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Cancers Mar 2021Highly proliferative (G3) neuroendocrine neoplasms are divided into well differentiated tumors (NETs) and poorly differentiated carcinomas (NECs), based on the... (Review)
Review
BACKGROUND
Highly proliferative (G3) neuroendocrine neoplasms are divided into well differentiated tumors (NETs) and poorly differentiated carcinomas (NECs), based on the morphological appearance. This systematic review aims to evaluate the clinicopathological features and the treatment response of the NEC subgroup with a Ki67 labeling index (LI) < 55%.
METHODS
A literature search was performed using MEDLINE, Cochrane Library, and Scopus between December 2019 and April 2020, last update in October 2020. We included studies reporting data on the clinicopathological characteristics, survival, and/or therapy efficacy of patients with NECs, in which the Ki67 LI was specified.
RESULTS
8 papers were included, on a total of 268 NEC affected patients. NECs with a Ki67 LI < 55% have been reported in patients of both sexes, mainly of sixth decade, pancreatic origin, and large-cell morphology. The prevalent treatment choice was chemotherapy, followed by surgery and, in only one study, peptide receptor radionuclide therapy. The subgroup of patients with NEC with a Ki67 LI < 55% showed longer overall survival and progression free survival and higher response rates than the subgroup of patients with a tumor with higher Ki67 LI (≥55%).
CONCLUSIONS
NECs are heterogeneous tumors. The subgroup with a Ki67 LI < 55% has a better prognosis and should be treated and monitored differently from NECs with a Ki67 LI ≥ 55%.
PubMed: 33809007
DOI: 10.3390/cancers13061247 -
Frontiers in Systems Neuroscience 2022Although neural plasticity is now widely studied, there was a time when the idea of adult plasticity was antithetical to the mainstream. The essential stumbling block...
Although neural plasticity is now widely studied, there was a time when the idea of adult plasticity was antithetical to the mainstream. The essential stumbling block arose from the seminal experiments of Hubel and Wiesel who presented convincing evidence that there existed a critical period for plasticity during development after which the brain lost its ability to change in accordance to shifts in sensory input. Despite the zeitgeist that mature brain is relatively immutable to change, there were a number of examples of adult neural plasticity emerging in the scientific literature. Interestingly, some of the earliest of these studies involved visual plasticity in the adult cat. Even earlier, there were reports of what appeared to be functional reorganization in adult rat somatosensory thalamus after dorsal column lesions, a finding that was confirmed and extended with additional experimentation. To demonstrate that these findings reflected more than a response to central injury, and to gain greater control of the extent of the sensory loss, peripheral nerve injuries were used that eliminated ascending sensory information while leaving central pathways intact. Merzenich, Kaas, and colleagues used peripheral nerve transections to reveal unambiguous reorganization in primate somatosensory cortex. Moreover, these same researchers showed that this plasticity proceeded in no less than two stages, one immediate, and one more protracted. These findings were confirmed and extended to more expansive cortical deprivations, and further extended to the thalamus and brainstem. There then began a series of experiments to reveal the physiological, morphological and neurochemical mechanisms that permitted this plasticity. Ultimately, Mowery and colleagues conducted a series of experiments that carefully tracked the levels of expression of several subunits of glutamate (AMPA and NMDA) and GABA (GABAA and GABAB) receptor complexes in primate somatosensory cortex at several time points after peripheral nerve injury. These receptor subunit mapping experiments revealed that membrane expression levels came to reflect those seen in early phases of critical period development. This suggested that under conditions of prolonged sensory deprivation the adult cells were returning to critical period like plastic states, i.e., developmental recapitulation. Here we outline the heuristics that drive this phenomenon.
PubMed: 36762289
DOI: 10.3389/fnsys.2022.1086680 -
Nutrition Reviews Jun 2017Accumulation of brain iron is linked to aging and protein-misfolding neurodegenerative diseases. High iron intake may influence important brain health outcomes in later... (Review)
Review
CONTEXT
Accumulation of brain iron is linked to aging and protein-misfolding neurodegenerative diseases. High iron intake may influence important brain health outcomes in later life.
OBJECTIVE
The aim of this systematic review was to examine evidence from animal and human studies of the effects of high iron intake or peripheral iron status on adult cognition, brain aging, and neurodegeneration.
DATA SOURCES
MEDLINE, Scopus, CAB Abstracts, the Cochrane Central Register of Clinical Trials, and OpenGrey databases were searched.
STUDY SELECTION
Studies investigating the effect of elevated iron intake at all postnatal life stages in mammalian models and humans on measures of adult brain health were included.
DATA EXTRACTION
Data were extracted and evaluated by two authors independently, with discrepancies resolved by discussion. Neurodegenerative disease diagnosis and/or behavioral/cognitive, biochemical, and brain morphologic findings were used to study the effects of iron intake or peripheral iron status on brain health. Risk of bias was assessed for animal and human studies. PRISMA guidelines for reporting systematic reviews were followed.
RESULTS
Thirty-four preclinical and 14 clinical studies were identified from database searches. Thirty-three preclinical studies provided evidence supporting an adverse effect of nutritionally relevant high iron intake in neonates on brain-health-related outcomes in adults. Human studies varied considerably in design, quality, and findings; none investigated the effects of high iron intake in neonates/infants.
CONCLUSIONS
Human studies are needed to verify whether dietary iron intake levels used in neonates/infants to prevent iron deficiency have effects on brain aging and neurodegenerative disease outcomes.
Topics: Aging; Anemia, Iron-Deficiency; Animals; Behavior, Animal; Brain; Cognition; Databases, Factual; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Humans; Iron; Iron Deficiencies; Iron, Dietary; Meta-Analysis as Topic; Nutritional Status; Observational Studies as Topic; Publication Bias; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 28505363
DOI: 10.1093/nutrit/nux015 -
Autoimmunity Reviews Oct 2016Shrinking lung syndrome (SLS) is a rare respiratory manifestation of systemic lupus erythematosus (SLE), characterized by dyspnea, chest pain, elevated hemidiaphragm and... (Review)
Review
Shrinking lung syndrome associated with systemic lupus erythematosus: A multicenter collaborative study of 15 new cases and a review of the 155 cases in the literature focusing on treatment response and long-term outcomes.
INTRODUCTION
Shrinking lung syndrome (SLS) is a rare respiratory manifestation of systemic lupus erythematosus (SLE), characterized by dyspnea, chest pain, elevated hemidiaphragm and a restrictive pattern on pulmonary function tests. Here, we report 15 new observations of SLS during SLE and provide a systematic literature review. We studied the clinical, biological, functional and morphologic characteristics, the treatments used and their efficacy.
METHODS
The inclusion criteria were all patients with SLE defined by the American College of Rheumatology criteria Hochberg (1997) , associated with a restrictive pattern on pulmonary function tests. The exclusion criteria were all differential diagnoses of restrictive patterns, including obesity and pulmonary fibrosis. The patients were recruited from local databases through chest physicians, rheumatologists and internists. The data for the literature review were extracted from the Medline database using "shrinking lung syndrome" and "lupus" as key words.
RESULTS
All 15 new cases were women with a median age at SLS onset of 27years old (range 17-67years). All of them complained of dyspnea and all but one of chest pain. The antibodies were similar to those found in SLE, although the anti-SS-A was positive in 10 of 13 cases. Thoracic imaging showed elevated hemidiaphragm (12/15) and/or basal atelectasia (8/15). All of the patients had an isolated restrictive pattern on PFT, with a median decrease >50% of lung volume. All of the patients were treated, using corticosteroids (11/15), immunosuppressive drugs (8/15), beta-mimetics (2/15), physiotherapy (3/15) and/or colchicine (1/15). Improvement was described in 9 of 12 patients and stability in 3 of 12. We extracted 155 cases of SLE-associated SLS from the Medline database. The clinical, biological and functional parameters were similar to our cases. Clinical improvement was described in 48 of 52 cases (94%) and PFT improvement in 36 of 47 cases. Worsening occurred in 4 cases.
CONCLUSION
SLS is a rare SLE manifestation. Pain and parietal inflammation seem to play important pathogenic roles. Steroids and antalgics are the most commonly used therapies with good responses. There is no proof of efficacy with immunosuppressive drugs for this entity. Rituximab can be discussed after failure of corticosteroids, as well as antalgics, theophylline and beta-mimetics.
Topics: Adolescent; Adult; Aged; Female; Humans; Immunosuppressive Agents; Lung Diseases; Lupus Erythematosus, Systemic; Middle Aged; Multicenter Studies as Topic; Retrospective Studies; Syndrome; Treatment Outcome; Young Adult
PubMed: 27481038
DOI: 10.1016/j.autrev.2016.07.021 -
Diseases of the Colon and Rectum Jun 2014Conventional MRI is limited in the assessment of nodal status and T status after neoadjuvant chemoradiotherapy. Multiparametric MRI strives to overcome these issues by... (Review)
Review
BACKGROUND
Conventional MRI is limited in the assessment of nodal status and T status after neoadjuvant chemoradiotherapy. Multiparametric MRI strives to overcome these issues by directly measuring the local microcirculation and cellular environment, thus possibly allowing for a more reliable evaluation of response to therapy.
OBJECTIVE
We assessed the available literature for the value of multiparametric MRI sequences (diffusion-weighted and dynamic contrast-enhanced imaging) in determining the response to neoadjuvant chemoradiotherapy in patients with rectal cancer.
DATA SOURCES
We conducted a systematic literature research in the PubMed database.
STUDY SELECTION
English-language publications of the years 2000-2013 that applied multiparametric MRI in the neoadjuvant setting were included in this study.
INTERVENTION
Patients received neoadjuvant chemoradiotherapy and MRI examinations for staging and assessment of response.
MAIN OUTCOME MEASURES
Accuracy, specificity, and sensitivity of MRI in prediction/assessment of response to therapy were the included measures.
RESULTS
Forty-three studies were included in this review; 30 of them included diffusion-weighted imaging sequences, and 13 included dynamic contrast-enhanced MRI. Conventional MRI is limited in the accuracy of both T and N stages and response assessment. Diffusion-weighted imaging and dynamic contrast-enhanced MRIs showed additional value in both the prediction and detection of (complete) response to therapy compared with conventional sequences alone, as well as in correct N staging along with new experimental contrast agents.
LIMITATIONS
The lack of standardization represents an important technical limitation. Most studies are conducted in an experimental setting; therefore, larger multicenter prospective studies are needed to verify the present findings.
CONCLUSIONS
Advanced, functional MRI techniques allow for the quantification of tumor biological processes, such as microcirculation, vascular permeability, and tissue cellularity. This new technology has begun to show potential advantages over standard morphologic imaging in the restaging of rectal cancer, allowing for more accurate prognostication of response and potentially introducing an era allowing earlier treatment alteration and more accurate noninvasive surveillance, which could improve patient outcomes.
Topics: Chemoradiotherapy, Adjuvant; Contrast Media; Diffusion Magnetic Resonance Imaging; Humans; Neoadjuvant Therapy; Rectal Neoplasms; Sensitivity and Specificity
PubMed: 24807605
DOI: 10.1097/DCR.0000000000000127 -
International Journal of Environmental... Feb 2023This study aimed to investigate the effects of eccentric cycling (ECC) training on performance, physiological, and morphological parameters in comparison to concentric... (Meta-Analysis)
Meta-Analysis Review
This study aimed to investigate the effects of eccentric cycling (ECC) training on performance, physiological, and morphological parameters in comparison to concentric cycling (CON) training. Searches were conducted using PubMed, Embase, and ScienceDirect. Studies comparing the effect of ECC and CON training regimens on performance, physiological, and/or morphological parameters were included. Bayesian multilevel meta-analysis models were used to estimate the population's mean difference between chronic responses from ECC and CON training protocols. Group levels and meta-regression were used to evaluate the specific effects of subjects and study characteristics. Fourteen studies were included in this review. The meta-analyses showed that ECC training was more effective in increasing knee extensor strength, vastus lateralis fiber cross-sectional area, and six-minute walking distance compared to CON. Moreover, ECC was as effective as CON in decreasing body fat percentage. CON was more effective in increasing V˙O2max and peak power output attained during concentric incremental tests. However, group-level analyses revealed that ECC was more effective than CON in improving V˙O2max in patients with cardiopulmonary diseases. ECC is a viable modality for exercise interventions aiming to improve parameters of muscle strength, hypertrophy, functional capacity, aerobic power, and body composition, with more advantages than CON training in improving neuromuscular variables.
Topics: Humans; Bayes Theorem; Muscle Strength; Quadriceps Muscle; Knee; Knee Joint; Adaptation, Physiological; Muscle, Skeletal; Resistance Training
PubMed: 36833557
DOI: 10.3390/ijerph20042861 -
Journal of Neuroinflammation Mar 2023Diabetes mellitus is a heterogeneous chronic metabolic disorder characterized by the presence of hyperglycemia, commonly preceded by a prediabetic state. The excess of... (Review)
Review
Diabetes mellitus is a heterogeneous chronic metabolic disorder characterized by the presence of hyperglycemia, commonly preceded by a prediabetic state. The excess of blood glucose can damage multiple organs, including the brain. In fact, cognitive decline and dementia are increasingly being recognized as important comorbidities of diabetes. Despite the largely consistent link between diabetes and dementia, the underlying causes of neurodegeneration in diabetic patients remain to be elucidated. A common factor for almost all neurological disorders is neuroinflammation, a complex inflammatory process in the central nervous system for the most part orchestrated by microglial cells, the main representatives of the immune system in the brain. In this context, our research question aimed to understand how diabetes affects brain and/or retinal microglia physiology. We conducted a systematic search in PubMed and Web of Science to identify research items addressing the effects of diabetes on microglial phenotypic modulation, including critical neuroinflammatory mediators and their pathways. The literature search yielded 1327 records, including 18 patents. Based on the title and abstracts, 830 papers were screened from which 250 primary research papers met the eligibility criteria (original research articles with patients or with a strict diabetes model without comorbidities, that included direct data about microglia in the brain or retina), and 17 additional research papers were included through forward and backward citations, resulting in a total of 267 primary research articles included in the scoping systematic review. We reviewed all primary publications investigating the effects of diabetes and/or its main pathophysiological traits on microglia, including in vitro studies, preclinical models of diabetes and clinical studies on diabetic patients. Although a strict classification of microglia remains elusive given their capacity to adapt to the environment and their morphological, ultrastructural and molecular dynamism, diabetes modulates microglial phenotypic states, triggering specific responses that include upregulation of activity markers (such as Iba1, CD11b, CD68, MHC-II and F4/80), morphological shift to amoeboid shape, secretion of a wide variety of cytokines and chemokines, metabolic reprogramming and generalized increase of oxidative stress. Pathways commonly activated by diabetes-related conditions include NF-κB, NLRP3 inflammasome, fractalkine/CX3CR1, MAPKs, AGEs/RAGE and Akt/mTOR. Altogether, the detailed portrait of complex interactions between diabetes and microglia physiology presented here can be regarded as an important starting point for future research focused on the microglia-metabolism interface.
Topics: Humans; Microglia; Diabetes Mellitus; Hyperglycemia; Central Nervous System; Dementia
PubMed: 36869375
DOI: 10.1186/s12974-023-02740-x -
PloS One 2013The growing concern about cannabis use, the most commonly used illicit drug worldwide, has led to a significant increase in the number of human studies using... (Review)
Review
BACKGROUND
The growing concern about cannabis use, the most commonly used illicit drug worldwide, has led to a significant increase in the number of human studies using neuroimaging techniques to determine the effect of cannabis on brain structure and function. We conducted a systematic review to assess the evidence of the impact of chronic cannabis use on brain structure and function in adults and adolescents.
METHODS
Papers published until August 2012 were included from EMBASE, Medline, PubMed and LILACS databases following a comprehensive search strategy and pre-determined set of criteria for article selection. Only neuroimaging studies involving chronic cannabis users with a matched control group were considered.
RESULTS
One hundred and forty-two studies were identified, of which 43 met the established criteria. Eight studies were in adolescent population. Neuroimaging studies provide evidence of morphological brain alterations in both population groups, particularly in the medial temporal and frontal cortices, as well as the cerebellum. These effects may be related to the amount of cannabis exposure. Functional neuroimaging studies suggest different patterns of resting global and brain activity during the performance of several cognitive tasks both in adolescents and adults, which may indicate compensatory effects in response to chronic cannabis exposure.
LIMITATIONS
However, the results pointed out methodological limitations of the work conducted to date and considerable heterogeneity in the findings.
CONCLUSION
Chronic cannabis use may alter brain structure and function in adult and adolescent population. Further studies should consider the use of convergent methodology, prospective large samples involving adolescent to adulthood subjects, and data-sharing initiatives.
Topics: Adolescent; Adult; Cannabinoids; Cannabis; Cerebellum; Cognition; Databases, Bibliographic; Female; Frontal Lobe; Humans; Male; Marijuana Abuse; Neuroimaging; Neuropsychological Tests; Temporal Lobe
PubMed: 23390554
DOI: 10.1371/journal.pone.0055821 -
The Lancet. Haematology May 2023Given the paucity of high-certainty evidence, and differences in opinion on the use of nuclear medicine for hematological malignancies, we embarked on a consensus... (Review)
Review
Given the paucity of high-certainty evidence, and differences in opinion on the use of nuclear medicine for hematological malignancies, we embarked on a consensus process involving key experts in this area. We aimed to assess consensus within a panel of experts on issues related to patient eligibility, imaging techniques, staging and response assessment, follow-up, and treatment decision-making, and to provide interim guidance by our expert consensus. We used a three-stage consensus process. First, we systematically reviewed and appraised the quality of existing evidence. Second, we generated a list of 153 statements based on the literature review to be agreed or disagreed with, with an additional statement added after the first round. Third, the 154 statements were scored by a panel of 26 experts purposively sampled from authors of published research on haematological tumours on a 1 (strongly disagree) to 9 (strongly agree) Likert scale in a two-round electronic Delphi review. The RAND and University of California Los Angeles appropriateness method was used for analysis. Between one and 14 systematic reviews were identified on each topic. All were rated as low to moderate quality. After two rounds of voting, there was consensus on 139 (90%) of 154 of the statements. There was consensus on most statements concerning the use of PET in non-Hodgkin and Hodgkin lymphoma. In multiple myeloma, more studies are required to define the optimal sequence for treatment assessment. Furthermore, nuclear medicine physicians and haematologists are awaiting consistent literature to introduce volumetric parameters, artificial intelligence, machine learning, and radiomics into routine practice.
Topics: Humans; Consensus; Nuclear Medicine; Artificial Intelligence; Hematologic Neoplasms; Molecular Imaging
PubMed: 37142345
DOI: 10.1016/S2352-3026(23)00030-3 -
Frontiers in Plant Science 2023The C4 grass pearl millet is one of the most drought tolerant cereals and is primarily grown in marginal areas where annual rainfall is low and intermittent. It was...
The C4 grass pearl millet is one of the most drought tolerant cereals and is primarily grown in marginal areas where annual rainfall is low and intermittent. It was domesticated in sub-Saharan Africa, and several studies have found that it uses a combination of morphological and physiological traits to successfully resist drought. This review explores the short term and long-term responses of pearl millet that enables it to either tolerate, avoid, escape, or recover from drought stress. The response to short term drought reveals fine tuning of osmotic adjustment, stomatal conductance, and ROS scavenging ability, along with ABA and ethylene transduction. Equally important are longer term developmental plasticity in tillering, root development, leaf adaptations and flowering time that can both help avoid the worst water stress and recover some of the yield losses asynchronous tiller production. We examine genes related to drought resistance that were identified through individual transcriptomic studies and through our combined analysis of previous studies. From the combined analysis, we found 94 genes that were differentially expressed in both vegetative and reproductive stages under drought stress. Among them is a tight cluster of genes that are directly related to biotic and abiotic stress, as well as carbon metabolism, and hormonal pathways. We suggest that knowledge of gene expression patterns in tiller buds, inflorescences and rooting tips will be important for understanding the growth responses of pearl millet and the trade-offs at play in the response of this crop to drought. Much remains to be learnt about how pearl millet's unique combination of genetic and physiological mechanisms allow it to achieve such high drought tolerance, and the answers to be found may well be useful for crops other than just pearl millet.
PubMed: 36844091
DOI: 10.3389/fpls.2023.1059574