Search

Background: Lipidapheresis techniques are increasingly used to treat drug-resistant hyperlipidemia but few efficacy studies under routine application are available. In this multicenter observational study we investigated direct adsorption of lipoproteins (DALI) and lipoprotein filtration (MONET) for the short and the long-term effects on lipid-lowering effects., Methods: Data of 122 apheresis patients from 11 centers (DALI: n = 78, MONET: n = 44) were prospectively collected for a period of 2 years. Routine lipid measurements were evaluated (2154 DALI and 1297 MONET sessions). It was investigated whether the relative reduction of LDL-C during apheresis session achieves at least 60%. Also relative reduction of total cholesterol, HDL, triglyceride, and Lp(a) were analyzed., Results: The relative reduction of LDL-C was at least 60%: DALI: 70.62%, 95% CI = [69.34; 71.90] and MONET: 64.12%, 95% CI = [60.79; 67.46]. Also triglycerides were reduced with both systems: DALI 38.63%, 95% CI = [33.95; 43.30] vs. MONET 57.68%, 95% CI = [51.91; 63.45]. Relative reductions of total cholesterol were in the range of 50% (DALI 95% CI = [46.49; 49.65] MONET 95% CI = [48.93; 55.26]) and of Lp(a) in the range of 65% (DALI 95% CI = [61.92; 65.83] MONET 95% CI = [63.71; 70.30]. HDL reduction was: DALI 15.01%, 95% CI = [13.22; 16.79] and MONET 22.59%, 95% CI = [19.33; 25.84]. For both devices treated patient plasma/blood volume and in case of DALI the use of the larger adsorber configurations (DALI 1000 and DALI 1250) were independent positive predictors of the relative reduction of LDL-C and of Lp(a)., Conclusions: Both systems effectively improved lipid profile and reduced atherogenic lipids. The results point to the importance of the individualized application of these valuable therapies to achieve clinical targets., (Copyright © 2017. Published by Elsevier B.V.)

Background: Lipidapheresis was introduced for intractable hyperlipidemia as a more selective therapy than plasma exchange aiming to enhance efficacy and limit side-effects. Although this therapy is regarded safe, multicenter data from routine application are limited. We investigated direct adsorption of lipoproteins (DALI) and lipofiltration (MONET) regarding the short and the long-term safety aspects., Methods: This multicenter observational study prospectively evaluated 2154 DALI and 1297 MONET sessions of 122 patients during a period of 2 years. Safety parameters included clinical side-effects (adverse device effects, ADEs), technical complications, blood pressure and pulse rate. Also routinely performed laboratory parameters were documented. Analysis of laboratory parameters was not corrected for blood dilution., Results: Overall 0.4% DALI and 0.5% MONET treatments were affected by ADE. Technical complications occurred in 2.1% and in 0.8% DALI and MONET sessions, respectively. The most frequent ADE was hypotension, and the majority of technical problems were related to vascular access. Both types of treatments led to a drop of thrombocytes in the range of 7-8%. Hematocrit and erythrocytes decreased only during the DALI treatments by about 6%. Leucocytes decreased during the DALI therapy (∼15%), whereas they increased during the MONET application (∼11%). MONET treatment was associated with a higher reduction of proteins (fibrinogen: 58% vs. 23%, albumin: 12% vs. 7%, CRP: 33% vs. 19% for MONET and DALI, respectively). Apart from severe thrombocytopenia in two DALI patients, changes of other parameters were typically transient., Conclusions: Under routine use the frequency of side-effects was low. Still, monitoring of blood count and proteins in chronic apheresis patients is recommended., (Copyright © 2017. Published by Elsevier B.V.)

Background: Numerous healthcare studies have shown that more than 90% of all patients with dyslipidaemia are not treated adequately., Objectives: The "Deutsche Gesellschaft zur Bekämpfung von Fettstoffwechselstörungen und ihren Folgeerkrankungen (DGFF)" [German Society of Lipidology], a non-profit professional membership organization, has already made a series of efforts to improve the care of patients suffering from dyslipidaemia. A recent outcome is the nationwide implementation and certification of Lipidological Competence Centres and Networks (LCCNs)., Methods and Results: By involving numerous external medical cooperation partners and combining the detailed work of different in-house medical specialists, the Medical Care Centre Kempten-Allgäu was able to improve both the diagnosis and treatment of patients exhibiting disorders of lipid metabolism (DLM). This local lipidological network is so successful, that it may serve as a nationwide standard model for outpatient lipidological care. Detailed organizational structures for improved lipidological care which are suitable to provide a template for future guidelines for the certification of LCCNs have been developed by the Medical Care Centre Kempten-Allgäu. Stringent requirements of implementation with respect to medical staff, content and structure, staff training, patient education and public relations as well as to documentation, quality assurance and quality improvement must be fulfilled both by the lipidological competence centre (LCC) and the cooperation partners within the lipidological network (LN). Finally, members of the health care system (e.g. health policy and health insurances) should be involved in this attempt and convinced of financial support., Conclusion: The implementation and certification of national LCCNs supported by DGFF could contribute to a comprehensive improvement in the care of patients with dyslipidaemia, resulting in prevention of cardiovascular diseases and reduction of cardiovascular sequelae., (Copyright © 2017. Published by Elsevier B.V.)

We have previously shown that carbon nanofibers (CNFs) and carbon nanotubes (CNTs) can sensitize prostate cancer (PCa) cells to platinum-based chemotherapeutics. In order to further verify this concept and to avoid a bias, the present study investigates the chemosensitizing potential of CNFs and CNTs to the conventional chemotherapeutics docetaxel (DTX) and mitomycin C (MMC), which have different molecular structures and mechanisms of action than platinum-based chemotherapeutics. DU-145 PCa cells were treated with DTX and MMC alone or in combination with the carbon nanomaterials. The impact of the monotreatments and the combinatory treatments on cellular function was then systematically analyzed by using different experimental approaches (viability, short-term and long-term proliferation, cell death rate). DTX and MMC alone reduced the viability of PCa cells to 94% and 68%, respectively, whereas a combined treatment with CNFs led to less than 30% remaining viable cells. Up to 17- and 7-fold higher DTX and MMC concentrations were needed in order to evoke a similar inhibition of viability as mediated by the combinatory treatments. In contrast, the dose of platinum-based chemotherapeutics could only be reduced by up to 3-fold by combination with carbon nanomaterials. Furthermore, combinatory treatments with CNFs led mostly to an additive inhibition of short- and long-term proliferation compared to the individual treatments. Also, higher cell death rates were observed in combinatory treatments than in monotreatments, e.g., a combination of MMC and CNFs more than doubled the cell death rate mediated by apoptosis. Combinations with CNTs showed a similar, but less pronounced impact on cellular functions. In summary, carbon nanomaterials in combination with DTX and MMC evoked additive to partly synergistic anti-tumor effects. CNFs and CNTs possess the ability to sensitize cancer cells to a wide range of structurally diverse chemotherapeutics and thus represent an interesting option for the development of multimodal cancer therapies. Co-administration of chemotherapeutics with carbon nanomaterials could result in a reduction of the chemotherapeutic dosage and thus limit systemic side effects.

A disintegrin and metalloproteinase (ADAM) molecules are known for their unique potential to combine adhesion, proteolysis, and signaling. To understand the role of ADAM17/tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE) in pancreatic ductal adenocarcinoma (PDAC), we investigated its expression, function, and in vitro regulation. ADAM17/TACE mRNA was expressed in 3 of 10 normal pancreatic tissues, 6 of 8 samples from patients with chronic pancreatitis, 10 of 10 PDAC tissues, and 9 of 9 pancreatic cancer cell lines, but it was absent in primary duct epithelial cells. Immunohistochemical staining revealed positive cancer cells in 8 of 10 PDACs but no staining of ducts in normal pancreas. ADAM17/TACE was found in 0 of 16 pancreatic intraepithelial neoplasia (PanIN)-1A lesions, 1 of 30 PanIN-1B lesions, 2 of 13 PanIN-2 lesions but, in 13 of 15 PanIN-3 lesions, associated with PDAC. Western blot, flow cytometry, and confocal microscopy analyses showed the aberrant expression of ADAM17/TACE protein in pancreatic cancer cell lines. The proteolytic activity of ADAM17/TACE, assessed by the release of TNF-alpha, was inhibited by TNF-alpha protease inhibitor. ADAM17/TACE gene silencing using small interfering RNA technique in vitro reduced invasion behavior dramatically, whereas proliferation was unaffected. Furthermore, ADAM17/TACE mRNA expression was down-regulated in pancreatic cancer cells arrested in G2-M phase as well as in a time-dependent manner after TNF-alpha and interleukin-6 incubation. In conclusion, our findings provide evidence of aberrant expression of the proteolytically active ADAM17/TACE in advanced precursor lesions (PanIN-3) and PDAC while identifying its critical involvement in the invasion process.

No recent national data on expenditures and utilization are available to provide a benchmark for reform of mental health systems for children and adolescents. The most recent estimates, from 1986, predate the dramatic growth of managed care. This study provides updated national estimates. Treatment expenditures are estimated to be $11.68 billion ($172 per child). Adolescents have the highest expenditures at $293 per child followed by $163 per child aged 6 to 11 and $35 per preschool-aged child. Outpatient services account for 57%, inpatient for 33%, and psychotropic medications for 9% of the total. Unlike earlier reports, outpatient care now accounts for the majority of expenditures. This finding replicates the differences between recent managed care data and earlier actuarial databases for privately insured adults and confirms the trend from inpatient toward outpatient care. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Tumor necrosis factor-α (TNF-α) is expressed primarily in adipocytes, and elevated levels of this cytokine have been linked to obesity and insulin resistance. Recently, the A allele of a polymorphism in the 5'-flanking region of the TNF-α gene (G-308A) has been reported to be more frequent in obese than in lean subjects and has also been associated with increased expression of this cytokine in fat tissue and influences fat mass and insulin resistance. We, therefore, examined the relationship between this variant and obesity in a German Caucasian population. SUBJECTS AND METHODS: We genotyped 176 index subjects recruited within the framework of the BErG (Berlin Ernährung Geschwister)- Study for the TNF-α-G-308A polymorphism. Subjects were characterized for weight, height, waist and hip circumference, body mass index (BMI), body composition, glucose tolerance, leptin and angiotensinogen levels. RESULTS: The frequency of the -308A allele (0.18) was similar to that reported previously and genotype distribution was in Hardy-Weinberg equilibrium (GG, n = 118; GA, n = 53; AA, n = 5). There was a significant difference in allele frequencies of the polymorphism by BMI quartiles (I, < 27.3 kg/m²; II, 27.3-31.9 kg/m²; III, 31.9-36.5 kg/m²; IV, > 36.5 kg/m², in each quartile n = 44) with -308A allele carriers having a higher BMI than G allele carriers (P = 0.013). Despite previous smaller studies that have related insulin resistance to the G-308A polymorphism, we found no relationship between glucose and insulin response during an oral glucose tolerance test (OGTT) and the polymorphism. Furthermore, none of the plasma parameters were related to the polymorphism. CONCLUSION: Our findings support the hypothesis that the G-308A polymophism of the TNF-α gene is associated with BMI. The G-308A polymorphism may, therefore, represent a genetic marker for increased susceptibility for obesity in Caucasians. [ABSTRACT FROM AUTHOR]

CD44 is an integral cell-surface glycoprotein. Overexpression of the CD44 standard (CD44st) and its variants (CD44v) has been implicated in transformation and progression of many cancer types. Here, we investigated expression of CD44st, CD44v3-7, CD44v7/8, and v10 in five human pancreatic tumor cell lines and normal human pancreatic duct cells transfected with the SV40 large T antigen. CD44st and its variant proteins were quantified using immunocytochemistry and flow cytometry. CD44v7 was expressed at low levels, whereas CD44st, CD44v3, CD44 v4, CD44v, and CD44v6 were expressed at moderate levels in all pancreatic tumor cell lines. In contrast, CD44v7/8 and CD44v10 were expressed at very low levels in two out of the five pancreatic tumor cell lines. Overall, staining of CD44st and CD44 variants was significantly weaker compared to another surface molecule, ICAM-1, reported to be overexpressed in pancreatic cancer cells. Furthermore, the SV40 large T transfected duct cells showed only a weak staining for CD44st, CD44v5, and CD44v6. To determine a possible mechanism for the regulation of surface expression of CD44st, v5 and v6, we incubated Panc-1 cells with bFGF, TGF-beta1, EGF, TNFalpha, and IFNgamma. Only IFNgamma affected the CD44 expression by down-regulation of CD44v6. The constitutive expression of CD44 variants seems to be associated with the malignant state of invasive carcinoma.

The study of interface states and bulk traps and their connection to device instability is highly demanded to achieve reliable β-Ga2O3 metal-oxide-semiconductor (MOS) devices. However, a comprehensive analysis of the capture/emission behavior of interface states and bulk traps can be challenging due to widespread time constant distribution. In this study, using capacitance transient measurement tools, trap states of the ZrO2/β-Ga2O3 MOS gate stack were explicitly investigated, particularly its bias- and temperature-dependent relaxation kinetics. As forward bias is enlarged, it is observed that the interface state density (Dit) increases by 12.6%. Two bulk traps with discrete levels identified as 0.43 eV (E1) and 0.74 eV (E2) below the conduction band minimum were extracted by deep-level transient spectroscopy. It is further revealed that the emission processes of E1 and E2 are thermally enhanced, while the capture processes remain insensitive to temperature. The electric-field dependence of E1 indicates that the dominant mechanism follows the rule of Poole–Frenkel emission. The capacitance–voltage (C–V) hysteresis deteriorated at a higher forward bias due to the higher trap density and increased population of trapped charges. These findings provide an important framework for future device optimization to improve the reliability and performance of β-Ga2O3 MOS devices. [ABSTRACT FROM AUTHOR]

In this work, three atomic layer deposition (ALD) approaches are used to deposit an Al2O3 gate insulator on n-GaN for application in vertical GaN power switches: thermal ALD (ThALD), plasma-enhanced ALD (PEALD), and their stacked combination. The latter is a novel method to yield the most ideal insulating layer. Also, the influence of an in situ NH3 or H2 plasma pre-treatment is studied. Planar MIS capacitors are used to investigate the electrical properties and robustness of the gate insulators. In vacuo x-ray photoelectron spectroscopy (XPS) is used to study the changes in chemical composition after every surface treatment. XPS shows that all plasma pre-treatments efficiently remove all carbon contamination from the surface, but only NH3 plasma is observed to additionally remove the native oxide from the n-GaN surface. The water precursor step in the ThALD process does not completely remove the CH3 ligands of the trimethylaluminum precursor step, which might electrically be associated with a reduced forward bias robustness. The O2 plasma step in the PEALD process is associated with the removal of carbon and a tremendous increase of the O content in the GaN surface region. Electrically, this strongly correlates to an enhanced forward bias robustness and an increased forward bias hysteresis, respectively. The ThALD/PEALD stack method mitigates the shortcomings of both ALD processes while maintaining its advantages. Electrical measurements indicate that the stack method alongside NH3 plasma pretreatment provides the best characteristics in terms of hysteresis, threshold voltage, forward bias robustness, and interface trap density of states. [ABSTRACT FROM AUTHOR]

We investigate the sub-bandgap optical absorption (SOA) in 300-nm-thick Al1−xInxN alloys used in cladding layers of edge-emitting laser diodes and distributed Bragg reflectors of vertical-cavity surface-emitting lasers. Al1−xInxN alloys, with indium content x ranging from 0.114 to 0.185, were grown by metal-organic chemical vapor deposition on a c-plane GaN/sapphire template. SOAs on 300-nm-thick thin films were characterized using photothermal deflection spectroscopy (PDS). Thermal emission, such as nonradiative recombination with phonon emission, is the dominant energy relaxation process occurring after SOA in Al1−xInxN alloys. The absorption coefficient of the SOA was estimated to be 0.6–7.0 × 103 cm−1 in these samples by combining PDS and spectroscopic ellipsometry. The drastic increase in the SOA, when x exceeded the lattice-matched composition of the GaN/sapphire template, indicates that impurities, vacancy-type defects, and their complexes with increasing x are possible candidates that result in SOA in Al1−xInxN alloys. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the association between high-sensitivity C-reactive protein (hsCRP) levels and hepatic fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and assess its predictive efficacy. Methods: The study included 1,477 participants from the United States and 1,531 from China diagnosed with MASLD. Liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were assessed by vibration-controlled transient elastography (VCTE) to evaluate the presence and degree of hepatic fibrosis and steatosis. The relationship between hsCRP levels and hepatic fibrosis in MASLD patients was examined using multivariable-adjusted and restricted cubic spline (RCS) models. Additionally, subgroup analyses were conducted to investigate the potential heterogeneity among different characteristic subgroups. Results: The results demonstrated a significant correlation between elevated hsCRP levels and an increased risk of significant fibrosis, advanced fibrosis, and cirrhosis in the US cohort of MASLD patients (OR 2.22, 1.69, and 2.85, respectively; all P <0.05). The results of the Chinese cohort were consistent with those of the US cohort, and there was a significant and positive correlation between hsCRP levels and the risk of hepatic fibrosis in patients with MASLD (OR 2.53, 3.85, and 3.78, respectively, all P <0.001). The RCS analysis revealed a significant non-linear relationship between hsCRP levels and the degree of hepatic fibrosis, with disparate inflection point values observed across different cohorts (approximately 9 mg/L in the US cohort and 4 mg/L in the Chinese cohort). The impact of hsCRP levels on the risk of hepatic fibrosis varied across different subgroups with distinct characteristics. Conclusion: The present study demonstrated a significant correlation between hsCRP levels and the degree of hepatic fibrosis in patients with MASLD, with notable dose-response relationships and subgroup differences. [ABSTRACT FROM AUTHOR]

Background/Objectives: Fragile X syndrome (FXS) is one of the most common genetic causes of intellectual developmental disability and autism spectrum disorder (ASD), second only to Down's syndrome and associated with a broad range of neurodevelopmental, behavioral, and psychiatric challenges. FXS may be present in infants or young children with characteristic dysmorphic features, developmental delays, and behavioral challenges. The diagnosis of FXS is confirmed by the molecular genetic testing of the FMR1 gene encoding fragile X messenger RNA-binding protein (FMRP), involved in regulating the translation of multiple mRNAs which play a key role in neuronal development and synaptic plasticity. Understanding the genetic cause, pathophysiology, and natural history of FXS is crucial for identifying commonly associated comorbidities, instituting effective therapeutic interventions, and improving long-term outcomes. Methods: This systematic review employed a comprehensive literature search using multiple electronic databases including PubMed, Web of Science, and Scopus with keywords related to fragile X syndrome, lifespan, genetics, neurodevelopmental, behavioral, and psychiatric disorders. Results: FXS is associated with an increased risk for specific neurodevelopmental, or psychiatric disorders. Symptoms and challenges associated with FXS vary based on multiple factors, including genetic differences, age, sex, comorbid conditions, various environmental influences, the availability of support, and opportunities for therapeutic interventions. Knowledge of these associations helps guide caregivers and clinicians in identifying potentially treatable conditions that can help to improve the lives of affected patients and their families. Conclusions: The focus of this article is to explore and describe the genetic underpinnings of FXS, identify associated developmental, behavioral, and psychiatric conditions over the lifespan, and provide a review of clinical features, therapeutic interventions including investigational treatments, and current research updates. [ABSTRACT FROM AUTHOR]

Despite the potential of paid caregivers (e.g., home health aides and other home care workers) to improve their clients' health-related outcomes, paid caregivers are rarely integrated in the healthcare team. Geriatrician's perspective on paid caregivers can inform healthcare team approaches that leverage the paid caregiver role to improve older adult health. This secondary qualitative analysis (n = 9 geriatricians, n = 27 interviews) used thematic analysis to identify geriatrician perceptions of when paid caregivers do the most to support the health of older adults. Geriatricians perceived that paid caregiver contributions were greatest in the care of high-needs older adults (e.g., dementia) and that paid caregivers stepped up to fill healthcare gaps when families could not provide all needed support (e.g., no family). Future work should consider how to best integrate paid caregivers who are already providing health-related support into the care team and explore barriers to paid caregiver participation in health-related care more generally. [ABSTRACT FROM AUTHOR]

Introduction: Home care workers (HCWs) are paid caregivers who provide support to patients with chronic conditions and functional limitations. Additionally, they provide emotional support to patients and familial support. Although several qualitative studies have been conducted on HCWs, they focused more on studying prevalently the lived experiences about the workplace violence, the end of life, stressor and resilience, during the COVID-19 pandemic or focused more in dementia and heart failure, but not on feelings and working conditions. Methods: The study was carried out using Cohen's phenomenological methodology. The subjects were enrolled in several cities of Central Italy and interviewed with open questions to allow them full freedom of expression and asked to describe their lived experience of HCWs who helped people with chronic diseases. Each interview was recorded audio and lasted between 20 and 60 min. Researchers involved in the analysis were independently immersed in the data by reading and rereading the transcripts to gain a sense of the entire data set. The extrapolation of the themes followed. The individual researchers compared the various extrapolated themes. Results: Seventeen HCWs, all women, with a mean age of 54 years were enrolled in this study. All had more than a year (from 4 to 26 years) of experience in Italy, and almost the whole sample lived with the person they were assisting. Three themes were identified in the interviews: (1) feeling inadequate as a nurse, (2) feeling valued in this role, and (3) uncertain future. Feeling inadequate due to lack of training, difficulties related to the Italian language, or uncertainty about their future were topics identified by the HCWs. Conclusions: Since HCWs represent an important resource which, if properly trained, could positively influence the quality of life of the elderly population and a valid support for their families, understanding the lived experience can suggest interventions that could be implemented by a health care professional and provide evidence to inform political decision makers to increase the support for HCWs. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) driven by the KRAS-G12D mutation presents a formidable health challenge because of limited treatment options. MRTX1133 is a highly selective and first-in-class KRAS-G12D inhibitor under clinical development. Here, we report that the advanced glycosylation end product–specific receptor (AGER) plays a key role in mediating MRTX1133 resistance in PDAC cells. The up-regulation of AGER within cancer cells instigates macropinocytosis, facilitating the internalization of serum albumin and subsequent amino acid generation. These amino acids are then used to synthesize the antioxidant glutathione, leading to resistance to MRTX1133 treatment due to the inhibition of apoptosis. The underlying molecular mechanism involves AGER's interaction with diaphanous-related formin 1 (DIAPH1), a formin protein responsible for driving Rac family small GTPase 1 (RAC1)–dependent macropinosome formation. The effectiveness and safety of combining MRTX1133 with pharmacological inhibitors of the AGER-DIAPH1 complex (using RAGE299) or macropinocytosis (using EIPA) were confirmed in patient-derived xenografts, orthotopic models, and genetically engineered mouse PDAC models. This combination therapy also induces high-mobility group box 1 (HMGB1) release, resulting in a subsequent antitumor CD8+ T cell response in immunocompetent mice. Collectively, the study findings underscore the potential to enhance the efficacy of KRAS-G12D blockade therapy by targeting AGER-dependent macropinocytosis. Editor's summary: Selective KRAS-G12D inhibitors have become an important treatment option for patients with KRAS-G12D–driven cancers, but the development of drug resistance can limit their efficacy. In this study by Li et al., the authors found that advanced glycosylation end product–specific receptor (AGER) contributed to MRTX1133 resistance in pancreatic ductal adenocarcinoma (PDAC) through modulation of macropinocytosis and glutathione synthesis using patient-derived xenografts and orthotopic and genetically engineered mouse models. The combination of MRTX1133 with inhibition of AGER or macropinocytosis improved survival and reduced tumor burden in a CD8+ T cell–dependent manner. These results suggest that this combination treatment may be an effective strategy to improve MRTX1133 efficacy in KRAS-G12D–driven PDAC and related cancers. —Allison Williams [ABSTRACT FROM AUTHOR]

Marfan syndrome (MFS) is an inherited disorder that affects the connective tissues and mainly presents in the bones, eyes, and cardiovascular system, etc. Aortic pathology is the leading cause of death in patients with Marfan syndrome. The fibrillin-1 gene (FBN1) is a major gene involved in the pathogenesis of MFS. It has been shown that the aortic pathogenesis of MFS is associated with the imbalances of the transforming growth factor-beta (TGF-β) signaling pathway. However, the exact molecular mechanism of MFS is unclear. Animal models may partially mimic MFS and are vital to the study of MFS. Several species of animals have been used for MFS studies, including chicks, cattle, mice, pigs, zebrafishes, Caenorhabditis elegans , and rabbits. These models were developed spontaneously or in combination with genetic engineering techniques. This review is to describe the TGF-β signaling pathway in MFS and the potential application of animal models to provide new therapeutic strategies for patients with MFS. [ABSTRACT FROM AUTHOR]

Simple Summary: The use of feed additives has been increasing in the aquaculture feed industry due to their potential to enhance production and profitability through physiological benefits, such as increased growth rates and fillet quality. Guanidinoacetic acid is a promising feed additive due to its physiological role as creatine precursor and its heat stability during feed manufacturing. The current study was designed to evaluate the effect of increasing doses of guanidinoacetic acid (0.00, 0.06, 0.12, and 0.18%) in rainbow trout (Oncorhynchus mykiss) growth, weight gain, and meat quality. We hypothesised that trout fed with the feed additive would have better performance, reaching its optimal physiological response at 0.12%. The results showed that trout fed guanidinoacetic acid presented better weight gain than trout 0.00%, with an optimal growth rate when fed 0.12%. Nonetheless, the level used was not enough to affect fillet quality. This study contributes to the aquaculture industry by determining the optimal level of guanidinoacetic acid for trout performance and its effects on fillet quality. These results can later be adapted to the reality of the aquaculture feed industry to improve fish performance and, consequently, profitability. Guanidinoacetic acid (GAA) plays an important role in cellular energy use and protein synthesis. The objectives of this study were to determine the optimal level of dietary GAA regarding the growth performance and fillet characteristics of rainbow trout (Oncorhynchus mykiss). A total of 300 trout (initial weight, 66.84 ± 7.82 g) were fed isonitrogenous (34%) and isocaloric (20.6 MJ kg−1) diets with increasing levels of GAA (0.00, 0.06, 0.12, 0.18%) for 90 days. The results showed that trout fed GAA (either 0.06, 0.12, or 0.18%) yielded better (p < 0.05) performance (BW, BWG, FCR, and SGR) than trout fed the control diet (0.00% GAA inclusion). No differences (p > 0.05) were observed for BW, BWG, nor FCR among trout fed GAA. Nonetheless, trout fed a diet with a 0.12% GAA inclusion had the highest (p < 0.01) SGR. Fillet quality was not affected by GAA supplementation (p > 0.05) for cook loss, shear force, nor colour. Trout fed 0.06% GAA inclusion tended (p = 0.08) to have a higher WHC. Moreover, trout fed 0.12 and 0.18% GAA had lower (p < 0.05) pH values than trout fed the control diet and 0.06% GAA. Our findings give insights for the growth promotion and fillet quality of trout fed diets supplemented with GAA, especially at the level of 0.12%. [ABSTRACT FROM AUTHOR]

No biomarker can effectively screen for early gastric cancer (EGC). Players in the A disintegrin and metalloproteinase (ADAM)-natural killer group 2 member D (NKG2D) receptor axis may have a role for that. As a proof-of-concept pilot study, the expression of ADAM8, ADAM9, ADAM10, ADAM12, ADAM17, and major histocompatibility complex (MHC) class I chain-related sequence A (MICA), a ligand for NKG2D, in gastric cancer was investigated in silico using The Cancer Genome Atlas (TCGA) database. Subsequently, the mRNA and protein expression levels of these markers except ADAM8 were tested in blood samples from patients with EGC and healthy controls. In the TCGA data analyses, EGC tissues (n = 57) expressed significantly higher mRNA levels of ADAM8, ADAM9, ADAM10, ADAM12, and ADAM17 than normal tissues (n = 35) (p < 0.005). In human blood sample analyses, ADAM12 (p = 0.0007), ADAM17 mRNA (p < 0.0001) and ADAM10 (p < 0.0017) protein were significantly elevated in patients with EGC (n = 27 for mRNA and n = 25 for protein) compared to the controls (n = 30 for mRNA and n = 26 for protein). Areas under the curves calculated by receiver-operating characteristic analysis for ADAM12, ADAM17 mRNA and ADAM10 protein were 0.7568 (95% confidence interval [CI]: 0.6334 to 0.8802), 0.8062 (95% CI: 0.6889 to 0.9234; p < 0.0001), and 0.8108 (95% CI: 0.6895 to 0.9320; p = 0.0001), respectively. Thus, ADAM12, ADAM17 mRNA and ADAM10 protein levels in peripheral blood could hold potential as biomarkers for screening EGC, and further investigations are required. [ABSTRACT FROM AUTHOR]

Simple Summary: Poultry are unable to synthesize arginine. Thus, it is essential to include enough arginine in poultry feed. One can save some arginine by means of providing the molecules in which arginine is needed as a building block. However, the question is how much arginine can these kinds of molecules replace in poultry feed. Herein, these questions are addressed in two trials comparing guanidinoacetic acid and arginine. Moreover, the energy-saving potential of guanidinoacetic acid is evaluated. Optimal performance in broiler chickens was achieved when birds were provided with higher dietary arginine content compared to the available recommendation tables. Supplementation of either arginine or guanidinoacetic acid with a low-arginine feed alleviated the lower performance. However, more guanidinoacetic acid was needed to provide the same level of growth attained with arginine (1 to 0.57 ratio). Reduction of dietary energy by 50 and 100 kcal/kg did not significantly influence the performance of birds at all stages of growth. Moreover, guanidinoacetic acid had no energy-sparing effect. This study helps the industry to accurately meet the arginine and energy requirements of broiler chickens. Two 35-day trials were conducted to determine the arginine (Arg) requirement of broiler chickens and the Arg and energy-sparing effects of guanidinoacetic acid (GAA). In experiment 1, a low-Arg diet (basal diet) was supplemented with increasing levels (0.06–0.61%) of L-Arg or GAA. In experiment 2, a diet meeting the energy and amino acid requirements of broiler chickens served as the positive control (PC). Two negative control (NC) groups were assigned by reducing either 50 (NC1) or 100 (NC2) kcal nitrogen-corrected metabolizable energy. Test groups were supplemented with 0.06% GAA for NC1 and 0.12% GAA for NC2 to compensate for the lower energy in the feed. The low dietary Arg concentration (starter: 1.02%, grower: 0.88%, finisher: 0.75%) significantly reduced overall performance (p < 0.05). Supplementation of either L-Arg or GAA with a low-Arg diet both alleviated the lower performance (p < 0.05). However, more GAA was needed to provide the same level of growth attained with L-Arg at an equivalency rate of 1 GAA to 0.57 Arg. Reduction of dietary energy by 50 and 100 kcal did not significantly influence the performance of birds at all stages of growth. Moreover, no effect of GAA supplementation at 0.06% or 0.12% was observed. [ABSTRACT FROM AUTHOR]

The rising prevalence of Alzheimer's disease and Alzheimer's disease–related dementias has led to renewed public discourse and policy changes in response to the care needs of persons living with dementia and their care partners. Comprehensive dementia care models are central to many recent policy initiatives, most notably the Centers for Medicare & Medicaid Services Guiding an Improved Dementia Experience model. Gerontological nursing research is uniquely positioned to design and lead research investigating the effectiveness of these initiatives, as well as the dissemination and scaling of existing comprehensive dementia care models. The current Annual State of the Science Review provides an overview of the current state of comprehensive dementia care models in the United States and relevant policies. Challenges and opportunities for nursing education, research, and implementation across the translational research continuum are also outlined. [Research in Gerontological Nursing, 18(1), 7–16.] [ABSTRACT FROM AUTHOR]

Recent studies have shown that carbon nanomaterials such as carbon nanofibres (CNFs) and multi-walled carbon nanotubes (CNTs) can exert antitumor activities themselves and sensitize cancer cells to conventional chemotherapeutics such as carboplatin and cisplatin. In the present study, the chemosensitizing effect of CNFs and CNTs on cancer cells of urological origin was investigated regarding the underlying mechanisms. Prostate cancer (DU-145, PC-3) and bladder cancer (EJ28) cells were treated with carbon nanomaterials (CNFs, CNTs) and chemotherapeutics (carboplatin, cisplatin) alone as well as in combination for 24 h. Forty-eight(EJ28) or 72 h (DU-145, PC-3) after the end of treatment the effects on cellular proliferation,clonogenic survival, cell death rate and cell cycle distribution were evaluated. Depending on the cell line, simultaneous administration of chemotherapeutics and carbon nanomaterials produced an additional inhibition of cellular proliferation and clonogenic survival of up to 77% and 98%, respectively, compared to the inhibitory effects of the chemotherapeutics alone. These strongly enhanced antiproliferative effects were accompanied by an elevated cell death rate, which was predominantly mediated via apoptosis and not by necrosis. The antitumor effects of combinations with CNTs were less pronounced than those with CNFs. The enhanced effects of the combinatory treatments on cellular function were mostly of additive to partly synergistic nature. Furthermore, cell cycle analysis demonstrated an arrest at the G2/M phase mediated by a monotreatment with chemotherapeutics. Following combinatory treatments, mostly less than or nearly additive increases of cell fractions in the G2/M phase could be observed. In conclusion,the pronounced chemosensitizing effects of CNFs and CNTs were mediated by an enhanced apoptosis and inhibition of proliferation. The combination of carbon-based nanomaterials and conventional chemotherapeutics represents a novel approach in cancer therapy to bypass chemoresistance by minimizing the chemotherapeutic dosing.