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Metastatic breast cancer (mBC) is a complex and life-threatening disease and although it is difficult to cure, patients can benefit from sequential anticancer treatment, including endocrine therapy, targeted therapy and cytotoxic chemotherapy. The patient-derived xenograft (PDX) model is suggested as a practical tool to predict the clinical outcome of this disease as well as to screen novel drugs. This study aimed to establish PDX models in Korean patients and analyze their genomic profiles and utility for translational research.

Percutaneous core needle biopsy or punch biopsy samples were used for xenotransplantation. Whole exome sequencing and transcriptome analysis were performed to assess the genomic and RNA expression profiles, respectively. Copy number variation and mutational burden were analyzed and compared with other metastatic breast cancer genomic results. Mutational signatures were also analyzed. The antitumor effect of an ATR inhibitor was tested in the relevant PDX model.

Of the 151 casesaracteristics and could be used for the interpretation of clinical outcomes.

Our PDX model was established using core needle biopsy samples from primary and metastatic tissues. Genomic profiles of the samples reflected their original tissue characteristics and could be used for the interpretation of clinical outcomes.

Usutu virus (USUV) is an emerging neurotropic arthropod-borne virus recently involved in massive die offs of wild birds predominantly reported in Europe. Although primarily asymptomatic or presenting mild clinical signs, humans infected by USUV can develop neuroinvasive pathologies (including encephalitis and meningoencephalitis). check details Similar to other flaviviruses, such as West Nile virus, USUV is capable of reaching the central nervous system. However, the neuropathogenesis of USUV is still poorly understood, and the virulence of the specific USUV lineages is currently unknown. One of the major complexities of the study of USUV pathogenesis is the presence of a great diversity of lineages circulating at the same time and in the same location.

The aim of this work was to determine the neurovirulence of isolates from the six main lineages circulating in Europe using mouse model and several neuronal cell lines (neurons, microglia, pericytes, brain endothelial cells, astrocytes, and in vitro Blood-Brain Barrier model).

Our results indicate that all strains are neurotropic but have different virulence profiles. The Europe 2 strain, previously described as being involved in several clinical cases, induced the shortest survival time and highest mortality in vivo and appeared to be more virulent and persistent in microglial, astrocytes, and brain endothelial cells, while also inducing an atypical cytopathic effect. Moreover, an amino acid substitution (D3425E) was specifically identified in the RNA-dependent RNA polymerase domain of the NS5 protein of this lineage.

Altogether, these data show a broad neurotropism for USUV in the central nervous system with lineage-dependent virulence. Our results will help to better understand the biological and epidemiological diversity of USUV infection.

Altogether, these data show a broad neurotropism for USUV in the central nervous system with lineage-dependent virulence. Our results will help to better understand the biological and epidemiological diversity of USUV infection.

Benign prostatic hyperplasia (BPH) is the most common urologic disease among elderly men. The diagnosis of BPH is usually driven by lower urinary tract symptoms (LUTS) that can significantly affect patients' quality of life. This phase II prospective, randomized double-blinded, placebo-controlled study aimed to determine the efficacy and safety of a novel whole tomato-based food supplement on LUTS of patients diagnosed with BPH.

Forty consecutive patients with histologically proved BPH were randomized 11 to receive daily for 2 months a sachet (5g) of a newly developed whole tomato food supplement (WTFS) (treatment = Group A) or placebo (Group B). Patients were asked to fill the International Prostatic Symptom Score (IPSS) questionnaire before and after treatment.

All but 1 patient in Group B successfully completed the scheduled regimen. No side effects were recorded. Unlike placebo, treatment significantly reduced (P < 0.0002) LUTS since mean IPSS decreased from 9.05 ± 1.15 to 7.15 ± 1.04 (paired t-test, two-tailed P-value < 0.001), and improved life quality (P < 0.0001). A trend toward a reduction of total PSA levels was observed in WTFS treated patients (8.98ng/mL ± 1.52 vs 6.95 ± 0.76, P = 0.065), with changes being statistically significant only in the subgroup of patients with baseline levels above 10ng/mL (18.5ng/mL ± 2.7 vs 10.3 ± 2.1, P = 0.009).

The new WTFS may represent a valid option for the treatment of symptomatic BPH patients. Unlike pharmacological treatments, the supplement is side effects free and highly accepted among patients.

The new WTFS may represent a valid option for the treatment of symptomatic BPH patients. Unlike pharmacological treatments, the supplement is side effects free and highly accepted among patients.

Extensive research has demonstrated the role of the Home Environment (HE) in shaping children's energy balance behaviours. Less is known about direct relationships with bodyweight. This review examines associations between the social and physical aspects of three pre-defined Home Environment domains (food, physical activity and media) and adiposity measures in children ≤12 years.

Six electronic databases (PubMed, Medline, EBSCO CINAHL, EMBASE, Web of Science, PsycInfo) were systematically searched up to October 2020. Studies reporting at least one physical and/or social aspect of the food, physical activity and/or media domains of the Home Environment in relation to child adiposity outcomes were included (n= 62).

Most studies examined one (n = 41) or two domains (n = 16). Only five studies assessed all three domains of the Home Environment. Most consistent relationships were observed for physical aspects of the home media environment; with greater availability of electronic devices associated with higheer agreement on definitions and the measurement of the obesogenic home environment is required in order to clarify the strength and direction of relationships with child adiposity. Robust longitudinal research using comprehensive measures of the holistic home environment is needed to better identify which aspects contribute to excess weight gain in childhood.

PROSPERO Systematic review registration number CRD42018115139 .

PROSPERO Systematic review registration number CRD42018115139 .Poor health worker motivation, and the resultant shortages and geographic imbalances of providers, impedes the provision of quality care in low- and middle-income countries (LMICs). This systematic review summarizes the evidence on interventions used to motivate health workers in LMICs. A standardized keyword search strategy was employed across five databases from September 2007 -September 2017. Studies had to meet the following criteria original study; doctors and/or nurses as target population for intervention(s); work motivation as study outcome; study design with clearly defined comparison group; categorized as either a supervision, compensation, systems support, or lifelong learning intervention; and conducted in a LMIC setting. Two independent reviewers screened 3845 titles and abstracts and, subsequently, reviewed 269 full articles. Seven studies were retained from China (n = 1), Ghana (n = 2), Iran (n = 1), Mozambique (n = 1), and Zambia (n = 2). Study data and risk of bias were extracted using a stane of social and professional characteristics. Robust studies that use validated and culturally appropriate tools to assess worker motivation are greatly needed in the Sustainable Development Goals era.

Necrotizing enterocolitis (NEC) remains a fatal gastrointestinal disorder in neonates and has very limited therapeutic options. Sialylated human milk oligosaccharides (SHMOs) improve pathological changes in experimental NEC models. The objectives of this study were to investigate the involvement of NLRP3 inflammasome in NEC pathology and to explore the effects of SHMOs on toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB)/NLRP3 inflammatory pathway in experimental NEC.

The intestinal-tissue segments were collected from NEC infants, NLRP3 and caspase-1 positive cell were examined by immunohistochemistry. Newborn rats were hand-fed with formula containing or non-containing SHMOs (1500mg/L) and exposed to hypoxia/cold stress to induce experimental NEC. The NEC pathological scores were evaluated; ileum protein expression of membrane TLR4 (mTLR4), inhibitor κB-α (IκB-α), NF-κB p65 subunit and phospho-NF-κB p65, as well as NLRP3 and caspase-1 were analyzed; ileum concentrations of interleukin-1β, interleukin ileum of NEC rats. SHMOs pre-treatment improved Caco-2 cell viability, mitigated loss of mitochondrial membrane potential and modulated MMP-2 activities in the presence of lipopolysaccharide in-vitro.

This study provided clinical evidence of involvement of NLRP3 inflammasome in NEC pathology, and demonstrated the protective actions of SHMOs might be owing to the suppression of TLR4/NF-κB/NLRP3-mediated inflammation in NEC.

This study provided clinical evidence of involvement of NLRP3 inflammasome in NEC pathology, and demonstrated the protective actions of SHMOs might be owing to the suppression of TLR4/NF-κB/NLRP3-mediated inflammation in NEC.

Cost effectiveness was a criterion used to revise Ethiopia's essential health service package (EHSP) in 2019. However, there are few cost-effectiveness studies from Ethiopia or directly transferable evidence from other low-income countries to inform a comprehensive revision of the Ethiopian EHSP. Therefore, this paper reports average cost-effectiveness ratios (ACERs) of 159 health interventions used in the revision of Ethiopia's EHSP.

In this study, we estimate ACERs for 77 interventions on reproductive maternal neonatal and child health (RMNCH), infectious diseases and water sanitation and hygiene as well as for 82 interventions on non-communicable diseases. We used the standardised World Health Organization (WHO) CHOosing Interventions that are cost effective methodology (CHOICE) for generalised cost-effectiveness analysis. The health benefits of interventions were determined using a population state-transition model, which simulates the Ethiopian population, accounting for births, deaths and disease epat could substantially reduce Ethiopia's disease burden if scaled up. The use of the World Health Organization's generalised cost-effectiveness analysis tool allowed us to rapidly calculate country-specific cost-effectiveness analysis values for 159 health interventions under consideration for Ethiopia's EHSP.

The present study shows that several potential cost-effective interventions are available that could substantially reduce Ethiopia's disease burden if scaled up. The use of the World Health Organization's generalised cost-effectiveness analysis tool allowed us to rapidly calculate country-specific cost-effectiveness analysis values for 159 health interventions under consideration for Ethiopia's EHSP.