Integrated early warning surveillance. Achilles′ heel of one health?

Emerging and re-emerging infectious diseases and zoonoses indicate the importance of the One Health (OH) approach for early warning. At present, even when surveillance data are available, they are infrequently timeously shared between the health sectors. In the context of the MediLabSecure (MLS) Project, we investigated the collection of a set of surveillance indicators able to provide data for the implementation of integrated early warning systems in the 22 MLS countries of the Mediterranean, Black Sea and Sahel regions. We used an online questionnaire (covering vector, human, and animal sectors), focusing on seven relevant arboviruses, that was submitted to 110 officially appointed experts. Results showed that West Nile virus was perceived as the most relevant zoonotic pathogen, while Dengue virus was the most relevant non-zoonotic pathogen in the study area. Data collection of early warning indicators is in place at a different level for all the investigated pathogens and in almost all the MLS Countries. Further assessments on the reliability of the collection in place and on the feasibility of piloting an integrated early warning system for arbovirus could verify if integrated early warning really represents the Achilles’ heel of OH

Imaging of mandibular fractures: a pictorial review

Mandibular fractures are among the most common maxillofacial fractures observed in emergency rooms and are mainly caused by road accidents. The clinical features of mandibular fractures include malocclusion and loss of mandibular function. Panoramic radiography is usually limited to isolated lesions, whereas computed tomography is the tool of choice for all other facial traumatic events. No reference standard classification system for the different types of mandibular fractures is defined. Therapeutic options include a conservative approach or surgical treatment based on the anatomic area and the severity of fracture. The main purpose of this pictorial review is to illustrate a practical description of the pathophysiology of mandibular fractures and describe both the imaging techniques to recognise them and the therapeutic indications

Techniques, Tricks, and Stratagems of Oral Cavity Computed Tomography and Magnetic Resonance Imaging

The oral cavity constitutes a complex anatomical area that can be affected by many devel-opmental, inflammatory, and tumoural diseases. MultiSlice Computed Tomography (MSCT) and Magnetic Resonance Imaging (MRI) currently represent the essential and complementary imaging techniques for detecting oral cavity abnormalities. Advanced MRI with diffusion-weighted imaging (DWI) and dynamic contrast-enhanced perfusion-weighted imaging (DCE-PWI) has recently increased the ability to characterise oral lesions and distinguish disease recurrences from post therapy changes. The analysis of the oral cavity area via imaging techniques is also complicated both by mutual close appositions of different mucosal surfaces and metal artifacts from dental materials. Nevertheless, an exact identification of oral lesions is made possible thanks to dynamic manoeuvres and specific stratagems applicable on MSCT and MRI acquisitions. This study summarises the currently available imaging techniques for oral diseases, with particular attention to the role of DWI, DCE-PWI, and dynamic manoeuvres. We also propose MSCT and MRI acquisition protocols for an accurate study of the oral cavity area

Mass measurements during lymphocytic leukemia cell polyploidization decouple cell cycle- and cell size-dependent growth

Cell size is believed to influence cell growth and metabolism. Consistently, several studies have revealed that large cells have lower mass accumulation rates per unit mass (i.e., growth efficiency) than intermediate-sized cells in the same population. Sizedependent growth is commonly attributed to transport limitations, such as increased diffusion timescales and decreased surface-to-volume ratio. However, separating cell size- and cell cycle-dependent growth is challenging. To address this, we monitored growth efficiency of pseudodiploid mouse lymphocytic leukemia cells during normal proliferation and polyploidization. This was enabled by the development of large-channel suspended microchannel resonators that allow us to monitor buoyant mass of single cells ranging from 40 pg (small pseudodiploid cell) to over 4,000 pg, with a resolution ranging from ∼1% to ∼0.05%. We find that cell growth efficiency increases, plateaus, and then decreases as cell cycle proceeds. This growth behavior repeats with every endomitotic cycle as cells grow into polyploidy. Overall, growth efficiency changes 33% throughout the cell cycle. In contrast, increasing cell mass by over 100-fold during polyploidization did not change growth efficiency, indicating exponential growth. Consistently, growth efficiency remained constant when cell cycle was arrested in G2. Thus, cell cycle is a primary determinant of growth efficiency. As growth remains exponential over large size scales, our work finds no evidence for transport limitations that would decrease growth efficiency

Determining therapeutic susceptibility in multiple myeloma by single-cell mass accumulation

Multiple myeloma (MM) has benefited from significant advancements in treatment that have improved outcomes and reduced morbidity. However, the disease remains incurable and is characterized by high rates of drug resistance and relapse. Consequently, methods to select the most efficacious therapy are of great interest. Here we utilize a functional assay to assess the ex vivo drug sensitivity of single multiple myeloma cells based on measuring their mass accumulation rate (MAR). We show that MAR accurately and rapidly defines therapeutic susceptibility across human multiple myeloma cell lines to a gamut of standard-of-care therapies. Finally, we demonstrate that our MAR assay, without the need for extended culture ex vivo, correctly defines the response of nine patients to standard-of-care drugs according to their clinical diagnoses. This data highlights the MAR assay in both research and clinical applications as a promising tool for predicting therapeutic response using clinical samples

Microfluidic active loading of single cells enables analysis of complex clinical specimens

A fundamental trade-off between flow rate and measurement precision limits performance of many single-cell detection strategies, especially for applications that require biophysical measurements from living cells within complex and low-input samples. To address this, we introduce ‘active loading’, an automated, optically-triggered fluidic system that improves measurement throughput and robustness by controlling entry of individual cells into a measurement channel. We apply active loading to samples over a range of concentrations (1–1000 particles μL[superscript −1]), demonstrate that measurement time can be decreased by up to 20-fold, and show theoretically that performance of some types of existing single-cell microfluidic devices can be improved by implementing active loading. Finally, we demonstrate how active loading improves clinical feasibility for acute, single-cell drug sensitivity measurements by deploying it to a preclinical setting where we assess patient samples from normal brain, primary and metastatic brain cancers containing a complex, difficult-to-measure mixture of confounding biological debris.National Cancer Institute (U.S.) (R01 CA170592)National Cancer Institute (U.S.) (R33 CA191143)National Cancer Institute (U.S.) (Cancer Center Support (Core) Grant P30-CA14051)Bridge Projec

Microfluidic active loading of single cells enables analysis of complex clinical specimens

A fundamental trade-off between flow rate and measurement precision limits performance of many single-cell detection strategies, especially for applications that require biophysical measurements from living cells within complex and low-input samples. To address this, we introduce ‘active loading’, an automated, optically-triggered fluidic system that improves measurement throughput and robustness by controlling entry of individual cells into a measurement channel. We apply active loading to samples over a range of concentrations (1–1000 particles μL[superscript −1]), demonstrate that measurement time can be decreased by up to 20-fold, and show theoretically that performance of some types of existing single-cell microfluidic devices can be improved by implementing active loading. Finally, we demonstrate how active loading improves clinical feasibility for acute, single-cell drug sensitivity measurements by deploying it to a preclinical setting where we assess patient samples from normal brain, primary and metastatic brain cancers containing a complex, difficult-to-measure mixture of confounding biological debris.National Cancer Institute (U.S.) (R01 CA170592)National Cancer Institute (U.S.) (R33 CA191143)National Cancer Institute (U.S.) (Cancer Center Support (Core) Grant P30-CA14051)Bridge Projec