Generation, detection and applications of in vitro oxygen gradients

Oxygen homeostasis is critical for the functioning of multicellular organisms. Deficiency of oxygen or hypoxia can lead to several pathological conditions such as ischemia, tumorigenesis and drug resistance. Most studies utilize specialized O2 incubators to generate singular oxygen concentrations that vary significantly from the physiological conditions where hypoxic gradients exist within the tissue e.g. in solid tumors. Current microfluidic technology using polydimethylsiloxane-based (PDMS) devices enables generation of such oxygen concentration gradients, but yield low-to-moderate spatial resolution, involve tedious device assembly and are not feasible for practical research or pharmaceutical screening. We have developed a novel and simplistic approach of reproducibly and rapidly generating stable biomimetic oxygen gradients with high spatial resolution and integrated detection capability. The microfluidic split and recombine strategy utilizing O2-rich and O2-depleted media allows generation of prolonged dissolved oxygen (DO) gradients while an underlying platinum based sensor layer (PtOEPK) allows real-time detection of DO gradients generated. Deposition of an approximately 5-7µm thick three-sided glass coating prevents multi-directional diffusion of ambient oxygen through PDMS maintaining the gradient stability for hours or days. Two variations of the gradient devices have been developed, one offering the ability to generate continuous gradients within a single channel while another containing multiple outlet chambers each maintaining a specific concentration of DO (Figure 1). Please click Additional Files below to see the full abstract

Perceptions of eye health in schools in Pakistan

BACKGROUND: Research exploring children's and their teachers' perceptions of eye health is lacking. This paper reports for the first time on perceptions of primary schoolchildren and their teachers of healthy and diseased eyes, things that keep eyes healthy and damage them, and what actions to be taken in case of an eye injury. METHODS: Using draw and write technique, 160 boys and girls (9–12 years old) attending four primary schools in Abbottabad district, northern Pakistan, were invited to draw pictures in response to a set of semi-structured questions and then label them. Sixteen teachers who were currently teaching the selected students were interviewed one-on-one. RESULTS: Analysis of text accompanying 800 drawings and of the interview scripts revealed that most children and teachers perceived healthy eyes to be those which could see well, and diseased eyes to be those which have redness, watering, dirty discharge, pain, and itching; or those which have "weak eyesight" and blindness. Among things that students and teachers thought damage the eyes included sun, television, and sharp pointed objects, particularly pencils. Teachers noted that children with eye problems "have difficulty seeing the blackboard well", "screw up their eyes", and "hold their books too close". CONCLUSION: We conclude that schoolchildren and their teachers had a good knowledge of eye health, but many of them had serious misconceptions e.g., use of kohl, medicines and eye drops keeps eyes healthy. Kohl is an important source of lead and can reduce children's intelligence even at low blood levels. Health education in schools must take into account children's existing knowledge of and misconceptions about various aspects of eye health. Such steps if taken could improve the relevance of eye health education to schoolchildren

A word sense disambiguation corpus for Urdu

The aim of word sense disambiguation (WSD) is to correctly identify the meaning of a word in context. All natural languages exhibit word sense ambiguities and these are often hard to resolve automatically. Consequently WSD is considered an important problem in natural language processing (NLP). Standard evaluation resources are needed to develop, evaluate and compare WSD methods. A range of initiatives have lead to the development of benchmark WSD corpora for a wide range of languages from various language families. However, there is a lack of benchmark WSD corpora for South Asian languages including Urdu, despite there being over 300 million Urdu speakers and a large amounts of Urdu digital text available online. To address that gap, this study describes a novel benchmark corpus for the Urdu Lexical Sample WSD task. This corpus contains 50 target words (30 nouns, 11 adjectives, and 9 verbs). A standard, manually crafted dictionary called Urdu Lughat is used as a sense inventory. Four baseline WSD approaches were applied to the corpus. The results show that the best performance was obtained using a simple Bag of Words approach. To encourage NLP research on the Urdu language the corpus is freely available to the research community

Histone deacetylase (HDAC) inhibitors in recent clinical trials for cancer therapy

Heritable changes in gene expression that are not based upon alterations in the DNA sequence are defined as epigenetics. The most common mechanisms of epigenetic regulation are the methylation of CpG islands within the DNA and the modification of amino acids in the N-terminal histone tails. In the last years, it became evident that the onset of cancer and its progression may not occur only due to genetic mutations but also because of changes in the patterns of epigenetic modifications. In contrast to genetic mutations, which are almost impossible to reverse, epigenetic changes are potentially reversible. This implies that they are amenable to pharmacological interventions. Therefore, a lot of work in recent years has focussed on the development of small molecule enzyme inhibitors like DNA-methyltransferase inhibitors or inhibitors of histone-modifying enzymes. These may reverse misregulated epigenetic states and be implemented in the treatment of cancer or other diseases, e.g., neurological disorders. Today, several epigenetic drugs are already approved by the FDA and the EMEA for cancer treatment and around ten histone deacetylase (HDAC) inhibitors are in clinical development. This review will give an update on recent clinical trials of the HDAC inhibitors used systemically that were reported in 2009 and 2010 and will present an overview of different biomarkers to monitor the biological effects

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Designing Magnetically Responsive Biohybrids Composed of Cord Blood-Derived Natural Killer Cells and Iron Oxide Nanoparticles.

We report the generation of magnetically responsive, cord blood-derived natural killer (NK) cells using iron oxide nanoparticles (IONPs). NK cells are a promising immune cell population for cancer cell therapy as they can target and lyse target tumor cells without prior education. However, NK cells cannot home to disease sites based on antigen recognition, instead relying primarily on external stimuli and chemotactic gradients for transport. Hence, we hypothesized that conjugating IONPs onto the surface of NK cells provides an added feature of magnetic homing to the NK cells, improving their therapeutic function. We describe a robust design for conjugating the IONPs onto the surface of NK cells, which maintains their intrinsic phenotype and function. The conferred magnetic-responsiveness is utilized to improve the cytolytic function of the NK cells for target cells in 2D and 3D models. These findings demonstrate the feasibility of improving NK cell homing and therapeutic efficacy with our NK:IONP “biohybrid”

Administrative stressors and Islamic coping strategies among Muslim primary principals in Malaysia: a mixed method study

Principals are school leaders who experienced stress while leading their schools towards excellence. However, principals stress experiences are always ignored and least studied. This mixed-methods study investigates primary principals’ stress experiences and their Islamic coping strategies used in incapacitating the stress experiences. A total of 216 Muslim primary principals across different gender, types of schools and years of experiences as school leaders responded to the administrative stress and the Islamic coping strategies items. In addition, seven primary principals were purposefully selected and interviewed in exploring their reasons of using Islamic coping strategies for their relieving process. Results discovered that primary principals experienced fairly stress level and they perceived managing students’ academic achievement was the most stressor followed by managing teachers’ capabilities. Although findings revealed that no significant differences in terms primary principals’ demographics; male primary principals, and experienced between 6 and 10 years and positioned in schools with least students (SLS) category have slightly higher level of stress. In terms of Islamic coping strategies used by primary principals, saying dhua to Allah, performing dhikir and reciting the Yassen are selected coping approaches employed in handling their stress. From interviews, primary principals also revealed that they used Islamic religious approaches as part of meaningful activities not just to overcoming their stress but also as part of religious approaches in remembering Allah, thinking back their past mistakes as part of the Muhasabah process. Therefore, we believed that religious approaches should be taken into consideration in principals’ training as it provides peaceful and treatment in managing principals’ stress issue