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Archives of Gynecology and Obstetrics Aug 2022Endometrial hyperplasia (EH) is the precursor lesion for endometrioid adenocarcinoma of the endometrium (EC), which represents the most common malignancy of the female... (Review)
Review
Endometrial hyperplasia (EH) is the precursor lesion for endometrioid adenocarcinoma of the endometrium (EC), which represents the most common malignancy of the female reproductive tract in industrialized countries. The most important risk factor for the development of EH is chronic exposure to unopposed estrogen. Histopathologically, EH can be classified into EH without atypia (benign EH) and atypical EH/endometrial intraepithelial neoplasia (EIN). Clinical management ranges from surveillance or progestin therapy through to hysterectomy, depending on the risk of progression to or concomitant EC and the patient´s desire to preserve fertility. Multiple studies support the efficacy of progestins in treating both benign and atypical EH. This review summarizes the evidence base regarding risk factors and management of EH. Additionally, we performed a systematic literature search of the databases PubMed and Cochrane Controlled Trials register for studies analyzing the efficacy of progestin treatment in women with EH.
Topics: Endometrial Hyperplasia; Endometrial Neoplasms; Endometrium; Female; Humans; Progestins; Risk Factors
PubMed: 35001185
DOI: 10.1007/s00404-021-06380-5 -
Frontiers in Immunology 2023Gout arthritis (GA) is a common and curable type of inflammatory arthritis that has been attributed to a combination of genetic, environmental and metabolic factors.... (Review)
Review
Gout arthritis (GA) is a common and curable type of inflammatory arthritis that has been attributed to a combination of genetic, environmental and metabolic factors. Chronic deposition of monosodium urate (MSU) crystals in articular and periarticular spaces as well as subsequent activation of innate immune system in the condition of persistent hyperuricemia are the core mechanisms of GA. As is well known, drugs for GA therapy primarily consists of rapidly acting anti-inflammatory agents and life-long uric acid lowering agents, and their therapeutic outcomes are far from satisfactory. Although MSU crystals in articular cartilage detected by arthrosonography or in synovial fluid found by polarization microscopy are conclusive proofs for GA, the exact molecular mechanism of NLRP3 inflammasome activation in the course of GA still remains mysterious, severely restricting the early diagnosis and therapy of GA. On the one hand, the activation of Nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome requires nuclear factor kappa B (NF-κB)-dependent transcriptional enhancement of NLRP3, precursor (pro)-caspase-1 and pro-IL-1β, as well as the assembly of NLRP3 inflammasome complex and sustained release of inflammatory mediators and cytokines such as IL-1β, IL-18 and caspase-1. On the other hand, NLRP3 inflammasome activated by MSU crystals is particularly relevant to the initiation and progression of GA, and thus may represent a prospective diagnostic biomarker and therapeutic target. As a result, pharmacological inhibition of the assembly and activation of NLRP3 inflammasome may also be a promising avenue for GA therapy. Herein, we first introduced the functional role of NLRP3 inflammasome activation and relevant biological mechanisms in GA based on currently available evidence. Then, we systematically reviewed therapeutic strategies for targeting NLRP3 by potentially effective agents such as natural products, novel compounds and noncoding RNAs (ncRNAs) in the treatment of MSU-induced GA mouse models. In conclusion, our present review may have significant implications for the pathogenesis, diagnosis and therapy of GA.
Topics: Humans; Animals; NLR Family, Pyrin Domain-Containing 3 Protein; Arthritis, Gouty; Inflammasomes; Polymorphism, Genetic; Genetic Predisposition to Disease; Cytokines
PubMed: 37051231
DOI: 10.3389/fimmu.2023.1137822 -
A systematic review of the effect of L-tryptophan supplementation on mood and emotional functioning.Journal of Dietary Supplements 2021L-tryptophan (TRP), one of the essential amino acids in humans, is a precursor of serotonin, and hence its intake is closely related to the suppression of depressed and...
L-tryptophan (TRP), one of the essential amino acids in humans, is a precursor of serotonin, and hence its intake is closely related to the suppression of depressed and anxious moods. We did a systematic review of RCTs to examine the effects of tryptophan intake on the mood of healthy adults by searching PubMed, the Cochrane Library, and Ichu-shi according to PRISMA guidelines. As a result, 11 RCTs met the criteria and were accepted. Four RCTs showed the effects of tryptophan intake on negative feelings and happy feelings in healthy individuals, with significant differences between the treatment and the control groups. This suggests that TRP intake may be an effective approach to decrease anxiety and increase positive mood in healthy individuals. On the other hand, the effectiveness of TRP for aggressive feelings was not recognized. Reviewing these 11 RCTs, we concluded that taking 0.14-3g of TRP per day in addition to the usual meal can be expected to improve the mood of healthy individuals. In order to estimate the optimum amount of TRP intake more accurately, further studies need to be conducted with more appropriate settings of intake period, intake frequency, and intake method.
Topics: Adult; Affect; Dietary Supplements; Emotions; Humans; Randomized Controlled Trials as Topic; Serotonin; Tryptophan
PubMed: 32272859
DOI: 10.1080/19390211.2020.1746725 -
JAMA May 2021Colorectal cancer (CRC) remains a significant cause of morbidity and mortality in the US.
IMPORTANCE
Colorectal cancer (CRC) remains a significant cause of morbidity and mortality in the US.
OBJECTIVE
To systematically review the effectiveness, test accuracy, and harms of screening for CRC to inform the US Preventive Services Task Force.
DATA SOURCES
MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for relevant studies published from January 1, 2015, to December 4, 2019; surveillance through March 26, 2021.
STUDY SELECTION
English-language studies conducted in asymptomatic populations at general risk of CRC.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently appraised the articles and extracted relevant study data from fair- or good-quality studies. Random-effects meta-analyses were conducted.
MAIN OUTCOMES AND MEASURES
Colorectal cancer incidence and mortality, test accuracy in detecting cancers or adenomas, and serious adverse events.
RESULTS
The review included 33 studies (n = 10 776 276) on the effectiveness of screening, 59 (n = 3 491 045) on the test performance of screening tests, and 131 (n = 26 987 366) on the harms of screening. In randomized clinical trials (4 trials, n = 458 002), intention to screen with 1- or 2-time flexible sigmoidoscopy vs no screening was associated with a decrease in CRC-specific mortality (incidence rate ratio, 0.74 [95% CI, 0.68-0.80]). Annual or biennial guaiac fecal occult blood test (gFOBT) vs no screening (5 trials, n = 419 966) was associated with a reduction of CRC-specific mortality after 2 to 9 rounds of screening (relative risk at 19.5 years, 0.91 [95% CI, 0.84-0.98]; relative risk at 30 years, 0.78 [95% CI, 0.65-0.93]). In observational studies, receipt of screening colonoscopy (2 studies, n = 436 927) or fecal immunochemical test (FIT) (1 study, n = 5.4 million) vs no screening was associated with lower risk of CRC incidence or mortality. Nine studies (n = 6497) evaluated the test accuracy of screening computed tomography (CT) colonography, 4 of which also reported the test accuracy of colonoscopy; pooled sensitivity to detect adenomas 6 mm or larger was similar between CT colonography with bowel prep (0.86) and colonoscopy (0.89). In pooled values, commonly evaluated FITs (14 studies, n = 45 403) (sensitivity, 0.74; specificity, 0.94) and stool DNA with FIT (4 studies, n = 12 424) (sensitivity, 0.93; specificity, 0.85) performed better than high-sensitivity gFOBT (2 studies, n = 3503) (sensitivity, 0.50-0.75; specificity, 0.96-0.98) to detect cancers. Serious harms of screening colonoscopy included perforations (3.1/10 000 procedures) and major bleeding (14.6/10 000 procedures). CT colonography may have harms resulting from low-dose ionizing radiation. It is unclear if detection of extracolonic findings on CT colonography is a net benefit or harm.
CONCLUSIONS AND RELEVANCE
There are several options to screen for colorectal cancer, each with a different level of evidence demonstrating its ability to reduce cancer mortality, its ability to detect cancer or precursor lesions, and its risk of harms.
Topics: Age Factors; Aged; Aged, 80 and over; Colonoscopy; Colorectal Neoplasms; Early Detection of Cancer; Female; Humans; Male; Middle Aged; Occult Blood; Practice Guidelines as Topic; Risk; Sigmoidoscopy; Tomography, X-Ray Computed
PubMed: 34003220
DOI: 10.1001/jama.2021.4417 -
Clinical Lymphoma, Myeloma & Leukemia Jan 2021Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) is a subgroup of B-cell precursor ALL (BCP-ALL) with a gene expression profile analogous to... (Review)
Review
Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) is a subgroup of B-cell precursor ALL (BCP-ALL) with a gene expression profile analogous to Philadelphia-positive ALL and recurrent IKAROS Family Zinc Finger 1 (IKZF1) gene deletion despite lacking BCR-ABL1 (Breakpoint cluster region-ABL protooncogene) translocation. Although recognized to occur at all ages, the proportion of cases among BCP-ALL varies (< 10% in children and up to 30% in adolescents). In all age groups, males are more commonly affected. Generally, Ph-like ALL is associated with adverse clinical features and an increased risk of treatment failure with conventional approaches. Genetic alterations such as aberrant expression, point mutations, or fusion translocations lead to activation of cytokine receptors and signaling kinases, which affect the ABL1 (ABL class fusion) or Janus Kinase (JAK) signaling pathways. Several clinical trials are being conducted to understand whether specific tyrosine kinase inhibitor therapy can improve cure rates. This review summarizes the current literature available about this entity.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Young Adult
PubMed: 33485429
DOI: 10.1016/j.clml.2020.08.011 -
Cureus Oct 2022Psilocybin is a plant alkaloid that is derived from precursors of tryptamine and is present in many different types of mushrooms. It has been utilized by indigenous... (Review)
Review
Psilocybin is a plant alkaloid that is derived from precursors of tryptamine and is present in many different types of mushrooms. It has been utilized by indigenous peoples of Central and South America for centuries in a ceremonial setting to promote spiritual experiences. Indigenous societies have long employed psilocybin and other 5-HT 2A agonist classic psychedelics in their rites. They were a focus in psychiatry in the middle of the 20th century as both experimental medicines and tools for studying brain function. Due to the fact that traditional psychedelics were being used for purposes other than medical research and in connection with the burgeoning counterculture by the late 1960s and early 1970s, these scientific investigations fell out of favor. However, thanks to a number of encouraging studies that validated the earlier research, interest in traditional psychedelics has surged among scientists in the 21st century. In this review, we examine therapeutic studies on psilocybin, the traditional psychedelic that has received the lion's share of recent attention. According to three controlled studies, psilocybin may reduce symptoms of depression and anxiety in the context of cancer-related psychological discomfort for at least six months after a single acute treatment for mood and anxiety disorders. Three months after two acute doses, individuals in a small, open-label study with treatment-resistant depression reported fewer depressive and anxiety symptoms. Small, open-label pilot studies on addiction have demonstrated encouraging success rates for alcohol and cigarette addiction. The review also briefly discusses the synthesis, mechanism of action, effects, molecular pharmacology, adverse effects, and contraindications of psilocybin.
PubMed: 36381758
DOI: 10.7759/cureus.30214 -
European Journal of Cancer (Oxford,... Sep 2021Gastrointestinal cancers account for approximately 20% of all cancer diagnoses and are responsible for 22.5% of cancer deaths worldwide. Artificial intelligence-based...
BACKGROUND
Gastrointestinal cancers account for approximately 20% of all cancer diagnoses and are responsible for 22.5% of cancer deaths worldwide. Artificial intelligence-based diagnostic support systems, in particular convolutional neural network (CNN)-based image analysis tools, have shown great potential in medical computer vision. In this systematic review, we summarise recent studies reporting CNN-based approaches for digital biomarkers for characterization and prognostication of gastrointestinal cancer pathology.
METHODS
Pubmed and Medline were screened for peer-reviewed papers dealing with CNN-based gastrointestinal cancer analyses from histological slides, published between 2015 and 2020.Seven hundred and ninety titles and abstracts were screened, and 58 full-text articles were assessed for eligibility.
RESULTS
Sixteen publications fulfilled our inclusion criteria dealing with tumor or precursor lesion characterization or prognostic and predictive biomarkers: 14 studies on colorectal or rectal cancer, three studies on gastric cancer and none on esophageal cancer. These studies were categorised according to their end-points: polyp characterization, tumor characterization and patient outcome. Regarding the translation into clinical practice, we identified several studies demonstrating generalization of the classifier with external tests and comparisons with pathologists, but none presenting clinical implementation.
CONCLUSIONS
Results of recent studies on CNN-based image analysis in gastrointestinal cancer pathology are promising, but studies were conducted in observational and retrospective settings. Large-scale trials are needed to assess performance and predict clinical usefulness. Furthermore, large-scale trials are required for approval of CNN-based prediction models as medical devices.
Topics: Deep Learning; Gastrointestinal Neoplasms; Humans; Treatment Outcome
PubMed: 34391053
DOI: 10.1016/j.ejca.2021.07.012 -
Oxidative Medicine and Cellular... 2021Despite evidence of health benefits from kefir administration, a systematic review with meta-analysis on bioactive compounds associated with these benefits is still... (Meta-Analysis)
Meta-Analysis
Despite evidence of health benefits from kefir administration, a systematic review with meta-analysis on bioactive compounds associated with these benefits is still absent in the literature. Kefir is fermented milk resulting from the metabolism of a complex microbiota in symbiosis. Recent researches have investigated the bioactive compounds responsible for the preventive and therapeutic effects attributed to kefir. However, differences in functional potential between industrial and artisanal kefir are still controversial. Firstly, we identified differences in the microbial composition among both types of kefir. Available evidence concerning the action of different bioactive compounds from kefir on health, both from and studies, was subsequently summarized to draw a primary conclusion of the dose and the intervention time for effect, the producer microorganisms, the precursor in the milk, and the action mechanism. Meta-analysis was performed to investigate the statistically significant differences ( < 0.05) between intervention and control and between both types of kefir for each health effect studied. In summary, the bioactive compounds more commonly reported were exopolysaccharides, including kefiran, bioactive peptides, and organic acids, especially lactic acid. Kefir bioactive compounds presented antimicrobial, anticancer, and immune-modulatory activities corroborated by the meta-analysis. However, clinical evidence is urgently needed to strengthen the practical applicability of these bioactive compounds. The mechanisms of their action were diverse, indicating that they can act by different signaling pathways. Still, industrial and artisanal kefir may differ regarding functional potential-OR of 8.56 (95% CI: 2.27-32.21, ≤ .001)-according to the observed health effect, which can be associated with differences in the microbial composition between both types of kefir.
Topics: Animals; Anti-Infective Agents; Antineoplastic Agents; Biological Products; Fermentation; Humans; Immunomodulating Agents; Kefir; Milk
PubMed: 34745425
DOI: 10.1155/2021/9081738 -
Experimental Gerontology Apr 2020Nicotinamide adenine dinucleotide (NAD+) is an essential pyridine nucleotide that is present in all living cells. NAD+ acts as an important cofactor and substrate for a...
Nicotinamide adenine dinucleotide (NAD+) is an essential pyridine nucleotide that is present in all living cells. NAD+ acts as an important cofactor and substrate for a multitude of biological processes including energy production, DNA repair, gene expression, calcium-dependent secondary messenger signalling and immunoregulatory roles. The de novo synthesis of NAD+ is primarily dependent on the kynurenine pathway (KP), although NAD+ can also be recycled from nicotinic acid (NA), nicotinamide (NAM) and nicotinamide riboside (NR). NAD+ levels have been reported to decline during ageing and age-related diseases. Recent studies have shown that raising intracellular NAD+ levels represents a promising therapeutic strategy for age-associated degenerative diseases in general and to extend lifespan in small animal models. A systematic review of the literature available on Medline, Embase and Pubmed was undertaken to evaluate the potential health and/or longevity benefits due to increasing NAD+ levels. A total of 1545 articles were identified and 147 articles (113 preclinical and 34 clinical) met criteria for inclusion. Most studies indicated that the NAD+ precursors NAM, NR, nicotinamide mononucleotide (NMN), and to a lesser extent NAD+ and NADH had a favourable outcome on several age-related disorders associated with the accumulation of chronic oxidative stress, inflammation and impaired mitochondrial function. While these compounds presented with a limited acute toxicity profile, evidence is still quite limited and long-term human clinical trials are still nascent in the current literature. Potential risks in raising NAD+ levels in various clinical disorders using NAD+ precursors include the accumulation of putative toxic metabolites, tumorigenesis and promotion of cellular senescence. Therefore, NAD+ metabolism represents a promising target and further studies are needed to recapitulate the preclinical benefits in human clinical trials.
Topics: Aging; Animals; Humans; Inflammation; Mice; NAD; Neurodegenerative Diseases; Niacinamide; Nicotinamide Mononucleotide; Oxidative Stress; Pyridinium Compounds; Rats; Risk Assessment
PubMed: 31917996
DOI: 10.1016/j.exger.2020.110831 -
Clinical Infectious Diseases : An... Jan 2020Because of the diverse etiologies of community-acquired pneumonia (CAP) and the limitations of current diagnostic modalities, serum procalcitonin levels have been... (Meta-Analysis)
Meta-Analysis
Because of the diverse etiologies of community-acquired pneumonia (CAP) and the limitations of current diagnostic modalities, serum procalcitonin levels have been proposed as a novel tool to guide antibiotic therapy. Outcome data from procalcitonin-guided therapy trials have shown similar mortality, but the essential question is whether the sensitivity and specificity of procalcitonin levels enable the practitioner to distinguish bacterial pneumonia, which requires antibiotic therapy, from viral pneumonia, which does not. In this meta-analysis of 12 studies in 2408 patients with CAP that included etiologic diagnoses and sufficient data to enable analysis, the sensitivity and specificity of serum procalcitonin were 0.55 (95% confidence interval [CI], .37-.71; I2 = 95.5%) and 0.76 (95% CI, .62-.86; I2 = 94.1%), respectively. Thus, a procalcitonin level is unlikely to provide reliable evidence either to mandate administration of antibiotics or to enable withholding such treatment in patients with CAP.
Topics: Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; Humans; Pneumonia; Pneumonia, Bacterial; Procalcitonin; Protein Precursors
PubMed: 31241140
DOI: 10.1093/cid/ciz545