Transcutaneous electrical nerve stimulation (TENS) for pain management in sickle cell disease.

BACKGROUND: Sickle cell disease (SCD), one of the most common inherited disorders, is associated with vaso-occlusive pain episodes and haemolysis leading to recurrent morbidity, hospital admissions and work or school absenteeism. The crises are conventionally treated with opioids, non-opioids and other adjuvants with the risk of developing complications, addictions and drug-seeking behaviour. Different non-pharmacological treatments, such as transcutaneous electrical nerve stimulation (TENS) have been used for managing pain in other painful conditions. Hence, the efficacy of TENS for managing pain in SCD needs to be reviewed. OBJECTIVES: To assess the benefits and harms of TENS for managing pain in people with SCD who experience pain crises or chronic pain (or both). SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Register, comprising of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries and the reference lists of relevant articles and reviews. Date of the last search: 26 Febraury 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs, where TENS was evaluated for managing pain in people with SCD. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility of the trials identified by the literature searches according to the inclusion criteria. Two review authors then independently extracted data, assessed for risk of bias using the Cochrane standard tool and rated the quality of evidence using the GRADE guidelines. MAIN RESULTS: One double-blind cross-over RCT with 22 participants with SCD (aged 12 to 27 years) was eligible for inclusion. Following stratification into four pain crises severity grades, participants were then randomised to receive TENS or placebo (sham TENS). The trial was concluded after 60 treatment episodes (30 treatment episodes of each treatment group). There is a lack of clarity regarding the trial design and the analysis of the cross-over data. If a participant was allocated to TENS treatment for an episode of pain and subsequently returned with a further episode of a similar degree of pain, they would then receive the sham TENS treatment (cross-over design). For those experiencing a pain episode of a different severity, it is not clear whether they were re-randomised or given the alternate treatment. Reporting and analysis was based on the total number pain events and not on the number of participants. It is unclear how many participants were crossed over from the TENS group to the sham TENS group and vice versa. The trial had a high risk of bias regarding random sequence generation and allocation concealment; an unclear risk regarding the blinding of participants and personnel; and a low risk regarding the blinding of the outcome assessors and selective outcome reporting. The trial was small and of very low quality; furthermore, given the issue with trial design we were unable to quantitatively analyse the data. Therefore, we present only a narrative summary and caution is advised in interpreting the results. In relation to our pre-defined primary outcomes, the included trial did not report pain relief at two to four weeks post intervention. The trial authors reported that no difference was found in the changes in pain ratings (recorded at one hour and four hours post intervention) between the TENS and the placebo groups. In relation to our secondary outcomes, the analgesic usage during the trial also did not show any difference between groups. Given the quality of the evidence, we are uncertain whether TENS improves overall satisfaction as compared to sham TENS. The ability to cope with activities of daily living was not evaluated. Regarding adverse events, although one case of itching was reported in the TENS group, the site and nature of itching was not clearly stated; hence it cannot be clearly attributed to TENS. Also, two participants receiving 'sham' TENS reported a worsening of pain with the intervention. AUTHORS' CONCLUSIONS: Since we have only included one small and very low-quality trial, with a high risk of bias across several domains, we are unable to conclude whether TENS is harmful or beneficial for managing pain in people with SCD. There is a need for a well-designed, adequately-powered, RCT to evaluate the role of TENS in managing pain in people with SCD.

Metabolic adaptability in liver and gastrocnemius muscle of mice following subacute lead toxicity.

Lead (Pb) is one of several environmental pollutants that adversely affect human health by producing toxicity at the tissue level. The aim of the study was to understand the effects of Pb on the metabolic profiles of liver and gastrocnemius muscle of mice in relation to carbohydrate and fat metabolisms. Swiss albino mice were chosen and divided into two groups, control and Pb-treated. The Pb-treated animals were exposed to Pb at a dose of 5 mg/kg body weight for 30 days orally, which resulted in hypoglycemia, glycosuria, and increased glycogenolysis in the liver and gastrocnemius muscle of treated mice. Pyruvic acid, the end product of glycolysis decreased in muscular tissue and increased in the liver. Additionally, the activity of G-6Pase was depressed in the liver, whereas lactate dehydrogenase activity was increased in skeletal muscle only. An adaptive mechanism was initiated by stimulating glycogenolytic and retarding glycolytic activity in the liver and also by alteration of liver and muscle pyruvate dehydrogenase activity along with increased activity of malate dehydrogenase in skeletal muscle. There was enhancement of succinate dehydrogenase and nicotinamide adenine dinucleotide phosphate oxidase activities in the studied tissues. Interestingly, cholesterol, high-density lipoprotein, and low-density lipoprotein levels were elevated, whereas those of triglycerides were decreased in Pb-treated mice serum. The activities of fatty acid synthase and glyceraldehyde 3 phosphate dehydrogenase were depressed in Pb-treated mice livers. Pb also significantly altered the morphological features of the liver, skeletal muscle, and pancreas. These data suggested that subacute Pb exposure was responsible for metabolic modulation in an adaptive fashion in the liver and skeletal muscle of mice.

Catalytic Reductive Vinylidene Transfer Reactions.

Methylenecyclopropanes are important synthetic intermediates that possess strain energies exceeding those of saturated cyclopropanes by >10 kcal/mol. This report describes a catalytic reductive methylenecyclopropanation reaction of simple olefins, utilizing 1,1-dichloroalkenes as vinylidene precursors. The reaction is promoted by a dinuclear Ni catalyst, which is proposed to access Ni2(vinylidenoid) intermediates via C-Cl oxidative addition.

Evaluating the Effect of Catalyst Nuclearity in Ni-Catalyzed Alkyne Cyclotrimerizations.

An evaluation of catalyst nuclearity effects in Ni-catalyzed alkyne oligomerization reactions is presented. A dinuclear complex, featuring a Ni-Ni bond supported by a naphthyridine-diimine (NDI) ligand, promotes rapid and selective cyclotrimerization to form 1,2,4-substituted arene products. Mononickel congeners bearing related N-donor chelates (2-iminopyridines, 2,2'-bipyridines, or 1,4,-diazadienes) are significantly less active and yield complex product mixtures. Stoichiometric reactions of the dinickel catalyst with hindered silyl acetylenes enable characterization of the alkyne complex and the metallacycle that are implicated as catalytic intermediates. Based on these experiments and supporting DFT calculations, the role of the dinuclear active site in promoting regioselective alkyne coupling is discussed. Together, these results demonstrate the utility of exploring nuclearity as a parameter for catalyst optimization.

Myoepithelial neoplasm of nasal cavity: an uncommon tumor presenting with an unusual clinical presentation.

Myoepithelial tumors are rare malignant tumors of salivary glands with uncertain biological behaviors and clinical course. Parotid gland is the common involvement site. In this article, we present a rare case of myoepithelial neoplasm of nasal cavity in an 11-year-old boy in the light of literature data.

Evanescent wave assisted nanomaterial coating.

In this work we present a novel nanomaterial coating technique using evanescent wave (EW). The gradient force in the EW is used as an optical tweezer for tweezing and self-assembling nanoparticles on the source of EW. As a proof of the concept, we have used a laser coupled etched multimode optical fiber, which generates EW for the EW assisted coating. The section-wise etched multimode optical fiber is horizontally and superficially dipped into a silver/gold nanoparticles solution while the laser is switched on. The fiber is left until the solution recedes due to evaporation leaving the fiber in air. The coating time usually takes 40-50 min at room temperature. The scanning electron microscope image shows uniform and thin coating of self-assembled nanoparticles due to EW around the etched section. A coating thickness <200 nm is achieved. The technique could be useful for making surface-plasmon-resonance-based optical fiber probes and other plasmonic circuits.

Structural studies of arginine induced enhancement in the activity of T7 RNA polymerase.

Addition of arginine enhances the activity of the enzyme T7 RNA polymerase. Different methods have been employed to understand the enhancement in the light of arginine induced alteration of the tertiary structure. The increase in activity of the enzyme reaches a maximum value around a concentration of 125 mM arginine. Fluorescence, circular dichroism and dynamic light scattering studies indicate an alteration in the tertiary structure of the enzyme. Enthalpy change as a function of input concentration of arginine to a fixed concentration of the enzyme (5 µM) shows a dip at 100 mM concentration of arginine. Differential scanning calorimetric studies of the denaturation of the enzyme in absence and presence of arginine indicates arginine induced destabilization of the C-terminal domain of the enzyme. Structural alterations induced by arginine have been compared with those induced by the denaturant guanidine hydrochloride.

Optical fiber tip for field-enhanced second harmonic generation.

We propose a simple optical fiber tip for field-enhanced second harmonic generation (SHG). The tip shows nonlinear phenomena of SHG over a wide range of sources, at least from 630 to 830 nm. The optical field corresponding to the second harmonic appears as a nondiffracting bottle beam with voids due to the surface curvature of the tip. The field-enhanced second harmonic can also induce surface plasmons, converting the tip to a plasmonic probe with reduced background signal. The tip can be useful in nanophotonics characterization. As an example, we demonstrate the tip's response as a surface-enhanced Raman spectroscopy probe.

Nickel-catalyzed insertions of vinylidenes into Si-H bonds.

A nickel-catalyzed reductive cyclization of 1,1-dichloroalkenyl silanes is reported. The products of this reaction are unsaturated five- or six-membered silacycles. Intermolecular variants are also described, providing access to trisubstituted vinyl silanes that are not accessible by alkyne hydrosilylation or sila-Heck-type processes. A variety of silanes can be utilized, including those that serve as nucleophilic partners in Hiyama cross-coupling reactions. Mechanistic studies using deuterium-labelled silanes are described.

Information Retrieval and Awareness about Evidence-Based Dentistry among Dental Undergraduate Students-A Comparative Study between Students from Malaysia and Finland.

BACKGROUND: A fundamental skill in education includes the ability to search for, evaluate, and synthesize information, and this cannot be underestimated in dental education. The aim of this study was to assess how dental students from Malaysia and Finland acquire scientific information and to compare their information retrieval skills. METHODS: Fourth and fifth-year dental students from Malaysia and Finland were invited to participate. A self-administered structured questionnaire including items about the use of information sources, subjective assessment of literature retrieval skills and knowledge was used. RESULTS: A total of 226 dental students participated in the survey: 131 from Malaysia and 95 from Finland. In both countries, the highest interest for data retrieval among students was found in the oral surgery specialty. The three most used sources of information among Malaysian students were personal lecture notes, dental textbooks, and colleagues; while Finnish students used colleagues, lecture notes, and current clinical guidelines. Students' knowledge of evidence-based practice was inadequate in both student groups. Though the majority of participants reported that they had good or passable skills in literature retrieval, more students from Finland judged themselves to have at least good skills compared to those from Malaysia. CONCLUSION: Dental education in both countries includes information retrieval studies and mandatory research projects. However, students did not often use those sources that are considered essential in evidence-based dentistry. Universities should further develop educational and training interventions that guide students to use knowledge resources more effectively for critically appraising scientific evidence.

Rapid detection of Escherichia coli using fiber optic surface plasmon resonance immunosensor based on biofunctionalized Molybdenum disulfide (MoS2) nanosheets.

The molybdenum disulfide (MoS2) nanosheets functionalized fiber optic surface plasmon resonance (SPR) immunosensor has been reported for the sensitive detection of Escherichia coli (E. coli). The MoS2 nanosheets were prepared by chemical exfoliation method. The synthesised nanostructures were characterized for their structural, morphological and optical properties. The E. coli monoclonal antibodies were successfully immobilized on the MoS2 functionalized sensing platform via hydrophobic interactions. An alternative method simplifying the antibodies immobilization process by functionalization of 2D nanomaterial (MoS2 nanosheets) for rapid (~15 mins) bacterial quantification is presented in this study. The immunosensor uses wavelength interrogation method and a strong linear relationship (R2 = 0.994) was observed between spectral response of immunosensor and different concentration of E. coli. The nonspecificity and cross-reactivity studies of the developed immunosensor were investigated with detection of Salmonella Typhimurium and Staphylococcus aureus. To demonstrate the practical application, spiked samples of water and orange juice were analysed with acceptable recovery results. The label-free immunosensor exhibits better performance, detection limit (94 CFU/mL), high sensitivity (2.9 nm/1000 CFU mL-1; 3135 nm/RIU) and profound specificity as compared to conventional fiber optic SPR sensor (detection limit: 391 CFU/mL, sensitivity: 0.6 nm/1000 CFU mL-1; 1646 nm/RIU). This sensing platform shows promising applications in regular water and food quality monitoring for various pathogenic microorganisms.

Dietary protein-carbohydrate ratio: exogenous modulator of immune response with age.

Manipulation of dietary variables is one the most described events to retard the aging process and maintain immune function. The present study deals with the effect of variable dietary protein-carbohydrate ratios (without caloric restriction) on the alteration of immune response of male albino rats at the level of lymphocyte viability, proliferation, cytotoxicity, DNA fragmentation of blood, spleen and thymus and corticosterone levels in plasma and adrenal gland in relation to aging and duration of dietary exposure. Young (3 months) and aged rats (18 months) maintained with control diet [protein (20%)-carbohydrate (68%)] showed age-induced decrease in immune response with an increase in plasma corticosterone level. Consumption of low protein (8%)-high carbohydrate (80%) (LP-HC) diet for short-term period (15 consecutive days) decreased immune response of young rats with little immunopotentiation of aged rats but prolongation of consumption (for 60 consecutive days) of the LP-HC diet potentiated these immunopotentiation effects. High protein (50%)-low carbohydrate (38%) (HP-LC) diet under short-term exposure contrarily showed little immunopotentiation in young with an immunosuppression in aged rats. Prolongation of exposure (for 60 consecutive days) to the HP-LC diet produced similar but more amplified effects in young rats; whereas, in aged rats a pronounced decrease in peripheral immune response with an activation in thymus-dependent immune response was observed under similar conditions. These results thus suggest that diets with variable dietary protein-carbohydrate ratios act as an exogenous modulator of immune response with age and LP-HC diet may be beneficial to slow down/reduce the impairment of immune response in aged individuals.

Chromatin as a target for the DNA-binding anticancer drugs.

Chemotherapy has been a major approach to treat cancer. Both constituents of chromatin, chromosomal DNA and the associated chromosomal histone proteins are the molecular targets of the anticancer drugs. Small DNA binding ligands, which inhibit enzymatic processes with DNA substrate, are well known in cancer chemotherapy. These drugs inhibit the polymerase and topoisomerase activity. With the advent in the knowledge of chromatin chemistry and biology, attempts have shifted from studies of the structural basis of the association of these drugs or small ligands (with the potential of drugs) with DNA to their association with chromatin and nucleosome. These drugs often inhibit the expression of specific genes leading to a series of biochemical events. An overview will be given about the latest understanding of the molecular basis of their action. We shall restrict to those drugs, synthetic or natural, whose prime cellular targets are so far known to be chromosomal DNA.

Metabolic adaptability in hexavalent chromium-treated renal tissue: an in vivo study.

BACKGROUND: Hexavalent chromium [Cr(VI)], an environmental pollutant that originates mostly from anthropogenic sources, is a serious threat to human health. After entering into cells, Cr(VI) is capable of producing excessive free radicals and causing tissue damage. The present study aims to reveal the toxic manifestation of Cr(VI) on the metabolic activity of renal tissue. METHODS: Male Swiss albino mice were treated orally with potassium dichromate (K2Cr2O7) at a dose of 10 mg/kg body weight for a period of 30 days. Important tricarboxylic acid (TCA) cycle enzyme activities like isocitrate dehydrogenase, succinate dehydrogenase and malate dehydrogenase, as well as the activities of enzymes involved in oxidative phosphorylation such as Nicotinamide adenine dinucleotide (NADH) dehydrogenase, were measured. Additionally, transaminase and protease (pronase, cathepsin and trypsin) activities, tissue protein and free amino nitrogen were estimated in renal tissue. Glucose-6-phosphatase, glucose-6-phosphate dehydrogenase and alkaline phosphatase activities, as well as lactic acid, pyruvic acid and chromium contents, of kidneys were determined following standard protocols. Kidney histology was performed by hematoxylin and eosin staining. RESULTS: Cr(VI) suppresses the rate-limiting enzymes of the TCA cycle and oxidative phosphorylation indicating an inhibition of renal ATP production. It decreases protease activity by eliminating the protein substrates and alters the gluconeogenic pathway. Cr(VI) worsens the normophysiological attributes of renal tissue by enhancing the activity of alkaline phosphatase, pointing towards kidney disease. Histopathological observations confirmed these biochemical results through the presence of chronic tubular nephritis and altered glomerular structure. Cr(VI) retention occurs to a greater extent in renal tissue, which intensifies the toxic manifestation of this pollutant in the kidney. CONCLUSIONS: Cr(VI) disrupts the metabolic interaction between carbohydrates and proteins in mammalian renal tissue.

Association of antitumor antibiotics, mithramycin and chromomycin, with Zn(II).

Chromomycin A(3) (CHR) and mithramycin (MTR), members of the aureolic acid anticancer antibiotics, supposedly act by inhibiting transcription via reversible association with DNA. The complex(es) with bivalent cation such as Mg(2+) and Zn(2+) is (are) the DNA-binding ligand(s). In this paper, we report a detailed study of the association of these antibiotics with the biologically important bivalent cation, Zn(2+), because the zinc chelating ability of the antibiotics has therapeutic potential in the treatment of diseases relating to zinc dyshomeostasis. Spectroscopic methods such as absorbance, fluorescence, and circular dichroism and NMR spectroscopy have been used to characterize and understand the mechanism of complex formation. Our data show that both antibiotics form a single complex with Zn(2+) in the mole ratio of 2:1 in terms of antibiotic:Zn(2+) with an apparent binding affinity in the micro molar range. The complex has been characterized as [(D)(2)Zn(2+)] (where 'D' stands for the antibiotic). The kinetics study of the complex formation between the antibiotic(s) and Zn(2+) suggests the following mechanism: [reaction: see text] Isothermal calorimetric titration has shown that the association is entropy driven, implying the role of water molecules in complex formation. (1)H NMR spectroscopic data of the complex favor a tetrahedral arrangement around the Zn(2+) ion with the antibiotic acting as a bidentate ligand.

A clinicopathologic and epidemiologic study of chronic white lesions in the oral mucosa.

Invasive oral squamous cell carcinoma is often preceded by the presence of clinically identifiable premalignant changes of the oral mucosa, including white lesions. We conducted a cross-sectional, observational study to assess the clinicopathologic and epidemiologic aspects of chronic oral mucosal white lesions to determine the necessity of early biopsy in these cases. Our study population was made up of 77 patients-50 males and 27 females, aged 15 to 70 years (mean: 42.9)-who presented with white lesions persisting for at least 4 weeks. All but 3 patients underwent a biopsy; the 3 exceptions were diagnosed with smear-proven candidiasis. Patients with moderate or severe dysplasia underwent an excision biopsy. The buccal mucosa was the single most common site of white lesions, occurring in 15 patients (19.5%), although 21 patients (27.3%) exhibited a diffuse involvement of the oral mucosa. Of the 77 patients, 59 (76.6%) had concerning findings: premalignant lesions in 45 patients (58.4%) and malignant lesions in 14 (18.2%). Also, dysplasia was seen in 8 patients (10.4%), all of whom had premalignant lesions. Tobacco chewing (p = 0.008) and betel quid chewing (p = 0.029) were significantly associated with the development of premalignant and malignant lesions; a longer duration of tobacco chewing (≥10 yr) was significantly associated with a higher risk of malignant but not premalignant lesions (p = 0.031). Finally, illiteracy was a significant risk factor for premalignant and malignant lesions (p = 0.03). Our findings support the necessity of biopsy in every case. Early detection of oral carcinoma by biopsy of all oral white lesions would not only prevent patients from undergoing disfiguring surgery and chemoradiation, but it also would increase the 5-year survival rate.

Dinuclear oxidative addition reactions using an isostructural series of Ni2, Co2, and Fe2 complexes.

A family of low-valent Ni2, Co2, and Fe2 naphthyridine-diimine (NDI) complexes is presented. Ligand-based π* orbitals are sufficiently low-lying to fall within the metal 3d manifold, resulting in electronic structures that are highly delocalized across the conjugated [NDI]M2 system. This feature confers stability to metal-metal interactions during two-electron redox reactions, as demonstrated in a prototypical oxidative addition of allyl chloride.

Epistaxis Due to Leech Infestation in Nose: A Report of Six Cases and Review of Literature.

The aim of this study is to report unusual cause of epistaxis due to leech infestation in nose in hilly area and its management. The study was carried out for a period of 4 years (2008-2012) in a secondary level hospital in hilly area of Darjeeling, West Bengal, India with data collected from the OPD and Emergency register of the patients. This retrospective case series consisted of six cases. All the cases presented with unilateral recurrent epistaxis and foreign body nose. Anterior rhinoscopy revealed fleshy greenish brown mobile mass inside the nasal cavity which was removed by forceps. The animate foreign body was identified as leech in all the cases. To conclude, in hilly areas leech infestation can present as animate foreign body in nose and it should be considered as important cause of epistaxis.

Comparison of a microsliced modified chondroperichondrium shield graft and a temporalis fascia graft in primary type I tympanoplasty: A prospective randomized controlled trial.

We conducted a prospective, randomized, controlled trial to compare outcomes in type I tympanoplasty patients who received an autologous microsliced modified cartilage perichondrium shield graft (cartilage group) and those who received an autologous temporalis muscle fascia graft (fascia group). Our three outcomes measures were (1) anatomic success rates at 3 months, (2) hearing results at 6 months, and (3) rates of morphologic success (i.e., the absence of reperforation, retraction, and graft displacement) at 2 years among those in each group who had an intact graft at 3 months. Of 56 patients who were initially enrolled and who underwent one of these type I tympanoplasty procedures, 51 completed the study-28 in the cartilage group and 23 in the fascia group. The former was made up of 11 males and 17 females, aged 15 to 48 years (mean: 27.4), and the latter included 9 males and 14 females, aged 15 to 52 years (mean: 31.7). The overall graft take rate at 3 months with respect to perforation closure (anatomic success) was 93.3% in the cartilage group and 91.7% in the fascia group, which was not a statistically significant difference. The mean hearing gain at 6 months was 11.7 ± 7.6 dB in the cartilage group and 12.6 ± 6.0 dB in the fascia group-again, not statistically significant. At 2 years, morphologic success rates were 92.3 and 81.0%, respectively-again, not statistically significant. We conclude that autologous microsliced modified cartilage perichondrium shield graft tympanoplasty is as effective as conventional temporalis fascia tympanoplasty in terms of graft take rates and functional results. Indeed, medium-term outcomes (2-yr follow-up) revealed that sustainable morphologic success was actually better with the cartilage technique than with the fascia technique because it was associated with fewer revision surgeries.

Prospective protective role of melatonin against arsenic-induced metabolic toxicity in Wistar rats.

Subchronic exposure to arsenic is associated with alteration of glucose homeostasis. Arsenic treatment (as sodium arsenite) of male Wistar rats (weighing 130-150 g) at a dose of 5.55 mg kg(-1) body weight (equivalent to 35% of LD(50)) (i.p.) per day for a period of 30 days produced hypoglycemia, with associated increased urinary excretion of glucose and depletion of liver glycogen and pyruvic acid contents. Mobilization of free amino acids from kidney to liver was facilitated by arsenic treatment. Arsenic exposure significantly decreased the glutamate-pyruvate transaminase activity in kidney. Glucose 6-phosphatase activity in liver tissue was also significantly decreased after arsenic treatment. In addition to these, liver lactate dehydrogenase activity was elevated due to arsenic treatment. Melatonin supplementation (i.p.) at a dose of 10 mg kg(-1) day(-1) for last five days prior to sacrifice reversed most of the above changes caused by arsenic. Melatonin, being a potent free radical scavenger may reduce arsenic-induced free radical production, and thereby, eliminating its toxic effects. So, arsenic-induced hypoglycemia, with associated glycogenolytic as well as glycolytic activities of liver can be partially counteracted by melatonin supplementation. Accordingly, it may be suggested that melatonin can serve as a prospective protective agent against arsenic-induced metabolic toxicity.