Lab-On-A-Chip for the Development of Pro-/Anti-Angiogenic Nanomedicines to Treat Brain Diseases.

There is a huge demand for pro-/anti-angiogenic nanomedicines to treat conditions such as ischemic strokes, brain tumors, and neurodegenerative diseases such as Alzheimer's and Parkinson's. Nanomedicines are therapeutic particles in the size range of 10-1000 nm, where the drug is encapsulated into nano-capsules or adsorbed onto nano-scaffolds. They have good blood-brain barrier permeability, stability and shelf life, and able to rapidly target different sites in the brain. However, the relationship between the nanomedicines' physical and chemical properties and its ability to travel across the brain remains incompletely understood. The main challenge is the lack of a reliable drug testing model for brain angiogenesis. Recently, microfluidic platforms (known as "lab-on-a-chip" or LOCs) have been developed to mimic the brain micro-vasculature related events, such as vasculogenesis, angiogenesis, inflammation, etc. The LOCs are able to closely replicate the dynamic conditions of the human brain and could be reliable platforms for drug screening applications. There are still many technical difficulties in establishing uniform and reproducible conditions, mainly due to the extreme complexity of the human brain. In this paper, we review the prospective of LOCs in the development of nanomedicines for brain angiogenesis-related conditions.

Quantification of cellular penetrative forces using lab-on-a-chip technology and finite element modeling.

Tip-growing cells have the unique property of invading living tissues and abiotic growth matrices. To do so, they exert significant penetrative forces. In plant and fungal cells, these forces are generated by the hydrostatic turgor pressure. Using the TipChip, a microfluidic lab-on-a-chip device developed for tip-growing cells, we tested the ability to exert penetrative forces generated in pollen tubes, the fastest-growing plant cells. The tubes were guided to grow through microscopic gaps made of elastic polydimethylsiloxane material. Based on the deformation of the gaps, the force exerted by the elongating tubes to permit passage was determined using finite element methods. The data revealed that increasing mechanical impedance was met by the pollen tubes through modulation of the cell wall compliance and, thus, a change in the force acting on the obstacle. Tubes that successfully passed a narrow gap frequently burst, raising questions about the sperm discharge mechanism in the flowering plants.

Wave propagation analysis in spiral geometries.

In this paper wave propagation in strings of exponential and conical spiral geometries and in an exponential spiral horn of increasing circular cross-section area is studied. The three-dimensional wave equation in cylindrical coordinates is investigated, as the theoretical solution in the exponential spiral horn is derived and in the case of the strings, numerical simulation mainly using a centered in time and space finite difference scheme is carried out. The results suggest non-harmonic resonance modes in both of the conical and exponential spiral strings.

Optimization of flow assisted entrapment of pollen grains in a microfluidic platform for tip growth analysis.

A biocompatible polydimethylsiloxane (PDMS) biomicrofluidic platform is designed, fabricated and tested to study protuberance growth of single plant cells in a micro-vitro environment. The design consists of an inlet to introduce the cell suspension into the chip, three outlets to conduct the medium or cells out of the chip, a main distribution chamber and eight microchannels connected to the main chamber to guide the growth of tip growing plant cells. The test cells used here were pollen grains which produce cylindrical protrusions called pollen tubes. The goal was to adjust the design of the microfluidic network with the aim to enhance the uniformly distributed positioning of pollen grains at the entrances of the microchannels and to provide identical fluid flow conditions for growing pollen tubes along each microchannel. Computational fluid analysis and experimental testing were carried out to estimate the trapping efficiencies of the different designs.

Simultaneous Presentation of Takayasu Arteritis and Crohn's Disease in a Middle-Aged Patient: Are they two sides of the same coin?

Autoimmune disorders have a wide spectrum of symptoms, often with multiorgan involvement. Multiple autoimmune disorders also often occur concurrently in the same patient. These two possibilities must be distinguished in patients with multiorgan involvement to ensure early diagnosis and treatment. Here, we report a case of a previously healthy man who presented with simultaneous Takayasu arteritis and Crohn's disease. He presented with heart failure with reduced ejection fraction and severe aortic regurgitation. An echocardiogram demonstrated a greatly dilated aorta, and a diagnosis of Takayasu arteritis was made, confirmed with CT aortogram. Inpatient treatment was begun, but the patient subsequently developed bloody diarrhoea a few days after admission. Colonoscopy done to locate the source of bleeding showed colonic ulcers; a biopsy confirmed a diagnosis of Crohn's disease. The patient was successfully managed with medical management of heart failure, steroids, mesalamine and azathioprine, and has been in remission for the last 2 years.

Tuberculous pyomyositis presenting as septic arthritis and multiple site pyomyositis.

Primary tropical pyomyositis, commonly caused by Staphylococcus aureus, is characterised by suppuration in skeletal muscles, which manifests as single or multiple abscesses. Another rare causative organism is Mycobacterium tuberculosis in endemic areas. Here, we report a case of primary tuberculous pyomyositis presenting as septic arthritis of the right knee and multiple site pyomyositis of the right thigh and chest wall. A tuberculous aetiology was overlooked at first, which resulted in a diagnostic delay. The patient was initially diagnosed, using ultrasonography, MRI and an absence of systemic symptoms of tuberculosis, with bacterial pyomyositis and treated with broad-spectrum antibiotics. However, further investigations performed on knee joint aspirate yielded negative cultures and a positive cartridge-based nucleic acid amplification test, which, along with a non-resolution of his symptoms, suggested a primary tuberculous pyomyositis. He was successfully managed with incision and drainage of the lesions and completion of anti-tubercular therapy.

Interdigitated comb-like electrodes for continuous separation of malignant cells from blood using dielectrophoresis.

In this paper, a method for continuous flow separation of circulating malignant cells from blood in a microfluidic device using dielectrophoresis is discussed. Separation of MDA231 breast cancer cells after mixing with normal blood cells was achieved with a level of accuracy that enabled precise counting of the malignant cells, separation and eventually, sub-culturing. MDA231 cells were separated from the blood to a daughter channel using two pairs of interdigitated activated comb-like electrode structures. All experiments are performed with conductivity adjusted medium samples. The electrode pairs were positioned divergent and convergent with respect to the flow. The AC signals used in the separation are 20 V peak-to-peak with frequencies of 10-50 kHz. The separation is based on balance of magnitude of the dielectrophoretic force and hydrodynamic force. The difference in response between circulating malignant cells and normal cells at a certain band of alternating current frequencies was used for rapid separation of cancer cells from blood. The significance of these experimental results is discussed in this paper, with detailed reporting on the suspension medium, preparation of cells, flow condition and the fabrication process of the microfluidic chip. The present technique could potentially be applied to identify incident cancer at a stage and size that is not yet detectable by standard diagnostic techniques (imaging and biochemical testing). Alternatively, it may also be used to detect cancer recurrences.

The use of bumetanide for oliguric acute renal failure in preterm infants.

OBJECTIVE: To determine the effects of bumetanide in preterm infants with oliguric acute renal failure (OARF). STUDY DESIGN: Retrospective data review and multivariate analysis of urine output and serum creatinine, blood urea nitrogen, Na, K, Cl, and Ca levels before, during, and after bumetanide therapy in preterm infants with OARF whose conditions did not respond to furosemide therapy. RESULTS: A total of 35 infants received bumetanide for OARF after an initial trial of furosemide. Their birth weight, gestational age at birth, and postconceptional age at OARF were 811 ± 326 g, 26 ± 2.75 wks, and 29.2 ± 2.7 wks, respectively. Twenty-nine of the 35 infants (83%) responded to bumetanide. Seventeen of the 35 infants subsequently died in the hospital due to multiorgan dysfunction. For the survivors (n = 18) and 11 of 17 of nonsurvivors, urine output increased from 0.6 ± 0.6 mL/kg/hr to 3.0 ± 2.1 mL/kg/hr during bumetanide therapy (p < .0005). Serum creatinine levels increased from 2.13 ± 0.83 mg/dL to 2.3 ± 0.92 mg/dL (p = .04) during bumetanide treatment, whereas blood urea nitrogen levels decreased after bumetanide therapy from 38 ± 19 mg/dL to 31.67 ± 21.6 mg/dL (p = .049). No significant changes were noted in serum sodium, chloride, or calcium concentration. CONCLUSIONS: Bumetanide therapy significantly increased urine output within 24-48 hrs, but its use was associated with a transient increase in serum creatinine level. Bumetanide can be used in preterm infants to reverse oliguria when therapy with furosemide fails. Prospective, randomized, controlled trials with long-term follow-up in preterm infants are necessary to establish the usefulness of bumetanide for OARF.

Parent decision making for life support for extremely premature infants: from the prenatal through end-of-life period.

Most deaths of extremely premature infants occur in the perinatal period. Yet, little is known about how parents make life support decisions in such a short period of time. In the paper, how parents make life support decisions for extremely premature infants from the prenatal period through death from the perspectives of parents, nurses, and physicians is described. Five cases, comprised of five mothers, four neonatologists, three nurses, and one neonatal nurse practitioner, are drawn from a larger collective case study. Prenatal, postnatal and end-of-life interviews were conducted, and medical record data were obtained. In an analysis by two research team members, mothers were found to exhibit these characteristics: desire for and actual involvement in life support decisions, weighing pain, suffering and hope in decision making, and wanting everything done for their infants. All mothers received decision making help and support from partners and family, but relationships with providers were also important. Finally, external resources impacted parental decision making in several of the cases. By understanding what factors contribute to parents' decision making, providers may be better equipped to prepare and assist parents when making life support decisions for their extremely premature infants.

Varicella pneumonia masquerading as interstitial lung disease: Non-specific interstitial pneumonitis.

Varicella-zoster virus infection also known as chickenpox is a common clinical entity especially among unvaccinated children and adults. It is said that severity increases as the age increases. Approximately 5%-15% of adult varicella can produce pulmonary manifestations. Varicella pneumonitis occurs especially in at-risk individuals like pregnant, smokers, chronic lung diseases like chronic obstructive pulmonary disease, and immunosuppression. The authors describe a case of severe varicella pneumonitis in a healthy immunocompetent middle-aged woman which posed a great diagnostic challenge. The authors also want to highlight that how a common disease can pose a diagnostic dilemma and present with life-threatening organ failure and timely intervention is needed to prevent mortality.

Identification of deregulated genes by single wall carbon-nanotubes in human normal bronchial epithelial cells.

To identify genes affected by single-walled carbon nanotubes (SWCNTs) in human normal lung cells, we compared the gene expression profiles of untreated human normal bronchial epithelial (HNBE) cells to profiles of HNBE cells treated with SWCNTs. A complementary DNA microarray analysis consisting of 54,675 human genes revealed marked changes in the expression of 14,294 genes, with 7,029 genes being upregulated and 7,265 being downregulated. This comprehensive list of genes included those associated with cell cycle, apoptosis, cell survival, cell adhesion and motility, signal transduction, and transcription regulation. Additional analysis of 19 genes using reverse transcription-polymerase chain reaction confirmed the microarray analysis. More specifically, our study demonstrates to our knowledge for the first time, evidence that 9 of the 19 genes (most of which encode cell apoptotic, signal transduction, and transcription regulator products) are upregulated in the SWCNTs-treated HNBE cells as compared with untreated cells, whereas the remaining 10 of the 19 (involved in cell adhesion and motility, cell proliferation, and cell survival) are downregulated in SWCNTs-treated HNBE cells in comparison with untreated controls. These findings provide a large body of information regarding gene expression profiles associated with SWCNTs exposure in human lung bronchial epithelial cells, and also represent a source to investigate the mechanism of the effect of SWCNTs in human normal lung cells. From the clinical editor: In this study, the gene expression profile of human normal bronchial epithelial cells was compared with single-wall carbon nanotubes-treated cells. A cDNA microarray analysis consisting of 54,675 human genes revealed significant changes in the expression of 14,294 genes, with 7,029 genes being up-regulated and 7,265 being down-regulated. This serves as a first step in clarification of mechanisms of action and to investigate toxicity in this model.

Characterization of thick and thin film SiCN for pressure sensing at high temperatures.

Pressure measurement in high temperature environments is important in many applications to provide valuable information for performance studies. Information on pressure patterns is highly desirable for improving performance, condition monitoring and accurate prediction of the remaining life of systems that operate in extremely high temperature environments, such as gas turbine engines. A number of technologies have been recently investigated, however these technologies target specific applications and they are limited by the maximum operating temperature. Thick and thin films of SiCN can withstand high temperatures. SiCN is a polymer-derived ceramic with liquid phase polymer as its starting material. This provides the advantage that it can be molded to any shape. CERASET™ also yields itself for photolithography, with the addition of photo initiator 2, 2-Dimethoxy-2-phenyl-acetophenone (DMPA), thereby enabling photolithographical patterning of the pre-ceramic polymer using UV lithography. SiCN fabrication includes thermosetting, crosslinking and pyrolysis. The technology is still under investigation for stability and improved performance. This work presents the preparation of SiCN films to be used as the body of a sensor for pressure measurements in high temperature environments. The sensor employs the phenomenon of drag effect. The pressure sensor consists of a slender sensitive element and a thick blocking element. The dimensions and thickness of the films depend on the intended application of the sensors. Fabrication methods of SiCN ceramics both as thin (about 40-60 µm) and thick (about 2-3 mm) films for high temperature applications are discussed. In addition, the influence of thermosetting and annealing processes on mechanical properties is investigated.

Effect of Supervised Exercise Program on Individuals in Peripheral Arterial Disease with Type 2 Diabetes Mellitus - A Systematic Review.

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is usually accompanied by various micro and macro vascular complications. Peripheral Arterial Disease (PAD) is one of the major complications of diabetes which is accountable for morbidity and mortality throughout the world. The first line of treatment in these individuals is life style modification and exercise. There is a dearth of literature on effect of supervised exercise program in PAD with T2DM on quality of life, walking impairment, change in Ankle Brachial Index (ABI) values. So, we conducted a systematic review to explore the available literature on supervised exercise program in PAD with T2DM. METHODS: We conducted a systematic review (PubMed, Web of Science, CINAHL and Cochrane) to summarise the evidence on a supervised exercise program in PAD with T2DM. Randomised and nonrandomised studies were included in the review. RESULTS: Three studies met the inclusion criteria. The outcomes taken into accounts by the studies were the quality of life, walking impairment questionnaire, Ankle brachial index. Neither of the studies matched in their supervised exercise program nor in their outcome. CONCLUSION: In conclusion, the data evaluating the supervised exercise program in PAD with T2DM is inadequate to determine its effect on this population. Future large-scale studies can be conducted on both subjective and objective outcomes of PAD with T2DM to have a better understanding of the condition and for a universally acceptable exercise program for these individuals which the healthcare practitioners can use in their practice. Prospero registration number: CRD42018112465.

Prevalence of peripheral arterial disease among type 2 diabetes mellitus in coastal Karnataka.

Peripheral Arterial Disease (PAD) is one of the leading complications of Type 2 Diabetes Mellitus (T2DM). According to American Heart Association, PAD is defined as, "a narrowing of peripheral arteries to the legs, stomach, arms and the head-most commonly the arteries of leg." The global prevalence for PAD with age adjusted prevalence is approximately 12%, and it affects relatively 8 to 12 million British people. The prevalence of PAD is 2-3 times higher in person with v/s without type 2 diabetes mellitus (T2DM). Various subjective and objective methods are available to diagnose PAD, which includes questionnaires for pain and quality of life as subjective and Ankle Brachial Index (ABI), toe brachial index (TBI), arterial doppler for objective. ABI is one of the most reliable and easy to carry out method in clinical setups to diagnose PAD. The normal range for ABI is 0.9-1.29, 0.91 to 0.99 are considered as borderline, 0.41 to 0.91 are considered as mild to moderate diseased and below 0.4 is severe PAD. The objective of the study is to estimate the prevalence of peripheral arterial disease with type 2 diabetes mellitus in coastal Karnataka. METHODOLOGY: A total of 317 participants were recruited for the study based on inclusion criteria. Ethical clearance was taken from the Institutional Ethics Committee. Participants were explained about the study and informed consent was obtained from the participants. Inclusion criteria was any individual with T2DM on medication. A subjective questionnaire specific to PAD was administered to the participants. Along with this the objective measure, ABI was done on the individuals. RESULT: The mean age of all the participants was 57.36 ±â€¯10.43 in years. The average Body Mass Index (BMI) was 24.62 ±â€¯11.80 in Kg/m2. The mean duration of diabetes was found to be 9.13 ±â€¯6.56 in years. The prevalence of peripheral arterial disease was found to be 8.52% in the study population. CONCLUSION: The prevalence of peripheral arterial disease was found to be 8.52% in the study population.

Serum Uric Acid Levels in Type 2 Diabetes Mellitus: Is There a Linear Relationship with Severity of Carotid Atherosclerosis?

AIMS: The aim of this study was to correlate serum uric acid (SUA) levels and carotid intima-media thickness (CIMT) in patients with type 2 diabetes mellitus (DM). SETTINGS AND DESIGN: This study was a cross-sectional observational study on 103 diabetic patients conducted from September 2015 to May 2017. SUBJECTS AND METHODS: We screened 103 patients with type 2 DM between the ages of 30-65 years. SUA levels and the CIMT were measured. The patients were divided into quartiles based on uric acid level. The CIMT of the quartiles is compared and analyzed. STATISTICAL ANALYSIS USED: Chi-squared test, Analysis of Variance, and Pearson's correlation. RESULTS: Uric acid levels were positively associated with CIMT (P = 0.001). The association remained significant after further adjustment for potential confounders. Strong correlation was found among them as depicted by correlation coefficient (r = 0.779). CONCLUSIONS: Carotid atherosclerosis as measured by IMT is associated with SUA levels in patients with type 2 DM.

Comparison between stylet and bougie with the C-MAC D-blade in cervical simulated immobility. A prospective randomized controlled trial

Introduction The C-MAC D-blade was designed for difficult airway intubation scenarios. To facilítate easier and faster endotracheal intubation in the laryngoscopy paradox, an introducer is preferred. Hence, we decided to conduct a study to compare the 60° angled C-MAC stylet and the gum elastic bougie as aids to intubation while using the C-MAC D-blade laryngoscope in a simulated difficult airway setting. Objective To compare the ease of oral intubation with the use of the C-MAC stylet (60° angled stylet) versus intubation performed over a bougie inserted using the C-MAC D-blade guidance in patients with simulated restricted cervical mobility. Method Prospective, randomized controlled single-center study. Intubation using the C-MAC D-blade laryngoscope was performed in 48 surgical patients randomly assigned to 2 groups of 24 each: Stylet group, Group S (using 60° angled stylet) and Bougie group, Group B (using bougie) after providing manual in-line stabilization to restrict cervical mobility. The Mann-Whitney U test and the Chi square test were used as applicable. Results The use of stylet resulted in easier (Group S 75% vs. Group B 16.7%) and faster (Group S 26.83 ± 8.61s vs. Group B 47.18 ± 16.46s) intubation with fewer attempts compared to group B. Both groups experienced a similar hemodynamic stress response to intubation. Conclusions The 60° angled C-MAC Stylet is a more effective and time-saving intubation aid with C-MAC D-blade compared to bougie.

Introducción: El videolaringoscopio C-MAC D-blade se diseñó para los casos de intubación de la vía aérea difícil. Para facilitar una intubación más rápida y sencilla en la paradoja de la laringoscopía se prefiere un introductor. Por tanto, decidimos realizar un estudio para comparar el estilete de 60° C-MAC y el bougie elástico de goma como ayudas para la intubación utilizando el laringoscopio C-MAC D-blade en una situación simulada de vía aérea difícil. Objetivo: Comparar la facilidad de intubación oral mediante el uso del estilete del C-MAC (estilete angulado de 60°) con la intubación realizada sobre un bougie insertado con la guía del C-MAC D0-blade en pacientes con restricción simulada de la movilidad cervical. Métodos: Estudio prospectivo, aleatorizado y controlado realizado en un solo centro. Se realizó intubación utilizando el laringoscopio C-MAC D-blade D en 48 pacientes quirúrgicos asignados aleatoriamente a 2 grupos de 24 cada uno: grupo de estilete, grupo S (con el estilete angulado de 60°) y el grupo de bougie o grupo B (con bougie) después de establecer una estabilización manual del eje para restringir la movilidad cervical. Se aplicaron las pruebas U de Mann-Whitney U y de Chi cuadrado según correspondiera. Resultados: Con el estilete fue más fácil (Grupo S 75% vs. Grupo B 16.7%) y más rápida (Grupo S 26.83 ± 8.61s vs. Grupo B 47.18 ± 16.46s) la intubación, requiriéndose un menor número de intentos en comparación con el Grupo B. Los dos grupos experimentaron un estrés hemodinámico similar en respuesta a la intubación. Conclusiones: El estilete angulado de 60° C-MAC es una ayuda más efectiva y ahorra más tiempo con el C-MAC D-blade en comparación con el bougie.

Paroxysmal Atrial Fibrillation due to Venomous Snake Bite.

Snake bites are common all around the world with a great prevalence in South Asia and the Indian subcontinent. Although they are associated with common complications such as local swelling, bleeding at site of bite, coagulopathy, etc., few rare cardiac complications such as myocardial infarctions and arrhythmias have also been described in literature. The following is a case report of a patient who had a snake bite with a Russell's viper which resulted in atrial fibrillation, which resolved on treatment with anti snake venom.

A Rare Cause of Anaemia in HIV/AIDS.

Patients living with HIV are commonly diagnosed with anaemia which can have various aetiologies. However, one of the rare causes of anaemia in such patients is Auto Immune Haemolytic Anaemia (AIHA), which is difficult to diagnose due to the absence of reticulocytosis in HIV patients. Such patients can be treated with corticosteroids which can gradually be tapered off over a period of time. The following is a case of a 52-year-old male living with HIV who was diagnosed to have AIHA and was successfully treated with steroids.

Transient Thyrotoxicosis in Molar Pregnancy.

Molar pregnancy is one of the components of a broader spectrum of diseases known as Gestational Trophoblastic Disease (GTD), presenting with amenorrhoea and irregular bleeding which may be rarely associated with passage of vesicles per vagina. However, it can rarely be associated with hyperthyroidism, which may be associated with clinical features of hyperthyroidism. The following is a report of a 20-year-old woman who presented with amenorrhea followed by irregular bleeding per vagina, thyromegaly and abnormal levels of thyroid hormones. Transvaginal ultrasound revealed features consistent with molar pregnancy. A suction evacuation was done following which serum levels of ß-hCG reduced and the levels of thyroid hormones also reduced. On follow up, six weeks later, ß-hCG and thyroid hormones were within normal limits. The case and relevant literature are presented here.

Enteric Cholestatic Hepatitis with Ascites: A Rare Entity.

Typhoid fever is a very common illness in developing countries. Patients most often present with a history of fever, vomiting, anorexia, abdominal pain, etc. Rarely there is hepatic involvement due to the disease process. This is a case report of a 26-year-old male who had presented with fever, jaundice and ascites. The widal titres were found to be within normal limits (1:80) however the patient was found to have Salmonella typhi on ascitic fluid culture. The patient was treated with the appropriate antibiotics and was later discharged.