Search

Laser epilation (LE) is effective in decreasing pilonidal disease (PD) recurrence, but laser use has not been a standard practice in pediatric surgery clinic. We hypothesized that "appointment tickets" can 1) track utilization and clinic visit delays, 2) inform patients of their clinic progress in real time. An observation study was performed on LE patients treated at our PD clinic 3/2021-7/2022. Two exam rooms were utilized for manual shaving and one for LE. After gluteal cleft hair shaving, various anesthetic (topical lidocaine, ice, or cryotherapy) was applied prior/during LE. At each visit, patient received an "appointment ticket" on which providers recorded the visit start/end time, manual shaving duration, local anesthetic application/wait time, LE duration. Visits were scheduled for 20 min-slots. Clinic staff recorded any delays (>20 min). 1317 visits were recorded. Mean number of visits per week was 18 ± 6. Mean total visit length was 60 ± 22 min, mean shaving time 15 ± 11 min, mean anesthetic application/wait time 16 ± 11 min, mean LE time 14 ± 9 min. Over the study period, average visit length has decreased, and average visits/clinic day has increased. Most delays occurred in months April, May, October–December. Delays due to patient late arrival occurred in May, July, and August of 2021, none in 2022. LE visits have multiple components that required close coordination to ensure no clinic delays. Clinic delays spiked prior to summer and winter holidays. "Appointment tickets" provided patients with real-time visit progress tracked clinic utilization to improve the quality of pilonidal care delivery. Level IV. [ABSTRACT FROM AUTHOR]

The objective of this study was to complete a comprehensive retrospective chart review of the mandible fracture patterns amongst trauma patients in an urban level 1 trauma hospital. The authors propose that an urban environment influences these patterns. We reviewed 1914 patient charts treated for 3946 facial fractures between 2008 and 2017. Those with mandibular fractures were studied in detail by collecting demographics, injury mechanism, location of injury, and treatment information. Wilcoxon-rank sum tests were used for comparing groups with continuous outcomes while Chi-square/Fisher's exact test was used for comparing groups with categorical outcomes of interest. 19.9% (382) of the 1914 patients who suffered facial trauma in this study suffered a mandible fracture. 382 (20%) of these patients suffered at least one mandible fracture, and of these 163 suffered fratures at multiple sites, totaling 577 fractures overall. 69% of the mandible fractures occurred in men and 31% in women. The median age of patients who sustained a mandible fracture was 33. The median age among males was 29, and females, 54. The most common site of mandible fracture was the ramus/angle of the mandible (30.3%). The most common mechanism of injury was a result of activities of daily living, such as falls. 73.9% (176) of all mandible fractures were treated with a combination of open reduction internal fixation and closed reduction maxillomandibular fixation. In an urban population, significant mandibular fractures may occur more frequently after non-classic low kinetic energy events, such as falls. Compared to other studies, our study more frequently included older, female patients, which may be reflective of urban demographics. It is important to maintain a high degree of suspicion for mandibular injuries in all urban facial trauma patients, regardless of mechanism. [ABSTRACT FROM AUTHOR]

• Mean ADC values are robust across different scanners with imaging protocol standardisation. • Radiomic features of ADC map in a homogeneous phantom show substantial variation between MRI systems, even after ComBat harmonisation. • Resampling to a smaller voxel size provides more repeatable and reproducible radiomic features than resampling to a larger voxel size. The aim of this study was to perform a quantitative quality assurance of diffusion-weighted MRI to assess the variability of the mean apparent diffusion coefficient (ADC) and other radiomic features across the scanners involved in the REGINA trial. The NIST/QIBA diffusion phantom was acquired on six 3 T scanners from five centres with a rectum-specific diffusion protocol. All sequences were repeated in each scan session without moving the phantom from the table. Linear interpolation to two isotropic voxel spacing (0.9 and 4 mm) was performed as well as the ComBat feature harmonisation method between scanners. The absolute accuracy error was evaluated for the mean ADC. Repeatability and reproducibility within-subject coefficients of variation (wCV) were computed for 142 radiomic features. For the mean ADC, accuracy error ranged between 0.1 % and 8.5 %, repeatability was <1 % and reproducibility was <3 % for diffusivity range between 0.4 and 1.1x10-3mm2/s. For the other radiomic features, wCV was below 10 % for 24 % and 15 % features for repeatability with resampling 0.9 mm and 4 mm, respectively, and 13 % and 11 % feature for reproducibility. ComBat method could improve significantly the wCV compared to reproducibility without ComBat (p-value < 0.001) but variation was still high for most of the features. Our study provided the first investigation of feature selection for development of robust predictive models in the REGINA trial, demonstrating the added value of such a quality assurance process to select conventional and radiomic features in prospective multicentre trials. [ABSTRACT FROM AUTHOR]

• Glucose has potent postoral actions (appetition) that enhance its reward value in C57BL/6 mice. • Glucose appetition is revealed in tests with initially preferred nonnutritive sweetener solutions. • Glucose appetition was similar in mice tested with 0.8% sucralose or 0.1% sucralose + 0.1% saccharin. • Glucose appetition was more pronounced in food-restricted then food ad lib mice. • Male and female mice displayed similar glucose appetition responses. In addition to its sweet taste, glucose has potent and rapid postoral actions (appetition) that enhance its reward value. This has been demonstrated by the experience-induced preference for glucose over initially preferred nonnutritive sweetener solutions in 24-h choice tests. However, some sweetener solutions (e.g., 0.8% sucralose) have inhibitory postoral actions that may exaggerate glucose appetition whereas others (e.g., 0.1% sucralose + 0.1% saccharin, S+S) do not. Experiment 1 revealed that food-restricted (FR) male C57BL/6J mice displayed similar rapid glucose appetition effects (stimulation of glucose licking within minutes) and conditioned flavor preferences following 1-h experience with flavored 0.8% sucralose or 0.1% S+S and 8% glucose solutions. Thus, the inhibitory effects of 0.8% sucralose observed in 24-h tests were not apparent in 1-h tests. Experiment 2 evaluated the effects of food deprivation state and sweetener concentration on glucose appetition in female mice. Unlike FR mice tested with 0.1% S+S and 8% glucose, ad libitum (AL) fed mice displayed no stimulation of 8% glucose licking in the 1-h tests. A second ad libitum group (AL) tested with 0.2% S+S and 16% glucose solutions displayed stimulation of 16% glucose licking by the third 1-h test. Both AL groups, like the FR group, developed a preference for the glucose-paired flavor over the S+S paired flavor. Thus, food restriction promotes increased glucose licking but is not required for a conditioned preference. The FR male mice (Exp. 1) and FR female mice (Exp. 2) showed similar appetition responses (licking stimulation and flavor preference) to 8% glucose. [ABSTRACT FROM AUTHOR]

As demonstrated in a recent study, the deep epigastric lymph node (DELN), at the level of the inferior epigastric artery, may represent a possible dissemination pathway for PMCRC, from the peritoneum to the extraperitoneal compartment.[3] The objective of our study was to evaluate the lymphatic pattern of recurrence, focusing on the previously overlooked DELN, in PMCRC patients treated with CRS. Moreover, patients with suspicious DELNs had a higher PCI (mean = 18) than patients in other groups suggesting that this pathway is essentially involved in patients with high peritoneal tumor burden. [Extracted from the article]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2006.09.035 Byline: Begona de Velasco (a), Ted Erclik (b)(c), Diana Shy (a), Joey Sclafani (a), Howard Lipshitz (b)(c), Roderick McInnes (b)(c), Volker Hartenstein (a) Keywords: Drosophila; Embryo; Pars intercerebralis; Neuroendocrine; Brain; Dchx Abstract: The central neuroendocrine system in the Drosophila brain includes two centers, the pars intercerebralis (PI) and pars lateralis (PL). The PI and PL contain neurosecretory cells (NSCs) which project their axons to the ring gland, a complex of peripheral endocrine glands flanking the aorta. We present here a developmental and genetic study of the PI and PL. The PI and PL are derived from adjacent neurectodermal placodes in the dorso-medial head. The placodes invaginate during late embryogenesis and become attached to the brain primordium. The PI placode and its derivatives express the homeobox gene Dchx1 and can be followed until the late pupal stage. NSCs labeled by the expression of Drosophila insulin-like peptide (Dilp), FMRF, and myomodulin form part of the Dchx1 expressing PI domain. NSCs of the PL can be followed throughout development by their expression of the adhesion molecule FasII. Decapentaplegic (Dpp), secreted along the dorsal midline of the early embryo, inhibits the formation of the PI and PL placodes; loss of the signal results in an unpaired, enlarged placodeal ectoderm. The other early activated signaling pathway, EGFR, is positively required for the maintenance of the PI placode. Of the dorso-medially expressed head gap genes, only tailless (tll) is required for the specification of the PI. Absence of the corpora cardiaca, the endocrine gland innervated by neurosecretory cells of the PI and PL, does not affect the formation of the PI/PL, indicating that inductive stimuli from their target tissue are not essential for early PI/PL development. Author Affiliation: (a) Department of Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA 90095, USA (b) Program in Developmental Biology, Research Institute, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8 (c) Department of Molecular and Medical Genetics, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8 Article History: Received 14 June 2006; Revised 19 September 2006; Accepted 20 September 2006

• Immune checkpoint inhibitors are especially effective for dMMR/MSI-H gastrointestinal cancers. • In early-stage tumours, high rates of complete response have been reported. • Definitive immune checkpoint inhibition is an attractive option for these patients. • Non-operative management can promptly be considered for dMMR/MSI-H rectal cancer. • Organ-sparing strategies for dMMR/MSI-H gastric and colon cancers remain investigational. Surgery is a standard treatment for early-stage gastrointestinal cancers, often preceded by neoadjuvant chemo(radio)therapy or followed by adjuvant therapy. While leading to cure in a proportion of patients, it has some drawbacks such as intra/post-operative complications, mutilation and life-long functional sequelae. Further to the unprecedented efficacy data from studies of immune checkpoint inhibitors for advanced mismatch repair deficient/microsatellite instable (dMMR/MSI-H) tumours, a strong interest has recently emerged for the investigation of such agents in the neoadjuvant setting. Although limited by the exploratory design and small sample size, trials of neoadjuvant immune checkpoint inhibitors for early-stage dMMR/MSI-H gastrointestinal cancers have consistently reported complete response rates ranging from 70 % to 100 %. As a result, the question has arisen as to whether surgery is still needed or organ-preserving strategies should be offered to this especially immuno-sensitive population. In this article, we discuss the available evidence for neoadjuvant immune checkpoint inhibitors in dMMR/MSI-H gastrointestinal cancers and analyse opportunities and challenges to the implementation of non-operative management approaches in this setting. [ABSTRACT FROM AUTHOR]

Ancient wheat varieties are considered to be healthier than modern ones, but the data are not univocal. We investigated changes in hematochemical parameters and evaluated microbiota data before and after a set period on a diet containing a whole-meal ancient wheat mix. 29 cloistered nuns were recruited. The study comprised two consecutive 30-day periods; during the first one (T1), the nuns received wheat-based foods produced with refined "modern" flour (" Simeto "); during the second one (T2) received wheat-based foods produced with an unrefined flour mix composed of "ancient" cultivars. At entry to the study (T0) and at the end of T1 and T2 hematochemical parameters and fecal microbiota and metabolome were evaluated. At the end of T2, there was a significant reduction in serum iron, ferritin, creatinine, sodium, potassium, magnesium, total cholesterol, LDL- and HDL-cholesterol and folic acid. Furthermore, increased the abundance of cultivable enterococci, lactic acid bacteria and total anaerobes. The ability of the gut microbiome to metabolize carbohydrates increased after the period of diet containing ancient grain products. Several volatile organic compounds increased after the one month on the diet enriched with ancient grain products. Our data showed the beneficial effects deriving from a diet including ancient whole-meal/unrefined wheat flours. [ABSTRACT FROM AUTHOR]

Targeted agents have been increasingly used in different malignancies and are associated with improved survival outcomes, including gastrointestinal cancers. Their use in the treatment of older patients is appealing given their favorable toxicity profile. In the last years, this subgroup of patients has been attracting increased interest given their representativeness and specific clinical needs. Nonetheless, the lack of data on efficacy and safety of standard treatments in older patients hinders proper evidence-based decision-making, leaving most therapeutic recommendations to be extrapolated from registration trials with low representation of older and frail patients. However, even if most decisions regarding the use of targeted agents in older patients with gastrointestinal cancer remain guided by subanalyses of large trials, data from recent older adult-specific trials are beginning to emerge, particularly in colorectal cancer. This review aims to summarize the existing evidence on treatment of older patients with gastrointestinal carcinomas (colon and rectum, stomach, esophagus, liver, and pancreas) with targeted agents (cetuximab, panitumumab, bevacizumab, ramucirumab, aflibercept, regorafenib, encorafenib, trastuzumab, sorafenib, lenvatinib, cabozantinib, erlotinib, olaparib), and place the evidence in a geriatric oncology perspective. [ABSTRACT FROM AUTHOR]

The hypothesis that intra-specific mate-choice copying is adaptive under certain conditions is tested using guppies, Poecilia reticulata. A study replicating the influential work of Dugatkin is presented. The study shows no tendency towards female mate-choice copying in guppies and it is concluded that further research needs to be undertaken before the existence of such behaviour can be confirmed.

Cerebrospinal fluid (CSF) circulates throughout the ventricles, cranial and spinal subarachnoid spaces, and central spinal cord canal. CSF protects the central nervous system through mechanical cushioning, regulation of intracranial pressure, regulation of metabolic homeostasis, and provision of nutrients. Recently, investigators have characterized the glial-lymphatic (glymphatic) system, the analog of the lymphatic system in the central nervous system, and described a fourth meningeal layer; the subarachnoid lymphatic-like membrane (SLYM)relevant to the CSF. A narrative review was conducted. In this review, we summarize these advances. We describe the development of the original model, controversies, a revised model, and a new conceptual framework. We characterize the biological functions, influence of sleep-wake cycles, and effect of aging with relevance to the glymphatic system. We highlight the role of the glymphatic system in Alzheimer's disease, idiopathic normal pressure hydrocephalus, ischemic stroke, subarachnoid hemorrhage, and traumatic brain injury. Next, we characterize the structure and role of the SLYM. Finally, we explore the relevance of the glymphatic system and SLYM to neurosurgery. This manuscript will inform clinicians and scientists regarding preclinical and translational advances in the understanding of the structure, dynamics, and function of the CSF. [ABSTRACT FROM AUTHOR]

• Surgery +/- adjuvant chemotherapy is the standard of care for early-stage colon cancer. • Four available randomised trials explored neoadjuvant chemotherapy in this setting. • Among these, only the FOxTROT trial met its primary endpoint. • Suboptimal patient selection and overtreatment are important concerns. • Except for selected cases, neoadjuvant chemotherapy remains an investigational approach. Surgery with or without adjuvant chemotherapy is the standard treatment for early-stage colon cancer. However, evidence has recently emerged for neoadjuvant chemotherapy, with the results of randomised clinical trials sparking debates within multidisciplinary teams and splitting the gastrointestinal oncology community. Further to a systematic search of the literature, we provide a thorough and in-depth analysis of the findings from these trials, highlighting the advantages and disadvantages of neoadjuvant chemotherapy. We conclude that, while there is a potential value of moving systemic therapy from the post-operative to the pre-operative setting, the available evidence does not justify a shift in the treatment paradigm of early-stage colon cancer, and surgery with or without adjuvant chemotherapy should remain the standard approach for these patients. [ABSTRACT FROM AUTHOR]

Cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC) is the only potentially curative treatment that can improve the survival prognosis for patients with peritoneal metastasis (PM) of colorectal origin. The main independent prognostic factors are extent of disease, as measured by the Peritoneal Cancer Index (PCI), and completion of CRS (CC-0 or R1). Despite thorough preoperative work-up for selection of surgical candidates, 20%–25 % of CRS procedures are stopped after exploration during laparotomy. These patients undergo "open-and-close" procedures associated with a risk of complications and without any benefit. The aim of this study was to identify preoperative predictors of non-resectability and/or non-completion of CRS in patients with colorectal PMs who were candidates for surgery. Retrospective, monocentric study including patients admitted for CRS ± HIPEC at the Jules Bordet Institute between January 01, 2010 and December 31, 2021. The preoperative epidemiological, pathological, clinical, radiological, and biological features of patients with unresectable disease were compared with those of patients treated with CRS. One hundred nineteen patients were included, 60 men and 59 women (median age 61 years). Twenty-one CRS procedures (17.65 %) were stopped during exploratory laparotomy. Statistically significant factors associated with non-completion were age (p = 0.0183), PCI (p = 0.0001), presence of sub/occlusive episode(s) prior to CRS (p = 0.0012), and multifocal-diffuse uptakes on PET-scan (p = 0.0017). Almost 18 % of patients had an "open-and-close" procedure. PCI was the major determinant of non-completion of CRS. Other predictive factors of unresectability of colorectal PM were age, the presence of sub/occlusive episodes, and PET/CT with multiple peritoneal uptakes. [ABSTRACT FROM AUTHOR]

While adjuvant chemotherapy is an established treatment for pathological stage II and especially stage III colon cancer, its role in the multimodal management of rectal cancer remains controversial. As a result, there is substantial variation in the use of this treatment in clinical practice. Even among centres and physicians who consider adjuvant chemotherapy as a standard treatment, notable heterogeneity exists with regard to patient selection criteria and chemotherapy regimens. The controversy around this topic is confirmed by the lack of full consensus among national and international clinical guidelines. While most of the clinical trials do not support the contention that adjuvant chemotherapy may improve survival outcomes if pre-operative (chemo)radiotherapy is also given, these suffer from many limitations that preclude drawing definitive conclusions. Nevertheless, in the era of evidence-based medicine, physicians should be guided by the available data and refrain from extrapolating results of adjuvant colon cancer trials to inform treatment decisions for rectal cancer. Patients should be informed of the evidence gap, be given the opportunity to carefully discuss pros and cons of all the possible management options and be empowered in the decision making. In this article we review the available evidence on adjuvant chemotherapy for rectal cancer and propose a risk-adapted decisional algorithm that largely relies on informed patient preferences. [ABSTRACT FROM AUTHOR]

Highlights • Touch improves infant health, but little is known about behavioral effects of touch. • We explored the influence of neonatal social touch on rhesus macaque monkeys. • Newborns who received extra handling responded more positively to novelty. • Higher rates of touch were associated with better cognitive and social development. • Neonatal touch may broadly support infants' development. Abstract Touch is one of the first senses to develop and one of the earliest modalities for infant-caregiver communication. While studies have explored the benefits of infant touch in terms of physical health and growth, the effects of social touch on infant behavior are relatively unexplored. Here, we investigated the influence of neonatal handling on a variety of domains, including memory, novelty seeking, and social interest, in infant monkeys (Macaca mulatta ; n = 48) from 2 to 12 weeks of age. Neonates were randomly assigned to receive extra holding, with or without accompanying face-to-face interactions. Extra-handled infants, compared to standard-reared infants, exhibited less stress-related behavior and more locomotion around a novel environment, faster approach of novel objects, better working memory, and less fear towards a novel social partner. In sum, infants who received more tactile stimulation in the neonatal period subsequently demonstrated more advanced motor, social, and cognitive skills—particularly in contexts involving exploration of novelty—in the first three months of life. These data suggest that social touch may support behavioral development, offering promising possibilities for designing future early interventions, particularly for infants who are at heightened risk for social disorders. [ABSTRACT FROM AUTHOR]

• Isomaltulose is a slowly digested isomer of sucrose and allulose is a noncaloric epimer of fructose. • C57BL/6 mice preferred isomaltulose but avoided allulose relative to water in 24 h tests. • Isomaltulose preference increased with exposure in C57BL/6 and FVB/N mice. • Exposure effects are attributed to postoral appetition actions of isomaltulose. • Isomaltulose appetition appears less pronounced than that of sucrose. Isomaltulose, a slowly digested isocaloric analog of sucrose, and allulose, a noncaloric fructose analog, are promoted as "healthful" sugar alternatives in human food products. Here we investigated the appetite and preference conditioning actions of these sugar analogs in inbred mouse strains. In brief-access lick tests (Experiment 1), C57BL/6 (B6) mice showed similar concentration dependent increases in licking for allulose and fructose, but less pronounced concentration-dependent increases in licking for isomaltulose than sucrose. In Experiment 2, B6 mice were given one-bottle training with a CS+ flavor (e.g., grape) mixed with 8% isomaltulose or allulose and a CS- flavor (e.g., cherry) mixed in water followed by two-bottle CS flavor tests. The isomaltulose mice showed only a weak CS+ flavor preference but a strong preference for the sugar over water. The allulose mice strongly preferred the CS- flavor and water over the sugar. The allulose avoidance may be due to gut discomfort as reported in humans consuming high amounts of the sugar. Experiment 3 found that the preference for 8% sucrose over 8% isomaltulose could be reversed or blocked by adding different concentrations of a noncaloric sweetener mixture (sucralose + saccharin, SS) to the isomaltulose. Experiment 4 revealed that the preference of B6 or FVB/N mice for isomaltulose+0.01%SS or sucrose over 0.1%SS increased after separate experience with the sugars and SS. This indicates that isomaltulose, like sucrose, has postoral appetition effects that enhances the appetite for the sugar. In Experiments 5 and 6, the appetition actions of the two sugars were directly compared by giving mice isomaltulose+0.05%SS vs. sucrose choice tests before and after separate experience with the two sugars. In general, the initial preference the mice displayed for isomaltulose+0.05%SS was reduced or reversed after separate experience with the two sugars although some strain and sex differences were obtained. This indicates that isomaltulose has weaker postoral appetition effects than sucrose. [ABSTRACT FROM AUTHOR]

In a nutrient self-selection study, CAST/EiJ mice consumed more carbohydrate than fat while C57BL/6J (B6) mice showed the opposite preference. The present study revealed similar strain differences in preferences for isocaloric fat (Intralipid) and carbohydrate (sucrose, maltodextrin) solutions in chow-fed mice. In initial 2-day choice tests, percent fat intakes of CAST and B6 mice were 4–9% and 71–81% respectively. In subsequent nutrient vs. water tests, CAST mice consumed considerably less fat but not carbohydrate compared to B6 mice. Orosensory rather than postoral factors are implicated in the very low fat preference and intake of CAST mice. This is supported by results of a choice test with Intralipid mixed with non-nutritive sweeteners vs. non-sweet maltodextrin. The preference of CAST mice for sweetened fat exceeded that of B6 mice (94 vs. 74%) and absolute fat intakes were similar in the two strains. When given unsweetened Intralipid vs. water tests at ascending fat concentrations CAST mice displayed reduced fat preferences at 0.1–5% and reduced intakes at 0.5–5% concentrations, compared to B6 mice. The differential fat preferences of CAST and B6 mice may reflect differences in fat taste sensing or in central neural processes related to fat selection. [ABSTRACT FROM AUTHOR]

I review the main themes of my 50-year research career in ingestive behavior as a graduate student at the University of Chicago and a professor at the City University of New York. A seminar course with my Ph.D. mentor, S. P. Grossman, sparked my interest in the hypothalamic obesity syndrome. I developed a wire knife to dissect the neuropathways and the functional disorder responsible for the syndrome. An elevated appetite setpoint that permitted the overconsumption of palatable foods appeared central to the hypothalamic syndrome. In brain-intact rats, providing an assortment of highly palatable foods (the cafeteria diet) stimulated diet-induced obesity that mimicked elements of hypothalamic obesity. Studies of the determinants of food palatability led to the discovery of a “new” carbohydrate taste (maltodextrin taste) and the confirmation of a fatty taste. In addition to oral taste receptors, gut nutrient sensors stimulated the intake/preference for carbohydrate- and fat-rich foods via an appetition process that stimulates brain reward systems. My research career greatly benefited from many diligent and creative students, collaborators and technicians and research support from my university and the National Institutes of Health. [ABSTRACT FROM AUTHOR]

Previous developmental research suggests that motor experience supports the development of action perception across the lifespan. However, it is still unknown when the neural mechanisms underlying action-perception coupling emerge in infancy. The goal of this study was to examine the neural correlates of action perception during the emergence of grasping abilities in newborn rhesus macaques. Neural activity, recorded via electroencephalogram (EEG), while monkeys observed grasping actions, mimed actions and means-end movements during the first (W1) and second week (W2) of life was measured. Event-related desynchronization (ERD) during action observation was computed from the EEG in the alpha and beta bands, two components of the sensorimotor mu rhythm associated with activity of the mirror neuron system (MNS). Results revealed age-related changes in the beta band, but not the alpha band, over anterior electrodes, with greater desynchronization at W2 than W1 for the observation of grasping actions. Additionally, desynchronization to observed grasping actions at W2 was associated with infants’ motor skills – measured by a separate behavioral task – such that more grasping attempts were associated to greater beta ERD. These findings suggest the emergence of an early action-perception system, that relies on motor experience, shortly after birth. [ABSTRACT FROM AUTHOR]

Summary Background The buccal space is an integral deep facial space which is involved in a variety of intra- and extra-oral pathologies and provides a good location for the harvest of the facial artery. The age-related anatomy of this space was investigated and compared to previous reports. Methods We conducted anatomic dissections in 102 fresh frozen human cephalic specimens (45 males, 57 females; age range 50–100 years) and performed additional computed tomographic, magnetic resonance and 3-D surface volumetric imaging studies to visualize the boundaries and the contents of the buccal space after injection of contrast enhancing material. Results The mean vertical extent of contrast agent injected into the buccal space was 25.2 ± 4.3 mm and did not significantly differ between individuals of different age (p = 0.77) or gender (p = 0.13). The maximal injected volume was 10.02 cc [range: 3.09–10.02] without significant influence of age (p = 0.13) or gender (p = 0.81). The change in surface volume was 3.64 ± 1.04 cc resulting in a mean surface-volume-coefficient of 0.87 ± 0.12 without being statistically significant influenced by age (p = 0.53) or gender (p = 0.78). Conclusions The facial artery was constantly identified within the buccal space whereas the facial vein was found to course within its posterior boundary. The buccal space did not undergo age-related changes in volume or size which highlights this space is a reliable and predictable landmark for various plastic, reconstructive and aesthetic procedures. [ABSTRACT FROM AUTHOR]

Recent studies suggest that preferences are conditioned by nutritive (sucrose) but not by non-nutritive (sucralose) sweeteners in mice. Here we compared the effectiveness of nutritive and non-nutritive sweeteners to condition flavor preferences in three mouse strains. Isopreferred sucrose and sucralose solutions both conditioned flavor preferences in C57BL/6J (B6) mice but sucrose was more effective, consistent with its post-oral appetition action. Subsequent experiments compared flavor conditioning by fructose, which has no post-oral appetition effect in B6 mice, and a sucralose + saccharin mixture (SS) which is highly preferred to fructose in 24-h choice tests. Both sweeteners conditioned flavor preferences but fructose induced stronger preferences than SS. Training B6 mice to drink a flavored SS solution paired with intragastric fructose infusions did not enhance the SS-conditioned preference. Thus, the post-oral nutritive actions of fructose do not explain the sugar's stronger preference conditioning effect. Training B6 mice to drink a flavored fructose solution containing SS did not reduce the sugar-conditioned preference, indicating that SS does not have an off-taste that attenuates conditioning. Although B6 mice strongly preferred flavored SS to flavored fructose in a direct choice test, they preferred the fructose-paired flavor to the SS-paired flavor when these were presented in water. Fructose conditioned a stronger flavor preference than an isopreferred saccharin solution, indicating that sucralose is not responsible for the limited SS conditioning actions. SS is highly preferred by FVB/NJ and CAST/EiJ inbred mice, yet conditioned only weak flavor preferences. It is unclear why highly or equally preferred non-nutritive sweeteners condition weaker preferences than fructose, when all stimulate the same T1r2/T1r3 sweet receptor. Recent findings support the existence of non-T1r2/T1r3 glucose taste sensors; however, there is no evidence for receptors that respond to fructose but not to non-nutritive sweeteners. [ABSTRACT FROM AUTHOR]

Background Up to 15% of colorectal cancers exhibit microsatellite instability (MSI), where errors in replication go unchecked due to defects in the mismatch repair system. This study aimed to determine survival in a large single-centre series of 1250 consecutive colorectal cancers subjected to universal MSI testing. Methods Clinical and pathological features of patients with colorectal cancer identified on prospectively maintained colorectal and pathology databases at St. Vincent's University Hospital from 2004 to May 2012 were examined. Mismatch repair (MMR) status was determined by immunohistochemistry. Kaplan–Meier curves, the log-rank test and Cox regression were used to associate survival with clinical and pathological characteristics. Results Of the 1250 colorectal cancers in the study period, 11% exhibited MSI (n = 138). Patients with MSI tumours had significantly lower rates of lymph node and distant metastases (MSI N+ rate: 24.8% compared with MSS N+ rate: 46.2%, p < 0.001). For Stage I and II disease MSI was associated with improved disease free survival (DSS) compared with MSS colon cancer. However, patients with Stage III MSI colon cancers had a worse DSS than those with MSS tumours. Stage III MSI tumours exhibited higher rates of lymphovascular invasion and perineural invasion than Stage I/II MSI tumours. Conclusion MSI is associated with a reduced risk of nodal and distant metastases, with an improved DSS in Stage I/II colon cancer. However, when MSI tumours progress to Stage III these patients had worse outcomes and pathological features. New strategies for this cohort of patients may be required to improve outcomes. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have marked a new era of cancer treatment, showing remarkable efficacy in a wide range of solid malignancies. In colorectal cancer (CRC), however, the therapeutic potential of ICIs is limited to the small group (≈5%) of patients with mismatch repair deficient (dMMR)/high microsatellite instable (MSI-H) tumours, which are characterised by high mutational/neo-antigen burden, and an inflammatory tumour microenvironment with abundant tumour-infiltrating lymphocytes. Over the last few years, research has focused on immuno-modulatory strategies that could overcome the inherent resistance to ICIs that is observed in the vast group (≈95%) of patients with mismatch repair proficient (pMMR)/microsatellite stable (MSS) tumours. Among these, the combination of ICIs with multi-kinase inhibitors has gained traction in preclinical studies and clinical trials. Thanks to their multiple targets and mechanisms of action, generally involving key cancer pathways such as oncogenesis, angiogenesis, metastasis, and tumour immunity, these agents can exert synergistic effects with ICIs, eventually turning inherently cold cancers into hot tumours, that can be efficiently recognised and targeted by an activated immune system. Regorafenib is routinely used for chemorefractory CRC with limited efficacy. Preliminary evidence, however, suggests that this multi-kinase inhibitor could be an optimal combination partner for ICIs. In this review article, we explain the biological rationale underlying the synergism between regorafenib and ICIs, discuss the available clinical data in CRC, and take a glance into future perspectives by presenting ongoing trials and possible research developments in this setting. [ABSTRACT FROM AUTHOR]

Mice are attracted to the tastes of sugar and maltodextrin solutions. Sugar taste is mediated by the T1R2/T1R3 sweet taste receptor, while maltodextrin taste is dependent upon a different as yet unidentified receptor. In a prior study sweet-sensitive C57BL/6J (B6) mice displayed similar preferences for sucrose and maltodextrin solutions in 24-h saccharide vs. water choice tests that exceeded those of sweet-subsensitive 129P3/J (129) mice. In a subsequent experiment reported here, sucrose and maltodextrin (Polycose) preference and acceptance were compared in the two strains in saccharide vs. saccharide choice tests with isocaloric concentrations (0.5–32%). The 129 mice displayed significantly greater maltodextrin preferences than B6 mice at mid-range concentrations (2–8%), while the mice displayed an opposite preference profile at the highest concentration (32%). As in prior studies, 129 mice consumed less total saccharide than B6 mice at lower concentrations. These findings show that the conclusions reached from tastant vs. water tests may differ from those pitting one tastant against another. The increased sucrose preference and intake of B6 mice, relative to 129 mice, is consistent with their sweet-sensitive phenotype. [ABSTRACT FROM AUTHOR]

The post-oral actions of glucose stimulate intake and condition flavor preferences in rodents. Hypothalamic melanin-concentrating hormone (MCH) neurons are implicated in sugar reward, and this study investigated their involvement in glucose preference conditioning in mice. In Exp. 1 MCH receptor 1 knockout (KO) and C57BL/6 wildtype (WT) mice learned to prefer 8% glucose over an initially more-preferred non-nutritive 0.1% sucralose + saccharin (S+S) solution. In contrast, the KO and WT mice preferred S+S to 8% fructose, which is consistent with this sugar's weak post-oral reinforcing action. In Exp. 2 KO and WT mice were trained to drink a flavored solution (CS+) paired with intragastric (IG) infusion of 16% glucose and a different flavored solution (CS −) paired with IG water. Both groups drank more CS+ than CS − in training and preferred the CS+ to CS − in a 2-bottle test. These results indicate that MCH receptor signaling is not required for flavor preferences conditioned by the post-oral actions of glucose. This contrasts with other findings implicating MCH signaling in other types of sugar reward processing. [ABSTRACT FROM AUTHOR]

Background: EXPERT and EXPERT-C were phase II clinical trials of neoadjuvant chemotherapy (NACT) followed by chemoradiotherapy (CRT) in high-risk, locally advanced rectal cancer (LARC). Design: We pooled individual patient data from these trials. The primary objective was overall survival (OS) in the intention-to-treat (ITT) population. Prognostic factors were also analysed. Results: A total of 269 patients were included. Of these, 91.1% completed NACT, 88.1% completed CRT and 240 (89.2%) underwent curative surgery (R0/R1). After a median follow-up of 71.9 months, 5-year progression-free survival (PFS) and OS were 66.4% and 73.3%, respectively. In the group of R0/R1 resection patients, 5-year relapse-free survival (RFS) and OS were 71.6% and 77.2%, respectively, with local recurrence occurring in 5.5% and distant metastases in 20.6% of cases. Significant prognostic factors after multivariate analyses included age, tumour grade and MRI extramural venous invasion (mrEMVI) at baseline, MRI tumour regression grade (mrTRG) after CRT, ypT stage after surgery and adherence to study treatment. mrTRG after NACT was associated with PFS (P = 0.002) and OS (P = 0.018) and appeared to stratify patients based on the incremental benefit from sequential CRT. Among the outcome measures considered, in the subgroup of R0/R1 resection patients, ypT and ypStage had the highest predictive accuracy for RFS (concordance index: 0.6238 and 0.6252, respectively) and OS (concordance index: 0.6094 and 0.6132, respectively). Conclusions: Administering NACT before CRT could be a potential strategy for high-risk LARC. In this setting, mrTRG after CRT is an independent prognostic factor, while mrTRG after NACT should be tested as a parameter for treatment selection in trials of NACT ± CRT. ypT stage may be a valuable surrogate end point for future phase II trials investigating intensified neoadjuvant treatments in similar patient populations. [ABSTRACT FROM AUTHOR]

A multimodality disciplinary approach is paramount for the management of locally advanced rectal cancer. Over the last decade, (chemo)radiotherapy followed by surgery plus or minus adjuvant chemotherapy has represented the mainstay of treatment for this disease. Nevertheless, robust evidence suggesting the optimal timing and sequence of therapies in this setting has been overall limited. A number of questions are still unsolved including the length of the interval between neoadjuvant radiotherapy and surgery or the timing of systemic chemotherapy. Interestingly, emerging data support the contention that altering sequence or timing or both of the components of this multimodality approach may provide an opportunity to implement treatment strategies that far better address the risk and expectations of individual patients. In this article, we review the available evidence on timing of therapies in the multidisciplinary treatment of locally advanced rectal cancer and discuss the potential implications for routine practice that may derive from a change of the currently accepted treatment paradigm. [ABSTRACT FROM AUTHOR]

Intragastric (IG) flavor conditioning studies in rodents indicate that isocaloric sugar infusions differ in their reinforcing actions, with glucose and sucrose more potent than fructose. Here we determined if the sugars also differ in their ability to maintain operant self-administration by licking an empty spout for IG infusions. Food-restricted C57BL/6J mice were trained 1 h/day to lick a food-baited spout, which triggered IG infusions of 16% sucrose. In testing, the mice licked an empty spout, which triggered IG infusions of different sugars. Mice shifted from sucrose to 16% glucose increased dry licking, whereas mice shifted to 16% fructose rapidly reduced licking to low levels. Other mice shifted from sucrose to IG water reduced licking more slowly but reached the same low levels. Thus IG fructose, like water, is not reinforcing to hungry mice. The more rapid decline in licking induced by fructose may be due to the sugar's satiating effects. Further tests revealed that the Glucose mice increased their dry licking when shifted from 16% to 8% glucose, and reduced their dry licking when shifted to 32% glucose. This may reflect caloric regulation and/or differences in satiation. The Glucose mice did not maintain caloric intake when tested with different sugars. They self-infused less sugar when shifted from 16% glucose to 16% sucrose, and even more so when shifted to 16% fructose. Reduced sucrose self-administration may occur because the fructose component of the disaccharide reduces its reinforcing potency. FVB mice also reduced operant licking when tested with 16% fructose, yet learned to prefer a flavor paired with IG fructose. These data indicate that sugars differ substantially in their ability to support IG self-administration and flavor preference learning. The same postoral reinforcement process appears to mediate operant licking and flavor learning, although flavor learning provides a more sensitive measure of sugar reinforcement. [ABSTRACT FROM AUTHOR]