Nanomechanical sensors: Measuring a response in blood

Nanomechanical cantilevers can determine the concentration of active drugs in human serum

Dissociating the influence of perceptual biases and contextual artefacts within target configurations during the planning and control of visually guided action

The failure of perceptual illusions to elicit corresponding biases within movement supports the view of two visual pathways separately contributing to perception and action. However, several alternative findings may contest this overarching framework. The present study aimed to examine the influence of perceptual illusions within the planning and control of aiming. To achieve this, we manipulated and measured the planning/control phases by respectively perturbing the target illusion (relative size-contrast illusion; Ebbinghaus/Titchener circles) following movement onset and detecting the spatiotemporal characteristics of the movement trajectory. The perceptual bias that was indicated by the perceived target size estimates failed to correspondingly manifest within the effective target size. While movement time (specifically, time after peak velocity) was affected by the target configuration, this outcome was not consistent with the direction of the perceptual illusions. These findings advocate an influence of the surrounding contextual information (e.g., annuli) on movement control that is independent of the direction predicted by the illusion

Using small molecules to facilitate exchange of bicarbonate and chloride anions across liposomal membranes

Bicarbonate is involved in a wide range of biological processes, which include respiration, regulation of intracellular pH and fertilization. In this study we use a combination of NMR spectroscopy and ion-selective electrode techniques to show that the natural product prodigiosin, a tripyrrolic molecule produced by microorganisms such as Streptomyces and Serratia, facilitates chloride/bicarbonate exchange (antiport) across liposomal membranes. Higher concentrations of simple synthetic molecules based on a 4,6-dihydroxyisophthalamide core are also shown to facilitate this antiport process. Although it is well known that proteins regulate Cl-/HCO3- exchange in cells, these results suggest that small molecules may also be able to regulate the concentration of these anions in biological systems

Neutropenia induced in outbred mice by a simplified low-dose cyclophosphamide regimen: characterization and applicability to diverse experimental models of infectious diseases

BACKGROUND: For its low cost and ease of handling, the mouse remains the preferred experimental animal for preclinical tests. To avoid the interaction of the animal immune system, in vivo antibiotic pharmacodynamic studies often employ cyclophosphamide (CPM) to induce neutropenia. Although high doses (350–450 mg/kg) are still used and their effects on mouse leukocytes have been described, a lower dose (250 mg/kg) is widely preferred today, but the characteristics and applicability of this approach in outbred mice have not been determined. METHODS: Fifteen female ICR mice were injected intraperitoneally with 150 and 100 mg/kg of CPM on days 1 and 4, respectively. Blood samples (~160 μL) were drawn from the retro-orbital sinus of each mouse on days 1, 4, 5, 6, 7 and 11. Leukocytes were counted manually and the number of granulocytes was based on microscopic examination of Wright-stained smears. The impact of neutropenia induced by this method was then determined with a variety of pathogens in three different murine models of human infections: pneumonia (Klebsiella pneumoniae, Streptococcus pneumoniae, Staphylococcus aureus), meningoencephalitis (S. pneumoniae), and the thigh model (S. aureus, Escherichia coli, Bacteroides fragilis). RESULTS: The basal count of leukocytes was within the normal range for outbred mice. On day 4, there was an 84% reduction in total white blood cells, and by day 5 the leukopenia reached its nadir (370 ± 84 cells/mm(3)). Profound neutropenia (≤10 neutrophils/mm(3)) was demonstrated at day 4 and persisted through days 5 and 6. Lymphocytes and monocytes had a 92% and 96% decline between days 1 and 5, respectively. Leukocytes recovered completely by day 11. Mice immunosupressed under this protocol displayed clinical and microbiological patterns of progressive and lethal infectious diseases after inoculation in different organs with diverse human pathogens. CONCLUSION: A CPM total dose of 250 mg/kg is sufficient to induce profound and sustained neutropenia (<10 neutrophils/mm(3)) at least during 3 days in outbred mice, is simpler than previously described methods, and allows successful induction of infection in a variety of experimental models

Risdiplam in Type 1 Spinal Muscular Atrophy

BACKGROUND: Type 1 spinal muscular atrophy is a rare, progressive neuromuscular disease that is caused by low levels of functional survival of motor neuron (SMN) protein. Risdiplam is an orally administered, small molecule that modifies SMN2 pre-messenger RNA splicing and increases levels of functional SMN protein. METHODS: We report the results of part 1 of a two-part, phase 2-3, open-label study of risdiplam in infants 1 to 7 months of age who had type 1 spinal muscular atrophy, which is characterized by the infant not attaining the ability to sit without support. Primary outcomes were safety, pharmacokinetics, pharmacodynamics (including the blood SMN protein concentration), and the selection of the risdiplam dose for part 2 of the study. Exploratory outcomes included the ability to sit without support for at least 5 seconds. RESULTS: A total of 21 infants were enrolled. Four infants were in a low-dose cohort and were treated with a final dose at month 12 of 0.08 mg of risdiplam per kilogram of body weight per day, and 17 were in a high-dose cohort and were treated with a final dose at month 12 of 0.2 mg per kilogram per day. The baseline median SMN protein concentrations in blood were 1.31 ng per milliliter in the low-dose cohort and 2.54 ng per milliliter in the high-dose cohort; at 12 months, the median values increased to 3.05 ng per milliliter and 5.66 ng per milliliter, respectively, which represented a median of 3.0 times and 1.9 times the baseline values in the low-dose and high-dose cohorts, respectively. Serious adverse events included pneumonia, respiratory tract infection, and acute respiratory failure. At the time of this publication, 4 infants had died of respiratory complications. Seven infants in the high-dose cohort and no infants in the low-dose cohort were able to sit without support for at least 5 seconds. The higher dose of risdiplam (0.2 mg per kilogram per day) was selected for part 2 of the study. CONCLUSIONS: In infants with type 1 spinal muscular atrophy, treatment with oral risdiplam led to an increased expression of functional SMN protein in the blood. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT02913482.)

Systematic review of communication technologies to promote access and engagement of young people with diabetes into healthcare

Background: Research has investigated whether communication technologies (e.g. mobile telephony, forums, email) can be used to transfer digital information between healthcare professionals and young people who live with diabetes. The systematic review evaluates the effectiveness and impact of these technologies on communication. Methods: Nine electronic databases were searched. Technologies were described and a narrative synthesis of all studies was undertaken. Results: Of 20,925 publications identified, 19 met the inclusion criteria, with 18 technologies assessed. Five categories of communication technologies were identified: video-and tele-conferencing (n = 2); mobile telephony (n = 3); telephone support (n = 3); novel electronic communication devices for transferring clinical information (n = 10); and web-based discussion boards (n = 1). Ten studies showed a positive improvement in HbA1c following the intervention with four studies reporting detrimental increases in HbA1c levels. In fifteen studies communication technologies increased the frequency of contact between patient and healthcare professional. Findings were inconsistent of an association between improvements in HbA1c and increased contact. Limited evidence was available concerning behavioural and care coordination outcomes, although improvement in quality of life, patientcaregiver interaction, self-care and metabolic transmission were reported for some communication technologies. Conclusions: The breadth of study design and types of technologies reported make the magnitude of benefit and their effects on health difficult to determine. While communication technologies may increase the frequency of contact between patient and health care professional, it remains unclear whether this results in improved outcomes and is often the basis of the intervention itself. Further research is needed to explore the effectiveness and cost effectiveness of increasing the use of communication technologies between young people and healthcare professionals

Lack of Cetuximab induced skin toxicity in a previously irradiated field: case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Mutation, amplification or dysregulation of the EGFR family leads to uncontrolled division and predisposes to cancer. Inhibiting the EGFR represents a form of targeted cancer therapy.</p> <p>Case report</p> <p>We report the case of 79 year old gentlemen with a history of skin cancer involving the left ear who had radiation and surgical excision. He had presented with recurrent lymph node in the left upper neck. We treated him with radiation therapy concurrently with Cetuximab. He developed a skin rash over the face and neck area two weeks after starting Cetuximab, which however spared the previously irradiated area.</p> <p>Conclusion</p> <p>The etiology underlying the sparing of the previously irradiated skin maybe due to either decrease in the population of EGFR expressing cells or decrease in the EGFR expression.</p> <p>We raised the question that "Is it justifiable to use EGFR inhibitors for patients having recurrence in the previously irradiated field?" We may need further research to answer this question which may guide the physicians in choosing appropriate drug in this scenario.</p

How did the latest increase in fees in England affect student enrolment and inequality?

This paper presents a first analysis of the increase of undergraduate tuition fees to £9,000 (€11.000) in English higher education in 2012. I use a semi-experimental research design to estimate the effect of the reforms, based on student enrolment data drawn from the Higher Education Statistics Agency (HESA). Taking into account possible anticipation effects of the fee increase, I find that enrolment declined by 15 % in the treated groups as a result of the tuition fee increase. This number is almost three times higher than what previous studies have found, and may represent a serious long term cost for the English economy. The decline in enrolments is particularly pronounced for students in older age groups and students from the service class and the middle class. No effect is visible for students from the working class, indicating that the reforms did not lead to a much-feared increase in class bias in higher education enrolment. The reforms also seem not to have exacerbated ethnic inequality in higher education, as all ethnic groups were negatively affected by the reforms. These results are consistent with earlier research in the United States and the United Kingdom, although they expand our understanding of student price responsiveness in other important ways. The paper argues that younger and older students face different costs and benefits. Older students may be less certain about their benefits, and therefore be more sensitive towards price increases. The strong decrease in mature learners may require a policy response, taking into account these differing incentives