Biofilms: Formation, drug resistance and alternatives to conventional approaches.

Biofilms are aggregates of bacteria, in most cases, which are resistant usually to broad-spectrum antibiotics in their typical concentrations or even in higher doses. A trend of increasing multi-drug resistance in biofilms, which are responsible for emerging life-threatening nosocomial infections, is becoming a serious problem. Biofilms, however, are at various sensitivity levels to environmental factors and are versatile in infectivity depending on virulence factors. This review presents the fundamental information about biofilms: formation, antibiotic resistance, impacts on public health and alternatives to conventional approaches. Novel developments in micro-biosystems that help reveal the new treatment tools by sensing and characterization of biofilms will also be discussed. Understanding the formation, structure, physiology and properties of biofilms better helps eliminate them by the usage of appropriate antibiotics or their control by novel therapy approaches, such as anti-biofilm molecules, effective gene editing, drug-delivery systems and probiotics.

OpenKBP-Opt: an international and reproducible evaluation of 76 knowledge-based planning pipelines.

Objective.To establish an open framework for developing plan optimization models for knowledge-based planning (KBP).Approach.Our framework includes radiotherapy treatment data (i.e. reference plans) for 100 patients with head-and-neck cancer who were treated with intensity-modulated radiotherapy. That data also includes high-quality dose predictions from 19 KBP models that were developed by different research groups using out-of-sample data during the OpenKBP Grand Challenge. The dose predictions were input to four fluence-based dose mimicking models to form 76 unique KBP pipelines that generated 7600 plans (76 pipelines × 100 patients). The predictions and KBP-generated plans were compared to the reference plans via: the dose score, which is the average mean absolute voxel-by-voxel difference in dose; the deviation in dose-volume histogram (DVH) points; and the frequency of clinical planning criteria satisfaction. We also performed a theoretical investigation to justify our dose mimicking models.Main results.The range in rank order correlation of the dose score between predictions and their KBP pipelines was 0.50-0.62, which indicates that the quality of the predictions was generally positively correlated with the quality of the plans. Additionally, compared to the input predictions, the KBP-generated plans performed significantly better (P< 0.05; one-sided Wilcoxon test) on 18 of 23 DVH points. Similarly, each optimization model generated plans that satisfied a higher percentage of criteria than the reference plans, which satisfied 3.5% more criteria than the set of all dose predictions. Lastly, our theoretical investigation demonstrated that the dose mimicking models generated plans that are also optimal for an inverse planning model.Significance.This was the largest international effort to date for evaluating the combination of KBP prediction and optimization models. We found that the best performing models significantly outperformed the reference dose and dose predictions. In the interest of reproducibility, our data and code is freely available.

The utility and complications of plasma administration in cirrhotic patients undergoing minimally invasive procedures.

Patients with cirrhosis have coagulopathy often necessitating correction with blood products, such as plasma products (fresh frozen plasma and plasma frozen within 24 h) prior to certain invasive procedures. However, plasma administration has the potential for substantial negative adverse effects such as volume overload, transfusion-related lung injury and allergic/anaphylactic reactions. In addition, its effectiveness in preventing bleeding is similarly unclear. The purpose of this study was to determine the safety and efficacy of plasma administration in cirrhotic patients undergoing minimally invasive procedures, specifically vascular access placement, transjugular liver biopsies, renal biopsies and thoracenteses. In this retrospective cohort study, we identified patients receiving plasma products in preparation for an invasive procedure, with the primary outcomes of volume overload and bleeding. Of the 145 transfusion events that met the criteria from 2015 to 2018, the median INR decreased from 2.7 to 2.2 pre and post plasma administration and 13.8% of recipients had complications of volume overload. The cost of acquisition of plasma administered below clinically impactful doses accumulates to an estimated 19 000 dollars over this time period, not including nursing preparation or production costs. Plasma products minimally, if at all, improved laboratory values of coagulation and in some patients led to adverse effects.

Racial Differences in Gastroenteropancreatic Neuroendocrine Tumor Treatment and Survival in the United States.

OBJECTIVES: The objective of this study was to evaluate racial differences in cancer treatment and survival in gastroenteropancreatic neuroendocrine tumor (GEP-NET) patients. METHODS: Using the Surveillance, Epidemiology, and End Results Registry, we identified patients with GEP-NETs of the stomach, small intestine (SI), colon, rectum, appendix, and pancreas diagnosed between 1973 and 2014. Demographic, cancer, and treatment information were collected and compared using χ2 tests. Multivariable logistic and Cox regression were used to determine disparities in receiving treatment and overall survival. RESULTS: We identified 19,031 GEP-NET patients: 2839 were non-Hispanic Blacks, 12,832 non-Hispanic Whites, 2098 Hispanics, and 1262 Asians. African Americans and Hispanics with SI and pancreatic NETs were less likely to be treated with surgery (odds ratio, 0.6; 95% confidence interval [CI], 0.46-0.69; odds ratio, 0.71; 95% CI, 0.51-0.99, respectively). African American race was not an independent predictor of survival; there was a strong trend in stomach, SI, and pancreas NETs (hazard ratio [HR], 1.31; 95% CI, 1-1.7; HR, 1.2; 95% CI, 0.99-1.45; HR, 1.22; 95% CI, 1-1.48, respectively). CONCLUSIONS: Our study provides evidence of racial disparities in treatment and survival across GEP-NET primary sites and racial groups. Further studies should be performed to improve our understanding of the reason for these disparities.

Surveillance of high-risk individuals for pancreatic cancer with EUS and MRI: A meta-analysis.

BACKGROUND/OBJECTIVES: Consensus guidelines recommend surveillance of high-risk individuals (HRIs) for pancreatic cancer (PC) using endoscopic ultrasonography (EUS) and/or magnetic resonance imaging (MRI). This study aims to assess the yield of PC surveillance programs of HRIs and compare the detection of high-grade dysplasia or T1N0M0 adenocarcinoma by EUS and MRI. METHODS: The MEDLINE and Embase (Ovid) databases were searched for prospective studies published up to April 11, 2019 using EUS and/or MRI to screen HRIs for PC. Baseline detection of focal pancreatic abnormalities, cystic lesions, solid lesions, high-grade dysplasia or T1N0M0 adenocarcinoma, and all pancreatic adenocarcinoma were recorded. Weighted pooled proportions of outcomes detected were compared between EUS and MRI using random effects modeling. RESULTS: A total of 1097 studies were reviewed and 24 were included, representing 2112 HRIs who underwent imaging. The weighted pooled proportion of focal pancreatic abnormalities detected by baseline EUS (0.34, 95% CI 0.30-0.37) was significantly higher (p = 0.006) than by MRI (0.31, 95% CI 0.28-0.33). There were no significant differences between EUS and MRI in detection of other outcomes. The overall weighted pooled proportion of patients with high-grade dysplasia or T1N0M0 adenocarcinoma detected at baseline (regardless of imaging modality) was 0.0090 (95% CI 0.0022-0.016), corresponding to a number-needed-to-screen (NNS) of 111 patients to detect one high-grade dysplasia or T1N0M0 adenocarcinoma. CONCLUSIONS: Surveillance programs are successful in detecting high-risk precursor lesions. No differences between EUS and MRI were noted in the detection of high-grade dysplasia or T1N0M0 adenocarcinoma, supporting the use of either imaging modality.

Elaboration and Biocompatibility of an Eggshell-Derived Hydroxyapatite Material Modified with Si/PLGA for Bone Regeneration in Dentistry.

Hydroxyapatite (HAp) is the most commonly used biomaterial in modern bone regeneration studies because of its chemical similarity to bone, biocompatibility with different polymers, osteoconductivity, low cost, and lack of immune response. However, to overcome the disadvantages of HAp, which include fragility and low mechanical strength, current studies typically focus on property modification through the addition of other materials. Objective. To develop and evaluate the biocompatibility of a HAp material extracted from eggshells and modified with silicon (Si) and poly(lactic-co-glycolic) acid (PLGA). Materials and Methods. An in vitro experimental study in which a HAp material prepared from eggshells was synthesized by wet chemical and conventional chemical precipitation. Subsequently, this material was reinforced with Si/PLGA using the freezing/lyophilization method, and then osteoblast cells were seeded on the experimental material (HAp/Si/PLGA). To analyse the biocompatibility of this composite material, scanning electron microscopy (SEM) and fluorescence confocal microscopy (FCM) techniques were used. PLGA, bovine bone/PLGA (BB/PLGA), and HAp/PLGA were used as controls. Results. A cellular viability of 96% was observed for the experimental HAp/Si/PLGA material as well as for the PLGA. The viability for the BB/PLGA material was 90%, and the viability for the HAp/PLGA was 86%. Cell adhesion was observed on the exterior surface of all materials. However, a continuous monolayer and the presence of filopodia were observed over both external and internal surface of the experimental materials. Conclusions. The HAp/Si/PLGA material is highly biocompatible with osteoblastic cells and can be considered promising for the construction of three-dimensional scaffolds for bone regeneration in dentistry.

Evaluation and Management of Cirrhotic Patients Undergoing Elective Surgery.

PURPOSE OF REVIEW: Cirrhotic patients have an increased risk of surgical complications and higher perioperative morbidity and mortality based on the severity of their liver disease. Liver disease predisposes patients to perioperative coagulopathies, volume overload, and encephalopathy. The goal of this paper is to discuss the surgical risk of cirrhotic patients undergoing elective surgeries and to discuss perioperative optimization strategies. RECENT FINDINGS: Literature thus far varies by surgery type and the magnitude of surgical risk. CTP and MELD classification scores allow for the assessment of surgical risk in cirrhotic patients. Once the decision has been made to undergo elective surgery, cirrhotic patients can be optimized pre-procedure with the help of a checklist and by the involvement of a multidisciplinary team. Elective surgeries should be performed at hospital centers staffed by healthcare providers experienced in caring for cirrhotic patients. Further research is needed to develop ways to prepare this complicated patient population before elective surgery.

Familial Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC), although a rare disease, has a poor prognosis. With 5-year overall survival of 8%, there is a critical need to detect PDAC early or at a premalignant stage. Current screening methods are largely imaging based, but a more focused screening approach based on modifiable and nonmodifiable risk factors may improve the efficacy and likely outcomes of screening. In addition, the pathologic mechanisms that lead to the development of PDAC are discussed in an effort to further understand the targets of pancreatic cancer screening. The focus of this article will be inherited pancreatic cancer syndromes and familial pancreatic cancer, which together compose up to 10% of PDAC. Understanding the methods and targets of PDAC screening in high-risk individuals may translate to improved morbidity and mortality.

Generalized Growth of Estuarine, Household and Clinical Isolates of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic pathogen of particular concern to immune-compromised people, such as cystic fibrosis patients and burn victims. These bacteria grow in built environments including hospitals and households, and in natural environments such as rivers and estuaries. However, there is conflicting evidence whether recent environments like the human lung and open ocean affect P. aeruginosa growth performance in alternate environments. We hypothesized that bacteria recently isolated from dissimilar habitats should grow differently in media containing artificial versus natural resources. To test this idea, we examined growth of P. aeruginosa isolates from three environments (estuary, household, and clinic) in three media types: minimal-glucose lab medium, and media prepared from sugar maple leaves or big bluestem grass. We used automated spectrophotometry to measure high-resolution growth curves for all isolate by media combinations, and studied two fitness parameters: growth rate and maximum population density. Results showed high variability in growth rate among isolates, both overall and in its dependence on assay media, but this variability was not associated with habitat of isolation. In contrast, total growth (change in absorbance over the experiment) differed overall among habitats of isolation, and there were media-specific differences in mean total growth among habitats of isolation, and in among-habitat variability in the media-specific response. This was driven primarily by greater total growth of estuary isolates when compared with those from other habitats of origin, and greater media-specific variability among household isolates than those from other habitats of origin. Taken together, these results suggest that for growth rate P. aeruginosa bacteria appear to be broad generalists without regard to current or recent habitat, whereas for total growth a signature of recent ecological history can be detected.

Protocolo de adquisición de imágenes diagnósticas por termografía infrarroja / Acquisition protocol of diagnostic imaging by infrared thermography

Introducción: en aplicaciones biomédicas, la termografía infrarroja ha permitido visualizar el patrón de distribución de temperatura de la piel y el tejido subyacente, permitiendo diagnosticar problemas vasculares o nerviosos y, particularmente, trastornos en la termorregulación como el fenómeno de Raynaud y la intolerancia al frío. Sin embargo, las publicaciones no detallan el protocolo de adquisiciónde imágenes ni validan el mismo; factores determinantes para la calidad y relevancia de la informacióndiagnóstica obtenida. Objetivo: diseñar y validar un protocolo de adquisición de imágenes por termografía infrarroja para analizar la termorregulación en la mano. Materiales y métodos: Se diseñó un nuevo protocolo de adquisición de imágenes por termografía infrarroja utilizando un estímulofrío en la mano. Se analizaron estadísticamente regiones de interés de imágenes termográficas de 18 mediciones intrasujeto en un único sujeto y mediciones intersujeto en 17 individuos sanos. Resultados: En las mediciones intrasujeto e intersujeto se encontró que 10 minutos después del estímulo frío el porcentaje de recuperación de la temperatura fue cercano al 100%, excepto en un individuo en el cual, a pesar de no reportar enfermedades o lesiones previas, la punta de los dedos después del estímulo alcanzó apenas los 28 ºC. La prueba de fatiga en uno de los sujetos sanos mostró alteraciones en el proceso de termorregulación de la mano cuando el protocolo se repite en corto tiempo.

Introduction: in biomedical applications, infrared thermography has allowed to visualize the temperaturedistribution patterns of skin and underlying tissue, allowing the diagnosis of vascular or nervous disorders, particularly disturbances in the thermoregulation process as Raynaud’s phenomenon and cold intolerance. However, most papers not detailed the images acquisition protocol or its validation, being these two determining factors to the quality and relevance of the obtained diagnostic information.Objective: To design and validate an acquisition protocol of diagnostic imaging by infrared thermographyto analyze the thermoregulation process in hand. Material and methods: It was designed a new acquisition protocol of diagnostic imaging by infrared thermography using a cold stimulus in hand. It was statistically analyzed the regions of interest of thermographic images of 18 intrasubject measurements (in one individual) and intersubject measurements in 17 healthy individuals. Results: In the intrasubject and intersubject measurements, it found that 10 minutes after the cold stimulus the temperature measured was close to 100% of initial temperature, except for one of healthy subjects who, despite not report diseases or previous injuries, the temperature of the fingertips after stimulus barely reached 28 °C. The fatigue test in one healthy subject presents alterations in the thermoregulation process in hand when the protocol was repeated in a short time.