Search Results (44,419)

Objectives: This systematic review aimed to evaluate current surgical and non-surgical management strategies for malignant bowel obstruction (MBO) in patients with gynaecological cancer. Methods: Comprehensive literature searches were conducted across MEDLINE, Embase, CENTRAL, and Scopus, without restrictions on language or publication date. Following the removal of duplicates, 4866 articles were screened, with 34 meeting the inclusion criteria. Results: Surgical intervention remains the definitive treatment for MBO, offering longer symptom-free periods and improved survival, particularly when conservative methods fail. However, the selection of surgical candidates is crucial due to the high risk of morbidity and the potential for significant complications. Non-surgical treatments, such as the use of Gastrografin, Octreotide, and Dexamethasone, along with invasive procedures like nasogastric tubing, percutaneous gastrostomy, and stent placement, offer varying degrees of symptom relief and are often considered when surgery is not feasible. Conclusions: In this article we provide a potential therapeutic algorithm for the management of patients with MBO. This review underscores the urgent need for high-quality research to develop clear, evidence-based guidelines for MBO management in patients with gynaecologic cancer. Establishing standardised protocols will improve patient outcomes by aiding clinicians in making informed, individualised treatment decisions. Full article

Multi-cancer detection (MCD) tests are blood-based assays that screen for multiple cancers concurrently and offer a promising approach to improve early cancer detection and screening uptake. To date, there have been two prospective interventional studies evaluating MCD tests as a screening tool in human subjects. No MCD tests are currently approved by the FDA, but there is one commercially available MCD test. Ongoing trials continue to assess the efficacy, safety, and cost implications of MCD tests. In this review, we discuss the performance of CancerSEEK and Galleri, two leading MCD platforms, and discuss the clinical consideration for the broader application of this new technology. Full article

Gastric cancer stands as the fourth leading cause of cancer-related deaths globally, primarily comprising adenocarcinomas, categorized by anatomic location and histologic type. Often diagnosed at advanced stages, gastric cancer prognosis remains poor. To address the critical need for accurate tumoral markers for gastric cancer diagnosis, we conducted a study to assess classical markers like CEA and CA-19-9 alongside the novel marker miR-106. Our investigation revealed distinct dynamics of these markers compared to non-cancerous groups, although no disparities were observed across different disease stages. Univariable and multivariable logistic regression analyses demonstrated that elevated levels of miR-106, CEA and CA 19-9 were predictive of a positive histopathological exam, with the respective odds ratios of 12.032 (95% CI: 1.948–74.305), 30 (95% CI: 3.141–286.576), and 55.866 (95% CI: 4.512–691.687). Subsequently, we utilized predicted probabilities from regression models to construct receiver operating characteristic (ROC) curves, identifying CA 19-9 as the optimal predictor for gastric adenocarcinoma diagnosis when considering age and gender, with an area under the curve (AUC) of 0.936 (p < 0.001). Hence, classical markers exhibit superior performance compared to the novel marker miR-106 in predicting gastric adenocarcinoma. Full article

Non-alcoholic fatty liver disease (NAFLD) has emerged as the leading cause of chronic liver disease worldwide. Caspase 8 and FADD-like apoptosis regulator (CFLAR) has been identified as a potent factor in mitigating non-alcoholic steatohepatitis (NASH) by inhibiting the N-terminal dimerization of apoptosis signal-regulating kinase 1 (ASK1). While arginine methyltransferase 1 (PRMT1) was previously reported to be associated with increased hepatic glucose production, its involvement in hepatic lipid metabolism remains largely unexplored. The interaction between PRMT1 and CFLAR and the methylation of CFLAR were verified by Co-IP and immunoblotting assays. Recombinant adenoviruses were generated for overexpression or knockdown of PRMT1 in hepatocytes. The role of PRMT1 in NAFLD was investigated in normal and high-fat diet-induced obese mice. In this study, we found a significant upregulation of PRMT1 and downregulation of CFLAR after 48h of fasting, while the latter significantly rebounded after 12h of refeeding. The expression of PRMT1 increased in the livers of mice fed a methionine choline-deficient (MCD) diet and in hepatocytes challenged with oleic acid (OA)/palmitic acid (PA). Overexpression of PRMT1 not only inhibited the expression of genes involved in fatty acid oxidation (FAO) and promoted the expression of genes involved in fatty acid synthesis (FAS), resulting in increased triglyceride accumulation in primary hepatocytes, but also enhanced the gluconeogenesis of primary hepatocytes. Conversely, knockdown of hepatic PRMT1 significantly alleviated MCD diet-induced hepatic lipid metabolism abnormalities and liver injury in vivo, possibly through the upregulation of CFLAR protein levels. Knockdown of PRMT1 suppressed the expression of genes related to FAS and enhanced the expression of genes involved in FAO, causing decreased triglyceride accumulation in OA/PA-treated primary hepatocytes in vitro. Although short-term overexpression of PRMT1 had no significant effect on hepatic triglyceride levels under physiological conditions, it resulted in increased serum triglyceride and fasting blood glucose levels in normal C57BL/6J mice. More importantly, PRMT1 was observed to interact with and methylate CFLAR, ultimately leading to its ubiquitination-mediated protein degradation. This process subsequently triggered the activation of c-Jun N-terminal kinase 1 (JNK1) and lipid deposition in primary hepatocytes. Together, these results suggested that PRMT1-mediated methylation of CFLAR plays a critical role in hepatic lipid metabolism. Targeting PRMT1 for drug design may represent a promising strategy for the treatment of NAFLD. Full article

Promoting appropriate behaviors in early childhood is crucial for children’s future development. This systematic review aimed to explore the efficacy of social story (SS) intervention in teaching expected behaviors among preschool children. A structured search strategy was applied to five online electronic databases. The references were systematically screened in accordance with the PRISMA statements. Randomized or non-randomized controlled studies, as well as single-subject studies, in which SSs served as a behavioral training approach for children aged 2 to 6 years were included. Information related to study design, characteristics of the participants, target behaviors, and implementation of SS intervention was extracted. A meta-analysis was performed using the random-effects model, where similar outcomes were evaluated by similar intervention across multiple studies. Twenty-one studies were identified for qualitative analysis, while two studies formed the basis of the meta-analysis. SS interventions were employed to teach a variety of behaviors among typically developing children as well as those with various disabilities, such as autism, developmental delay, hearing impairments, attention deficit hyperactivity disorder, or other disabilities. The target behaviors included oral health practices, peer interaction, staying on-task, self-regulation, sleep habits, and controlling aggressive behavior during group activities. The SSs were used either alone or combined with other strategies, such as positive reinforcement, music therapy, role play, group discussion, video self-modeling, immediate practices, or additional audio commentary. Most studies reported improvements in appropriate behaviors and/or reductions in unfavorable behaviors. The meta-analysis indicated that children practiced more toothbrushing steps when using SS interventions compared to conventional oral health instruction (Z = 3.60, MD = 0.66, 95%CI 0.30 to 1.02, p < 0.001). SS interventions have the potential to teach target behaviors, particularly toothbrushing behaviors, among preschool children. More well-designed randomized controlled trials are warranted to determine the efficacy of SS interventions among children with various developmental profiles. Full article

Despite progress in treating rheumatoid arthritis, this autoimmune disorder confers an increased risk of developing cardiovascular disease (CVD). Widely used screening protocols and current clinical guidelines are inadequate for the early detection of CVD in persons with rheumatoid arthritis. Traditional CVD risk factors alone cannot be applied because they underestimate CVD risk in rheumatoid arthritis, missing the window of opportunity for prompt intervention to decrease morbidity and mortality. The lipid profile is insufficient to assess CVD risk. This review delves into the connection between systemic inflammation in rheumatoid arthritis and the premature onset of CVD. The shared inflammatory and immunologic pathways between the two diseases that result in subclinical atherosclerosis and disrupted cholesterol homeostasis are examined. The treatment armamentarium for rheumatoid arthritis is summarized, with a particular focus on each medication’s cardiovascular effect, as well as the mechanism of action, risk–benefit profile, safety, and cost. A clinical approach to CVD screening and treatment for rheumatoid arthritis patients is proposed based on the available evidence. The mortality gap between rheumatoid arthritis and non-rheumatoid arthritis populations due to premature CVD represents an urgent research need in the fields of cardiology and rheumatology. Future research areas, including risk assessment tools and novel immunotherapeutic targets, are highlighted. Full article

We used the Vienna ab initio Simulation Package (VASP), X-ray photoelectron spectroscopy (XPS) and diffuse reflectance (DRS) to optimize anode material for a photoelectric catalytic system. After screening how the doping of TiO₂ by N and S affects its photoelectric properties, N-doped TiO₂ was selected to fabricate the photoelectron catalytic (PEC) system. TiO₂ nanotubes modified by N-doped TiO₂ nanocrystals and activated carbon were used as an anode and as a photocathode, respectively, to decompose carbamazepine in water samples from the constructed wetlands. The calculations showed that the N-TiO₂ NCs/TNTAs-AC/PTFE system had the highest content of •OH. The highest carbamazepine removal rate under the N-TiO₂ NCs/TNTAs-AC/PTFE composite presence was at pH = 8, and 69% of carbamazepine was removed within 180 min of the constructed wetland water treatment at pH = 7.8. The PEC system containing modified (with nano N-TiO₂) TiO₂ nanotubes as an anode and activated carbon as a photocathode can effectively decompose carbamazepine in the constructed wetlands. Full article

Spatiotemporal parameters such as gait velocity and stride length are simple indicators of functional status and can be used to predict major adverse outcomes in older adults. A smartphone can be used for gait analysis by providing spatiotemporal parameters useful for improving the diagnosis and rehabilitation processes in frail people. The aim of this study was to review articles published in the last 20 years (from 2004 to 2024) concerning the application of smartphones to assess the spatiotemporal parameters of gait in older adults. This systematic review was performed in line with Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA), and original articles were identified by searching seven electronic databases: SciVerse (ScienceDirect), Excerpta Medica Database (EMBASE), Medline, Scopus, PubMed, Web of Science and the Cochrane Library. Studies were rigorously screened using the inclusion criteria of smartphones and mobile apps, older adults and spatiotemporal gait parameters, and results were narratively synthesized. Seventy-three articles were initially identified while searching the scientific literature regarding this topic. Eleven articles were selected and included in this review. Analysis of these studies covered information about gait assessment using mobile apps recorded in 723 older adults and 164 control cases. Analysis of data related to the application of smartphones to assess spatiotemporal parameters of gait in older adults showed moderate-to-excellent test–retest reliability and validity (ICCs around 0.9) of gait speed, the most common parameter reported. Additionally, gait speeds recorded with mobile apps showed excellent agreement when compared to gold standard systems. Smartphones and mobile apps are useful, non-invasive, low-cost and objective tools that are being extensively used to perform gait analysis in older adults. Smartphones and mobile apps can reliably identify spatiotemporal parameters related to adverse outcomes, such as a slow gait speed, as predictors and outcomes in clinical practice and research involving older adults. Full article

Methylmalonyl-CoA epimerase enzyme (MCEE) is responsible for catalyzing the isomeric conversion between D- and L-methylmalonyl-CoA, an intermediate along the conversion of propionyl-CoA to succinyl-CoA. A dedicated test for MCEE deficiency is not included in the newborn screening (NBS) panels but it can be incidentally identified when investigating methylmalonic acidemia and propionic acidemia. Here, we report for the first time the biochemical description of a case detected by NBS. The NBS results showed increased levels of propionylcarnitine (C3) and 2-methylcitric acid (MCA), while methylmalonic acid (MMA) and homocysteine (Hcy) were within the reference limits. Confirmatory analyses revealed altered levels of metabolites, including MCA and MMA, suggesting a block in the propionate degradation pathway. The analysis of methylmalonic pathway genes by next-generation sequencing (NGS) allowed the identification of the known homozygous nonsense variation c.139C>T (p.R47X) in exon 2 of the MCE gene. Conclusions: Elevated concentrations of C3 with a slight increase in MCA and normal MMA and Hcy during NBS should prompt the consideration of MCEE deficiency in differential diagnosis. Increased MMA levels may be negligible at NBS as they may reach relevant values beyond the first days of life and thus could be identified only in confirmatory analyses. Full article

Adolescence is a fundamental period for female athletes to develop athletic performance, mitigate injury risk, and gain collegiate sport scholarships, but there is also a high incidence of sport-related injuries. Physical profiling and athlete screening can support the individualisation of training programmes; however, there is a lack of data pertaining to the reliability of athletic performance and injury surrogate measures in adolescent female athletes. The aim of this study was to quantify the between-session reliability of an athletic performance and injury mitigation testing battery in female adolescent athletes. A total of 31 post-peak height velocity (PHV) (3.00 ± 0.82 years) female athletes (age: 16.20 ± 1.20 years; standing height: 166.00 ± 6.00 cm; mass: 65.5 ± 10.70 kg) from various sports (track and field = 1; lacrosse = 2; basketball = 2; soccer = 3; softball = 11; volleyball = 12) completed two sessions of a multicomponent testing battery 48 h to 1 week apart including the assessment of 33 measures addressing lower-limb isometric strength, eccentric strength, reactive strength, linear sprint and change of direction speed, and lower limb control. Of the 33 measures, between sessions, 29 had a high to nearly perfect intraclass correlation coefficient (ICC) (0.508–0.979), and 26 measures were not statistically significantly different between sessions (p ≤ 0.05). All measures demonstrated low to acceptable coefficient variation (CV%) (0.61–14.70%). The testing battery used can be utilised for recruitment and longitudinal monitoring within sports organisations for female adolescent athletes. Full article

Determining the safety of a newly developed experimental product is a crucial condition for its medical use, especially for clinical trials. In this regard, four hydrogel-type formulations were manufactured, all of which were based on carbomer (Blank-CP940) and encapsulated with caffeine (CAF-CP940), phosphorus derivatives (phenyl phosphinic (CAF-S1-CP940) and 2-carboxyethyl phenyl phosphinic acids (CAF-S2-CP940)). The main aim of this research was to provide a comprehensive outline of the biosafety profile of the above-mentioned hydrogels. The complex in vitro screening (cell viability, cytotoxicity, morphological changes in response to exposure, and changes in nuclei morphology) on two types of healthy skin cell lines (HaCaT—human keratinocytes and JB6 Cl 41-5a—murine epidermal cells) exhibited a good biosafety profile when both cell lines were treated for 24 h with 150 μg/mL of each hydrogel. A comprehensive analysis of the hydrogel’s impact on the genetic profile of HaCaT cells sustains the in vitro experiments. The biosafety profile was completed with the in vivo and in ovo assays. The outcome revealed that the developed hydrogels exerted good biocompatibility after topical application on BALB/c nude mice’s skin. It also revealed a lack of toxicity after exposure to the hen’s chicken embryo. Further investigations are needed, regarding the in vitro and in vivo therapeutic efficacy and safety for long-term use and potential clinical translatability. Full article

Virus-like nanoparticles (VNP) are regarded as efficient vaccination platforms and have proven to be useful for the non-anaphylactogenic delivery of allergen-specific immunotherapy in preclinical models previously. Herein, we sought to determine the mode of VNP uptake by antigen presenting cells (APC). Accordingly, we screened a collection of substances known to inhibit different uptake pathways by APC. The human leukemia monocytic cell line THP-1 and the murine dendritic cell line DC 2.4 were examined for the uptake of fluorescently labelled VNP in the presence or absence of inhibitors. The inhibitory effect of candidate substances that blocked VNP uptake in APC lines was subsequently evaluated in studies with primary APC present in splenocyte and lung cell homogenates in vitro and upon intratracheal application of VNP in vivo. The uptake of allergen-specific VNP in vitro and in vivo was mainly observed by macrophages and CD103⁺ dendritic cells and was sensitive to inhibitors that block macropinocytosis, such as hyperosmolarity induced by sucrose or the polyphenol compound Rottlerin at low micromolar concentrations but not by other inhibitors. Also, T-cell proliferation induced by allergen-specific VNP was significantly reduced by both substances. In contrast, substances that stimulate macropinocytosis, such as Heparin and phorbol myristate acetate (PMA), increased VNP-uptake and may, thus, help modulate allergen-specific T-cell responses. We have identified macropinocytosis as the principal uptake mechanism of APC for allergen-specific VNP in vitro and in vivo, paving the way for further improvement of VNP-based therapies, especially those that can be used for tolerance induction in allergy, in the future. Full article

A higher incidence of primary congenital hypothyroidism (CH) has been related to increased sensitivity in neonatal screening tests. The benefit of treatment in mild cases remains a topic of debate. We evaluated the impact of reducing the blood-spot TSH cut-off (b-TSH) from 10 (Group 2) to 6 mIU/L (Group 1) in a public neonatal screening program. During the study period, 40% of 123 newborns with CH (n = 162,729; incidence = 1:1323) had b-TSH between 6 and 10 mIU/L. Group 1 patients had fewer clinical signs (p = 0.02), lower serum TSH (p < 0.01), and higher free T4 (p < 0.01) compared to those in Group 2 at diagnosis. Reducing the b-TSH cut-off from 10 to 6 mIU/L increased screening sensitivity, allowing a third of diagnoses, mainly mild cases, not being missed. However, when evaluating the performances of b-TSH cut-offs (6, 7, 8, 9, and 10 mIU/L), the lower values were associated with low positive predictive values (PPVs) and unacceptable increased recall rates (0.57%) for a public health care program. A proposed strategy is to adopt a higher b-TSH cut-off in the first sample and a lower one in the subsequent samples from the same child, which yields a greater number of diagnoses with an acceptable PPV. Full article

The volume of difficult-to-process keratin waste is increasing as a result of rising global meat production. If not properly managed, this waste can contribute to environmental pollution and pose a threat to human and animal welfare. An interesting and more sustainable alternative is therefore the bioconversion of keratin using microorganisms and their enzymes. This work aimed to isolate bacteria from soil samples and zoonotic keratins and to evaluate their enzymatic capacity to degrade α- and β-keratin wastes. A total of 113 bacterial strains were isolated from environmental samples and subjected to taxonomic identification using the MALDI-TOF MS technique and to a two-step screening for proteolytic and keratinolytic activity. The ability to degrade a β-rich keratin substrate was observed in almost all of the strains isolated from soil and horsehairs. In contrast, when an α-rich keratin substrate was used, the highest levels of hydrolysis were observed only for Ker39, Ker66, Ker85, Ker100, and Ker101. Strains with the highest biodegradation potential were identified using molecular biology methods. Phylogenetic analysis of 16S rDNA gene sequences allowed the assignment of selected keratinolytic microorganisms to the genera Exiguobacterium, Priestia, Curtobacterium, Stenotrophomonas, Bacillus, Kocuria, or Pseudomonas. The results of this study are a promising precursor for the development of new, more sustainable methods of managing keratin waste to produce high-value hydrolysates. Full article

Bog bilberry (Vaccinium uliginosum L.) is considered a highly valued non-wood forest product (NWFP) species with edible and medicinal uses in East Asia. It grows in the northeastern forests of China, where stand attributes and structure jointly determine its population characteristics and individuals’ growth. Mapping the regional distributions of its population characteristics can be beneficial in the management of its natural resources, and this mapping should be predicted using machine learning modeling to obtain accurate results. In this study, a total of 60 stands were randomly chosen and screened to investigate natural bog bilberry populations in the eastern mountains of Heilongjiang and Jilin provinces in northeastern China. Individual height, canopy cover area, and fresh weight all increased in stands at higher latitudes, and shoot height was also higher in the eastern stands. The rootstock grove density showed a polynomial quadratic distribution pattern along increasing topographical gradients, resulting in a minimum density of 0.43–0.52 groves m⁻² in stands in the southern part (44.3016° N, 129.4558° E) of Heilongjiang. Multivariate linear regression indicated that the bog bilberry density was depressed by host forest tree species diversity; this was assessed using both the Simpson and Shannon–Wiener indices, which also showed polynomial quadratic distribution patterns (with a modeling minimum of 0.27 and a maximum of 1.21, respectively) in response to the increase in latitude. Structural equation models identified positive contributions of tree diameter at breast height and latitude to shoot height and a negative contribution of longitude to the bog bilberry canopy area. Random forest modeling indicated that dense populations with heavy individuals were distributed in eastern Heilongjiang, and large-canopy individuals were distributed in Mudanjiang and Tonghua. In conclusion, bog bilberry populations showed better attributes in northeastern stands where host forest trees had low species diversity, but the dominant species had strong trunks. Full article