Handheld vital microscopy for the identification of microcirculatory alterations in cervical intraepithelial neoplasia and cervical cancer.

BACKGROUND: Ninety percent of cervical cancer (CC) diagnoses and deaths occur in low and middle-income countries (LMICs). Especially in these countries, where human and material resources are limited, there is a need for real-time screening methods that enable immediate treatment decisions (i.e., 'see and treat'). OBJECTIVE: To evaluate whether handheld vital microscopy (HVM) enables real-time detection of microvascular alterations associated with cervical intraepithelial neoplasia (CIN) and CC. METHODS: A cross-sectional study was conducted in an oncologic hospital and outpatient clinic, and included ten healthy controls, ten women with CIN, and ten women with CC. The microvasculature was assessed in four quadrants of the uterine cervix using HVM. The primary outcome was the presence of abnormal angioarchitecture (AA). Secondary outcomes included capillary loop density (CD), total vessel density (TVD), functional capillary density (FCD), and the proportion of perfused vessels (PPV). RESULTS: 198 image sequences of the cervical microvasculature were recorded. Compared to healthy controls, significantly more abnormal image sequences were observed in women with high-grade CIN (11 % vs. 44 %, P < 0.001) and women with CC (11 % vs. 69 %, P < 0.001). TVD, FCD, and PPV were lower in women with CIN and CC. CONCLUSIONS: HVM enables easy, real-time, non-invasive assessment of cervical lesions through the detection of microvascular alterations. Thereby, HVM potentially provides an opportunity for point-of-care screening, which may enable immediate treatment decisions (see and treat) and reduce the number of unnecessary surgical interventions.

Embedded macrophages induce intravascular coagulation in 3D blood vessel-on-chip.

Macrophages are innate immune cells that prevent infections and help in wound healing and vascular inflammation. While these cells are natural helper cells, they also contribute to chronic diseases, e.g., by infiltrating the endothelial layer in early atherosclerosis and by promoting vascular inflammation. There is a crosstalk between inflammatory pathways and key players in thrombosis, such as platelets and endothelial cells - a phenomenon known as 'thromboinflammation'. The role of the embedded macrophages in thromboinflammation in the context of vascular disease is incompletely understood. Blood vessels-on-chips, which are microfluidic vascular cell culture models, have been used extensively to study aspects of vascular disease, like permeability, immune cell adhesion and thrombosis. Blood perfusion assays in blood vessel-on-chip models benefit from multiple unique aspects of the models, such as control of microvessel structure and well-defined flow patterns, as well as the ability to perform live imaging. However, due to their simplified nature, blood vessels-on-chip models have not yet been used to capture the complex cellular crosstalk that is important in thromboinflammation. Using induced pluripotent stem cell-derived endothelial cells and polarized THP-1 monocytes, we have developed and systematically set up a 3D blood vessel-on-chip with embedded (lipid-laden) macrophages, which is created using sequential cell seeding in viscous finger patterned collagen hydrogels. We have set up a human whole blood perfusion assay for these 3D blood vessels-on-chip. An increased deposition of fibrin in the blood vessel-on-chip models containing lipid-laden macrophages was observed. We anticipate the future use of this advanced vascular in vitro model in drug development for early atherosclerosis or aspects of other vascular diseases.

In situ spatiotemporal characterization and analysis of chemical reactions using an ATR-integrated microfluidic reactor.

Determining kinetic reaction parameters with great detail has been of utmost importance in the field of chemical reaction engineering. However, commonly used experimental and computational methods however are unable to provide sufficiently resolved spatiotemporal information that can aid in the process of understanding these chemical reactions. With our work, we demonstrate the use of a custom designed single-bounce ATR-integrated microfluidic reactor to obtain spatiotemporal resolution for in situ monitoring of chemical reactions. Having a single-bounce ATR accessory allows us to individually address different sensing areas, thereby providing the ability to obtain spatially and temporally resolved information. To further enhance the spatial resolution, we utilize the benefits of synchrotron IR radiation with the smallest beam spot-size ∼150 µm. An on-flow modular microreactor additionally allows us to monitor the chemical reaction in situ, where the temporal characterization can be controlled with the operational flowrate. With a unique combination of experimental measurements and numerical simulations, we characterize and analyse a model SN2 reaction. For a chemical reaction between benzyl bromide (BB) and sodium azide (SA) to produce benzyl azide (BA), we successfully show the capability of our device to determine the diffusion coefficients of BB and SA as 0.367 ± 0.115 10-9 m2 s-1 and 1.17 ± 0.723 10-9 m2 s-1, respectively. Finally, with the above characteristics of our device, we also calculate a reaction rate of k = 0.0005 (m3s-1mol-1) for the given chemical reaction.

Osseointegration of photodynamic active biomaterials for bone regeneration in an animal bone model over a period of 12 months.

OBJECTIVES: Previous efforts led to the development of two different polymeric biomaterials for periodontal regeneration with antibacterial photodynamic surface activity. The present study aimed to investigate osseointegration and bone formation of both materials in an ovine model. METHODS: Both biomaterials: 1) urethane dimethacrylate-based Biomaterial 1 (BioM1) and 2) tri-armed oligoester-urethane methacrylate-based Biomaterial 2 (BioM2) are enriched with beta-tri-calcium phosphate and the photosensitizer meso-tetra(hydroxyphenyl)chlorin (mTHPC). These materials were implanted in non-critical size bone defects in the sheep femur (n = 16) and tibia (n = 8). Empty defects served as controls (n = 16). Polyfluorochrome sequential bone labeling was carried out at baseline and after 3, 6, and 12 months. Animals were sacrificed after 12 months. Bone specimens (n = 40) were fixed and subjected to microtomographic analysis (µCT) for the evaluation of the bone-volume-fraction (BV/TV), trabecular number and trabecular thickness. Subsequently, histological sections were arranged and polyfluorochrome sequential bone labeling was analyzed by confocal laser scanning microscopy (cLSM). RESULTS: cLSM analysis revealed that highest remodeling and bone formation activity occurred during the second half of the study period (6-12 months). Bone formation in the tibia was significantly lower for the control (2.71 ± 1.26%) as compared to BioM1 (6.01 ± 2.99%) and BioM2 (6.45 ± 2.12%); (p = 0.006, p = 0004). Micro-computed tomography revealed a BV/TV volume fraction of 44.72 ± 9.01% in femur defects filled with BioM1 which was significantly higher compared to the control (32.27 ± 7.02%; p = 0.01). Bone architecture (trabecular number, trabecular thickness) did not significantly differ from the self-healed defects. SIGNIFICANCE: Both biomaterials, especially BioM1 showed good osseointegration and bone formation characteristics and can be recommended for further examination in periodontal regeneration studies.

Refrigerated multi-dose insulin vials remain sterile through 6 months of use.

OBJECTIVES: To evaluate sterility in refrigerated multi-dose insulin vials through 6 months of routine aspiration. MATERIALS AND METHODS: Twelve vials of insulin, six of insulin glargine U100 (Lantus®, 10 mL multi-dose vial, Sanofi, Bridgewater, NJ) containing the preservative metacresol, and six of protamine zinc insulin U40 (ProZinc®, 10 mL multi-dose vial, Boehringer Ingelheim, Duluth, GA) containing the preservative phenol, were refrigerated and aspirated twice daily for 6 months, using a new insulin syringe each time. Three vials of each insulin type were wiped with a single-use alcohol swab before sampling. Three times weekly, aspirated samples were inoculated in Tryptic Soy Broth enrichment media and incubated for evidence of microbial growth. Positive broth was cultured and speciated. Endpoints were microbial vial contamination (defined as three consecutive positive cultures of the same organism) and completion of the six-month study period. RESULTS: Microbial contamination was not identified in any vial throughout the study period. A total of 454 aspirated samples were cultured, one of which exhibited non-repeatable growth of Staphylococcus epidermidis. This vial was prematurely lost to breakage after 59 culture samples (29 after the positive growth). CLINICAL SIGNIFICANCE: Refrigerated phenol- and metacresol-containing multi-dose insulin products carry minimal risk for iatrogenic infection through 6 months of use, regardless of alcohol swab preparation.

The barriers and needs of transgender men in pregnancy and childbirth: A qualitative interview study.

OBJECTIVE: Transgender and gender diverse individuals are individuals whose gender identity differs from their sex assigned at birth. The discordance between gender identity and sex assignment may cause significant psychological distress: gender dysphoria. Transgender individuals may choose to undergo gender-affirming hormone treatment or surgery, but some decide to (temporarily) refrain from surgery and gender affirming hormone treatment and hence retain the possibility to become pregnant. Pregnancy may enhance feelings of gender dysphoria and isolation. To improve perinatal care for transgender individuals and their health care providers, we conducted interviews to explore the needs and barriers of transgender men in family planning, pregnancy, childbirth, puerperium and perinatal care. DESIGN: In this qualitative study five in-depth semi-structured interviews were conducted with Dutch transgender men who had given birth while identifying on the transmasculine spectrum. The interviews were conducted online through a video remote-conferencing software program (n=4) or live (n=1). Interviews were transcribed verbatim. An inductive approach was used to find patterns and collect data from the participants' narratives and constant comparative method was adapted in analysing the interviews. MEASUREMENTS AND FINDINGS: The experiences of transgender men regarding the preconception period, pregnancy and puerperium and with perinatal care varied widely. Though all participants expressed overall positive experiences, their narratives emphasized they had to overcome substantial hurdles pursuing pregnancy. For instance the necessity to prioritise becoming pregnant over gender transitioning, lack of support by healthcare providers and increased gender dysphoria and isolation during pregnancy KEY CONCLUSIONS: Since pregnancy in transgender men enhances feelings of gender dysphoria, transgender men comprise a vulnerable group in perinatal care. Health care providers are perceived as feeling unaccustomed for the care of transgender patients, as they are perceived to often lack the right tools and knowledge to provide adequate care. Our findings help strengthen the foundation of insight in the needs and hurdles of transgender men pursuing pregnancy and therefore may guide health care providers to provide equitable perinatal care, and emphasize the necessity of patient-centred gender-inclusive perinatal care. A guideline including the option for consultation of an expertise center is advised to facilitate patient-centered gender-inclusive perinatal care.

Cost-utility analysis of a structured medication review compared to usual care in Parkinson's disease.

PURPOSE: For controlling symptoms in Parkinson's disease (PD) together with treating additional comorbidities, patients often face complex medication regimens, with suboptimal adherence, drug-related problems, and diminished therapy efficacy as a common consequence. A medication review could potentially tackle these issues, among others by optimizing drug treatment. Even if no change in clinical outcomes is observed, this intervention might decrease health care costs by reducing drug-related problems and hospital admissions. This study aimed to gain more insight in the health benefits and costs of a structured medication review (SMR) in PD. METHODS: A cost-utility analysis was performed, based on a multicenter randomized controlled trial with 202 PD patients with polypharmacy. The intervention group received an SMR, whereas the control group received usual care. The intervention effect after 6 months of follow-up was presented as incremental quality-adjusted life years (QALY) using the EQ-5D-5L questionnaire. Costs were based on real-world data. Missing data was imputed using multiple imputation techniques. Bootstrapping was used to estimate the uncertainty in all health and economic outcomes. RESULTS: The QALY gain in the intervention group compared to the control group was - 0.011 (95% CI - 0.043; 0.020). Incremental costs were €433 (95% CI - 873; 1687). When adapting a willingness-to-pay threshold of €20,000/QALY and €80,000/QALY, the probability of SMRs being cost-effective was 18% and 30%, respectively. CONCLUSION: A community pharmacist-led SMR in PD patients in the current setting shows no apparent benefit and is not cost-effective after 6 months, compared to usual care. TRIAL REGISTRATION: Netherlands Trial Register, NL4360. Registered 17 March 2014.

Perioperative administration of tranexamic acid in hip fracture surgery (The PATHS study): national audit of current practice.

INTRODUCTION: Neck of femur fractures (NOFF) are associated with significant morbidity and mortality, exacerbated by anaemia. Evidence indicates tranexamic acid (TXA) administration in NOFF surgery reduces blood loss and transfusion requirements, without increasing complications. The aim of this study was to establish current TXA administration practice in patients undergoing surgery for NOFF in the UK. METHODS: We conducted a multicentre prospective study within the UK over a two-week period in March 2019. Pre-, intra- and postoperative data were collected locally and analysed centrally. RESULTS: Data for 917 patients were submitted from 66 institutions. Of those eligible, 48.0% received TXA perioperatively. Administration rates varied from 0 to 100%. Significantly greater numbers undergoing arthroplasty received TXA (57.6%) compared with internal fixation (38.4%, p<0.01). Some 15.2% of institutions had a protocol for TXA use in NOFF. Patients treated in these units were significantly more likely to receive TXA (86.7%) than those who were not (41.2% p<0.01). Of those receiving TXA, 92.3% were given 1g intravenously (IV) at anaesthetic administration. CONCLUSIONS: Despite supportive evidence for its use, a wide variation in the administration of TXA between hospitals and procedures has been demonstrated. Administration rates were higher for arthroplasty than for fixation procedures. Most centres do not have a protocol guiding TXA administration. We recommend administration of 1g IV TXA perioperatively for patients undergoing NOFF surgery, where not contraindicated, unless future randomised controlled trials support an alternative regimen. We recommend units include their own locally agreed TXA policy within a written protocol for the care of NOFF patients.

[The life quality of the disabled as a result of diseases of peripheral nervous system].

The article considers results of studying the quality of life of disabled patients because of diseases of peripheral nervous system. The significantly low level of indices of quality of life self-assessment was established on all scales of SF-36 questionnaire that are from 3 to 7 times lower than similar indices in population of Russia. The assessment of quality of life of disabled patients is necessary to determine effectiveness of applied rehabilitation measures and application of obtained results in planning further rehabilitation and habilitation activities.

[The social economic aspects of disability resulted from diseases of peripheral nervous system].

The diseases of peripheral nervous system (PNS diseases) are diagnosed in 48%-72% of workers in various branches of economy. They made up more than half of all occupational diseases and are the main cause of labor ability and of high level of disability able-bodied population. The purpose of the study is to assess social economic importance of disability because of PNS diseases of able-bodied population in the Republic of Bashkortostan. It is established that in 2014-2018 about 107 individuals of able-bodied age for the first time became disabled because of PNS diseases. The average annual level of individuals of able-bodied age with for the first time established disabilities because of PNS diseases made up to 0.1 cases per 10 thousand of population. Among the disabled 69.0 ± 5.4% are males. The disability rate in males (0.142o/ooo) is twice higher than in females (0.063o/ooo). The average age of the disabled is 48.7 ± 5.7 years. In the structure of disability dominate lumbosacral radiculopathy (50.9%), polyneuropathy of upper (15.3%) and lower (13.5%) extremities. In average, the disability develops in 11.3 years prior to age of 60 years and on 3.8-5.5 years earlier than in case of other diseases. The disability because of PNS diseases shortens healthy life expectancy by 16.0% in males and by 17.8% in females. Annual economic losses come to more than 26 million rubles of non-produced production. The disability because of PNS consists significant social economic problem of society and requires increased attention to prevention, early diagnostics, treatment, improvement of quality of medical social expertise, rehabilitation and habilitation.

Protocol for a randomized controlled multicenter trial assessing the efficacy of leuprorelin for severe polycystic liver disease: the AGAINST-PLD study.

BACKGROUND: In patients with severe polycystic liver disease (PLD), there is a need for new treatments. Estrogens and possibly other female sex hormones stimulate growth in PLD. In some patients, liver volume decreases after menopause. Female sex hormones could therefore be a target for therapy. The AGAINST-PLD study will examine the efficacy of the GnRH agonist leuprorelin, which blocks the production of estrogen and other sex hormones, to reduce liver growth in PLD. METHODS: The AGAINST-PLD study is an investigator-driven, multicenter, randomized controlled trial. Institutional review board (IRB) approval was received at the University Medical Center of Groningen and will be collected in other sites before opening these sites. Thirty-six female, pre-menopausal patients, with a very large liver volume for age (upper 10% of the PLD population) and ongoing liver growth despite current treatment options will be randomized to direct start of leuprorelin or to 18 months standard of care and delayed start of leuprorelin. Leuprorelin is given as 3.75 mg subcutaneously (s.c.) monthly for the first 3 months followed by 3-monthly depots of 11.25 mg s.c. The trial duration is 36 months. MRI scans to measure liver volume will be performed at screening, 6 months, 18 months, 24 months and 36 months. In addition, blood will be drawn, DEXA-scans will be performed and questionnaires will be collected. This design enables comparison between patients on study treatment and standard of care (first 18 months) and within patients before and during treatment (whole trial). Main outcome is annualized liver growth rate compared between standard of care and study treatment. Secondary outcomes are PLD disease severity, change in liver growth within individuals and (serious) adverse events. The study is designed as a prospective open-label study with blinded endpoint assessment (PROBE). DISCUSSION: In this trial, we combined the expertise of hepatologist, nephrologists and gynecologists to study the effect of leuprorelin on liver growth in PLD. In this way, we hope to stop liver growth, reduce symptoms and reduce the need for liver transplantation in severe PLD. Trial registration Eudra CT number 2020-005949-16, registered at 15 Dec 2020. https://www.clinicaltrialsregister.eu/ctr-search/search?query=2020-005949-16 .

Lifetime prevalence and determinants of hand eczema in an adolescent population in Germany: 15-year follow-up of the LISA cohort study.

BACKGROUND: Hand eczema is a common inflammatory skin disorder in both adolescence and adulthood. OBJECTIVES: We sought to assess the lifetime prevalence of hand eczema and associated exogenous and endogenous risk factors among adolescents in Germany. METHODS: This was a cross-sectional study embedded into a prospective population-based birth cohort in four regions of Germany, which recruited healthy neonates born between November 1997 and January 1999. We included 1736 participants who had completed the 15-year follow-up from birth cohort and 84.6% (1468/1736) had clearly reported whether they have ever had hand eczema. All the data were based on questionnaires and blood tests (immunoglobulin E). Multivariable logistic regression analysis was used to examine endogenous and exogenous factors in relation to the lifetime prevalence of hand eczema among adolescents. RESULTS: One thousand four hundred and sixty-eight adolescents (715 girls, 48.7%) were included in the final analysis. The lifetime prevalence of hand eczema among adolescents at the age of 15 was 10.4% (95% confidence interval [CI]: 8.9%-12.1%), with a significantly higher lifetime prevalence among girls than boys (12.7% vs. 8.2%, P = 0.005). Multivariable logistic regression analysis indicated statistically significant associations between the lifetime prevalence of hand eczema and having ever been diagnosed with atopic dermatitis (aOR = 1.8, 95% CI: 1.1-2.8) or having ever had dry skin (aOR = 1.9, 95% CI: 1.1-3.1), respectively. No statistically significant independent associations were found between asthma, hay fever, allergy-related clinical symptoms, immunoglobulin E positivity and other exogenous factors in relation to hand eczema. CONCLUSION: Our study fills a research gap on the epidemiological burden of hand eczema among adolescents. One out of ten ever suffered from hand eczema until age 15 years indicating that hand eczema constitutes a significant burden in paediatric populations. The role of atopic dermatitis in hand eczema reinforces previous findings. Exogenous risk factors warrant further investigation.

Functional MRI of visual cortex predicts training-induced recovery in stroke patients with homonymous visual field defects.

Post-chiasmatic damage to the visual system leads to homonymous visual field defects (HVDs), which can severely interfere with daily life activities. Visual Restitution Training (VRT) can recover parts of the affected visual field in patients with chronic HVDs, but training outcome is variable. An untested hypothesis suggests that training potential may be largest in regions with 'neural reserve', where cortical responses to visual stimulation do not lead to visual awareness as assessed by Humphrey perimetry-a standard behavioural visual field test. Here, we tested this hypothesis in a sample of twenty-seven hemianopic stroke patients, who participated in an assiduous 80-hour VRT program. For each patient, we collected Humphrey perimetry and wide-field fMRI-based retinotopic mapping data prior to training. In addition, we used Goal Attainment Scaling to assess whether personal activities in daily living improved. After training, we assessed with a second Humphrey perimetry measurement whether the visual field was improved and evaluated which personal goals were attained. Confirming the hypothesis, we found significantly larger improvements of visual sensitivity at field locations with neural reserve. These visual field improvements implicated both regions in primary visual cortex and higher order visual areas. In addition, improvement in daily life activities correlated with the extent of visual field enlargement. Our findings are an important step toward understanding the mechanisms of visual restitution as well as predicting training efficacy in stroke patients with chronic hemianopia.

Magnetic charge propagation upon a 3D artificial spin-ice.

Magnetic charge propagation in spin-ice materials has yielded a paradigm-shift in science, allowing the symmetry between electricity and magnetism to be studied. Recent work is now suggesting the spin-ice surface may be important in mediating the ordering and associated phase space in such materials. Here, we detail a 3D artificial spin-ice, which captures the exact geometry of bulk systems, allowing magnetic charge dynamics to be directly visualized upon the surface. Using magnetic force microscopy, we observe vastly different magnetic charge dynamics along two principal directions. For a field applied along the surface termination, local energetics force magnetic charges to nucleate over a larger characteristic distance, reducing their magnetic Coulomb interaction and producing uncorrelated monopoles. In contrast, applying a field transverse to the surface termination yields highly correlated monopole-antimonopole pairs. Detailed simulations suggest it is the difference in effective chemical potential as well as the energy landscape experienced during dynamics that yields the striking differences in monopole transport.

[Impact of postpartum depression on care use and work]. / Impact van postpartumdepressie op zorggebruik en arbeidsparticipatie.

OBJECTIVE: To describe the care which women with postpartum depression (PPD) in the Netherlands use for their complaints, and the impact of PPD on their general use of care for themselves and for their child, and on their participation in work. DESIGN: The data came from the control group of a prospective comparative study on the effectiveness of screening for PPD within the setting of Youth Health Care. METHOD: We obtained data by means of two online questionnaires. Three weeks postpartum, we examined the background characteristics of the mother. Twelve months postpartum, we inquired about depression since birth, care use for depressive symptoms, general care use since birth for both mother and child, and participation in work up to 12 months postpartum. To test differences, we used chi-square and student t-tests. RESULTS: Of the 1049 participating women, 99 (9.4%) indicated that they had experienced depression in the year since giving birth. Of the 99 'women with PPD', 71.0% made at least some use of care aimed at their PPD complaints. Of these women with PPD, 31.3% were diagnosed with depression, and 37.7% were actually treated. Mothers with PPD used considerably more care for themselves and their child than mothers without PPD. Absenteeism from work was significantly higher among women with PPD. CONCLUSION: The limited number of women with PPDreceiving care by and the social costs entailed by PPD justify investment in routine screening and customized care pathways for these women.

[Ayahuasca in the Netherlands: what the doctor should know about its side effects]. / Ayahuasca in de polder.

In the past few months, ayahuasca has received quite a bit of coverage in the lay press. Ayahuasca is a South American hallucinogenic tea that is gaining popularity in Europe and North America. In the Netherlands, ayahuasca is usually used in a group ceremony called an 'ayahuasca ceremony'. Use of ayahuasca is not associated with the development of substance dependency. The side effects of ayahuasca are considered mild. We describe a 36-year-old woman who developed severe hyponatremia after participating in an ayahuasca ceremony. We also discuss the mechanism of action, the effects, the therapeutic potential and the risks of this hallucinogenic agent.

Multiplexed blood-brain barrier organ-on-chip.

Organ-on-chip devices are intensively studied in academia and industry due to their high potential in pharmaceutical and biomedical applications. However, most of the existing organ-on-chip models focus on proof of concept of individual functional units without the possibility of testing multiple experimental stimuli in parallel. Here we developed a polydimethylsiloxane (PDMS) multiplexed chip with eight parallel channels branching from a common access port through which all eight channels can be addressed simultaneously without the need for extra pipetting steps thus increasing the reproducibility of the experimental results. At the same time, eight outlets provide individual entry to each channel with the opportunity to create eight different experimental conditions. A multiplexed chip can be assembled as a one-layer device for studying monocultures or as a two-layer device for studying barrier tissue functions. For a two-layer device, a ∼2 µm thick transparent PDMS membrane with 5 µm through-hole pores was fabricated in-house using a soft lithography technique, thereby allowing visual inspection of the cell-culture in real-time. The functionality of the chip was studied by recapitulating the blood-brain barrier. For this, human cerebral microvascular endothelial cells (hCMEC/D3) were cultured in mono- or coculture with human astrocytes. Immunostaining revealed a cellular monolayer with the expression of tight junction ZO-1 and adherence junction VE-cadherin proteins in endothelial cells as well as glial fibrillary acidic protein (GFAP) expression in astrocytes. Furthermore, multiplexed permeability studies of molecule passage through the cellular barrier exhibited expected high permeability coefficients for smaller molecules (4 kDa FITC-dextran) whereas larger molecules (20 kDa) crossed the barrier at a lower rate. With these results, we show that our device can be used as an organ-on-chip model for future multiplexed drug testing.