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ding these strategies allows nurses to improve care and support for rural mothers using a strength-based approach to build maternal resilience.

Findings from this study provide insight into the experiences of rural maternal caregivers of children with a chronic health condition and identify the strategies they adopt to overcome caregiver challenges. Understanding these strategies allows nurses to improve care and support for rural mothers using a strength-based approach to build maternal resilience.Processing 2D materials into printable or coatable inks for the fabrication of functional devices has proven to be quite difficult. Additives are often used in large concentrations to address the processing challenges, but they drastically degrade the electronic properties of the materials. To remove the additives a high-temperature post-deposition treatment can be used but this complicates the fabrication process and limits the choice of materials (i.e., no heat-sensitive materials). Here, by exploiting the unique properties of 2D materials, we have developed a universal strategy for the formulation of additive-free inks in which the roles of the additives are taken over by van der Waals (vdW) interactions. In this new class of inks, which we term vdW inks, solvents are dispersed within the interconnected network of 2D materials, minimizing the dispersibility-related limitations on solvent selection. Furthermore, flow behavior of the inks and mechanical properties of the resultant films are mainly controlled by the inter-flake vdW attractions. The structure of the vdW inks, their rheological properties, and film-formation behavior are discussed in detail. Large-scale production, and formulation of the vdW inks for major high-throughput printing and coating methods as well as their application for room-temperature fabrication of functional films/devices are demonstrated. This article is protected by copyright. All rights reserved.

This study aimed to investigate the clinical benefits of locoregional radiation therapy (RT) before, after, and concurrent with sorafenib therapy for Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) patients.

Patients treated with sorafenib for BCLC stage C HCC between January 2015 and December 2017 were retrospectively reviewed. In this study, only RT to locoregional sites, including the primary HCC, tumor thrombosis, or lymph node metastasis, was analyzed. Propensity score matching was used to adjust important baseline characteristics between groups.

Among 398 patients treated with sorafenib, 68 (17.1%) patients were treated with locoregional RT. Median progression-free survival and overall survival (OS) were 2.2 and 9.5months, respectively. In the multivariate analysis, locoregional RT (P<0.001) was associated with a favorable OS. After 11 propensity score matching, patients who did not receive locoregional RT showed a worse OS than those who received RT (median 9.6 vs 15.7months, P=0.017). Whereas locoregional RT before/concurrent with sorafenib did not result in prolonged OS, locoregional RT after sorafenib showed significantly prolonged OS compared with sorafenib without locoregional RT (P=0.003). Moreover, patients treated with ≥12weeks of sorafenib significantly benefited from locoregional RT (15.3 vs 23.6months, P=0.046).

Locoregional RT was associated with significantly longer survival in BCLC stage C HCC patients who were treated with sorafenib. Therefore, incorporating locoregional RT could improve the dismal prognosis for these patients.

Locoregional RT was associated with significantly longer survival in BCLC stage C HCC patients who were treated with sorafenib. Therefore, incorporating locoregional RT could improve the dismal prognosis for these patients.Precision oncology benefits from effective early phase drug discovery decisions. Recently, drugging inactive protein conformations has shown impressive successes, raising the cardinal questions of which targets can profit and what are the principles of the active/inactive protein pharmacology. Cancer driver mutations have been established to mimic the protein activation mechanism. We suggest that the decision whether to target an inactive (or active) conformation should largely rest on the protein mechanism of activation. We next discuss the recent identification of double (multiple) same-allele driver mutations and their impact on cell proliferation and suggest that like single driver mutations, double drivers also mimic the mechanism of activation. We further suggest that the structural perturbations of double (multiple) in cis mutations may reveal new surfaces/pockets for drug design. Finally, we underscore the preeminent role of the cellular network which is deregulated in cancer. Our structure-based review and outlook updates the traditional Mechanism of Action, informs decisions, and calls attention to the intrinsic activation mechanism of the target protein and the rewired tumor-specific network, ushering innovative considerations in precision medicine.

To investigate the effect of varying the fluid reservoir (FR) thickness of scleral lenses (SL) on corrected distance visual acuity (CDVA), contrast sensitivity (CS) and higher-order aberrations (HOAs) in keratoconic eyes.

Forty eyes with keratoconus were fitted with a diagnostic Boston Sight SL having three different FR thicknesses. CDVA, CS and HOAs were measured before and after 30min of lens wear. An i-Trace aberrometer and anterior segment optical coherence tomography (AS-OCT) were used to measure HOAs and FR thickness, respectively.

Statistically significant improvements in CDVA and CS were seen with different FR thickness lenses (p<0.01). Baseline CDVA (0.22±0.15) improved to 0.03±0.06, 0.04±0.07 and 0.07±0.08 with low, standard and high FR lenses, respectively. Post-hoc testing showed better CDVA with low (p=0.006) and standard FR (p=0.009) lenses compared to high FR lenses. Before lens wear, CS was 1.27±0.27, which improved to 1.67±0.11, 1.73±0.12 and 1.66±0.89 with low, standard and high FR ctive in improving vision, CS and reducing HOAs in keratoconus. Lenses with varying FR thickness showed equal effectiveness in visual performance and reducing HOAs. FR thickness should be considered an important factor to provide better vision and CS by minimising HOAs, as well as to maintain the normal physiology of eyes with keratoconus.We measured the effect of varieties of Fig leaves, Ficus exasperata Vahl. (FE) and Ficus asperifolia Miq (FA), commonly found in Sub-sahara Africa for managing hypertension on sexual performance in hypertensive rats, which is unknown. Hypertensive rats experienced erectogenic damage after exposure to 40 mg kg-1 bw-1 , N(G)-nitro-l-arginine-methyl-ester (L-NAME). Experimental rats were grouped into eight groups (n = 6) namely control rats, hypertensive rats, hypertensive treatment groups with atenolol (10 mg kg-1 day-1 ) and sildenafil (5.0 mg/kg), rats treated with FE- and FA-formulated biscuits at proportions of 2.5 g and 5.0 g respectively. Furthermore, we measured the level of sexual performance (Intromission number, latency, Mounting number, and latency), hormonal levels, phosphodiesterase-5 enzyme (PDE-5) activity and genes expressed using real-time quantitative polymerase chain reaction (RT-qPCR) in hypertensive rats. The result deduced revealed that treated hypertensive rats showed significantly reduced follicle-stimulating hormone, luteinising hormone levels, PDE-5 enzyme activity, tumour necrosis factor-alpha (TNF-α) expression while having a marked increase in testosterone level, sexual performance and endothelial nitric oxide synthase (eNOS) expression. Therefore, this study revealed the comparative dietary enhancing effect of FE- and FA-formulated biscuit on sexual behaviour activity, hormonal levels and the level of eNOS and TNF-α genes expressed in hypertensive rats.Nontoxic materials with natural origin are promising materials in the designing and preparation of the new drug delivery systems (DDSs). Today's, citric acid (CA) has attracted a great deal of attention because of its special features; green nature, biocompatibility, low price, biodegradability, and commercially available property. So, CA has been employed in the preparation of the various platforms to induce a suitable property on their structure. Recently, several research groups investigated the CA-based platforms in different forms like tablets, dendrimers, hyperbranched polymers, (co)polymer, hydrogels, and nanoparticles as efficient DDSs. ε-poly-L-lysine chemical structure By considering an increasing amount of published articles in this field, for the first time, in this review, an overview of the published works regarding CA applications in the design of various DDSs is presented with a detailed and insightful discussion.

Germline loss-of-function mutations in DEPDC5, and in its binding partners (NPRL2/3) of the mTOR repressor GATOR1 complex, cause focal epilepsies and increase the risk of sudden unexpected death in epilepsy (SUDEP). Here, we asked whether DEPDC5 haploinsufficiency predisposes to primary cardiac defects that could contribute to SUDEP and therefore impact the clinical management of patients at high risk of SUDEP.

Clinical cardiac investigations were performed in sixteen patients with pathogenic variants in DEPDC5, NPRL2 or NPRL3. Two novel Depdc5 mouse strains, a HA-tagged Depdc5 mouse strain and a Depdc5 heterozygous knockout with a neuron-specific deletion of the second allele (Depdc5

) were generated to investigate the role of Depdc5 in SUDEP and cardiac activity during seizures.

Holter, echocardiography and ECG exams provided no evidence for altered clinical cardiac function in the patient cohort, of whom three DEPDC5-patients succumbed to a SUDEP and six had a family history of SUDEP. There was no cardiac injury at autopsy in a postmortem DEPDC5-SUDEP case. The HA-tagged Depdc5 mouse revealed expression of Depdc5 in the brain, heart and lungs. Simultaneous EEG-ECG records on Depdc5

mice showed that spontaneous epileptic seizures resulting in a SUDEP-like event, are not preceded by cardiac arrhythmia.

Mouse and human data show neither structural nor functional cardiac damage that might underlie a primary contribution to SUDEP in the spectrum of DEPDC5-related epilepsies. This article is protected by copyright. All rights reserved.

Mouse and human data show neither structural nor functional cardiac damage that might underlie a primary contribution to SUDEP in the spectrum of DEPDC5-related epilepsies. This article is protected by copyright. All rights reserved.

Clinical and public health implications of the recent redefining of non-alcoholic fatty liver disease (NAFLD) to metabolic-associated fatty liver disease (MAFLD) remain unclear. We sought to determine the prevalence and compare MAFLD with NAFLD in a well-defined cohort.

A cross-sectional study was conducted in regional Victoria with participants from randomly selected households. Demographic and health-related clinical and laboratory data were obtained. Fatty liver was defined as a fatty liver index≥60 with MAFLD defined according to recent international expert consensus.

A total of 722 participants were included. Mean age was 59.3±16years, and 55.3% were women with a median body mass index of 27.8kg/m

. Most (75.2%) participants were overweight or obese. MAFLD was present in 341 participants giving an unadjusted prevalence of 47.2% compared with a NAFLD prevalence of 38.7%. Fifty-nine (17.5%) participants met the criteria of MAFLD but not NAFLD. The increased prevalence of MAFLD in this cohort was primarily driven by dual etiology of fatty liver.