaxis of anticoagulation therapy is associated with a better prognosis and low mortality during acute and post hospital discharge of patients with COVID-19., Summary: In this work, we provide a comprehensive review of the current literature on acute and post-acute COVID-19 cerebrovascular sequelae, symptomatology, and its pathophysiology mechanisms. Moreover, we discuss therapeutic strategies for these patients during acute and long-term care and point populations at risk. Our findings suggest that older patients with risk factors such as hypertension, diabetes, and medical history of vascular disease are more likely to develop cerebrovascular complications., Competing Interests: Conflict of InterestNikolaos Karvelas declares that he has no conflict of interest. Εleni Stefanou declares that she has no conflict of interest. Samuel Bennett declares that he has no conflict of interest. Christo Kole declares that he has no conflict of interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Galanin is a neurohormone as well as a neurotransmitter and plays versatile physiological roles for the neuroendocrine axis, such as regulating food intake, insulin level and somatostatin release. It is expressed in the central nervous system, including hypothalamus, pituitary, and the spinal cord, and colocalises with other neuronal peptides within neurons. Structural analyses reveal that the human galanin precursor is 104 amino acid (aa) residues in length, consisting of a mature galanin peptide (aa 33-62), and galanin message-associated peptide (GMAP; aa 63-104) at the C-terminus. GMAP appears to exhibit distinctive biological effects on anti-fungal activity and the spinal flexor reflex. Galanin-like peptide (GALP) has a similar structure to galanin and acts as a hypothalamic neuropeptide to mediate metabolism and reproduction, food intake, and body weight. Alarin, a differentially spliced variant of GALP, is specifically involved in vasoactive effect in the skin and ganglionic differentiation in neuroblastic tumors. Dysregulation of galanin, GALP and alarin has been implicated in various neuroendocrine conditions such as nociception, Alzheimer's disease, seizures, eating disorders, alcoholism, diabetes, and spinal cord conditions. Further delineation of the common and distinctive effects and mechanisms of various types of galanin family proteins could facilitate the design of therapeutic approaches for neuroendocrine diseases and spinal cord injury., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhu, Hu, Bennett, Charlesworth, Qin, Mai, Dou and Xu.)

Lipid metabolism disorder is a common pathological manifestation of menopausal women, and is also an important risk factor for many diseases at this stage of life. Epidemiological studies have shown that high levels of follicle-stimulating hormone (FSH) in menopausal women are closely associated with changes in body composition, central obesity, and cognitive decline. Exogenous FSH causes growth and proliferation of adipose, whereas blockage of the FSH signaling pathway leads to decline in adipose. Mechanistically, FSH, FSH receptor (FSHR), G protein coupling, gene mutation and other pathways are involved in adipogenesis and cognitive impairment. Here, we review the critical role and potential interactions of FSH in adipogenesis and cognitive impairment in menopausal women. Further understanding of the exact mechanisms of FSH aggravating obesity and cognitive impairment may provide a new perspective for promoting healthy aging in menopausal women., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mao, Wang, Bennett, Xu and Zou.)

Background: Cerebrospinal fluid (CSF) is commonly analyzed in South American camelids with suspected neurologic disease because of ease of collection and characteristic findings associated with certain diseases., Objectives: To assess CSF findings associated with short-term survival or non-survival in South American camelids in which neurologic disease was a differential diagnosis based on history and physical examination., Animals: Twenty-one llamas and 33 alpacas that underwent CSF analysis at the University of Missouri Veterinary Health Center., Methods: Retrospective study. Medical records of camelids that underwent CSF analysis between January 2005 and September 2021 were studied. Short-term survival was defined as survival to discharge from the Veterinary Health Center. A Fisher's exact test was used to compare species, CSF results, and survival., Results: Odds of survival were 3.9 times higher in camelids with a total nucleated cell count (TNCC) <3 cells/μL (P = .04). No significant association was found between survival and total protein concentration (TPC; P = .15) or percentage of eosinophils (P = 1.0). No significant correlation was found between species and increased TNCC (P = .63), TPC (P = .55), or percentage of eosinophils (P = .30). Among camelids diagnosed with Paralephostrongylus tenuis infestation, odds of survival were 4.95 times higher in alpacas (P = .05)., Conclusions: Cerebrospinal fluid TNCC ≥3 cells/μL is associated with decreased odds of short-term survival in South American camelids., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Junctional epithelium (JE) is a vital epithelial component which forms an attachment to the tooth surface at the gingival sulcus by the adhesion of protein complexes from its basal layer. Disruption of the JE is associated with the development of gingivitis, periodontal disease, and alveolar bone loss. Odontogenic ameloblast-associated (ODAM) is comprised of a signal peptide and an ODAM protein with 12 putative glycosylation sites. It is expressed during odontogenesis by maturation stage ameloblasts and is incorporated into the enamel matrix during the formation of outer and surface layer enamel. ODAM, as a secreted protein which is accumulated at the interface between basal lamina and enamel, mediates the adhesion of the JE to the tooth surface; and is involved with extracellular signalling of WNT and ARHGEF5-RhoA, as well as intracellular signalling of BMP-2-BMPR-IB-ODAM. ODAM is also found to be highly expressed in salivary glands and appears to have implications for the regulation of formation, repair, and regeneration of the JE. Bioinformatics and research data have identified the anti-cancer properties of ODAM, indicating its potential both as a prognostic biomarker and therapeutic target. Understanding the biology of ODAM will help to design therapeutic strategies for periodontal and dental disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhu, Xiang, Charlesworth, Bennett, Zhang, Zhou, Kujan and Xu.)

The mechanistic target of rapamycin (mTOR) signals through the mTOR complex 1 (mTORC1) and the mTOR complex 2 to maintain cellular and organismal homeostasis. Failure to finely tune mTOR activity results in metabolic dysregulation and disease. While there is substantial understanding of the molecular events leading mTORC1 activation at the lysosome, remarkably little is known about what terminates mTORC1 signaling. Here, we show that the AAA + ATPase Thorase directly binds mTOR, thereby orchestrating the disassembly and inactivation of mTORC1. Thorase disrupts the association of mTOR to Raptor at the mitochondria-lysosome interface and this action is sensitive to amino acids. Lack of Thorase causes accumulation of mTOR-Raptor complexes and altered mTORC1 disassembly/re-assembly dynamics upon changes in amino acid availability. The resulting excessive mTORC1 can be counteracted with rapamycin in vitro and in vivo. Collectively, we reveal Thorase as a key component of the mTOR pathway that disassembles and thus inhibits mTORC1., (© 2022. The Author(s).)

Fibrillin is the major constituent of extracellular microfibrils, which are distributed throughout connective tissues. Asprosin is derived from the C-terminal region of the FBN1 gene, which encodes profibrillin that undergoes cleavage by furin protein. In response to fasting with low dietary glucose, asprosin is released as a secreted factor from white adipose tissue, and is transported to the liver for the mediation of glucose release into the blood circulation. Through binding to OLFR734, an olfactory G-protein-coupled receptor in liver cells, asprosin induces a glucogenic effect to regulate glucose homeostasis. Bioinformatics analyses revealed that the FBN1 gene is abundantly expressed in human skeletal muscle-derived mesoangioblasts, osteoblast-like cells, and mesenchymal stem cells, indicating that the musculoskeletal system might play a role in the regulation of asprosin expression. Interestingly, recent studies suggest that asprosin is regulated by exercise. This timely review discusses the role of asprosin in metabolism, its receptor signalling, as well as the exercise regulation of asprosin. Collectively, asprosin may have a vital regulatory effect on the improvement of metabolic disorders such as diabetes mellitus and obesity via exercise., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Liu, Huang, Zhang, Zhu, Chen, Bennett, Xu and Zou.)

TAFA chemokine like family member 4 (TAFA4, also named FAM19A4) is a member of the TAFA chemokine like ligand or FAM19A family, which includes TAFA1, TAFA2, TAFA3, TAFA4, and TAFA5 (or FAM19A1, FAM19A2, FAM19A3, FAM19A4, and FAM19A5). They are also referred to as neurokines and are involved in the regulation of a diverse range of cellular processes, including chemotaxis of macrophages, phagocytosis, and release of reactive oxygen species (ROS). TAFA4 is a marker of C-low-threshold mechanoreceptors and is expressed predominantly in nociceptors, such as dorsal root ganglia (DRG). TAFA4 has been implicated in the sensory perception of pain in the spinal cord. Mice with deficiency of TAFA4 demonstrate altered excitability in lamina IIi neurons in DRG in addition to increased mechanical and chemical nociception following inflammation or injury. As a secreted protein, TAFA4 binds to cell surface receptor formyl peptide receptor 1 (FPR1), a G protein-coupled receptor to mediate the chemoattraction of macrophages, phagocytosis, and the inflammatory profile of macrophages. It also interacts with cell surface neurexin to mediate signalling across the synapse. Further understanding the mechanisms by which this conserved protein family regulates diverse biological processes such as in neuronal functions, inflammation, and tissue fibrosis will help to design therapeutic targets for the treatment of TAFA related diseases such as spinal cord injury and neuro-inflammatory disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhu, Hu, Bennett, Mai and Xu.)

Humanin (HN) belongs to a member of mitochondrial-derived peptides (MDPs) which are encoded by mitochondrial genes. HN shares sequence homology with thirteen HN-like proteins, named MTRNR2L1 to MTRNR2L13, which encompass 24-28 amino acid residues in length. HN mediates mitochondrial status and cell survival by acting via an intracellular mechanism, or as a secreted factor via extracellular signals. Intracellularly, it binds Bcl2-associated X protein (BAX), Bim and tBid, and IGFBP3 to inhibit caspase activity and cell apoptosis. When released from cells as a secreted peptide, HN interacts with G protein-coupled formyl peptide receptor-like 1 (FPRL1/2) to mediate apoptosis signal-regulating kinase (ASK) and c-Jun N-terminal kinase (JNK) signalling pathways. Additionally, it interacts with CNTFR-α/gp130/WSX-1 trimeric receptors to induce JAK2/STA3 signalling cascades. HN also binds soluble extracellular proteins such as VSTM2L and IGFBP3 to modulate cytoprotection. It is reported that HN plays a role in neuronal disorders such as Alzheimer's disease, as well as in diabetes mellitus, infertility, and cardiac diseases. Its roles in the skeletal system are emerging, where it appears to be involved with the regulation of osteoclasts, osteoblasts, and chondrocytes. Understanding the molecular structure and role of HN in neural and skeletal diseases is vital to the application of HN in tissue regeneration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhu, Hu, Bennett, Xu and Mai.)

Vascular regeneration is a challenging topic in tissue repair. As one of the important components of the neurovascular unit (NVU), pericytes play an essential role in the maintenance of the vascular network of the spinal cord. To date, subtypes of pericytes have been identified by various markers, namely the PDGFR-β, Desmin, CD146, and NG2, each of which is involved with spinal cord injury (SCI) repair. In addition, pericytes may act as a stem cell source that is important for bone development and regeneration, whilst specific subtypes of pericyte could facilitate bone fracture and defect repair. One of the major challenges of pericyte biology is to determine the specific markers that would clearly distinguish the different subtypes of pericytes, and to develop efficient approaches to isolate and propagate pericytes. In this review, we discuss the biology and roles of pericytes, their markers for identification, and cell differentiation capacity with a focus on the potential application in the treatment of SCI and bone diseases in orthopedics., (© 2022. The Author(s).)

Alzheimer's disease (AD) is the most common type of dementia responsible for more than 121,499 deaths from AD in 2019 making AD the sixth-leading cause in the United States. AD is a progressive neurodegenerative disorder characterized by decline of memory, behavioral impairments that affects a person's ability to function independently ultimately leading to death. The current pressing need for a treatment for (AD) and advances in the field of cell therapy, has rendered stem cell therapeutics a promising field of research. Despite advancements in stem cell technology, confirmed by encouraging pre-clinical utilization of stem cells in AD animal models, the number of clinical trials evaluating the efficacy of stem cell therapy is limited, with the results of many ongoing clinical trials on cell therapy for AD still pending. Mesenchymal stem cells (MSCs) have been the main focus in these studies, reporting encouraging results concerning safety profile, however their efficacy remains unproven. In the current article we review the latest advances regarding different sources of stem cell therapy and present a comprehensive list of every available clinical trial in national and international registries. Finally, we discuss drawbacks arising from AD pathology and technical limitations that hinder the transition of stem cell technology from bench to bedside. Our findings emphasize the need to increase clinical trials towards uncovering the mode of action and the underlying therapeutic mechanisms of transplanted cells as well as the molecular mechanisms controlling regeneration and neuronal microenvironment., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://sci.amegroups.com/article/view/10.21037/sci-2021-063/coif). The authors have no conflicts of interest to declare., (2022 Stem Cell Investigation. All rights reserved.)

Background: "Sleep Low-Train Low" is a training-nutrition strategy intended to purposefully reduce muscle glycogen availability around specific exercise sessions, potentially amplifying the training stimulus via augmented cell signalling. The aim of this study was to assess the feasibility of a 3-week home-based "sleep low-train low" programme and its effects on cycling performance in trained athletes., Methods: Fifty-five trained athletes (Functional Threshold Power [FTP]: 258 ± 52W) completed a home-based cycling training program consisting of evening high-intensity training (6 × 5 min at 105% FTP), followed by low-intensity training (1 hr at 75% FTP) the next morning, three times weekly for three consecutive weeks. Participant's daily carbohydrate (CHO) intake (6 g·kg-1·d-1) was matched but timed differently to manipulate CHO availability around exercise: no CHO consumption post- HIT until post-LIT sessions [Sleep Low (SL), n = 28] or CHO consumption evenly distributed throughout the day [Control (CON), n = 27]. Sessions were monitored remotely via power data uploaded to an online training platform, with performance tests conducted pre-, post-intervention., Results: LIT exercise intensity reduced by 3% across week 1, 3 and 2% in week 2 (P < 0.01) with elevated RPE in SL vs. CON (P < 0.01). SL enhanced FTP by +5.5% vs. +1.2% in CON (P < 0.01). Comparable increases in 5-min peak power output (PPO) were observed between groups (P < 0.01) with +2.3% and +2.7% in SL and CON, respectively (P = 0.77). SL 1-min PPO was unchanged (+0.8%) whilst CON improved by +3.9% (P = 0.0144)., Conclusion: Despite reduced relative training intensity, our data demonstrate short-term "sleep low-train low" intervention improves FTP compared with typically "normal" CHO availability during exercise. Importantly, training was completed unsupervised at home (during the COVID-19 pandemic), thus demonstrating the feasibility of completing a "sleep low-train low" protocol under non-laboratory conditions., Competing Interests: The authors have declared that no competing interests exist.

Fibrocartilage enthesis is the junction between bone and tendon with a typical characteristics of fibrocartilage transition zones. The regeneration of this transition zone is the bottleneck for functional restoration of bone tendon junction (BTJ). Biomimetic approaches, especially decellularized extracellular matrix (ECM) materials, are strategies which aim to mimic the components of tissues to the utmost extent, and are becoming popular in BTJ healing because of their ability not only to provide scaffolds to allow cells to attach and migrate, but also to provide a microenvironment to guide stem/progenitor cells lineage-specific differentiation. However, the cellular and molecular mechanisms of those approaches, especially the ECM proteins, remain unclear. For BTJ reconstruction, fibrocartilage regeneration is the key for good integrity of bone and tendon as well as its mechanical recovery, so the components which can guide stem cells to a chondrogenic commitment in biomimetic approaches might well be the key for fibrocartilage regeneration and eventually for the better BTJ healing. In this review, we firstly discuss the importance of cartilage-like formation in the healing process of BTJ. Next, we explore the possibility of tendon-derived stem/progenitor cells as cell sources for BTJ regeneration due to their multi-differentiation potential. Finally, we summarize the role of extracellular matrix components of BTJ in guiding stem cell fate to a chondrogenic commitment, so as to provide cues for understanding the mechanisms of lineage-specific potential of biomimetic approaches as well as to inspire researchers to incorporate unique ECM components that facilitate BTJ repair into design., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Monocyte chemoattractant protein-1, also called chemokine (C-C motif) ligand 2 (CCL2) or small inducible cytokine A2, is an inflammatory mediator capable of recruiting monocytes, memory T cells, and dendritic cells. CCL2 is a member of the CC chemokine superfamily, which binds to its receptor, C-C motif chemokine receptor-2 (CCR2), for the induction of chemotactic activity and an increase of calcium influx. It exerts multiple effects on a variety of cells, including monocytes, macrophages, osteoclasts, basophils, and endothelial cells, and is involved in a diverse range of diseases. This review discusses the molecular structure and role of CCL2 and CCR2 in skeletal biology and disease. Molecular structure analyses reveal that CCL2 shares a conserved C-C motif; however, it has only limited sequence homology with other CCL family members. Likewise, CCR2, as a member of the G-protein-coupled seven-transmembrane receptor superfamily, shares conserved cysteine residues, but exhibits very limited sequence homology with other CCR family members. In the skeletal system, the expression of CCL2 is regulated by a variety of factors, such as parathyroid hormone/parathyroid hormone-related peptide, interleukin 1b, tumor necrosis factor-α and transforming growth factor-beta, RANKL, and mechanical forces. The interaction of CCL2 and CCR2 activates several signaling cascades, including PI3K/Akt/ERK/NF-κB, PI3K/MAPKs, and JAK/STAT-1/STAT-3. Understanding the role of CCL2 and CCR2 will facilitate the development of novel therapies for skeletal disorders, including rheumatoid arthritis, osteolysis and other inflammatory diseases related to abnormal chemotaxis., (© 2021 Wiley Periodicals LLC.)

The freshwater crayfish is capable of regenerating limbs, following autotomy, injury and predation. In arthropod species, regeneration and moulting are two processes linked and strongly regulated by ecdysone. The regeneration of crayfish limbs is divided into wound healing, blastema formation, cellular reprogramming and tissue patterning. Limb blastema cells undergo proliferation, dedifferentiation and redifferentiation. A limb bud, containing folded segments of the regenerating limb, is encased within a cuticular sheath. The functional limb regenerates, in proecdysis, in two to three consecutive moults. Rapid tissue growth is regulated by hormones, limb nerves and local cells. The TGF-β/activin signalling pathway has been determined in the crayfish, P. fallax f. virginalis, and is suggested as a potential regulator of tissue regeneration. In this review article, we discuss current understanding of tissue regeneration in the crayfish and various crustaceans. A thorough understanding of the cellular, genetic and molecular pathways of these biological processes is promising for the development of therapeutic applications for a wide array of diseases in regenerative medicine., (© 2021 John Wiley & Sons Ltd.)

Importance: More conservative prescribing has the potential to reduce adverse drug events and patient harm and cost; however, no method exists defining the extent to which individual clinicians prescribe conservatively. One potential domain is prescribing a more limited number of drugs. Personal formularies-defined as the number and mix of unique, newly initiated drugs prescribed by a physician-may enable comparisons among clinicians, practices, and institutions., Objectives: To develop a method of defining primary care physicians' personal formularies and examine how they differ among primary care physicians at 4 institutions; evaluate associations between personal formularies and patient, physician, and practice site characteristics; and empirically derive and examine the variability of the top 200 core drugs prescribed at the 4 sites., Design, Setting, and Participants: This retrospective cohort study was conducted at 4 US health care systems among 4655 internal and family medicine physicians and 4 930 707 patients who had at least 1 visit to these physicians between January 1, 2017, and December 31, 2018., Exposures: Personal formulary size was defined as the number of unique, newly initiated drugs., Main Outcomes and Measures: Personal formulary size and drugs used, physician and patient characteristics, core drugs, and analysis of selected drug classes., Results: The study population included 4655 primary care physicians (2274 women [48.9%]; mean [SD] age, 48.5 [4.4] years) and 4 930 707 patients (16.5% women; mean [SD] age, 51.9 [8.3] years). There were 41 378 903 outpatient prescriptions written, of which 9 496 766 (23.0%) were new starts. Institution median personal formulary size ranged from 150 (interquartile range, 82.0-212.0) to 296 (interquartile range, 230.0-347.0) drugs. In multivariable modeling, personal formulary size was significantly associated with panel size (total number of unique patients with face-to-face encounters during the study period; 1.2 medications per 100 patients), physician's total number of encounters (5.7 drugs per 10% increase), and physician's sex (-6.2 drugs per 100 patients for female physicians). There were 1527 unique, newly prescribed drugs across the 4 sites. Fewer than half the drugs (626 [41.0%]) were used at every site. Physicians' prescribing of drugs from a pooled core list varied from 0% to 100% of their prescriptions., Conclusions and Relevance: Personal formularies, measured at the level of individual physicians and institutions, reveal variability in size and mix of drugs. Similarly, defining a list of commonly prescribed core drugs in primary care revealed interphysician and interinstitutional differences. Personal formularies and core medication lists enable comparisons and may identify outliers and opportunities for safer and more appropriate prescribing.

Management of socket fit is challenging for people using lower-limb prostheses because of residual limb volume fluctuation throughout the day. Releasing socket pressures during sitting (partial doffing) may help users increase their limb volume after they have undergone volume loss earlier in the day. The purpose of this research was to develop and evaluate a system to allow for quick and easy locking pin and socket panel release during sitting and relock upon standing. The system was to allow the partial doff tether length to be custom set for each user, accomplish release and relock in less than 2.0 s each, require only one hand, and require a finger push force comparable to a push button on a phone. A motor-driven release/relock system (<240 g build weight) housed within the socket adjusts locking pin tether length, and an instrumented ratcheting dial adjusts socket panel position. Three participants with a trans-tibial amputation operated the system properly using one hand. For a partial doff, users preferred a tether length between 5 and 6 cm. All users executed release within 1.5 s and relock within 1.5 s., Competing Interests: Declaration of Competing Interest None, (Copyright © 2021. Published by Elsevier Ltd.)

Generally, mammals are unable to regenerate complex tissues and organs however the deer antler provides a rare anomaly to this rule. This osseous cranial appendage which is located on the frontal bone of male deer is capable of stem cell-based organogenesis, annual casting, and cyclic de novo regeneration. A series of recent studies have classified this form of regeneration as epimorphic stem cell based. Antler renewal is initiated by the activation of neural crest derived pedicle periosteal cells (PPCs) found residing within the pedicle periosteum (PP), these PPCs have the potential to differentiate into multiple lineages. Other antler stem cells (ASCs) are the reserve mesenchymal cells (RMCs) located in the antlers tip, which develop into cartilage tissue. Antlerogenic periosteal cells (APCs) found within the antlerogenic periosteum (AP) form the tissues of both the pedicle and first set of antlers. Antler stem cells (ASCs) further appear to progress through various stages of activation, this coordinated transition is considered imperative for stem cell-based mammalian regeneration. The latest developments have shown that the rapid elongation of the main beam and antler branches are a controlled form of tumour growth, regulated by the tumour suppressing genes TP73 and ADAMTS18. Both osteoclastogenesis, as well as osteogenic and chondrogenic differentiation are also involved. While there remains much to uncover this review both summarises and comprehensively evaluates our existing knowledge of tissue regeneration in the deer antler. This will assist in achieving the goal of in vitro organ regeneration in humans by furthering the field of modern regenerative medicine., The Translational Potential of This Article: As a unique stem cell-based organ regeneration process in mammals, the deer antler represents a prime model system for investigating mechanisms of regeneration in mammalian tissues. Novel ASCs could provide cell-based therapies for regenerative medicine and bone remodelling for clinical application. A greater understanding of this process and a more in-depth defining of ASCs will potentiate improved clinical outcomes., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors.)

Objective: Teaching surgical skills is a labor intensive process, requiring a high tutor to student ratio for optimal success, and teaching for undergraduate students by consultant surgeons is not always feasible. A surgical skills course was developed, with the aim of assessing the effectiveness of undergraduate surgical peer-assisted learning., Design: Five surgical skills courses were conducted looking at eight domains in surgery, led by foundation year doctors and senior medical students, with a tutor to student ratio of 1:4. Precourse and postcourse questionnaires (Likert scales 0-10) were completed. Mean scores were compared precourse and postcourse., Setting: Surgical skills courses took place within clinical skills rooms in the Queen Elizabeth Hospital Birmingham (UK)., Participants: Seventy students (59 medical, 2 dental, and 9 physician associate students) from a range of academic institutions across the UK completed the course., Results: There was an overall increase in mean scores across all eight domains. Mean improvement score precourse and postcourse in WHO surgical safety checklist (+3.94), scrubbing (+2.99), gowning/gloving (+3.34), knot tying (+5.53), interrupted sutures (+5.89), continuous sutures (+6.53), vertical mattress sutures (+6.46), and local anesthesia (+3.73)., Conclusions: Peer-assisted learning is an effective and feasible method for teaching surgical skills in a controlled environment, subsequently improving confidence among healthcare undergraduates. Such teaching may provide the basis for feasibly mass-producing surgical skills courses for healthcare students., (Copyright © 2018 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Hemimandibular hyperplasia (HH), also known as hemimandibular hypertrophy, is characterised by excessive unilateral three-dimensional growth of the mandible after birth. Vertical unilateral elongation of the mandible becomes clinically evident as a rare form of vertical facial asymmetry. Aberrant growth of the facial skeleton affects the developing dentition and the dental compensatory mechanism is usually unable to maintain optimal occlusal relationships. The resulting malocclusion is effectively managed by combined surgical-orthodontic care to address the facial, skeletal and dental problems that confront clinicians. Orthodontists are advised to assess patients with HH during the post-treatment retention stage for continuing mandibular growth and assess the stability of treatment outcomes with long-term follow-up and records as required., Aim: To present a case of hemimandibular hyperplasia treated successfully by combined surgical-orthodontic care and evaluated for stability over a seven-year follow-up period., Methods: Surgical-orthodontic management was accomplished in four stages: 1) pre-surgical orthodontic; 21 surgical; 3) post-surgical orthodontic; and 4) post-treatment orthodontic retention. Complete orthodontic records, including extra- and intra-oral photographs, study models, and cephalograms plus panoramic radiographs were taken at the pretreatment, post-treatment, and seven-year orthodontic retention time-points., Results: Facial, skeletal and dental goals were achieved in the three planes of space and the long-term stability of the treatment results was shown during a post-treatment orthodontic retention period of seven years., Conclusion: Hemimandibular hyperplasia is a true growth anomaly which may be managed effectively. Clinicians may expect successful long-term correction and stability by utilising a comprehensive surgical-orthodontic treatment approach.

Dissociation of peptides induced by interaction with (free) electrons (electron-induced dissociation, EID) at electron energies ranging from near 0 to >30 eV was carried out using a radio-frequency-free electromagnetostatic (EMS) cell retrofitted into a triple quadrupole mass spectrometer. The product-ion mass spectra exhibited EID originating from electronically excited even-electron precursor ions, reduced radical cations formed by capture of low-energy electrons, and oxidized radical cations produced by interaction with high-energy electrons. The spectra demonstrate, within the limits of the triple quadrupole's resolving power, that high-energy EID product-ion spectra produced with an EMS cell exhibit essentially the same qualitative structural information, i.e., amino acid side-chain (SC) losses and backbone cleavages, as observed in high-energy EID spectra produced with a Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometer. The levels of fragmentation efficiency evident in the product-ion spectra recorded in this study, as was the case for those recorded in earlier studies with FT ICR mass spectrometers, is currently at the margin of analytical utility. Given that this shortcoming can be remedied, EMS cells incorporated into QqQ or QqTOF mass spectrometers could make tandem high-energy EID mass spectrometry more widely accessible for analysis of peptides, small singly charged molecules, pharmaceuticals, and clinical samples.

A radio frequency-free electromagnetostatic (EMS) cell devised for electron-capture dissociation (ECD) of ions has been retrofitted into the collision-induced dissociation (CID) section of a triple quadrupole mass spectrometer to enable recording of ECD product-ion mass spectra and simultaneous recording of ECD-CID product-ion mass spectra. This modified instrument can be used to produce easily interpretable ECD and ECD-CID product-ion mass spectra of tyrosine-phosphorylated peptides that cover over 50% of their respective amino-acid sequences and readily identify their respective sites of phosphorylation. ECD fragmentation of doubly protonated, tyrosine-phosphorylated peptides, which was difficult to observe with FT-ICR instruments, occurs efficiently in the EMS cell.

Carbon nanotubes (CNTs) are exciting new materials that have been intensively researched and are becoming increasingly used in consumer products. With rapid growth in production and use of CNTs in many applications, there is the potential for emissions to the environment and thus research is needed to assess the risks associated with CNTs in the environment. Here we show that commercial CNTs differ in their stability, photoactivity, metal leachate, and toxicity to freshwater algae. The behavior between raw and purified variants of the CNTs differs considerably; for example purified CNTs are generally more photoactive, producing singlet oxygen and superoxide, while raw CNTs show little or no photoactivity. Residual metal catalysts differ based on synthesis method used to prepare CNTs and thus may be comprised of elements with varying degrees of toxic potential. Influenced by pH and other constituents of the natural waters, our work shows that metals can leach out from all the commercial CNTs studied, even purified versions, albeit at different levels in many natural waters. As much as 10% of the total residual nickel leached from a purified CNT after 72 h. Aqueous concentrations of molybdenum leached from a different purified CNT were nearly 0.060 mg L(-1) after 72 h. With little sample preparation, CNTs are dispersible in most freshwaters and stable for several days. Not all tested CNTs were toxic; for those CNTs that did induce toxicity we show that photoactivity, not metal leaching, contributes to the toxicity of commercial CNTs to freshwater algae, with growth rates significantly reduced by as much as 200%., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Hemimandibular hyperplasia (HH), also known as hemimandibular hypertrophy, is characterised by excessive unilateral three-dimensional growth of the mandible after birth. Vertical elongation of the mandible on one side becomes clinically evident as a rare form of vertical facial asymmetry. Aberrant growth of the facial skeleton affects the developing dentition and dental compensation is usually unable to maintain optimal occlusal relationships. The resulting malocclusion is best managed surgically to address the various facial, skeletal and dental problems that confront clinicians., Aim: To present a case of hemimandibular hyperplasia treated using a combined surgical-orthodontic approach., Methods: Combined surgical-orthodontic treatment was accomplished in four phases: 1) presurgical orthodontic, 2) surgical, 3) post-surgical orthodontic and 4) orthodontic retention. Comprehensive records (including photographs, study models and radiographs) were taken at the pre-treatment, pre-surgery and debanding stages of treatment., Results: A significant improvement in facial symmetry and a positive occlusal outcome were achieved. A more balanced gingival display has improved the patient's smile aesthetics., Conclusion: Hemimandibular hyperplasia is a rare condition causing vertical facial asymmetry and a resulting malocclusion. A combined surgical-orthodontic approach is able to accomplish sound facial, skeletal and dental treatment outcomes.

Significant advances have been made on our understanding of the fate and transport of engineered nanomaterials. One unexplored aspect of nanoparticle aggregation is how environmental stimuli such as light exposure and temperature variations affect the mobility of engineered nanoparticles. In this study, TiO(2), ZnO, and CeO(2) were chosen as model materials for investigating the mobility of nanoparticles under three external stimuli: heat, light and sonication. Sunlight and high power sonication were able to partially disagglomerate metal oxide clusters, but primary particles bonded by solid state necks were left intact. A cycle of temperature increase from 25°C to 65°C and then decrease back was found to disagglomerate the compact clusters in the heating phase and reagglomerate them as more open fractal structures during the cooling phase. A fractal model summing the pair-wise DLVO interactions between primary particles within two fractal agglomerates predicts weak attractions on the order of a few kT. Our study shows that common environmental stimuli such as light exposure or temperature variation can disagglomerate nanoparticle clusters and enhance their mobility in open waters. This phenomenon warrants attention since it is likely that metal oxide nanoparticles will experience these natural stimuli during their transport in the environment.

Escherichia coli nucleoside diphosphate kinase (Ndk) catalyzes ATP-dependent synthesis of ribo- and deoxyribonucleoside triphosphates from the cognate diphosphate precursor. Recently, the Ndk polypeptide was reported to be a multifunctional base excision repair nuclease that processed uracil residues in DNA by acting sequentially as a uracil-DNA glycosylase inhibitor protein (Ugi)-sensitive uracil-DNA glycosylase, an apurinic/apyrimidiniclyase, and a 3'-phosphodiesterase [Postel, E. H. & Abramczyk, B. M. (2003) Proc. Natl. Acad. Sci. USA 100, 13247-13252]. Here we demonstrate that the E. coli Ndk polypeptide lacked detectable uracil-DNA glycosylase activity and, hence, was incapable of acting as a uracil-processing DNA repair nuclease. This finding was based on the following observations: (i) uracil-DNA glycosylase activity did not copurify with Ndk activity; (ii) Ndk purified from E. coli ung(-) cells showed no detectable uracil-DNA glycosylase activity; and (iii) Ndk failed to bind to a Ugi-Sepharose affinity column that tightly bound E. coli uracil-DNA glycosylase (Ung). Collectively, these observations demonstrate that the E. coli Ndk polypeptide does not possess inherent uracil-DNA glycosylase activity.