Size Dependent Uptake and Hemolytic Effect of Zinc Oxide Nanoparticles on Erythrocytes and Biomedical Potential of ZnO-Ferulic acid Conjugates.

Despite zinc oxide nanoparticles (ZnONPs) being increasingly used as carriers in biomedical fields due to their multifaceted properties and therapeutic importance, better understanding of the mechanisms and cellular consequences resulting from their interaction with cells and cellular components has been warranted. In the present study, we investigate the size-dependent interaction of ZnONPs on RBCs, and its impact on cell viability, DNA damage, ROS generation and morphological changes, employing cellular and analytical methods. Size, charge, stability and solubility were confirmed by DLS, zeta potential, ICP-AES and TEM analysis. Further ICP-AES, TEM, spectroscopic observations and cell based assays showed that ZnONPs exhibited a size dependent impact on RBCs and haemoglobin (Hb), particularly size <50 nm. Conversely, ferulic acid (FA) conjugates and serum albumin significantly reduced the adverse effects exhibited by ZnONPs. The extent of DNA damage and ROS generation is comparatively low in ZnONPs-FA than in ZnONPs alone treated cells. Thus our study documents a novel conceptualization delineating the influence of size on the material properties and therapeutic potential of nanoparticle.

Should sputum-negative presumptive TB patients be actively followed to identify missing cases in India?

Setting: Sputum smear microscopy, the primary diagnostic tool used for diagnosis of tuberculosis (TB) in India's Revised National TB Control Programme (RNTCP), has low sensitivity, resulting in a significant number of TB cases reported as sputum-negative. As the revised guidelines pose challenges in implementation, sputum-negative presumptive TB (SNPT) patients are subjected to 2 weeks of antibiotics, followed by chest X-ray (CXR), resulting in significant loss to care among these cases. Objective: To determine whether reducing delays in CXR would yield additional TB cases and reduce initial loss to follow-up for diagnosis among SNPT cases. Methods: In an ongoing intervention in five districts of Maharashtra, SNPT patients were offered upfront CXR. Results: Of 119 male and 116 female SNPT patients with a mean age of 45 years who were tested by CXR, 32 (14%) were reported with CXR suggestive of TB. Administering upfront CXR in SNPT patients yielded twice as many additional cases, doubling the proportion of cases detected among all those tested as against administering CXR 2 weeks after smear examination. Conclusion: Our interventional study showed that the yield of TB cases was significantly greater when upfront CXR examination was undertaken without waiting for a 2-week antibiotic trial.

Contexte : La microscopie de frottis de crachats, le premier outil utilisé dans le diagnostic de la TB dans le programme national TB révisé d'Inde (RNTCP), a une faible sensibilité, ce qui aboutit à un nombre significatif de cas de TB rapportés comme étant à frottis négatif. Comme la mise en œuvre des directives révisées reste un défi, les patients présumés TB à frottis négatif (SNPT) sont soumis à 2 semaines d'antibiotiques suivis par une radiographie pulmonaire (CXR), d'où un nombre significative de cas de SNPT perdus de vue.Objectif : Déterminer si la réduction du délai de CXR aboutit à détecter des cas de TB supplémentaires et réduit les pertes de vue initiales parmi les cas de SNPT.Méthodes : Dans le cadre d'une intervention en cours dans cinq districts de Maharashtra, on a offert aux cas de SNPT une CXR immédiate.Résultats : Un total de 119 hommes et 116 femmes, patients SNPT, d'âge moyen 45 ans, ont eu une CXR. Parmi ces 235 patients, 32 (14%) ont eu une CXR suggestive de TB. Le recours immédiat à une CXR chez les patients présumées TB à frottis négatif a produit deux fois plus de cas supplémentaires et doublé la proportion de cas détectés parmi les patients ayant bénéficié d'une CXR immédiate par rapport à ceux l'ayant eue 2 semaines après la microscopie de frottis.Conclusion : Notre étude d'intervention a montré que la détection de cas de TB était significativement plus importante en faisant une CXR immédiate sans attendre les 2 semaines de traitement d'essai par antibiotiques.

Marco de referencia: La baciloscopia del esputo es el principal instrumento utilizado en el diagnóstico de la tuberculosis (TB) en el marco del Programa Revisado de Control de la Tuberculosis de la India (RNTCP) y ofrece una baja sensibilidad, con lo cual un gran número de casos de TB se notifican con baciloscopia negativa. Dadas las dificultades de aplicación de una revisión reciente de las directrices, en los pacientes con presunción clínica de TB y un resultado negativo de la baciloscopia se administran antibióticos de amplio espectro durante 2 semanas seguidos de una radiografía de tórax (CXR), con la consiguiente pérdida de la atención de muchos de los pacientes con baciloscopia negativa.Objetivo: Determinar si el hecho de acortar la demora en la realización de la CXR mejora el rendimiento diagnóstico de casos de TB y disminuye las pérdidas iniciales durante el seguimiento de los casos con baciloscopia negativa.Método: En el marco de una intervención en curso en cinco distritos de Maharashtra, se propuso a los pacientes con presunción clínica de TB y baciloscopia negativa practicar de inmediato la CXR.Resultados: Se practicó la CXR en pacientes con presunción de TB pulmonar y baciloscopia negativa; participaron 119 pacientes de sexo masculino y 116 de sexo femenino, con una edad promedio de 45 años. De estas 235 personas, en 32 casos el informe de la CXR refería imágenes indicativas de TB (14%). La práctica inmediata de la CXR en los pacientes con presunción clínica de TB que reciben un resultado negativo de la baciloscopia aportó el doble de casos adicionales y duplicó así la proporción de casos detectados en todas las personas examinadas, en comparación con la CXR practicada 2 semanas después de la baciloscopia.Conclusión: El presente estudio de intervención reveló un aumento considerable del rendimiento diagnóstico de casos de TB cuando se practica la CXR de inmediato, en lugar de esperar el resultado de una antibioterapia de prueba de 2 semanas.

Experience of active tuberculosis case finding in nearly 5 million households in India.

In India, to increase tuberculosis (TB) case detection under the National Tuberculosis Programme, active case finding (ACF) was implemented by the Global Fund-supported Project Axshya, among high-risk groups in 300 districts. Between April 2013 and December 2014, 4.9 million households covering ~20 million people were visited. Of 350 047 presumptive pulmonary TB cases (cough of ⩾2 weeks) identified, 187 586 (54%) underwent sputum smear examination and 14 447 (8%) were found to be smear-positive. ACF resulted in the detection of a large number of persons with presumptive pulmonary TB and smear-positive TB. Ensuring sputum examination of all those with presumptive TB was a major challenge.

En Inde, le projet Axshya (soutenu par le Fonds Mondial) a mis en œuvre une recherche active des cas (ACF) afin d'en augmenter la détection sous l'égide du Programme Révisé National Contre la Tuberculose auprès des groupes à risque dans 300 districts. Entre avril 2013 et décembre 2014, 4,9 millions de foyers, soit environ 20 millions de personnes, ont été visités. De 350 047 cas présumés de tuberculose (TB) pulmonaire (toux ⩾2 semaines) identifiés, 187 586 (54%) ont bénéficié d'un examen de frottis de crachats et 14 447 (8%) ont eu un frottis positif. L'ACF a abouti à la détection d'un grand nombre de personnes présumées atteintes de TB pulmonaire et de TB à frottis positif. Assurer l'examen des crachats de tous les cas avec suspicion de TB a été un défi majeur.

Con el propósito de aumentar la detección de casos en la India, el Proyecto Axshya (financiado por el Fondo Mundial) introdujo un mecanismo de búsqueda activa de casos (ACF), dirigido a los grupos de alto riesgo en 300 distritos, en el marco del Programa Nacional Revisado Contra la Tuberculosis. De abril del 2013 a diciembre del 2014 se visitaron 4,9 millones de hogares, que cubrían una población cercana a 20 millones de personas. Se detectaron 350 047 casos con presunción de tuberculosis (TB) pulmonar (tos con una duración de ⩾2 semanas), se practicó la baciloscopia del esputo a 187 586 personas (54%), de las cuales 14 447 obtuvieron un resultado positivo (8%). La ACF dio lugar a la detección de un gran número de personas con presunción de TB pulmonar y baciloscopia positiva del esputo. La realización del examen microscópico del esputo en todas estas personas representó un gran desafío.

Probing the interaction of troxerutin with transfer RNA by spectroscopic and molecular modeling.

The studies on the interaction between tRNA (transfer RNA) and small molecules are an area of remarkable recent attention. For this notion a fundamental knowledge of the molecular features involving the interaction of small molecules with tRNA is crucial. Hence, in the present study we have investigated the interaction of TXER (troxerutin), natural bioflavonoid rutin derivative with yeast tRNA by using various spectroscopic techniques and molecular docking studies. The UV absorption and fluorescence emission studies demonstrated external binding of TXER on tRNA with low binding constant values as compared to strong binders. Circular dichroism (CD) spectroscopy study revealed that TXER did not show any significant modification on native conformation of tRNA. Furthermore in electrochemical study, the complex of TXER-tRNA did not expose any noticeable positive potential peak shift which indicated an interaction of TXER with tRNA by electrostatic or external binding mode. The docking study showed that the hydrogen and hydrophobic interactions were involved in binding of TXER-tRNA with docking score -7.0 kcal/mol. These findings led us to confirm the interaction of TXER on tRNA through external binding with low binding affinity, indicating its potential bioapplication in the future.

The Impact of Operating Room Distractions on Stress, Workload, and Teamwork.

OBJECTIVE: To investigate whether distractions in the operating room (OR) are associated with higher mental workload and stress, and poorer teamwork among OR personnel. BACKGROUND: Engaging in multiple tasks can affect performance. There is little research on the effect of distractions on surgical team members' behavior and cognitive processes. METHODS: Ninety general surgery cases were observed in real time. Cases were assessed by a surgeon and a behavioral scientist using 4 validated tools: OR Distractions Assessment Form, the Observational Teamwork Assessment for Surgery tool, NASA-Task Load Index, and short form of the State Trait Anxiety Inventory. Analysis of variance was performed to evaluate significant differences between teamwork, workload, and stress level among team members. Correlations (Pearson r) were computed to evaluate associations between variables. RESULTS: The most prevalent distractions were those initiated by external staff, followed by case-irrelevant conversations. Case-irrelevant conversations were associated with poorer team performance. Irrelevant conversations initiated by surgeons were associated with lower teamwork in surgeons (across team skills: r = -0.44 to -0.58, P < 0.05 to 0.01) and anesthesiologists (r = -0.38 and r = -0.40, for coordination and leadership; P < 0.05). Equipment-related distractions correlated with higher stress (r = 0.48, P < 0.05) and lower teamwork (across team skills: r = -0.42 to -0.50, P < 0.05) in nurses. Acoustic distractions correlated with higher stress in surgeons (r = 0.32, P < 0.05) and higher workload in anesthesiologists (r = 0.30, P < 0.05). CONCLUSIONS: Although some distractions may be inevitable in the OR, they can also be detrimental to the team. A deeper understanding of the effect of distractions on teams and their outcomes can lead to targeted quality improvement.

2-Tri-fluoro-methyl-10H-benzo[4,5]imidazo[1,2-a]pyrimidin-4-one.

In the mol-ecule of the title compound, C11H6F3N3O, the three fused rings of the benzo[4,5]imidazo[1,2-a]pyrimidine unit are essentially coplanar, the maximum deviation from the mean plane being 0.096 (2) Å. In the crystal, N-H⋯O hydrogen bonds link the mol-ecules into chains running along the b-axis direction.

Aptamer-based label-free detection of PDGF using ruthenium(II) complex as luminescent probe.

We report a simple, cost-effective, and label-free detection method, consisting of a platelet-derived growth factor (PDGF) binding aptamer and hydrophobic Ru(II) complex as a sensor system for PDGF. The binding of PDGF with the aptamer results in the weakening of the aptamer-Ru(II) complex, monitored by luminescence signal. A substantial enhancement in the luminescence intensity of Ru(II) complex is observed in the presence of aptamer due to the hydrophobic interaction. Upon addition of PDGF, the luminescence intensity is decreased, due to the stronger interaction between the aptamer and PDGF resulting in the displacement of Ru(II) complex to the aqueous solution. Our assay can detect a target specifically in a complex medium such as the mixture of proteins, at a concentration of 0.8 pM.

Cerebrogenic tachyarrhythmia in acute stroke.

The electrocardiac abnormalities following acute stroke are frequent and seen in both ischemic and hemorrhagic stroke. The changes seen in electrocardiogram (ECG) consist of repolarization abnormalities such as ST elevation, ST depression, negative T waves, and QT prolongation. Among tachyarrhythmias, atrial fibrillation is the most common and occurrence of focal atrial tachycardia is very rare though any cardiac arrhythmias can follow acute stroke. We report a case of focal atrial tachycardia following acute ischemic stroke in 50-year-old female without structural heart disease, and their mechanisms and clinical implications.

Binding and fluorescence resonance energy transfer (FRET) of ruthenium(II)-bipyridine-calixarene system with proteins--experimental and docking studies.

The investigation of the interaction of ruthenium(II)-bipyridine-tert-butylcalix[4]arene complexes (Rubc2 and Rubc3) with proteins (BSA and ovalbumin) using absorption, emission, excited state lifetime and circular dichroism techniques and by docking studies show that luminophore-receptor system bind strongly with proteins. An enhancement of absorption as well as emission intensity of Ru(II)-calixarene complexes in the presence of proteins, but the quenching of the emission intensity of proteins in the presence of Ru(II)-calixarene complexes are the interesting observations. The enhancement of emission intensity of Ru(II)-calixarene complex, in the presence of proteins, is due to the fluorescence resonance energy transfer (FRET) from protein to Ru(II)-calixarene complex. Among the two Ru(II)-calixarene complexes synthesized Rubc3 has more efficient binding and energy transfer than Rubc2 and BSA, with a large cavity size, has the advantage for binding over ovalbumin. Docking studies reveal that the presence of tert-butylcalix[4]arene moiety in Ru(II)-calixarene complexes facilitates binding with proteins. After the binding of Rubc2 and Rubc3 with proteins, the nearby fluorophores present in proteins are in optimal distance from the ruthenium centre for efficient FRET process to occur.

Inguinal herniae: Valuable clues to concurrent abdominal pathology: A series of case studies describing unusual findings in 'routine' hernia operations which demonstrate the need for thorough surgical training.

INTRODUCTION: The case series presented here demonstrates that the pathology encountered during inguinal hernia repair can often provide clues to concurrent pathology; the well trained surgeon's broader medical knowledge can lead to earlier diagnosis. PRESENTATION OF CASES: The case series examines four cases of men presenting with inguinal hernias, who were found to have concurrent abdominal pathology after further investigation of the intraoperative findings of the surgeon. DISCUSSION: Operating surgeons not only require the necessary surgical skills to deal with the unexpected, but must also rely on their ability to think laterally when interpreting atypical incidental findings during 'routine' procedures. CONCLUSION: Experience and knowledge gained through a surgeon's career is essential to enable them to correctly interpret their intraoperative findings and potentially diagnose concurrent pathology. The authors believe that surgical care practitioners, trained in just 2 years, would lack these essential skills.

Role of SLC5A8, a plasma membrane transporter and a tumor suppressor, in the antitumor activity of dichloroacetate.

There has been growing interest among the public and scientists in dichloroacetate (DCA) as a potential anticancer drug. Credible evidence exists for the antitumor activity of this compound, but high concentrations are needed for significant therapeutic effect. Unfortunately, these high concentrations produce detrimental side effects involving the nervous system, thereby precluding its use for cancer treatment. The mechanistic basis of the compound's antitumor activity is its ability to activate the pyruvate dehydrogenase complex through inhibition of pyruvate dehydrogenase kinase. As the compound inhibits the kinase at micromolar concentrations, it is not known why therapeutically prohibitive high doses are needed for suppression of tumor growth. We hypothesized that lack of effective mechanisms for the entry of DCA into tumor cells may underlie this phenomenon. Here we show that SLC5A8 transports DCA very effectively with high affinity. This transporter is expressed in normal cells, but expression is silenced in tumor cells by epigenetic mechanisms. The lack of the transporter makes tumor cells resistant to the antitumor activity of DCA. However, if the transporter is expressed in tumor cells ectopically, the cells become sensitive to the drug at low concentrations. This is evident in breast cancer cells, colon cancer cells and prostate cancer cells. Normal cells, which constitutively express the transporter, are however not affected by the compound, indicating tumor cell-selective therapeutic activity. The mechanism of the compound's antitumor activity still remains its ability to inhibit pyruvate dehydrogenase kinase and force mitochondrial oxidation of pyruvate. As silencing of SLC5A8 in tumors involves DNA methylation and its expression can be induced by treatment with DNA methylation inhibitors, our findings suggest that combining DCA with a DNA methylation inhibitor would offer a means to reduce the doses of DCA to avoid detrimental effects associated with high doses but without compromising antitumor activity.

Isoforms, expression, glycosylation, and tissue distribution of CTL2/SLC44A2.

Antibodies to the solute carrier protein, CTL2/SLC44A2, cause hearing loss in animals, are frequently found in autoimmune hearing loss patients, and are implicated in transfusion-related acute lung injury. We cloned a novel CTL2/SLC44A2 isoform (CTL2 P1) from inner ear and identified an alternate upstream promoter and exon 1a encoding a protein of 704 amino acids which differs in the first 10-12 amino acids from the known exon 1b isoform (CTL2 P2; 706 amino acids). The expression of these CTL2/SLC44A2 isoforms, their posttranslational modifications in tissues and their localization in HEK293 cells expressing rHuCTL2/SLC44A2 were assessed. P1 and P2 isoforms with differing glycosylation are variably expressed in cochlea, tongue, heart, colon, lung, kidney, liver and spleen suggesting tissue specific differences that may influence function in each tissue. Because antibodies to CTL2/SLC44A2 have serious pathologic consequences, it is important to understand its distribution and modifications. Heterologous expression in X. laevis oocytes shows that while human CTL2-P1 does not transport choline, human CTL2-P2 exhibits detectable choline transport activity.

Fat necrosis of the breast--a review.

Fat necrosis of the breast is a benign condition that most frequently affects peri-menopausal women. It can mimic breast cancer clinically or radiologically. In other cases it can obscure malignant lesions. The core of this review is derived from a MEDLINE database literature search from 1966-2004. Further references were from lateral search. In this paper, we review the pathogenesis and pathology clinical and radiological features of fat necrosis of the breast. The implication of fat necrosis in the management of patients with breast lump is also discussed. Fat necrosis of breast is a complex process. Therefore, a systematic review of this condition will enable surgeons, radiologists and oncologists working in the field of breast disease to understand it better and improve its management.

Axillary gland involvement in breast carcinomas is not always metastatic: a case report.

We describe an unusual case of coexistence of carcinoma in the breast and an ipsilateral enlargement of axillary lymph nodes caused by tuberculosis. Accurate diagnosis has helped us in down staging the carcinoma in the breast and also identifying curable disease.

Antioxidant-associated chemoprevention by sodium selenite in N-nitrosodiethylamine-induced and phenobarbital-promoted hepatocarcinogenesis in rats.

The anticarcinogenic/antioxidant potential of sodium selenite (Se), a micronutrient, was evaluated on liver tumourigenesis induced by N-nitrosodiethylamine (DEN) and promoted by phenobarbital (PB; 0.05% in diet). Male, albino rats of the Wistar strain were exposed intravenously to a single dose of DEN (200 mg x kg(-1) body weight). Se (4 ppm in drinking water) was supplemented before initiation, or during initiation and/or during the promotion period of carcinogenesis. At the end of 16 weeks (after DEN administration) nodular incidence, the total number of nodules and non-enzymic antioxidants such as vitamin E, vitamin C, total thiol, protein thiol and non-protein thiol contents were measured in hepatoma, surrounding tissue and kidney tissue of control and experimental groups. In hepatoma-bearing animals the above biochemical changes were decreased when compared with normal control animals. On Se treatment throughout the study, (20 weeks) the above biochemical changes reverted to normal levels. Pre- and post-treatment with Se also shows a tendency to reverse the above changes. The results indicate that prior application of Se significantly reverses the adverse changes produced during the tumourigenesis. Furthermore, prior applications of Se significantly reduced the cumulative number of tumours per tumour-bearing animals. The present study reveals the antitumour potential of Se against DEN-induced liver carcinogenesis.

Platelet large cell ratio in the differential diagnosis of abnormal platelet counts.

Platelet volume indices, estimated by automated blood cell analyzers, are useful in the diagnosis of various conditions with abnormal platelet counts. Platelet count (PLT), Platelet large cell ratio (P-LCR), Platelet distribution width (PDW) and mean platelet volume (MPV) were studied in 779 patients with normal platelet counts, 74 patients with high platelet counts and 41 cases with low platelet counts. P-LCR was significantly decreased in patients with thrombocytosis than in normal while it was increased in thrombocytopenia. In patients with high counts, P-LCR was significantly decreased in reactive thrombocytosis than neoplastic thrombocytosis. P-LCR was increased in destructive thrombocytopenia than those with hypoproliferative thrombocytopenia though it was not statistically significant. P-LCR was inversely related to platelet count and directly related to PDW and MPV. Platelet large cell ratio if properly utilised can be a good aid in the differential diagnosis of conditions associated with abnormal platelet counts.