Interweaving of reactive oxygen species and major neurological and psychiatric disorders.

Reactive oxygen species are found to be having a wide range of biological effects ranging from regulating functions in normal physiology to alteration and damaging various processes and cell components causing a number of diseases. Mitochondria are an important organelle responsible for energy production and in many signalling mechanisms. The electron transport chain in mitochondria, where oxidative phosphorylation takes place, is also coupled with the generation of reactive oxygen species (ROS). Changes in normal homeostasis and overproduction of reactive oxygen species by various sources are found to be involved in multiple neurological and major neurodegenerative diseases. This review summarises the role of reactive oxygen species and the mechanism of neuronal loss in major neuronal disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, depression, and schizophrenia.

3D printing in pharmaceuticals: An emerging technology full of challenges.

Although in its infancy, when compared with the other sectors, year 2005 marked the rapid evolution of 3 Dimensional printing (3DP) technologies in pharma sector with a huge potential in the dosage form designing and personalisation of the medication. 3DP is an innovative and highly promising way for the instant manufacturing in contrast with the tailored made conventional manufacturing. Various 3DP technologies are categorized into the various areas on the basis of the type of material used, deposition techniques and the solidification/fusion techniques. 3DP technologies have multiple pharmaceutical applications including formulation of the precise and unique dosage forms, medical research, personalization of medicine, tissues engineering and surgical application. In the present article, we have accentuated the comparative merits and demerits of various 3DP technologies used in the pharmaceutical sector. An insight in to the challenges, apropos availability and the choice of the excipients, as well as the printer, regulatory and safety concern of the product is provided.

Knowledge Translation Among General Dental Practitioners in the Field of Periodontics.

INTRODUCTION: Evidence-based practice (EBP) is an expectation of medical professionals and is positively received in the dental community. Investigations of evidence-based dentistry (EBD) have discussed its use in broad terms and daily clinical practice, but there is only limited information about its use and barriers with respect to particular dental specialities. METHODS: A cross-sectional questionnaire was developed to survey implementation and obstacles to EBP; EBD specific to periodontics; and preferences for types of dissemination of evidence. The target population was active general dentists in Nova Scotia (n = 446). An email link to the questionnaire was distributed to dentists, and reminders were sent 4 and 10 days later. RESULTS: The response rate was limited (16.6%). Most respondents were comfortable evaluating the growing body of research, although many reported use of low-level evidence, including that from other health professionals or expert opinion. A common barrier to use was insufficient time. Respondents who found strong evidence for certain periodontal procedures were more likely to refer these procedures, which included tissue regeneration and periodontics related to endodontics. On-site lecture-based dissemination was preferred by most respondents. CONCLUSION: General evidence-based concepts and use were similar to EBD results reported elsewhere, although external validity is limited by our low response rate and narrow target population. Specific data related to periodontics may be useful in directing a modified questionnaire to a broader target population. Respondents who are truly interested in EBD and responded to our questionnaire may ultimately benefit the most from our results, where further educational opportunities can be tailored to overcome the identified barriers and aid in more effective translation of evidence-based periodontal decisions in a general dental practice.

Deep learning for screening of interstitial lung disease patterns in high-resolution CT images.

AIM: To develop a screening tool for the detection of interstitial lung disease (ILD) patterns using a deep-learning method. MATERIALS AND METHODS: A fully convolutional network was used for semantic segmentation of several ILD patterns. Improved segmentation of ILD patterns was achieved using multi-scale feature extraction. Dilated convolution was used to maintain the resolution of feature maps and to enlarge the receptive field. The proposed method was evaluated on a publicly available ILD database (MedGIFT) and a private clinical research database. Several metrics, such as success rate, sensitivity, and false positives per section were used for quantitative evaluation of the proposed method. RESULTS: Sections with fibrosis and emphysema were detected with a similar success rate and sensitivity for both databases but the performance of detection was lower for consolidation compared to fibrosis and emphysema. CONCLUSION: Automatic identification of ILD patterns in a high-resolution computed tomography (CT) image was implemented using a deep-learning framework. Creation of a pre-trained model with natural images and subsequent transfer learning using a particular database gives acceptable results.

Correlation between cerebral co-oximetry (rSO2) and outcomes in traumatic brain injury cases: A prospective, observational study.

BACKGROUND: Traumatic brain injury (TBI) is known to be an important reason for the increase in disabilities and deaths worldwide. Studies have demonstrated that brain tissue oxygen (PO2) monitoring reduces mortality significantly but is a invasive method of monitoring. Therefore, there is a need to monitor cerebral ischemia in TBI by noninvasive methods. The study aims to correlate cerebral co-oximetry and possible outcomes in patients with TBI. METHODS: The study included 78 patients with TBI admitted in intensive care unit (ICU) with glascow coma scale (GCS) of 8 or less than 8. Near-infrared spectroscopy monitor is applied to the patients immediately after admission to ICU; readings are noted every 4 hours up to first 48 hours, and outcomes studied as survival or neurological deficit are noted at 28 days. RESULTS: A total of 12 (15.4%) deaths were seen in this study. Survived patients were further divided into good recovery 33 (42.3%), moderate disability 21(26.9%), major disability 8 (10.3%), and persistent vegetative state 4 (5.1%). The rSO2 values in surviving patients were ranging from mean of 60.74% (standard deviation [SD] 4.38) to a mean of 64.98% (SD 5.01), and the mean rSO2 values in patients who died were ranging from a mean of 52.17% (SD 4.11) to a mean of 37.17% (SD 12.48). Lower rSO2 values were correlating significantly with worse neurological outcome or death by using two independent sample t-test (p < 0.001). CONCLUSION: Cerebral co-oximetry is a simple noninvasive method for predicting the outcomes in TBI and can be used to guide the management of these patients.

Assessment of shoreline alterations using a Digital Shoreline Analysis System: a case study of changes in the Yesilirmak Delta in northern Turkey from 1953 to 2017.

The aim of our study was to determine the erosion rates and shoreline changes in the Yesilirmak Delta (Delta) between the oldest available date (1953) before construction of the large-scale dams on the Yesilirmak River in northern Turkey and 2017. To clearly illustrate the impacts of the dams on the Delta, we investigated the relationship between the dams and shoreline changes. To compute the net shoreline changes and erosion rates over these 64 years, we used a Digital Shoreline Analysis System. To digitize the shoreline changes at the mouth of the Yesilirmak River, 1:25000-scaled topographic maps from 1957, panchromatic aerial photographs from 1962, a KH-9 Hexagon satellite image from 1980, an Ikonos satellite image from 2002, and a WorldView-2 satellite image from 2017 were used. The west and east sides of the river mouth were divided into six main groups and assessed. Each group included a time series for the shorelines. The groupings were based on the time series. For each group, the net shoreline change (m) was calculated using the net shoreline movement (NSM), and erosion rate (m/year) was calculated using the linear regression rate (LRR). According to NSM computations, net shoreline change varied from - 235.04 to 379.18 m. The greatest evolutions in net shoreline change were observed for group I, with a minimum of - 1101.11 m. According to LRR analysis, the calculated erosion rate varied from - 6.83 to 19.06 m/year. The greatest changes in erosion rate were observed for group II, with a minimum of - 30.63 m/year. There is a close relationship between the construction dates of the dams in the Yesilirmak Basin and the shoreline changes in the Delta.

Differential expression of miRNAs in pancreatobiliary type of periampullary adenocarcinoma and its associated stroma.

Periampullary adenocarcinomas can be of two histological subtypes, intestinal or pancreatobiliary. The latter is more frequent and aggressive, and characterized by a prominent desmoplastic stroma, which is tightly related to the biology of the cancer, including its poor response to chemotherapy. Whereas miRNAs are known to regulate various cellular processes and interactions between cells, their exact role in periampullary carcinoma remains to be characterized, especially with respect to the prominent stromal component of pancreatobiliary type cancers. The present study aimed at elucidating this role by miRNA expression profiling of the carcinomatous and stromal component in twenty periampullary adenocarcinomas of pancreatobiliary type. miRNA expression profiles were compared between carcinoma cells, stromal cells and normal tissue samples. A total of 43 miRNAs were found to be differentially expressed between carcinoma and stroma of which 11 belong to three miRNA families (miR-17, miR-15 and miR-515). The levels of expression of miRNAs miR-17, miR-20a, miR-20b, miR-223, miR-10b, miR-2964a and miR-342 were observed to be higher and miR-519e to be lower in the stromal component compared to the carcinomatous and normal components. They follow a trend where expression in stroma is highest followed by carcinoma and then normal tissue. Pathway analysis revealed that pathways regulating tumor-stroma interactions such as ECM interaction remodeling, epithelial-mesenchymal transition, focal adhesion pathway, TGF-beta, MAPK signaling, axon guidance and endocytosis were differently regulated. The miRNA-mRNA mediated interactions between carcinoma and stromal cells add new knowledge regarding tumor-stroma interactions.

Reactive angioendotheliomatosis as a presenting cutaneous manifestation of Hughes syndrome.

BACKGROUND: Antiphospholipid antibody syndrome is an autoimmune disorder associated with pregnancy complications, venous and/or arterial thrombosis and the presence of antiphospholipid antibodies. This syndrome is known to present with various cutaneous features, but association with reactive angioendotheliomatosis has been described rarely in the literature. RESULTS: A woman in her thirties with a past history of three consecutive abortions developed purpuric, ulcerative plaque over the plantar aspect of the foot. Her biopsy showed marked expansion of dermal vasculature due to intravascular cellular proliferation suggestive of reactive angioendotheliomatosis. The intravascular cells stained positive for CD31. Her blood investigations showed positive lupus anticoagulant, antiphospholipid antibodies and anticardiolipin antibodies, leading to a diagnosis of antiphospholipid syndrome also known as Hughes syndrome. CONCLUSION: We suggest that a hypercoagulable state caused the formation of intravascular thrombi leading to reactive angioendotheliomatosis. We report a case of Hughes syndrome with reactive angioendotheliomatosis as the first clinical cutaneous manifestation and treated satisfactorily with anticoagulants and immunomodulators.

Pulmonary histoplasmosis in a renal allograft recipient.

Histoplasmosis, seen rarely in kidney transplantracipients, can vary from an innocuous illness often misdiagnosed as tuberculosis to a severe disseminated disease with a high mortality. We describe a case with non-specific signs in whom the diagnosis was made by histopathological examination of the lesion. Prompt introduction of specific treatment led to Histoplasmosis, seen rarely in kidney transplantracipients, can vary from an innocuous illness often misdiagnosed as tuberculosis to a severe disseminated disease with a high mortality. We describe a case with non-specific signs in whom the diagnosis was made by histopathological examination of the lesion. Prompt introduction of specific treatment led to the patient making an excellent recovery the patient making an excellent recovery.

Opposing effects of pro- and anti-inflammatory cytokine gene polymorphisms on the risk for breast cancer in western Indian women: a pilot study.

In an earlier study, the genotypes associated with higher level of transforming growth factor-ß1 (TGF-ß1) were found to reduce the risk for breast cancer in western Indian women. This observation implied that gene polymorphisms affecting the levels of pro- and anti-inflammatory cytokines may influence the risk for breast cancer in this population. Hence, we performed genotyping for three more functional single-nucleotide polymorphisms (SNPs) responsible for variations in the levels of cytokines associated with inflammation. To that effect, polymorphisms in genes coding for IL-4 (IL-4 C-590T; rs2243250), IFN-γ (IFN-G A + 874T; rs2430561) and MCP-1 (MCP-1 A-2578G; rs1024611) were examined in premenopausal, healthy women (N = 239) and patients with breast cancer (N = 182) from western India. In carriers of the IL-4*590T allele, a reduced risk for the disease (dominant model; OR = 0.61, 95% CI 0.37-0.98) was seen similar to that seen in TGF-B1*10C carriers. An opposite trend was observed with respect to the alleles associated with higher expression of MCP-1 or IFN-γ. In individuals positive for three or more alleles associated with higher levels of either pro- or anti-inflammatory cytokines, an additive effect on the modulation of risk for the disease was evident (for TGF-B1 & IL-4, OR = 0.33, 95% CI 0.12-0.87; for IFN-G & MCP-1, OR = 2.29, 95% CI 0.95-5.51). In the context of contrasting observations in other populations, these results indicate a significant contribution of anti-inflammatory genotypes in the modulation of risk for breast cancer in western Indian women.

Rapid Estimation of Tadalafil by Reverse-phase High-performance Liquid Chromatography Method in Bulk and Tablet Formulation.

The simple, selective, precise and accurate reverse-phase high-performance liquid chromatography method was developed and validated for analysis of tadalafil in bulk and tablet dosage form. The column was Inertsil C18 (150×4.6 mm; 5 µm) in isocratic mode. The mobile phase used was phosphate buffer (10 mM, pH 3.2) and acetonitrile (50:50% v/v) at the flow rate of 1.0 ml/min with ultraviolet detection at 295 nm at ambient temperature. The retention time for tadalafil was found to be 4.01 min. Linearity was observed in the concentration range from 60 to 140 µg/ml for tadalafil with a correlation coefficient of (r (2)) 0.9998. The method was validated according to International Conference on Harmonisation guidelines in terms of linearity, accuracy, precision and specificity. Hence, the proposed method can be utilized for routine quality control of tadalafil in bulk and tablet dosage form.

Development and Validation of an HPLC Method for Karanjin in Pongamia pinnata linn. Leaves.

A rapid, simple and specific reversed-phase HPLC method has been developed for analysis of karanjin in Pongamia pinnata Linn. leaves. HPLC analysis was performed on a C(18) column using an 85:13.5:1.5 (v/v) mixtures of methanol, water and acetic acid as isocratic mobile phase at a flow rate of 1 ml/min. UV detection was at 300 nm. The method was validated for accuracy, precision, linearity, specificity. Validation revealed the method is specific, accurate, precise, reliable and reproducible. Good linear correlation coefficients (r(2)>0.997) were obtained for calibration plots in the ranges tested. Limit of detection was 4.35 µg and limit of quantification was 16.56 µg. Intra and inter-day RSD of retention times and peak areas was less than 1.24% and recovery was between 95.05 and 101.05%. The established HPLC method is appropriate enabling efficient quantitative analysis of karanjin in Pongamia pinnata leaves.

Surveillance of bacterial contamination in small animal veterinary hospitals with special focus on antimicrobial resistance and virulence traits of enterococci.

OBJECTIVE: To determine the prevalence of bacterial contamination on 4 surfaces of 4 types of standard equipment in small animal veterinary hospitals. DESIGN: Surveillance study. SAMPLE: 10 small animal veterinary hospitals. PROCEDURES: Each hospital was visited 3 times at 4-month intervals; at each visit, a cage door, stethoscope, rectal thermometer, and mouth gag were swabbed. Swab samples were each plated onto media for culture of enterococci and organisms in the family Enterobacteriaceae. Enterococci were identified via a species-specific PCR assay and sodA gene sequencing; species of Enterobacteriaceae were identified with a biochemical test kit. Antimicrobial susceptibility was assessed via the disk diffusion method. Enterococci were screened for virulence traits and genotyped to assess clonality. RESULTS: Among the 10 hospitals, enterococci were isolated from cage doors in 7, from stethoscopes in 7, from thermometers in 6, and from mouth gags in 1; contamination with species of Enterobacteriaceae was rare. Enterococci were mainly represented by Enterococcus faecium (35.4%), Enterococcus faecalis (33.2%), and Enterococcus hirae (28.3%). Antimicrobial resistance was common in E. faecium, whereas virulence traits were present in 99% of E. faecalis isolates but not in E. faecium isolates. Clonal multidrug-resistant E. faecium was isolated from several surfaces at 1 hospital over multiple visits, whereas sporadic nonclonal contamination was detected in other hospitals. CONCLUSIONS AND CLINICAL RELEVANCE: Contamination of surfaces in small animal veterinary hospitals with multidrug-resistant enterococci is a potential concern for pets and humans contacting these surfaces. Implementing precautions to minimize enterococcal contamination on these surfaces is recommended.

An investigation of equine infectious anaemia infection in the central Anatolia region of Turkey.

In this study, 162 horses, 80 donkeys and 51 mule serum samples were collected in Konya city. Additionally, 64 horse serum samples from Ankara and 49 samples from Kayseri city were included in the study. A total of 406 serum samples were examined by agar gel immunodiffusion (AGID) and enzyme-linked immunosorbent assay (ELISA) for antibody to equine infectious anaemia virus (EIAV) and no positive result was detected.

Effects of subclinical bovine leukemia virus infection on some production parameters in a dairy farm in southern Turkey.

Some production parameters of seropositive cows (age, first calving age, 305 day mature equivalent last milk yield production, lifetime mature equivalent milk yield production, lifetime total milk production, lifetime total milking period, lifetime monthly milk production, lifetime daily milk production, lifetime total days of milking, number of inseminations per pregnancy (for last pregnancy), number of calves and calving interval (for last pregnancy)) were analysed in the current study. The study population was clinically healthy Holstein cows from a commercial dairy herd in southern Turkey. Of 109 animals, 65 cows were seropositive by ELISA and the prevalence of bovine leukemia virus (BLV) infection was 59.6%. The prevalence of seropositive cows in 2nd (62.8%), 3rd (64.7%), 4th (61.5%), and 5th (66.6 %) lactations was slightly higher than that of cows in 1st (52.6%) lactations. No statistical differences were observed between BLV seronegative and seropositive cows for production and reproduction parameters analysed in this study (P > 0.05).

A clinical trial of the efficacy and safety of montelukast as monotherapy in patients with chronic stable bronchial asthma.

This study is aimed to evaluate the efficacy and safety of montelukast, as monotherapy, in the treatment of chronic stable bronchial asthma in adults. This was a multicentre, open label, non-comparative, prospective, 4-week study. Eligible patients discontinued all anti-inflammatory medication (steroids, chromoglycate sodium) 2 weeks prior to starting therapy with montelukast (10 mg daily). The primary efficacy criteria were improvements in forced expiratory volume in one second (FEV1), peak exploratory flow rate (PEFR) after 4 weeks of therapy. Secondary efficacy criteria were improvement in the patients' symptoms (assessed on an ordinal scale), decrease in discomfort levels (scored on a scale of 0-100), change in peripheral eosinophil counts, decrease in total daily dose of inhaled beta2 agonist (salbutamol). A total of 148 patients, mean age (+/- SD) 40.21 +/- 13.70 years, were enrolled into the study. At the end of the study there were significant improvements in FEV1 and PEFR (29% and 28% increase respectively from baseline values, p<0.000001). The mean total daily dose of inhaled salbutamol decreased significantly from prestudy values of 461 +/- 332 microg/day to 161 +/- 207 microg/day (p<0.000001). The mean eosinophil counts fell from 5.80 +/- 4.90% (+/- SD) to 4.84 +/- 4.42% (+/- SD) (p=0.02). Symptom scores improved significantly as did subjective assessment of discomfort. A total of 29 (19.6%) adverse events were reported, all of which were of mild to moderate intensity. Monotherapy with montelukast significantly improved parameters of asthma control. It was well tolerated with no reports of serious or severe adverse events.

Pacemaker prevention therapies for the control of drug-refractory paroxysmal atrial fibrillation.

AIMS: Atrial septal pacing has been shown to prevent paroxysmal atrial fibrillation (PAF) refractory to drugs in patients without inappropriate bradycardia. This study assesses the effects of atrial septal pacing using new pacing algorithms designed to prevent the initiation or maintenance of PAF. METHODS AND RESULTS: Eleven Medtronic AT500 and 6 Guidant Pulsar Max pacemakers were implanted. The incremental benefit of prevention pacing therapies was compared with DDDR pacing by analysis of pacemaker-stored electrograms, ambulatory electrocardiography, symptoms and quality of life questionnaires. RESULTS: Atrial septal pacing reduced AF burden by >50% in 13/17 patients (76.5%). Activation of a combined pacing algorithm (atrial pacing preference; atrial rate stabilization; and post mode-switch overdrive pacing) in patients with AT500 pacemakers produced a marginal reduction in AF burden (mean %AF 0.61 ON, 0.73 OFF, P=0.53 ns). Conversely in the Pulsar Max group when atrial pacing preference was activated, AF burden was slightly increased (mean %AF 5.84 ON, 3.73 OFF,P =0.13). Symptoms improved with atrial septal pacing but did not change when prevention algorithms were activated. CONCLUSION: Atrial septal pacing resulted in a marked improvement in AF burden and symptoms. Activation of specific prevention pacing algorithms provided more continuous atrial pacing but had limited and heterogeneous effects on AF burden.

Atrial septal pacing in the prevention of paroxysmal atrial fibrillation refractory to antiarrhythmic drugs.

BACKGROUND: Early reports have shown that pacing the atria at a site or sites other than the right atrial appendage may prevent atrial fibrillation. Our centre has shown that pacing the atrial septum reduces the duration of atrial activation which is an important determinant of predisposition to paroxysmal atrial fibrillation. Ablation of the atrioventricular (AV) node together with implantation of a pacemaker can control symptoms due to paroxysmal atrial fibrillation in patients in whom antiarrhythmic drugs have failed. The aim of this study was to investigate the effect of atrial septal pacing on patients who were candidates for AV node ablation. METHODS: Atrial septal pacemakers were implanted in 28 patients with symptomatic, paroxysmal atrial fibrillation that had been unresponsive to two or more antiarrhythmic drugs. Pacing was not indicated for any reason other than the anticipated need to proceed to AV node ablation. Change in symptoms was assessed by quality of life questionnaires and recurrence of atrial fibrillation was measured objectively by pacemaker interrogation and ambulatory electrocardiographic monitoring. RESULTS: Atrial septal pacing in combination with an antiarrhythmic agent resulted in a substantial subjective improvement in 19 patients (68%). Objective data confirmed similar findings; atrial fibrillation was completely or markedly reduced in 17 patients (60%). Six patients experienced a modest improvement in symptoms; in only four patients was it necessary to proceed to AV node ablation. CONCLUSIONS: Atrial septal pacing together with continuance of previously ineffective antiarrhythmic therapy may prevent or markedly reduce the frequency of paroxysmal atrial fibrillation and obviate the need to ablate the AV node.

Protective effect of vitamin E in dimethoate and malathion induced oxidative stress in rat erythrocytes.

Organophosphate (OP) pesticides such as dimethoate and malathion intoxication has been shown to produce oxidative stress due to the generation of free radicals and alter the antioxidant defense system in erythrocytes. It is possible that vitamin E being present at the cell membrane site may prevent OP-induced oxidative damage. In the present study, rats were pretreated orally with vitamin E (250 mg/kg body wt, twice a week for 6 weeks) prior to oral administration of a single low dose of dimethoate and/or malathion (0.01% LD(50)). The result showed that treatment with OP increased lipid peroxidation (LPO) in erythrocytes, however, vitamin E pretreated rats administered OP's showed decreased LPO in erythrocytes. The increase in the activities of superoxide dismutase (SOD) and catalase (CAT) and total-SH content in erythrocytes from dimethoate and/or malathion treated rats as compared to control appears to be a response towards increased oxidative stress. Vitamin E pretreated animals administered OP's showed a lowering in these parameters as compared to OP treated rats which indicates that vitamin E provide protection against OP-induced oxidative stress. The glutathione-S-transferase (GST) activity in erythrocytes was inhibited in OP intoxicated rats which partially recovered in vitamin E pretreated animals administered OP's. Inhibition in erythrocyte and serum acetylcholinesterase (AChE) activity was not relieved in vitamin E pretreated rats administered OP's probably due to the competitive nature of enzyme inhibition by OP's. The results show that vitamin E may amelierate OP-induced oxidative stress by decreasing LPO and altering antioxidant defense system in erthrocytes.

Cytodiagnosis of retroperitoneal primitive neuroectodermal tumour (PNET)--a case report.

A rare case of Retroperitoneal Primitive Neuro Ectodermal Tumour (PNET) in thirty years old female is presented. Fine needle aspiration cytology (FNAC) characterised by small round cells with scanty cytoplasm, poorly to well formed rosettes with neurofibrillary background; whereas periodic acid-schiff (PAS) rarely react with Primitive Neuro Ectodermal Tumour (PNET), prompted the diagnosis of PNET at cytology itself. Cytological appearances of PNET have been reviewed and the various differential diagnoses are discussed.