Conformational changes of fibronectin deposited on poly(methyl methacrylate) and poly(acrylic acid) block copolymers with identical chemical compositions were detected using an antibody-functionalized atomic force microscope (AFM) tip. Based on the antibody-protein adhesive force maps and phase imaging, it was found that the nanomorphology of the triblock copolymer is conducive to the exposure of the arginine-glycine-aspartic acid (RGD) groups in fibronectin. For the first time, X-ray photoelectron spectroscopy (XPS) was used to elucidate surface chemical composition and confirm AFM results. The findings demonstrate that block copolymer nanomorphology can be used to regulate protein conformation and potentially cellular response.
block copolymers; atomic force microscopy; X-ray photoelectron spectroscopy; protein conformation
A 22-year-old male student with no past medical illness, presented with acute onset dysarthria, binocular diplopia, and dysphagia over 10 hours. On examination, he had tachycardia, hypertension, generalized hyper-reflexia, and bilateral pupil sparing oculomotor, troclear, abducens, trigeminal, facial, glossopharyngeal, and vagus nerve palsy. Rest examination was unremarkable. Facial nerve conduction study (NCS) showed decreased amplitude bilaterally and neurogenic pattern on electromyography. Limb NCS, repetitive nerve stimulation, neostigmine test, brain magnetic resonance imaging, cerebrospinal fluid, and biochemical tests were normal. Only positive tests were low thyroid-stimulating hormone (TSH) (<0.01), high free T3 (19.2 pmol/L), and high free T4 (39.2 pmol/L). Thyroid ultrasonography, anti-thyroid peroxidase, and anti-thyroglobulin antibody were normal. Patient was treated with anti-thyroid drugs, with which he completely recovered in 2 months. Though many cases with thyrotoxic myopathy have been reported, only few mention neuropathic cause of dysphagia or polyneuritis cranialis. Getting done thyroid function tests may be helpful in patients with polyneuritis cranialis of uncertain etiology.
Bulbar palsy; dysphagia; neuropathy; polyneuritis cranialis; thyrotoxicosis
Superoleophobic surfaces are of interest for anti-fouling, self-cleaning, anti-smudge, low-drag, anti-fog, and oil-water separation applications. Current bioinspired surfaces are of limited use due to a lack of mechanical durability. A so-called layer-by-layer approach, involving charged species with electrostatic interactions between layers, can provide the flexibility needed to improve adhesion to the substrate while providing a low surface tension coating at the air interface. In this work, a polyelectrolyte binder, SiO2 nanoparticles, and a fluorosurfactant are spray deposited separately to create a durable, superoleophobic coating. Polydiallyldimethylammonium chloride (PDDA) polyelectrolyte was complexed with a fluorosurfactant layer (FL), which provides oil repellency while being hydrophilic. This oleophobic/superhydrophilic behavior was enhanced through the use of roughening with SiO2 particles resulting in a superoleophobic coating with hexadecane contact angles exceeding 155° and tilt angles of less than 4°. The coating is also superhydrophilic, which is desirable for oil-water separation applications. The durability of these coatings was examined through the use of micro- and macrowear experiments. These coatings currently display characteristics of transparency. Fabrication of these coatings via the layer-by-layer technique results in superoleophobic surfaces displaying improved durability compared to existing work where either the durability or the oil-repellency is compromised.
Nano-objects have been investigated for drug delivery, oil detection, contaminant removal, and tribology applications. In some applications, they are subjected to friction and deformation during contact with each other and their surfaces on which they slide. Experimental studies directly comparing local and global deformation are lacking. This research performs nanoindentation (local deformation) and compression tests (global deformation) with a nanoindenter (sharp tip and flat punch, respectively) on molybdenum disulfide (MoS2) multi-walled nanotubes (MWNTs), ~500 nm in diameter. Hardness of the MoS2 nanotube was similar to bulk and does not follow the “smaller is stronger” phenomenon as previously reported for other nano-objects. Tungsten disulfide (WS2) MWNTs, ~300 nm in diameter and carbon nanohorns (CNHs) 80–100 nm in diameter were of interest and also selected for compression studies. These studies aid in understanding the mechanisms involved during global deformation when nano-objects are introduced to reduce friction and wear. For compression, highest loads were required for WS2 nanotubes, then MoS2 nanotubes and CNHs to achieve the same displacement. This was due to the greater number of defects with the MoS2 nanotubes and the flexibility of the CNHs. Repeat compression tests of nano-objects were performed showing a hardening effect for all three nano-objects.
Acute disseminated encephalomyelitis (ADEM) is commonly seen after viral and bacterial infections, immunization, and Plasmodium falciparum (PF) malaria. Plasmodium vivax (PV) rarely causes ADEM. We report a 14-year-old female patient who presented with acute onset bilateral cerebellar ataxia and optic neuritis, 2 weeks after recovery from PV. Magnetic resonance imaging showed bilateral cerebellar hyperintensities suggestive of ADEM. No specific viral etiology was found on cerebrospinal fluid examination. Patient responded well to treatment without any sequelae. Thus, PV too is an important cause of ADEM along with PF. Two of the previously reported cases had co-infection with falciparum malaria. The only other two reported cases, as also this patient, are from Asia. A geographical or racial predisposition needs to be evaluated. Also, a possibility of post-PV delayed cerebellar ataxia, which is classically described post-PF infection, may be considered as it may be clinically, radiologically, and prognostically indistinguishable from a milder presentation of ADEM.
Acute disseminated encephalomyelitis; delayed cerebellar ataxia; malaria; Plasmodium vivax malaria
Guillain–Barre syndrome (GBS) is rarely reported in children with acute lymphoblastic leukemia (ALL) and may be difficult to differentiate from vincristine induced neuropathy. Only few case reports highlighted GBS with ALL. We report a 10-year-old male child who was a diagnosed case of ALL since 3 month on chemotherapy. At 3rd week of chemotherapy, he developed rapidly progressive ascending motor quadriparesis over 2 days. Clinical and electrophysiology revealed acute motor axonal neuropathy (AMAN) variant of GBS. He was treated with intravenous immunoglobulin (2 g/kg) without discontinuing chemotherapy. Complete recovery took 12 weeks despite immunotherapy, and it was corroborating to slow remission. We concluded that AMAN variant is usually present in B-cell type ALL, may be causal for GBS and it takes 6–16 weeks to complete recovery which may correspond to remission of ALL. However, it needs to be studied. We also present a meta-analysis of previously reported cases of GBS in ALL.
Acute lymphoblastic leukemia; chemotherapy; children; Guillain–Barre syndrome
Neurocysticercosis, the most common parasitic infection of the nervous system, is known to affect the brain, eyes, muscular tissues and subcutaneous tissues. However, it is very rare for patients with ocular cysts to have concomitant cerebral cysts. Also, the dominant clinical manifestation of patients with cerebral cysts is either seizures or headache. We report a patient who presented with acute monocular painless vision loss due to intraocular submacular cysticercosis, who on investigation had multiple cerebral parenchymal cysticercal cysts, but never had any seizures. Although such a vision loss after initiation of antiparasitic treatment has been mentioned previously, acute monocular vision loss as the presenting feature of ocular cysticercosis is rare. We present a brief review of literature along with this case report.
Acute permanent monocular vision loss; cysticercosis; intraocular neurocysticercosis; neurocysticercosis; subretinal neurocysticercosis; sudden monocular vision loss; Taenea solium
Cluster headache (CH) is uncommon and most painful of all primary headaches, and continues to be managed suboptimally because of wrong diagnosis. It needs to be diagnosed correctly and specifically treated. There are few studies and none from this region on CH.
Materials and Methods:
To study the detailed clinical profile of CH patients and to compare them among both the genders. Study was conducted at Mahatma Gandhi hospital, Jodhpur (from January 2011to December 2013). Study comprises 30 CH patients diagnosed according to International Headache Society guidelines (ICHD-II). Routine investigations and MRI brain was done in all patients. All measurements were reported as mean ± SD. Categorical variables were compared using the Chi-square test, and continuous variables were compared using Student's t-test. SPSS for Windows, Version 16.0, was used for statistical analyses with the significance level set at P = 0.05.
M: F ratio was 9:1. Age at presentation was from 22-60 years (mean - 38 years). Latency before diagnosis was 3 months-12 years (mean - 3.5 years). All suffered from episodic CH and aura was found in none. Pain was strictly unilateral (right-19, left-11), predominantly over temporal region-18 (60%). Pain intensity was severe in 27 (90%) and moderate in 3 (10%). Pain quality was throbbing in 12 (40%). Peak intensity was reached in 5 minutes-30 minutes and attack duration varied from 30 minutes to 3 hours (mean - 2.45 hours). Among autonomic features, conjunctival injection-23 (76.6%) and lacrimation-25 (83.3%) were most common. Restlessness during episode was found in 80%. CH duration varied from 10 days to 12 weeks. Circadian periodicity for attacks was noted in 24 (80%).
Results are consistent with other studies on many accounts, but is different from Western studies with respect to low frequency of family history, chronic CH, restlessness and aura preceeding the attack. Detailed elicitation of history is paramount as misdiagnosis is common.
Autonomic; cluster headache; trigeminal
We describe a patient who presented with a history of lightning strike injury. Following the injury, he sustained acute right upper limb weakness with pain. Clinically, the lesion was located to the upper and middle trunk of the right brachial plexus, and the same confirmed with electrophysiological studies. Nerve damage due to lightning injuries is considered very rare, and a plexus damage has been described infrequently, if ever. Thus, the proposed hypothesis that lightning rarely causes neuropathy, as against high-voltage electric current, due to its shorter duration of exposure not causing severe burns which lead to nerve damage, needs to be reconsidered.
Axonal plexopathy; brachial plexopathy; lightning strike
Aim: To evaluate the comparative efficacy and safety of ramipril 5mg plus hydrochlorothiazide 12.5mg (R + HCTZ), telmisartan 40mg plus hydrochlorothiazide12.5mg (T + HCTZ) and ramipril 2.5mg plus telmisartan 20mg plus hydrochlorothiazide12.5mg (R + T + HCTZ) in patients with stage 2 hypertension.
Materials and Methods: A prospective, open label, randomized comparative study was conducted to study the comparative efficacy and safety of R+HCTZ (group 1), T+HCTZ (group 2)and R+T+TCTZ (group3) in 88 patients with stage 2 hypertension without co-morbid conditions. Echocardiography was done to assess left ventricular function. Patients were followed up to 24 weeks and any ADR occurring in this period was recorded.
Results: All the three treatment groups showed significant fall in both systolic and diastolic blood pressure compared to the baseline scores (p<0.0001). Intergroup comparison did not reveal any significant difference. Total number of adverse drug events reported were 15. Group III had higher percentage ADRs. Dry cough (8) was most common ADR. The echocardiography parameters did not change from baseline values with all three treatment regimens.
Conclusion: All three medications were of equal efficacy in patients with stage 2 hypertension without co morbid conditions, failing to prove superiority over each other.
Hydrochlorothiazide; Ramipril; Stage 2 hypertension; Telmisartan; Triple therapy
The drag of fluid flow at the solid–liquid interface in the micro/nanoscale is an important issue in micro/nanofluidic systems. Drag depends on the surface wetting, nanobubbles, surface charge and boundary slip. Some researchers have focused on the relationship between these interface properties. In this review, the influence of an applied voltage on the surface wettability, nanobubbles, surface charge density and slip length are discussed. The contact angle (CA) and contact angle hysteresis (CAH) of a droplet of deionized (DI) water on a hydrophobic polystyrene (PS) surface were measured with applied direct current (DC) and alternating current (AC) voltages. The nanobubbles in DI water and three kinds of saline solution on a PS surface were imaged when a voltage was applied. The influence of the surface charge density on the nanobubbles was analyzed. Then the slip length and the electrostatic force on the probe were measured on an octadecyltrichlorosilane (OTS) surface with applied voltage. The influence of the surface charge on the boundary slip and drag of fluid flow has been discussed. Finally, the influence of the applied voltage on the surface wetting, nanobubbles, surface charge, boundary slip and the drag of liquid flow are summarized. With a smaller surface charge density which could be achieved by applying a voltage on the surface, larger and fewer nanobubbles, a larger slip length and a smaller drag of liquid flow could be found.
atomic force microscopy; boundary slip; electrowetting; nanobubbles; surface charge
Paraneoplastic cerebellar degeneration (PCD) is a rare neurological disorder characterized by a widespread loss of Purkinje cells associated with a progressive pancerebellar dysfunction. PCD often precedes the cancer diagnosis by months to years. Here, we report a case of 44-year old postmenopausal woman who presented with PCD symptoms and high levels of anti-Yo antibodies titer since 8 months. We failed to conclude any neoplastic focus after thorough laboratory and imaging study. She minimally responded to methylprednisolone and immunoglobulin therapies. Despite therapy she was severely disabled. Planned abdominal hysterectomy with bilateral salpingo-oophorectomy (AHBSO) was done, histology revealed grade IIA borderline serous papillary carcinoma of ovary. Her neurological deficit responded dramatically to AHBSO. It is first case report who emphasize the response of AHBSO with presentation of anti-Yo antibody-mediated PCD and hidden nidus in post menopausal women.
Anti-Yo; abdominal hysterectomy with bilateral salpingo-oophorectomy; paraneoplastic cerebellar degeneration; postmenopausal
Nanoscale research of bulk solid surfaces, thin films and micro- and nano-objects has shown that mechanical properties are enhanced at smaller scales. Experimental studies that directly compare local with global deformation are lacking. In this research, spherical Au nanoparticles, 500 nm in diameter and 100 nm thick Au films were selected. Nanoindentation (local deformation) and compression tests (global deformation) were performed with a nanoindenter using a sharp Berkovich tip and a flat punch, respectively. Data from nanoindentation studies were compared with bulk to study scale effects. Nanoscale hardness of the film was found to be higher than the nanoparticles with both being higher than bulk. Both nanoparticles and film showed increasing hardness for decreasing penetration depth. For the film, creep and strain rate effects were observed. In comparison of nanoindentation and compression tests, more pop-ins during loading were observed during the nanoindentation of nanoparticles. Repeated compression tests of nanoparticles were performed that showed a strain hardening effect and increased pop-ins during subsequent loads.
gold (Au); Hall–Petch; hardness; nanoindentation; nano-objects
In this investigation, scanning electron microscopy was used to characterize the microstructure on the surfaces of animal heart valve cusps/leaflets. The results showed that though these surfaces appear smooth to the naked eye, they are actually comprised of a double hierarchical structure consisting of a cobblestone-like microstructure and nano-cilia along with mastoids with a directional arrangement. Such nanostructures could play a very important role in the hemocompatibility characteristics of heart valves. On this basis, the model of the microstructure was constructed and theoretical analysis was used to obtain optimal geometric parameters for the rough surface of artificial valve cusps/leaflets. This model may help improve reconstructive techniques and it may be beneficial in the design and fabrication of valve substitutes or partial substitutes. Namely, the model may help ameliorate heart valve replacement surgery.
contact angle; geometric parameter; heart valve; hemocompatibility; microstructure
In most beetles, the hind wings are thin and fragile; when at rest, they are held over the back of the beetle. When the hind wing unfolds, it provides the necessary aerodynamic forces for flight. In this paper, we investigate the hydraulic mechanism of the unfolding process of the hind wings in Dorcus titanus platymelus (Oder: Coleoptera). The wing unfolding process of Dorcus titanus platymelus was examined using high speed camera sequences (400 frames/s), and the hydraulic pressure in the veins was measured with a biological pressure sensor and dynamic signal acquisition and analysis (DSA) during the expansion process. We found that the total time for the release of hydraulic pressure during wing folding is longer than the time required for unfolding. The pressure is proportional to the length of the wings and the body mass of the beetle. A retinal camera was used to investigate the fluid direction. We found that the peak pressures correspond to two main cross-folding joint expansions in the hind wing. These observations strongly suggest that blood pressure facilitates the extension of hind wings during unfolding.
beetle; hind wing; unfolding; hydraulic mechanism; micro air vehicles (MAVs)
The conformational changes of fibronectin deposited on various block copolymers where one block is composed of poly(methyl methacrylate) (PMMA) and the other block is either poly(acrylic acid) (PAA) or poly(2-hydroxyethyl methacrylate) (PHEMA) were investigated using a functionalized atomic force microscope (AFM) tip. The tip was modified with an antibody sensitive to the exposure of the arginine-glycine-aspartic acid (RGD) groups in fibronectin. By studying the adhesive interactions between the antibody and the proteins adsorbed on the block copolymer surface and phase imaging, it was found that the triblock copolymers PAA-b-PMMA-b-PAA and PMMA-b-PHEMA-b-PMMA, which both have large domain sizes, are conducive to the exposure of the fibronectin RGD groups on the surface. Based on these results, it is concluded that the surface chemistry as well as the nanomorphology dictated by the block copolymer arrangement could both tune protein conformation and orientation and optimize cell adhesion to the biomaterial surface.
block copolymers; atomic force microscopy; protein conformation; fibronectin; antibody
Nano-object additives are used in tribological applications as well as in various applications in liquids requiring controlled manipulation and targeting. On the macroscale, nanoparticles in solids and liquids have been shown to reduce friction and wear. On the nanoscale, atomic force microscopy (AFM) studies have been performed in single- and multiple-nanoparticle contact, in dry environments, to characterize friction forces and wear. However, limited studies in submerged liquid environments have been performed and further studies are needed. In this paper, spherical Au nanoparticles were studied for their effect on friction and wear under dry conditions and submerged in water. In single-nanoparticle contact, individual nanoparticles, deposited on silicon, were manipulated with a sharp tip and the friction force was determined. Multiple-nanoparticle contact sliding experiments were performed on nanoparticle-coated silicon with a glass sphere. Wear tests were performed on the nanoscale with AFM as well as on the macroscale by using a ball-on-flat tribometer to relate friction and wear reduction on the nanoscale and macroscale. Results indicate that the addition of Au nanoparticles reduces friction and wear.
AFM; drug delivery; friction; gold nanoparticles; MEMS/NEMS; nanomanipulation
Skin can be damaged by the environment easily. Skin cream is an effective and rapid way to moisten the skin by changing the skin surface properties. Rat skin and pig skin are common animal models for studies and were used as skin samples in this study. The nano- and macroscale friction and durability of damaged skin were measured and compared with those of virgin (intact/undamaged) skin. The effect of skin cream on friction and durability of damaged and virgin skin samples is discussed. The effects of velocity, normal load, relative humidity and number of cycles were studied. The nanoscale studies were performed by using atomic force microscope (AFM), and macroscale studies were performed by using a pin-on-disk (POD) reciprocating tribometer. It was found that damaged skin has different mechanical properties, surface roughness, contact angle, friction and durability compared to that of virgin skin. But similar changes occur after skin cream treatment. Rat and pig skin show similar trends in friction and durability.
atomic force microscopy; damaged skin; pig skin; rat skin; skin cream
Obstructive sleep apnea (OSA) is associated with increased risk for metabolic syndrome in both adults and children. In adults with OSA, serum levels of fatty acid binding protein 4 (FABP4) are elevated and associated with the degree of metabolic insulin resistance, independent of obesity. Therefore, we assessed plasma FABP4 levels and FABP4 allelic variants in obese and non-obese children with and without OSA.
A total of 309 consecutive children ages 5-8 years were recruited. Children were divided into those with OSA and without OSA (NOSA) based on the apnea-hypopnea index (AHI). Subjects were also subdivided into obese (OB) and non-obese (NOB) based on BMI z score). Morning fasting plasma FABP4 levels were assayed using ELISA, and 11 single-nucleotide polymorphisms (SNPs) within the FABP4 region were genotyped.
Morning plasma FABP4 levels were increased in all children with OSA, even in NOB children. However, plasma FABP4 levels were strongly associated with BMI z score. Of the 11 SNPs tested, the frequency of rs1054135 (A/G) minor allele (A) was significantly increased in OSA. This SNP was also associated with increased plasma FABP4 levels in both OSA and obese subjects. The minor allele frequency of all other SNPs was similar in OSA and NOSA groups.
Childhood obesity and OSA are associated with higher plasma FABP4 levels and thus promote cardiometabolic risk. The presence of selective SNP (e.g., rs1054135) in the FABP4 gene may account for increased plasma FABP4 levels in the context of obesity and OSA in children.
Obstructive sleep apnea (OSA) is a prevalent condition and strongly associated with metabolic disorders. Sleep fragmentation (SF) is a major consequence of OSA, but its contribution to OSA-related morbidities is not known. We hypothesized that SF causes specific perturbations in transcriptional networks of visceral fat cells, leading to systemic metabolic disturbances. We simultaneously profiled visceral adipose tissue mRNA and miRNA expression in mice exposed to 6 hours of SF during sleep, and developed a new computational framework based on gene set enrichment and network analyses to merge these data. This approach leverages known gene product interactions and biologic pathways to interrogate large-scale gene expression profiling data. We found that SF induced the activation of several distinct pathways, including those involved in insulin regulation and diabetes. Our integrative methodology identified putative controllers and regulators of the metabolic response during SF. We functionally validated our findings by demonstrating altered glucose and lipid homeostasis in sleep-fragmented mice. This is the first study to link sleep fragmentation with widespread disruptions in visceral adipose tissue transcriptome, and presents a generalizable approach to integrate mRNA-miRNA information for systematic mapping of regulatory networks.
The adhesive interactions of block copolymers composed of poly(methyl methacrylate) (PMMA)/poly(acrylic acid) (PAA) and poly(methyl methacrylate)/poly(2-hydroxyethyl methacrylate) (PHEMA) with the proteins fibronectin, bovine serum albumin and collagen were studied by atomic force microscopy. Adhesion experiments were performed both at physiological pH and at a slightly more acidic condition (pH 6.2) to model polymer–protein interactions under inflammatory or infectious conditions. The PMMA/PAA block copolymers were found to be more sensitive to the buffer environment than PMMA/PHEMA owing to electrostatic interactions between the ionized acrylate groups and the proteins. It was found that random, diblock and triblock copolymers exhibit distinct adhesion profiles although their chemical compositions are identical. This implies that biomaterial nanomorphology can be used to control protein–polymer interactions and potentially cell adhesion.
block copolymers; atomic force microscopy; protein adhesion
Objectives: Obesity is associated with high levels proinflammatory cytokines like tumour necrosis factor alpha (TNF-α), which may play an important role in the genesis of insulin resistance. We evaluated the relationship of −308G/A polymorphism of TNF-α gene with obesity and insulin resistance in Asian Indians in north India.
Methods: This cross-sectional study included 151 apparently healthy individuals (79 males, 72 females) 18–50 yrs of age from New Delhi, India. Body composition by dual-energy x-ray absorptiometry (DEXA) and abdominal fat by magnetic resonance imaging (MRI) were measured. Biochemical measurements included OGTT, lipids, fasting insulin, hs-CRP and TNF-α levels. We analysed −308G/A polymorphism of TNF-α gene and studied its association with obesity and biochemical parameters.
Results: At comparable BMI, abdominal obesity was more prevalent in females (50%) as compared to males (20%). The wild genotype (GG) was present in 78.8%, GA in 17.9%, and AA in 3.3% subjects. Measures of body composition, abdominal fat distribution, lipids, insulin, hs-CRP and TNF-α levels were not influenced by the presence of −308G/A polymorphism. Serum TNF-α levels correlated significantly with fasting insulin in both genders.
Conclusion: TNF-α levels correlate with fasting insulin but not with indicators of body composition in Asian Indians. The −308G/A polymorphism of TNF-α gene is not associated with differences in the serum levels of TNF-α in Asian Indians.
TNF-α gene polymorphism; obesity; abdominal fat; insulin resistance; Asian Indians
Biocompatible polymers are known to act as scaffolds for the regeneration and growth of bone. Block copolymers are of interest as scaffold materials because a number of the blocks are biocompatible, and their nanostructure is easily tunable with synthetic techniques. In this paper, we report the synthesis of a novel class of biomaterials from block copolymers containing a hydrophobic block of methyl methacrylate and a hydrophilic block of either acrylic acid, dimethyl acrylamide, or 2-hydroxyethyl methacrylate. The block copolymers were synthesized using a combination of reversible addition-fragmentation chain transfer (RAFT) polymerization and click chemistry. Since the surface morphology is critical for successful cell growth, atomic force microscopy (AFM) studies were conducted for selected block copolymers. The topography, phase angle and friction maps were obtained in dry and physiological buffer environments to study the morphology. Results of AFM imaging identified the presence of polymer domains corresponding to the copolymer components. The distribution of nanoscale features in these block copolymers are comparable to those found on other surfaces that exhibit favorable cell adhesion and growth. In physiological buffer medium, the hydrophilic component of the block copolymer (acrylic acid or hydroxyethyl methacrylate) appear to be present in greater amounts on the surface as a consequence of water absorption and swelling.
block copolymers; RAFT; click coupling; atomic force microscopy