A compendium of single cell analysis in aging and disease

Cell is the fundamental structural and functional unit of complex multicellular organisms. Conventional methods which involve average analysis of cells in bulk populations can undermine physiologically significant cell populations, whereas analysis of cells at a single cell level may reveal unique biomarkers and other mechanisms that govern the genotype and phenotype in various physiological processes in presumed homogenous cell populations. Cellular abnormalities such as irregularities in cellular mechanisms have been linked to human aging and other major diseases including neurodegenerative, vascular, autoimmune, and cancer. Aging is a functional decline associated with various diseases in an organism, majorly arising from cellular abnormalities. Single cell analysis (SCA) which involves isolation and study of single cell proteomics, genomics, transcriptomics and metabolomics which enables research of cellular abnormalities with a molecular resolution, is gaining recognition in the research of human aging and disease. The advances in SCA are producing breakthrough information about cellular heterogeneity, disease progression, cellular microenvironment and its interactions, early diagnostics, improving precision medicine through high throughput drug screening and discovery of novel biomarkers; combinedly, these advances exhibit the potential of SCA to study of human aging and disease. Primarily, we review the role of SCA in understanding cellular mechanisms involved in aging and other major diseases including neurological, vascular, autoimmunity and cancer. Secondly, we also include review of SCA role in studying cell adhesion mechanisms which are involved in tissue development and maintenance and disease progression. Finally, SCA potential to empower precision medicine and its overall challenges along with future directions are discussed

Optical imaging of finger for blood pressure monitoring of the driver

Cardiovascular diseases (CVDs) are number one reason for human mortality around the world (Fig. 1) [1]. Pulse pressure (PP) and pulse rate (PR) are considered as the two most vital physiological markers for CVDs like myocardial infarction, cardiac arrhythmia, and heart failure. Currently, long-term PP and PR analysis is not possible due to the lack of systems that can frequently measure the data over a period of time. Motor vehicle drivers with known CVDs are at higher risk due to traffic air pollution. This paper presents our work on an inexpensive and readily deployable approach that keeps track of PP and PR with simple cameras. The computation of PP and PR makes the real-time monitoring possible. The approach makes it highly customizable and ready for on-the-go use in field by drivers, construction zone workers, healthcare workers, law enforcement agencies, etc. The video recordings of fingertips were made using a cellphone camera. The analysis extracted the pulse pressure, which was the difference between systolic and diastolic pressures, and pulse rate. The PP measured with this system was compared with a standard off-the-shelf tool. The comparison showed high accuracy. The measurement of PRs also showed a high level of reliability in comparison to the standard tool. The fundamental concept of the technology depended on the measurement of blood quantity in the fingertip arteries. The amount of blood on fingertips was different during systolic and diastolic phases. This created light intensity variations, which were extracted by analyzing the video frames. A simple embodiment of this approach can be in the dashboard of cars with a camera to create short high-resolution videos of fingertips. The doctors can remotely monitor their patients through a standard computer interface. The patients can also be trained to interpret the results of the measurement

Identifying Sick Cells From High-Resolution Solid-State Micropore Data

Early detection of diseases such as cancer can drastically improve prognosis and treatment. To this end, solid-state micropores can measure distinct mechanical properties of diseased cells from their translocation behavior — detected as pulses in the temporal data stream of ionic current — and help diagnose diseases at early stages. However, the obstacle in such approaches is that the accuracy of the sensor is affected by noise, making the pulse detection task too subjective. This is inefficient especially when the disease-relevant data is only a fraction of the total acquired data. Thus, it is important to intelligently automate the detection process to eliminate the noise and to identify useful patterns towards error-free decision-making in real-time. This work describes a pattern detection approach based on moving-average filtering, which mitigates the impact of noise. Moreover, a detection threshold is computed from the mean and standard deviation of the data. The threshold is then used to detect different types of pulses stemming from the healthy and diseased human cells when these translocate through micropores. Extent of smoothing is an important factor for the data: greater smoothing suppresses the noise but deteriorates the pulse shape and vice versa. Additionally, the design approach computes useful features of the detected data and delivers the results for real-time analysis. This can help physicians and scientists to change their strategies of diagnosis by providing a validation of manual reviews

Ion-Sensitive Field-Effect Transistors With Micropillared Gates for Measuring Cell Ion Exchange at Molecular Levels

The detection of small concentrations of cancer cells before cancer takes over the primary organ completely, or metastasizes to other areas of the body is important for early screening of cancer. One approach to address cancer early screening is through cell ion exchange bioelectricity, which characterizes voltage potential in non-neuronal cells to regulate shape changing, proliferation, differentiation, migration, and cancer formation. Herein, novel ion-sensitive field-effective transistor (ISFET) modality is shown to measure cell behavior during the change of cell properties at molecular levels. ISFETs produce low resistance signals and consume low power. The small size of ISFETs enables miniature diagnosis devices that can be affordably fabricated in a massive array format. A large number of cells can be measured in parallel. Therefore, ISFET allows the combination of low sample requirements and prompt response. ISFETs have the ability to measure the effect of ions from complex biological samples and can be used as affordable point of care devices

Upaya Meningkatkan Kebersihan Lingkungan Desa dengan Membersihkan Aliran Sungai dan Pengadaan Tong Sampah

Kebersihan lingkungan merupakan salah satu modal dasar penting bagi pembangunan manusia Indonesia karena kualitas lingkungan sangat berpengaruh terhadap kualitas hidup masyarakat. Lingkungan yang tidak terawat, kumuh dan kotor akan menjadi tempat berkembangnya berbagai macam mikroorganisme penyebab penyakit dan organisme pembawa penyakit. Akibatnya masyarakat menjadi rentan terhadap berbagai macam penyakit. Pengabdian masyarakat ini bertujuan untuk meningkatkan kebersihan didusun krajan putatlor gondanglegi. Kegiatan kebersihan lingkungan ini dilakukan dengan metode kerja bakti, yaitu kerja bakti membersihkan lingkungan dan aliran sungai. Dan pengadaan tong sampah dibeberapa titik tempat didusun krajan putatlor gondanglegi

Defining the geographical range of the plasmodium knowlesi reservoir

Background: The simian malaria parasite, Plasmodium knowlesi, can cause severe and fatal disease in humans yet it is rarely included in routine public health reporting systems for malaria and its geographical range is largely unknown. Because malaria caused by P. knowlesi is a truly neglected tropical disease, there are substantial obstacles to defining the geographical extent and risk of this disease. Information is required on the occurrence of human cases in different locations, on which non-human primates host this parasite and on which vectors are able to transmit it to humans. We undertook a systematic review and ranked the existing evidence, at a subnational spatial scale, to investigate the potential geographical range of the parasite reservoir capable of infecting humans.Methodology/Principal Findings: After reviewing the published literature we identified potential host and vector species and ranked these based on how informative they are for the presence of an infectious parasite reservoir, based on current evidence. We collated spatial data on parasite occurrence and the ranges of the identified host and vector species. The ranked spatial data allowed us to assign an evidence score to 475 subnational areas in 19 countries and we present the results on a map of the Southeast and South Asia region.Conclusions/Significance: We have ranked subnational areas within the potential disease range according to evidence for presence of a disease risk to humans, providing geographical evidence to support decisions on prevention, management and prophylaxis. This work also highlights the unknown risk status of large parts of the region. Within this unknown category, our map identifies which areas have most evidence for the potential to support an infectious reservoir and are therefore a priority for further investigation. Furthermore we identify geographical areas where further investigation of putative host and vector species would be highly informative for the region-wide assessment

Subtype-Specific and Co-Occurring Genetic Alterations in B-cell Non-Hodgkin Lymphoma

B-cell non-Hodgkin lymphoma (B-NHL) encompasses multiple clinically and phenotypically distinct subtypes of malignancy with unique molecular etiologies. Common subtypes of B-NHL, such as diffuse large B-cell lymphoma, have been comprehensively interrogated at the genomic level, but rarer subtypes, such as mantle cell lymphoma, remain less extensively characterized. Furthermore, multiple B-NHL subtypes have thus far not been comprehensively compared using the same methodology to identify conserved or subtype-specific patterns of genomic alterations. Here, we employed a large targeted hybrid-capture sequencing approach encompassing 380 genes to interrogate the genomic landscapes of 685 B-NHL tumors at high depth, including diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, and Burkitt lymphoma. We identified conserved hallmarks of B-NHL that were deregulated in the majority of tumors from each subtype, including frequent genetic deregulation of the ubiquitin proteasome system. In addition, we identified subtype-specific patterns of genetic alterations, including clusters of co-occurring mutations and DNA copy number alterations. The cumulative burden of mutations within a single cluster were more discriminatory of B-NHL subtypes than individual mutations, implicating likely patterns of genetic cooperation that contribute to disease etiology. We therefore provide the first cross-sectional analysis of mutations and DNA copy number alterations across major B-NHL subtypes and a framework of co-occurring genetic alterations that deregulate genetic hallmarks and likely cooperate in lymphomagenesis

Mitochondrial Superoxide Contributes to Blood Flow and Axonal Transport Deficits in the Tg2576 Mouse Model of Alzheimer's Disease

Alzheimer's disease (AD) is a neurodegenerative disease characterized by the progressive decline in cognitive functions and the deposition of aggregated amyloid beta (Abeta) into senile plaques and the protein tau into tangles. In addition, a general state of oxidation has long been known to be a major hallmark of the disease. What is not known however, are the mechanisms by which oxidative stress contributes to the pathology of AD.In the current study, we used a mouse model of AD and genetically boosted its ability to quench free radicals of specific mitochondrial origin. We found that such manipulation conferred to the AD mice protection against vascular as well as neuronal deficits that typically affect them. We also found that the vascular deficits are improved via antioxidant modulation of the endothelial nitric oxide synthase, an enzyme primarily responsible for the production of nitric oxide, while neuronal deficits are improved via modulation of the phosphorylation status of the protein tau, which is a neuronal cytoskeletal stabilizer.These findings directly link free radicals of specific mitochondrial origin to AD-associated vascular and neuronal pathology

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London