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In celebration of the National Institute on Aging's (NIA) 50th anniversary, this paper highlights the significant advances in cognitive aging research and the promotion of cognitive health among older adults. Since its inception in 1974, the NIA has played a pivotal role in understanding cognitive aging, including cognitive epidemiology, interventions, and methods, for measuring cognitive change. Key milestones include the shift toward understanding cognitive impairment and Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD), the development of large-scale longitudinal studies, and the incorporation of AD/ADRD-related biomarkers in cognitive aging cohorts. Additionally, NIA has championed diversifying the scientific workforce through initiatives, such as the Resource Centers for Minority Aging Research and the Butler-Williams Scholars Program. The next 50 years will continue to emphasize the importance of inclusion, innovation, and impactful research to enhance the cognitive health and well-being of older adults., (Published by Oxford University Press on behalf of The Gerontological Society of America 2024.)

The in vivo three-dimensional genomic architecture of adult mature neurons at homeostasis and after medically relevant perturbations such as axonal injury remains elusive. Here we address this knowledge gap by mapping the three-dimensional chromatin architecture and gene expression programme at homeostasis and after sciatic nerve injury in wild-type and cohesin-deficient mouse sensory dorsal root ganglia neurons via combinatorial Hi-C and RNA-seq. We find that cohesin is required for the full induction of the regenerative transcriptional program, by organising 3D genomic domains required for the activation of regenerative genes. Importantly, loss of cohesin results in disruption of chromatin architecture at regenerative genes and severely impaired nerve regeneration. Together, these data provide an original three-dimensional chromatin map of adult sensory neurons in vivo and demonstrate a role for cohesin-dependent chromatin interactions in neuronal regeneration., Competing Interests: COMPETING INTEREST All the authors declare no competing interests

Abdominal pain is a cardinal symptom of inflammatory bowel disease (IBD). Transient receptor potential (TRP) channels contribute to abdominal pain in preclinical models of IBD, and TRP melastatin 3 (TRPM3) has recently been implicated in inflammatory bladder and joint pain in rodents. We hypothesized that TRPM3 is involved in colonic sensation and is sensitized during colitis. We used immunohistochemistry, ratiometric Ca 2+ imaging, and colonic afferent nerve recordings in mice to evaluate TRPM3 protein expression in colon-projecting dorsal root ganglion (DRG) neurons, as well as functional activity in DRG neurons and colonic afferent nerves. Colitis was induced using dextran sulfate sodium (DSS) in drinking water. TRPM3 protein expression was observed in 76% of colon-projecting DRG neurons and was often colocalized with calcitonin gene-related peptide. The magnitudes of intracellular Ca 2+ transients in DRG neurons in response to the TRPM3 agonists CIM-0216 and pregnenolone sulfate sodium were significantly greater in neurons from mice with colitis compared with controls. In addition, the percentage of DRG neurons from mice with colitis that responded to CIM-0216 was significantly increased. CIM-0216 also increased the firing rate of colonic afferent nerves from control and mice with colitis. The TRPM3 inhibitor isosakuranetin inhibited the mechanosensitive response to distension of wide dynamic range afferent nerve units from mice with colitis but had no effect in control mice. Thus, TRPM3 contributes to colonic sensory transduction and may be a potential target for treating pain in IBD. NEW & NOTEWORTHY This is the first study to characterize TRPM3 protein expression and function in colon-projecting DRG neurons. A TRPM3 agonist excited DRG neurons and colonic afferent nerves from healthy mice. TRPM3 agonist responses in DRG neurons were elevated during colitis. Inhibiting TRPM3 reduced the firing of wide dynamic range afferent nerves from mice with colitis but had no effect in control mice.

Study Design: This study is a single-phase, qualitative study using grounded theory methodology., Introduction: Cumulative trauma disorders (CTDs) are musculoskeletal disorders that impact health and productivity. CTD risk factors are present in the workplace, home, and community. Occupational and physical therapists specializing in hand and upper extremity rehabilitation (hand therapists) are widely involved with this population. Hand therapists often employ a medical model in the assessment and treatment of these conditions; however, the medical model has not proven to be consistently effective in relieving symptoms or producing a durable return to daily living activities., Purpose of the Study: The purpose of this study was to explore the lived experiences of individuals diagnosed with CTD, and investigate the psychosocial phenomena influencing CTD development as an impediment to occupational performance., Methods: The principal investigator recruited 11 participants who met specific inclusion criteria, then used semi-structured interviews aimed at exploring the lived experiences of the participants while investigating the psychosocial phenomenon influencing CTD development. Interviews were transcribed and analyzed using a process of constant comparison, up until saturation occurred. Trustworthiness techniques were used in the data analysis phase and included peer reviews and member checking., Findings: The findings suggest that many psychosocial factors contribute to the development and impact of CTDs, at both onset of symptoms and throughout the duration of the condition. A significant number of contextual factors influence participants' function, behavior, relationships, and the course of medical care. Themes derived from the participants' expressions, included the following: 1) an initial strategy of "work through the pain," can be detrimental to symptom resolution and leads to progressive failure to meet role expectations, 2) a pervasive notion of CTDs as "an invisible disability," leaving participants feeling isolated and frustrated when significant others fail to offer support or reject them, 3) participants often delayed reporting symptom development to employers, family members, and medical personnel, risking permanent injury and disability, 4) a "stigma" is attached to CTDs that encourages isolation; however, the social support of even one significant other in a person's life can facilitate adaptation., Discussion and Conclusion: All participants experienced hardship because of their conditions; however, two of the eleven participants capably navigated the process, using past experience and support from family and employer to successfully adapt. These findings offer support that CTDs are adaptive disorders. The study's conclusion suggests a new model to describe CTD dysfunction and presents new ways of thinking for clinicians who treat the CTD population., (Copyright © 2021. Published by Elsevier Inc.)

Many marine animals have evolved sensory abilities to use electric and magnetic cues in essential aspects of life history, such as to detect prey, predators and mates as well as to orientate and migrate. Potential disruption of vital cues by human activities must be understood in order to mitigate potential negative influences. Cable deployments in coastal waters are increasing worldwide, in capacity and number, owing to growing demands for electrical power and telecommunications. Increasingly, the local electromagnetic environment used by electro- and magneto-sensitive species will be altered. We quantified biologically relevant behavioural responses of the presumed, magneto-receptive American lobster and the electro-sensitive Little skate to electromagnetic field (EMF) emissions of a subsea high voltage direct current (HVDC) transmission cable for domestic electricity supply. We demonstrate a striking increase in exploratory/foraging behaviour in skates in response to EMF and a more subtle exploratory response in lobsters. In addition, by directly measuring both the magnetic and electric field components of the EMF emitted by HVDC cables we found that there were DC and unexpectedly AC components. Modelling, restricted to the DC component, showed good agreement with measured results. Our cross-disciplinary study highlights the need to integrate an understanding of the natural and anthropogenic EMF environment together with the responses of sensitive animals when planning future cable deployments and predicting their environmental effects.

Aim: To assess the effect of treating chronic hepatitis C virus (HCV) infection with direct acting antiviral drugs (DAAs) on glycemic control in patients with concomitant diabetes mellitus (DM)., Methods: We performed a retrospective case-control study in a viral hepatitis ambulatory clinic in Shreveport, Louisiana, during the period 11/01/2014 to 12/31/2017. All the clinic patient ages 18 years and above with treatment-naïve/biopsy-proven chronic hepatitis C and DM (hemoglobin A1C level ≥ 6.5%) who were eligible for treatment were included in the study. Of 118 such patients, 59 were treated with oral DAAs for 8-12 weeks with the goal of achieving a sustained virologic response (SVR). A control group of 59 patients did not receive treatment for their hepatitis C and was followed in the clinic. Patients in the control group did not receive treatment either due to insurance issues or refusal of hepatitis C treatment., Results: Fifty-five of the 59 patients treated with DAAs (93%) achieved a SVR. Six months after treatment completion, their mean ± SEM HbA1C level had decreased by 1.1 ± 0.03% ( P < 0.0001). Four of the 59 patients treated with DAAs did not achieve a SVR. Their mean HbA1C 6 months after treatment completion had increased by 0.8 ± 0.2%. Furthermore, there was no improvement in HbA1C levels over time in the untreated group (mean HbA1C increase, 0.2 ± 0.05%; P < 0.0001 vs. the treatment group, which had a mean HbA1C decrease of 0.9 ± 0.2%)., Conclusion: This controlled study demonstrated that treatment of chronic hepatitis C with DAAs results in statistically significant and meaningful reductions in hemoglobin A1C levels in patients with coexisting diabetic mellitus if a SVR is achieved., Competing Interests: All the authors declared no financial/potential personal conflicts of interests., (Copyright © 2020 Pradeep Kumar Mada et al.)

In 2014, ISHAM formed a new working group: "Medical Phycology: Protothecosis and Chlorellosis." The purpose of this working group is to help facilitate collaboration and communication among people interested in the pathogenic algae, to share ideas and work together. Here we present reports on recent work we have done in five areas. 1. The history of medical phycology as a branch of science. 2. Aspects of the genetics of Prototheca. 3. Aspects of the proteins of Prototheca. 4. Human infections caused by Prototheca. 5. Dairy cow mastitis caused by Prototheca.

The goal of the NIH Science of Behavior Change (SOBC) Common Fund Program is to provide the basis for an experimental medicine approach to behavior change that focuses on identifying and measuring the mechanisms that underlie behavioral patterns we are trying to change. This paper frames the development of the program within a discussion of the substantial disease burden in the U.S. attributable to behavioral factors, and details our strategies for breaking down the disease- and condition-focused silos in the behavior change field to accelerate discovery and translation. These principles serve as the foundation for our vision for a unified science of behavior change at the NIH and in the broader research community., (Copyright © 2017. Published by Elsevier Ltd.)

Impacts of invasive species are context dependent and linked to the ecosystem they occur within. To broaden the understanding of the impact of a globally widespread invasive oyster, Crassostrea ( Magallana ) gigas, intertidal surveys were carried out at 15 different sites in Europe. The impact of C. gigas on macro- (taxa surrounding oyster > 1 cm) and epifaunal (taxa on oyster < 1 cm) benthic communities and α and β-diversity was assessed and compared to those associated with native ecosystem engineers, including the flat oyster Ostrea edulis . Whilst the effect of C. gigas on benthic community structures was dependent on habitat type, epifaunal communities associated with low densities of O. edulis and C. gigas did not differ and changes in benthic assemblage structure owing to the abundance of C. gigas were therefore attributed to the presence of oyster shells. Macrofaunal α-diversity increased with C. gigas cover in muddy habitats, while epifaunal α-diversity decreased at greater oyster densities. Macrofaunal β-diversity was greatest at low densities of C. gigas ; however, it did not differ between samples without and increased densities of oysters. In contrast, epifaunal β-diversity decreased with increasing oyster cover. Different environmental contexts enabled more independent predictions of the effect of C. gigas on native communities. These were found to be low and more importantly not differing from O. edulis . This indicates that, at low densities, C. gigas may be functionally equivalent to the declining native oyster in terms of biodiversity facilitation and aid in re-establishing benthic communities on shores where O. edulis has become extinct., Competing Interests: Compliance with ethical standardsThe authors declare that they have no conflict of interest.All applicable international, national and institutional guidelines for the use of animals were followed.

Objective: To evaluate and compare the long-term skeletodental stability of mandibular symphyseal distraction osteogenesis (MSDO) achieved with the use of tooth-borne vs. hybrid distraction appliances., Materials and Methods: Posttreatment and follow-up orthodontic records were collected for 33 patients. The 14 patients who underwent distraction with a tooth-borne appliance had a mean follow-up of 5.08 years. The 19 patients who underwent distraction with a hybrid appliance had a mean follow-up of 6.07 years. Records included intraoral photographs, study models, postero-anterior cephalometric radiographs, and lateral cephalometric radiographs. Total changes of 16 measurements were analyzed to compare patients who underwent the tooth-borne vs. the hybrid distraction., Results: Both groups shared several similar and significant (P < .05) changes from posttreatment to follow-up records. Cast analysis showed a decrease in intercanine width and arch length and an increase in irregularity index. The postero-anterior cephalometric radiograph showed an increase in the width of the interincisal apices. The lateral cephalometric radiograph showed a decrease in the MP-L1 angle. The only statistically significant difference between the two appliances was the intercentral incisor contact point., Conclusion: Changes found are consistent with those found in untreated and orthodontically treated individuals over time. The long-term changes in the current patient sample can be determined to be expected and acceptable. MSDO is a viable treatment option with the use of either a hybrid or tooth-borne appliance.

Long paleoecological records are critical for understanding evolutionary responses to environmental forcing and unparalleled tools for elucidating the mechanisms that lead to the development of regions of high biodiversity. We use a 1.2-My record from Lake Malawi, a textbook example of biological diversification, to document how climate and tectonics have driven ecosystem and evolutionary dynamics. Before ∼800 ka, Lake Malawi was much shallower than today, with higher frequency but much lower amplitude water-level and oxygenation changes. Since ∼800 ka, the lake has experienced much larger environmental fluctuations, best explained by a punctuated, tectonically driven rise in its outlet location and level. Following the reorganization of the basin, a change in the pacing of hydroclimate variability associated with the Mid-Pleistocene Transition resulted in hydrologic change dominated by precession rather than the high-latitude teleconnections recorded elsewhere. During this time, extended, deep lake phases have abruptly alternated with times of extreme aridity and ecosystem variability. Repeated crossings of hydroclimatic thresholds within the lake system were critical for establishing the rhythm of diversification, hybridization, and extinction that dominate the modern system. The chronology of these changes closely matches both the timing and pattern of phylogenetic history inferred independently for the lake's extraordinary array of cichlid fish species, suggesting a direct link between environmental and evolutionary dynamics., Competing Interests: The authors declare no conflict of interest.

Introduction: Members of the healthcare team must access and share patient information to coordinate interprofessional collaborative practice (ICP). Although some evidence suggests that electronic health records (EHRs) contribute to in-team communication breakdowns, EHRs are still widely hailed as tools that support ICP. If EHRs are expected to promote ICP, researchers must be able to longitudinally study the impact of EHRs on ICP across communication types, users, and physical locations., Objective: This paper presents a data collection and analysis tool, named the Map of the Clinical Interprofessional Communication Spaces (MCICS), which supports examining how EHRs impact ICP over time, and across communication types, users, and physical locations., Methods: The tool's development evolved during a large prospective longitudinal study conducted at a Canadian pediatric academic tertiary-care hospital. This two-phased study [i.e., pre-implementation (phase 1) and post implementation (phase 2)] of an EHR employed a constructivist grounded theory approach and triangulated data collection strategies (i.e., non-participant observations, interviews, think-alouds, and document analysis). The MCICS was created through a five-step process: (i) preliminary structural development based on the use of the paper-based chart (phase 1); (ii) confirmatory review and modification process (phase 1); (iii) ongoing data collection and analysis facilitated by the map (phase 1); (iv) data collection and modification of map based on impact of EHR (phase 2); and (v) confirmatory review and modification process (phase 2)., Results: Creating and using the MCICS enabled our research team to locate, observe, and analyze the impact of the EHR on ICP, (a) across oral, electronic, and paper communications, (b) through a patient's passage across different units in the hospital, (c) across the duration of the patient's stay in hospital, and (d) across multiple healthcare providers. By using the MCICS, we captured a comprehensive, detailed picture of the clinical milieu in which the EHR was implemented, and of the intended and unintended consequences of the EHR's deployment. The map supported our observations and analysis of ICP communication spaces, and of the role of the patient chart in these spaces., Conclusions: If EHRs are expected to help resolve ICP challenges, it is important that researchers be able to longitudinally assess the impact of EHRs on ICP across multiple modes of communication, users, and physical locations. Mapping the clinical communication spaces can help EHR designers, clinicians, educators and researchers understand these spaces, appreciate their complexity, and navigate their way towards effective use of EHRs as means for supporting ICP. We propose that the MCICS can be used "as is" in other academic tertiary-care pediatric hospitals, and can be tailored for use in other healthcare institutions., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Interactions between climate, fire and CO2 are believed to play a crucial role in controlling the distributions of tropical woodlands and savannas, but our understanding of these processes is limited by the paucity of data from undisturbed tropical ecosystems. Here we use a 28,000-year integrated record of vegetation, climate and fire from West Africa to examine the role of these interactions on tropical ecosystem stability. We find that increased aridity between 28-15 kyr B.P. led to the widespread expansion of tropical grasslands, but that frequent fires and low CO2 played a crucial role in stabilizing these ecosystems, even as humidity changed. This resulted in an unstable ecosystem state, which transitioned abruptly from grassland to woodlands as gradual changes in CO2 and fire shifted the balance in favor of woody plants. Since then, high atmospheric CO2 has stabilized tropical forests by promoting woody plant growth, despite increased aridity. Our results indicate that the interactions between climate, CO2 and fire can make tropical ecosystems more resilient to change, but that these systems are dynamically unstable and potentially susceptible to abrupt shifts between woodland and grassland dominated states in the future.

Background: Detection, monitoring and treatment of adverse drug reactions (ADRs) are paramount to patient safety. The use of a comprehensive electronic health record (EHR) system has the potential to address inadequacies in ADR documentation and to facilitate ADR reporting to health agencies. However, effective methods to maintain the quality of documented ADRs within an EHR have not been well studied., Objective: To evaluate the accuracy and effectiveness of ADR documentation transfer throughout the implementation of a comprehensive EHR system., Methods: Retrospective analysis of ADR documentation at a tertiary care pediatric hospital between January 2013 and June 2014. ADRs documented in the newly implemented ambulatory EHR, pharmacy system and hybrid health record system were extracted. Documentation inconsistencies and processes for managing ADR documentation within the EHR were reviewed., Results: A total of 115 patients with 260 unique ADRs were identified. Only 155 (60 %) of the identified ADRs were found in the ambulatory EHR system. The remaining 105 ADRs (40 %) were missing from the EHR when it was compared with the other systems. Seventy-two patients (63 %) returned for a follow-up visit, and each had their ADR documentation reviewed in the ambulatory EHR. Following the visit, 44 % of these ambulatory EHR records still included incorrect information., Conclusions: We identified discrepancies in ADR documentation within hospital systems, which need to be addressed as healthcare institutions transition to EHRs. Processes related to the transfer of ADR information into the EHR should be clearly defined. To improve the quality of ADR documentation, steps to force complete and continual ADR verification should be introduced at early stages of implementation of a new EHR, and all responsible providers should play a role., Competing Interests: Compliance with Ethical Standards Ethical approval This study was approved in accordance with the ethical standards set by the Children’s Hospital of Eastern Ontario Research Ethics Board, under the Protocol No. 14/82X. Funding Funding to conduct this work was provided by the Children’s Hospital of Eastern Ontario Research Institute Studentship program and by the Canadian Pharmacogenomics Network for Drug Safety. Conflict of interest Caleb Hui, Regis Vaillancourt, Lissa Bair, Elaine Wong and James W. King have no relevant conflicts of interests to declare.

The transport of moisture in the tropics is a critical process for the global energy budget and on geologic timescales, has markedly influenced continental landscapes, migratory pathways, and biological evolution. Here we present a continuous, first-of-its-kind 1.3-My record of continental hydroclimate and lake-level variability derived from drill core data from Lake Malawi, East Africa (9-15° S). Over the Quaternary, we observe dramatic shifts in effective moisture, resulting in large-scale changes in one of the world's largest lakes and most diverse freshwater ecosystems. Results show evidence for 24 lake level drops of more than 200 m during the Late Quaternary, including 15 lowstands when water levels were more than 400 m lower than modern. A dramatic shift is observed at the Mid-Pleistocene Transition (MPT), consistent with far-field climate forcing, which separates vastly different hydroclimate regimes before and after ∼800,000 years ago. Before 800 ka, lake levels were lower, indicating a climate drier than today, and water levels changed frequently. Following the MPT high-amplitude lake level variations dominate the record. From 800 to 100 ka, a deep, often overfilled lake occupied the basin, indicating a wetter climate, but these highstands were interrupted by prolonged intervals of extreme drought. Periods of high lake level are observed during times of high eccentricity. The extreme hydroclimate variability exerted a profound influence on the Lake Malawi endemic cichlid fish species flock; the geographically extensive habitat reconfiguration provided novel ecological opportunities, enabling new populations to differentiate rapidly to distinct species.

Context: As electronic health records (EHRs) are adopted by teaching hospitals, educators must examine how this change impacts trainee development., Objectives: We investigate this influence by studying clinician experiences of a hospital's move from paper charts to an EHR. We ask: how does each chart modality present conceptions of time and data interconnections? How do these conceptions affect clinical reasoning?, Methods: This two-phase, longitudinal study employed constructivist grounded theory. Data were collected at a paediatric teaching hospital before (Phase 1), during and after (Phase 2) the transition from a paper chart to an EHR system. Data collection consisted of field observations (146 hours involving 300 health care providers, 22 patients and 32 patient family members), think-aloud (n = 13) and think-after (n = 11) sessions, interviews (n = 39) and document retrieval (n = 392). Theories of rhetorical genre studies and visual rhetoric informed analysis., Results: In the paper flowsheet, clinicians recorded and viewed patient data in chronologically organised displays that emphasised data interconnections. In the EHR flowsheet, clinicians viewed and recorded individual data points that were largely chronologically and contextually isolated. Clinicians reported that this change resulted in: (i) not knowing the patient's evolving status; (ii) increased cognitive workload, and (iii) loss of clinical reasoning support mechanisms., Conclusions: Understanding how patient data are interconnected is essential to clinical reasoning. The use of EHRs supports this goal because the EHR is a tool for collecting dispersed data; however, these collections often deconstruct data interconnections. Where the paper flowsheet emphasises chronology and interconnectedness, the EHR flowsheet emphasises individual data values that are largely independent of time and other patient data. To prepare trainees to work with EHRs, the ways of thinking and acting that were implicitly learned through the use of paper charts must be made explicit. To support clinical reasoning, medical educators should provide lessons in connectivity – the chronologically framed data interconnections upon which clinicians rely to provide patient care., (© 2015 John Wiley & Sons Ltd.)

The monsoon is a fundamental component of Earth's climate. The Pliocene warm period is characterized by long-term global cooling yet concurrent monsoon dynamics are poorly known. Here we present the first fully quantified and calibrated reconstructions of separate Pliocene air temperature and East Asian summer monsoon precipitation histories on the Chinese Loess Plateau through joint analysis of loess/red clay magnetic parameters with different sensitivities to air temperature and precipitation. East Asian summer monsoon precipitation shows an intensified trend, paradoxically at the same time that climate cooled. We propose a hitherto unrecognized feedback where persistently intensified East Asian summer monsoon during the late Pliocene, triggered by the gradual closure of the Panama Seaway, reinforced late Pliocene Pacific freshening, sea-ice development and ice volume increase, culminating in initiation of the extensive Northern Hemisphere glaciations of the Quaternary Ice Age. This feedback mechanism represents a fundamental reinterpretation of the origin of the Quaternary glaciations and the impact of the monsoon.

The Indo-Pacific warm pool houses the largest zone of deep atmospheric convection on Earth and plays a critical role in global climate variations. Despite the region's importance, changes in Indo-Pacific hydroclimate on orbital timescales remain poorly constrained. Here we present high-resolution geochemical records of surface runoff and vegetation from sediment cores from Lake Towuti, on the island of Sulawesi in central Indonesia, that continuously span the past 60,000 y. We show that wet conditions and rainforest ecosystems on Sulawesi present during marine isotope stage 3 (MIS3) and the Holocene were interrupted by severe drying between ∼33,000 and 16,000 y B.P. when Northern Hemisphere ice sheets expanded and global temperatures cooled. Our record reveals little direct influence of precessional orbital forcing on regional climate, and the similarity between MIS3 and Holocene climates observed in Lake Towuti suggests that exposure of the Sunda Shelf has a weaker influence on regional hydroclimate and terrestrial ecosystems than suggested previously. We infer that hydrological variability in this part of Indonesia varies strongly in response to high-latitude climate forcing, likely through reorganizations of the monsoons and the position of the intertropical convergence zone. These findings suggest an important role for the tropical western Pacific in amplifying glacial-interglacial climate variability.

Objective: To evaluate and compare, retrospectively, the skeletal and dental effects of mandibular symphyseal distraction osteogenesis (MSDO) achieved through the use of tooth-borne versus hybrid distractors., Materials and Methods: Pretreatment (T1), predistraction (T2), postdistraction (T3), and posttreatment (T4) orthodontic records were collected and analyzed for 47 patients (20 tooth-borne, 27 hybrid). At each time point, records included intraoral photographs, study models, postero-anterior cephalometric radiographs, and lateral cephalometric radiographs. Submental vertex radiographs were taken at T2, T3, and T4. Changes in a total of 18 measurements were analyzed to compare patients undergoing tooth-borne versus hybrid distraction., Results: The cumulative effects of orthodontics and MSDO produced similar gains in measured arch widths, with a decreased irregularity index in both groups (P > .05). However, there were differences in the timing during which the expansion was achieved. The hybrid distractor group gained space during the distraction phase of treatment. The tooth-borne group showed greater gains during pre- and postdistraction orthodontics. Comparisons of intercanine and interbone marker widths demonstrated a more parallel separation of bone during distraction with the hybrid distractor (P < .001). Distraction with the tooth-borne distractor was disproportionate, with greater separation of the canines in alveolar bone than of the bone markers in basal bone. During postdistraction orthodontics, the tooth-borne distractor group showed statistically greater increases in measurements., Conclusion: Both skeletal and dental expansion was achieved with both appliances. Greater skeletal expansion was achieved with a hybrid distractor. Greater dental expansion was achieved with a tooth-borne distractor.

Objectives: To determine the effects of cognitive training on cognitive abilities and everyday function over 10 years., Design: Ten-year follow-up of a randomized, controlled single-blind trial (Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE)) with three intervention groups and a no-contact control group., Setting: Six U.S. cities., Participants: A volunteer sample of 2,832 persons (mean baseline age 73.6; 26% African American) living independently., Intervention: Ten training sessions for memory, reasoning, or speed of processing; four sessions of booster training 11 and 35 months after initial training., Measurements: Objectively measured cognitive abilities and self-reported and performance-based measures of everyday function., Results: Participants in each intervention group reported less difficulty with instrumental activities of daily living (IADLs) (memory: effect size = 0.48, 99% confidence interval (CI) = 0.12-0.84; reasoning: effect size = 0.38, 99% CI = 0.02-0.74; speed of processing: effect size = 0.36, 99% CI = 0.01-0.72). At a mean age of 82, approximately 60% of trained participants, versus 50% of controls (P < .05), were at or above their baseline level of self-reported IADL function at 10 years. The reasoning and speed-of-processing interventions maintained their effects on their targeted cognitive abilities at 10 years (reasoning: effect size = 0.23, 99% CI = 0.09-0.38; speed of processing: effect size = 0.66, 99% CI = 0.43-0.88). Memory training effects were no longer maintained for memory performance. Booster training produced additional and durable improvement for the reasoning intervention for reasoning performance (effect size = 0.21, 99% CI = 0.01-0.41) and the speed-of-processing intervention for speed-of-processing performance (effect size = 0.62, 99% CI = 0.31-0.93)., Conclusion: Each Advanced Cognitive Training for Independent and Vital Elderly cognitive intervention resulted in less decline in self-reported IADL compared with the control group. Reasoning and speed, but not memory, training resulted in improved targeted cognitive abilities for 10 years., (© 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.)

This review provides an update on the use of supercritical fluid (SCF) technology as applied to food-based materials. It advocates the use of the solubility parameter theory (SPT) for rationalizing the results obtained when employing sub- and supercritical media to food and nutrient-bearing materials and for optimizing processing conditions. Total extraction and fractionation of foodstuffs employing SCFs are compared and are illustrated by using multiple fluids and unit processes to obtain the desired food product. Some of the additional prophylactic benefits of using carbon dioxide as the processing fluid are explained and illustrated with multiple examples of commercial products produced using SCF media. I emphasize the role of SCF technology in the context of environmentally benign and sustainable processing, as well as its integration into an overall biorefinery concept. Conclusions are drawn in terms of current trends in the field and future research that is needed to secure new applications of the SCF platform as applied in food science and technology.

Approximately 50% of patients with cutaneous metastatic melanoma harbor a somatic BRAF mutation. BRAF inhibitors are now established in the treatment paradigm of BRAF mutant melanoma, following the approval of vemurafenib by the US FDA in 2011. The vast majority of patients obtain some degree of tumor shrinkage with oral BRAF inhibitors, and responses are often rapid. However, resistance inevitably develops, with a median progression-free survival of 5-7 months. The oral MEK inhibitor trametinib has also shown activity in BRAF mutant melanoma in Phase III trials. We review the rationale for treating BRAF mutant melanoma with trametinib, as single-agent therapy and in combination with BRAF inhibitors, as well as the clinical data to date.

Introduction: Lung cancer is the most frequently diagnosed cancer in men and comprises 23% of total cancer deaths worldwide. The majority of patients present with advanced disease, for whom the 5-year survival is < 5%. Since angiogenesis plays a central role in tumourigenesis, inhibiting this pathway may improve outcomes in non-small-cell lung cancer (NSCLC). Axitinib is one of the latest and most potent anti-angiogenic tyrosine kinase inhibitors (TKI) currently being evaluated to treat NSCLC., Areas Covered: In this review, the rationale for targeting angiogenesis in lung cancer, other angiogenic agents in NSCLC, axitinib's mechanism of action, pharmacology and metabolism, and the preclinical and clinical data to date in NSCLC will be discussed., Expert Opinion: Several TKI which target angiogenesis pathways have resulted in improved response rates and progression-free survival in NSCLC, but no improvement in overall survival in clinical trials. Axitinib is a more potent inhibitor of vascular endothelial growth factor receptors than other TKI, but this has yet to translate into a clinical benefit. Phase II trials are ongoing, but the published data to date has yet to support a role for axitinib in the treatment algorithm for NSCLC.

Cognition is 1 of 4 domains measured by the NIH Toolbox for the Assessment of Neurological and Behavioral Function (NIH-TB), and complements modules testing motor function, sensation, and emotion. On the basis of expert panels, the cognition subdomains identified as most important for health, success in school and work, and independence in daily functioning were Executive Function, Episodic Memory, Language, Processing Speed, Working Memory, and Attention. Seven measures were designed to tap constructs within these subdomains. The instruments were validated in English, in a sample of 476 participants ranging in age from 3 to 85 years, with representation from both sexes, 3 racial/ethnic categories, and 3 levels of education. This report describes the development of the Cognition Battery and presents results on test-retest reliability, age effects on performance, and convergent and discriminant construct validity. The NIH-TB Cognition Battery is intended to serve as a brief, convenient set of measures to supplement other outcome measures in epidemiologic and longitudinal research and clinical trials. With a computerized format and national standardization, this battery will provide a "common currency" among researchers for comparisons across a wide range of studies and populations.

We present a Prototheca wickerhamii wound infection case that failed treatment with ketoconazole but was cured with amphotericin-B plus tetracycline. The patient was immunocompetent but had had local steroid injections. We reviewed another 159 cases from the literature. Prototheca has infected many areas of the human body, but most often skin, olecranon bursa, or wounds. Prior treatment with steroids and immune deficiencies are contributing factors. Itraconazole and fluconazole are reasonable initial treatments for patients with mild infections. For serious infections, or for infections that have failed azole treatment, amphotericin-B is the treatment of choice.

Aims: To evaluate the relationship between preoperative resting arterial blood pressure and postoperative pain in patients undergoing nonsurgical root canal therapy., Methods: Written informed consent was obtained from normotensive patients seeking treatment for teeth with a preoperative diagnosis of pulpal necrosis and periradicular periodontitis. Preoperative resting blood pressure was recorded, and nonsurgical root canal therapy was initiated using a standardized protocol. Patients recorded their pre- and postoperative pain intensity on a 100-mm visual analog scale (VAS) for 7 days after the procedure. A linear regression model to predict postoperative VAS intensity used preoperative pain and blood pressure values as covariates. Pearson correlations were calculated to assess the relationship between the measures of preoperative blood pressure and both pre- and postoperative pain., Results: After controlling for preoperative pain, significant correlations were observed between preoperative systolic blood pressure and postoperative pain (P < .05), as well as between preoperative pulse pressure and postoperative pain (P < .005) on day 1., Conclusion: This study has provided further evidence of a functional interaction between the cardiovascular and trigeminal pain regulatory systems. Understanding this complex relationship may lead to enhanced pain management strategies.

Systematic cognitive training produces long-term improvement in cognitive function and less difficulty in performing activities of daily living. We examined whether cognitive training was associated with reduced rate of incident dementia. Participants were from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study (n = 2,802). Incident dementia was defined using a combination of interview- and performance-based methods. Survival analysis was used to determine if ACTIVE treatment affected the rate of incident dementia during 5 years of follow-up. A total of 189 participants met criteria for incident dementia. Baseline factors predictive of incident dementia were older age, male gender, African American race, fewer years of education, relationship other than married, no alcohol use, worse MMSE, worse SF-36 physical functioning, higher depressive symptomatology, diabetes, and stroke (all p < .05). A multivariable model with significant predictors of incident dementia and training group revealed that cognitive training was not associated with a lower rate of incident dementia. Cognitive training did not affect rates of incident dementia after 5 years of follow-up. Longer follow-up or enhanced training may be needed to fully explore the preventive capacity of cognitive training in forestalling onset of dementia.

Grape pomace contains appreciable amounts of polyphenolic compounds such as anthocyanins and procyanidins which can be recovered for use as food supplements. The extraction of these polyphenols from the pomace is usually accomplished at slightly elevated temperatures, frequently employing hydroethanolic solvents. Due to governmental regulations and the cost involved in using ethanol as a solvent, as well as the loss in polyphenolics due to thermal degradation, improved extraction techniques are required. In this study, a semicontinuous extraction apparatus employing only water was developed to maximize the recovery of anthocyanins and procyanidins from red grape pomace (Vitis vinifera). Water is preheated prior to its entry to the extraction cell containing the grape pomace sample, where it is allowed to then flow continuously through the unheated extraction vessel prior to its collection at ambient conditions. Extraction variables that impacted the polyphenolic recovery included pomace moisture content (crude or dried), sample mass, water flow rate, and extraction temperature. A response surface method was used to analyze the results from the extraction, and the optimal conditions were found to be 140 °C and 9 mL/min water flow rate. These conditions can produce an extract containing 130 mg/100 g DW of anthocyanins and 2077 mg/100 g DW of procyanidins. Higher yields of polyphenolics were observed using crude (wet) rather than dried pomace, hence avoiding the need to dry the pomace prior to extraction. The described semicontinuous extraction method using only water as the extraction solvent under subcritical conditions allowed the efficient extraction of polyphenols from red grape pomace without the attendant loss of polyphenolic content due to having to heat the extraction vessel prior to commencement of extraction.