Bacteria are a common group of foodborne pathogens presenting public health issues with a large economic burden for the food industry. Our work focused on a solution to this problem by evaluating antibiotic activity against two bacteria (Listeria monocytogenes and Escherichia coli) of relevance in the field of foodstuffs. We used two approaches: (i) structural modification of the antimicrobial peptides and (ii) nano-vehiculisation of the modified peptides into polymer-coated liposomes. To achieve this, two antimicrobial peptides, herein named 'peptide +2' and 'peptide +5' were synthesised using the solid phase method. The physicochemical characterisation of the peptides was carried out using measurements of surface tension and dynamic light scattering. Additionally, nanoliposomes were elaborated by the ethanol injection method and coated with a cationic polymer (Eudragit E-100) through the layer-by-layer process. Liposome characterisation, in terms of size, polydispersity and zeta potential, was undertaken using dynamic light scattering. The results show that the degree of hydrophilic modification in the peptide leads to different characteristics of amphipathicity and subsequently to different physicochemical behaviour. On the other hand, antibacterial activity against both bacteria was slightly altered after modifying peptide sequence. Nonetheless, after the encapsulation of the peptides into polymer-coated nano-liposomes, the antibacterial activity increased approximately 2000-fold against that of L. monocytogenes.

Esophageal cancer prognosis remains poor in current clinical practice. We previously reported that moscatilin can induce apoptosis and mitotic catastrophe in esophageal cancer cells, accompanied by upregulation of polo-like kinase 1 (Plk1) expression. We aimed to validate in vitro activity and Plk1 expression in vivo following moscatilin treatment and to examine the treatment's radiosensitizing effect. Human esophageal cancer cells were implanted in nude mice. Moscatilin was intraperitoneally (i.p.) injected into the mice. Tumor size, body weight, white blood cell counts, and liver and renal function were measured. Aberrant mitosis and Plk1 expression were assessed. Colony formation was used to measure survival fraction after radiation. Moscatilin significantly suppressed tumor growth in mice bearing human esophageal xenografts without affecting body weight, white blood cell counts, or liver and renal function. Moscatilin also induced aberrant mitosis and apoptosis. Plk1 expression was markedly upregulated in vivo. Moreover, moscatilin pretreatment enhanced CE81T/VGH and BE3 cell radioresponse in vitro. Moscatilin may inhibit growth of human esophageal tumors and sensitize esophageal cancer cells to radiation therapy.

Millions of users share images and videos generated by mobile devices with different profiles on social media platforms. When publishing illegal content, they prefer to use anonymous profiles. Multimedia Forensics allows us to determine whether videos or images have been captured with the same device, and thus, possibly, by the same person. Currently, the most promising technology to achieve this task exploits unique traces left by the camera sensor into the visual content. However, image and video source identification are still treated separately from one another. This approach is limited and anachronistic, if we consider that most of the visual media are today acquired using smartphones that capture both images and videos. In this paper we overcome this limitation by exploring a new approach that synergistically exploits images and videos to study the device from which they both come. Indeed, we prove it is possible to identify the source of a digital video by exploiting a reference sensor pattern noise generated from still images taken by the same device. The proposed method provides performance comparable with or even better than the state-of-the-art, where a reference pattern is estimated from video frames. Finally, we show that this strategy is effective even in the case of in-camera digitally stabilized videos, where a non-stabilized reference is not available, thus solving the limitations of the current state-of-the-art. We also show how this approach allows us to link social media profiles containing images and videos captured by the same sensor.

Microtia is a congenital malformation affecting one in 5000 individuals and is characterized by physical deformity or absence of the outer ear. Nowadays, surgical reconstruction with autologous tissue is the most common clinical practice. The procedure requires a high level of manual and artistic techniques of a surgeon in carving and sculpting of harvested costal cartilage of the patient to recreate an auricular framework to insert within a skin pocket obtained at the malformed ear region. The aesthetic outcomes of the surgery are highly dependent on the experience of the surgeon performing the surgery. For this reason, surgeons need simulators to acquire adequate technical skills out of the surgery room without compromising the aesthetic appearance of the patient. The current paper aims to describe and analyze the different materials and methods adopted during the history of autologous ear reconstruction (AER) simulation to train surgeons by practice on geometrically and mechanically accurate physical replicas. Recent advances in 3D modelling software and manufacturing technologies to increase the effectiveness of AER simulators are particularly described to provide more recent outcomes.

The lack of tumor-reactive T cells is one reason why immune checkpoint inhibitor therapies still fail in a significant proportion of melanoma patients. A vaccination that induces melanoma-specific T cells could potentially enhance the efficacy of immune checkpoint inhibitors. Here, we describe a vaccination strategy in which melanoma antigens are targeted to mouse and human CD169 and thereby induce strong melanoma antigen-specific T cell responses. CD169 is a sialic acid receptor expressed on a subset of mouse splenic macrophages that captures antigen from the blood and transfers it to dendritic cells (DCs). In human and mouse spleen, we detected CD169⁺ cells at an equivalent location using immunofluorescence microscopy. Immunization with melanoma antigens conjugated to antibodies (Abs) specific for mouse CD169 efficiently induced gp100 and Trp2-specific T cell responses in mice. In HLA-A2.1 transgenic mice targeting of the human MART-1 peptide to CD169 induced strong MART-1-specific HLA-A2.1-restricted T cell responses. Human gp100 peptide conjugated to Abs specific for human CD169 bound to CD169-expressing monocyte-derived DCs (MoDCs) and resulted in activation of gp100-specific T cells. Together, these data indicate that Ab-mediated antigen targeting to CD169 is a potential strategy for the induction of melanoma-specific T cell responses in mice and in humans.

Cellular communication within the tumor microenvironment enables important interactions between cancer cells and recruited adjacent populations including mesenchymal stroma/stem-like cells (MSC). These interactions were monitored in vivo following co-injection of GFP-labeled human MSC together with mcherry-labeled MDA-MB-231 breast cancer cells in NODscid mice. Within 14 days of tumor development the number of initially co-injected MSC had significantly declined and spontaneous formation of breast cancer/MSC hybrid cells was observed by the appearance of double fluorescing cells. This in vivo fusion displayed a rare event and occurred in less than 0.5% of the tumor cell population. Similar findings were observed in a parallel in vitro co-culture. Characterization of the new cell fusion products obtained after two consecutive flow cytometry cell sorting and single cell cloning revealed two populations, termed MDA-hyb3 and MDA-hyb4. The breast cancer fusion cells expressed both, GFP and mcherry and displayed more characteristics of the MDA-MB-231 cells than of the parental MSC. While little if any differences were determined in the proliferative capacity, a significant delay of MDA-hyb3 cells in tumor formation was observed when compared to the parental MDA-MB-231 cells. Moreover, MDA-hyb3 cells developed an altered pattern of distant organ metastases. These findings demonstrated dynamic tumor changes by in vivo and in vitro fusion with the development of new breast cancer hybrid cells carrying altered tumorigenic properties. Consequently, cancer cell fusion contributes to progressively increasing tumor heterogeneity which complicates a therapeutic regimen.

Uremic toxins accumulated in chronic kidney disease (CKD) increases the risk of cognitive impairment. Indoxyl sulfate (IS) is a well-known protein-bound uremic toxin that is correlated with several systemic diseases, but no studies on human brain cells are available. We investigated the effect of IS on primary human astrocytes through next-generation sequencing and cell experiment confirmation to explore the mechanism of IS-associated brain damage. Total RNAs extracted from IS-treated and control astrocytes were evaluated by performing functional and pathway enrichment analysis. The toxicities of IS in the astrocytes were investigated in terms of cell viability through flow cytometry; the signal pathway was then investigated through immunoblotting. IS stimulated the release of reactive oxygen species, increased nuclear factor (erythroid-derived 2)-like 2 levels, and reduced mitochondrial membrane potential. IS triggered astrocyte apoptosis by inhibiting the mitogen-activated protein kinase (MAPK) pathway, including extracellular-signal-regulated kinase (ERK), MAPK/ERK kinase, c-Jun N-terminal kinase, and p38. The decreased ERK phosphorylation was mediated by the upregulated dual-specificity phosphatase 1, 5, 8, and 16. In conclusion, IS can induce neurotoxicity in patients with CKD and the pathogenesis involves cell apoptosis through oxidative stress induction and MAPK pathway inhibition in human astrocytes.

Cells experience physical deformations to the plasma membrane that can modulate cell behaviors like migration. Understanding the molecular basis for how physical cues affect dynamic cellular responses requires new approaches that can physically perturb the plasma membrane with rapid, reversible, subcellular control. Here we present an optogenetic approach based on light-inducible dimerization that alters plasma membrane properties by recruiting cytosolic proteins at high concentrations to a target site. Surprisingly, this polarized accumulation of proteins in a cell induces directional amoeboid migration in the opposite direction. Consistent with known effects of constraining high concentrations of proteins to a membrane in vitro, there is localized curvature and tension decrease in the plasma membrane. Integrin activity, sensitive to mechanical forces, is activated in this region. Localized mechanical activation of integrin with optogenetics allowed simultaneous imaging of the molecular and cellular response, helping uncover a positive feedback loop comprising SFK- and ERK-dependent RhoA activation, actomyosin contractility, rearward membrane flow, and membrane tension decrease underlying this mode of cell migration.

Natural antisense transcripts (NATs) are widely present in mammalian genomes and act as pivotal regulator molecules of gene expression. However, studies on NATs in the chicken are relatively rare. We identified a novel antisense transcript in the chicken, designated GHR-AS-EST, transcribed from the growth hormone receptor (GHR) locus, which encodes a well-known regulatory molecule of muscle development and fat deposition. GHR-AS-EST is predominantly expressed in the chicken liver and muscle tissues. GHR-AS-EST sequence conservation among vertebrates is weak. GHR-AS-EST forms an RNA-RNA duplex with GHBP to increase its stability, and regulates the expression of GHR sense transcripts at both the mRNA and protein levels. Further, GHR-AS-EST promotes cell proliferation by stimulating the expression of signaling factors in the JAK2/STAT pathway, and contributes to fat deposition via downregulating the expression of signaling factors in the JAK2/SOCS pathway in LMH hepatocellular carcinoma cells. We expect that the discovery of a NAT for a regulatory gene associated with cell proliferation and lipolysis will further our understanding of the molecular regulation of both muscle development and fat deposition.

Studies in sub-Saharan Africa show that masculine identities contribute to men's relatively lower uptake of HIV services. Although useful, these studies pay less attention to men's agency to negotiate and refashion masculine identities which better suit their lives as men living with HIV. In this article, I analyze the refashioning of masculine identities among men living with HIV in Uganda, adjustment processes which helped their self-management, and adherence to treatment. In-depth interviews with 18 men are thematically analyzed. Physical recovery was the embodiment of recovered masculinity and underpinned the men's ability to refashion alternative, hybrid masculinities. Men negotiated and refashioned two forms of dominant masculinity already identified in this context, respectability and reputation, notably being a responsible father again and supporting other men with HIV, and being strong, resilient and an HIV survivor. Understanding men's refashioning of masculinities can inform service providers' approaches to reach more men with HIV treatment.

To improve national influenza vaccination recommendations, additional data on influenza A and B virus circulation are needed. Here, we describe the circulation of influenza A and B in the Czech Republic during 16 seasons.

Helicobacter pylori infection is associated with several extragastric conditions including dyslipidemia and metabolic syndrome. This study aimed to investigate additional metabolic parameters associated with H. pylori infection in a Chinese population.

Autoimmune factor was regarded as one of the risk factors in the pathogenesis of chronic pancreatitis (CP), especially for autoimmune pancreatitis (AIP). However, whether autoimmune factor plays a role in non-AIP CP or not was unknown.

Experiences and perceptions of poor quality of care is a powerful determinant of utilisation of maternity services. With many reports of disrespect and abuse in healthcare facilities in low-resource settings, women's and healthcare providers' understanding and perception of disrespect and abuse are important in eliminating disrespect and abuse, but these are rarely explored together.

Implementation of new programs within healthcare systems can be extraordinarily complex. Individuals within the same healthcare organization often have different perspectives on how implementation of a new program unfolds over time, and it is not always clear in the midst of implementation what issues are most important or how to address them. An implementation support team within the Veterans Health Administration (VHA) sought to develop an efficient method for eliciting an ongoing, detailed and nuanced account of implementation progress from multiple viewpoints that could support and inform active implementation of two new VHA programs.

Ureaplasma species (spp.) are commonly regarded as low-virulent commensals but may cause invasive diseases in immunocompromised adults and in neonates, including neonatal meningitis. The interactions of Ureaplasma spp. with host defense mechanisms are poorly understood. This study addressed Ureaplasma-driven cell death, concentrating on apoptosis as well as inflammatory cell death.

Emergency airway management (AM) is a major key for successful resuscitation of critically ill non-traumatic (CINT) patients. Details of the AM of these patients in German emergency departments (ED) are unknown. This observational study describes epidemiology, airway techniques, success rates and complications of AM in CINT ED patients in the resuscitation room (RR).

The pathophysiology of obstruction and swallowing dysfunction in snores and sleep apnea patients remains unclear. Neuropathy and to some extent myopathy have been suggested as contributing causes. Recently we reported an absence and an abnormal isoform of two cytoskeletal proteins, desmin, and dystrophin, in upper airway muscles of healthy humans. These cytoskeletal proteins are considered vital for muscle function. We aimed to investigate for muscle cytoskeletal abnormalities in upper airways and its association with swallowing dysfunction and severity of sleep apnea.

Personalized cancer vaccines based on neoantigens have reached the clinical trial stage in melanoma. Different vaccination protocols showed efficacy in preclinical models without a clear indication of the quality and the number of neoantigens required for an effective cancer vaccine.

Sarcoglycanopathies comprise four subtypes of autosomal recessive limb-girdle muscular dystrophy (LGMD2C, LGMD2D, LGMD2E, and LGMD2F) that are caused, respectively, by mutations in the SGCG, SGCA, SGCB, and SGCD genes. Knowledge about the clinical and genetic features of sarcoglycanopathies in Chinese patients is limited. The aims of this study were to investigate in detail the clinical manifestations, sarcoglycan expression, and gene mutations in Chinese patients with sarcoglycanopathies and to identify possible correlations between them.