A Review of Olmesartan-based Therapy in Targeting Effective Blood Pressure Control and Achieving Blood Pressure Goals.

For >3 decades now, angiotensin receptor blockers (ARB) have been used in the management of hypertension (HTN) and HTN-related cardiovascular (CV) diseases. Olmesartan medoxomil (OLM) is an angiotensin II type 1 (AT1) receptor antagonist (or blocker) that binds tightly to the AT1 receptor with long-lasting efficacy over the 24-hour period and safety demonstrated in several trials. It is well tolerated and effective in reducing blood pressure (BP) in mono and combination therapy with thiazide diuretics or calcium channel blockers across a wide range of patient subgroups. The effectiveness and safety of OLM-based combination therapies have good and tolerable profiles with high adherence in the fixed single-pill formulation. Consistent antihypertensive efficacy and good tolerability when used as monotherapy or as a combined therapy make OLM a valuable treatment option for adults with HTN. In this review, we discuss the important clinical implications of OLM as an optimal choice as monotherapy and combination therapy in managing patients with HTN.

Cilnidipine, a Dual L/N-type Ca2+ Channel Blocker in Hypertension Management: A Review.

Calcium channel blockers (CCBs) are widely used antihypertensive agents due to their effectiveness in reducing blood pressure (BP), along with their good tolerability and evidence of reducing hypertension (HTN)-related cardiovascular and renal diseases. Cilnidipine, a unique dihydropyridine calcium antagonist, exhibits potent inhibitory action on both N-type and L-type voltage-dependent calcium channels. With excellent oral absorption and a prolonged duration of action, it demonstrates a significant antihypertensive effect. It effectively reduces BP both systolic and diastolic while providing renal, neurological, and cardiovascular protection. Unlike L-type CCBs, cilnidipine does not increase pulse rates (PRs) and is associated with reduced occurrence of pedal edema. Cilnidipine is an effective treatment choice for individuals with mild to moderate essential HTN, whether it is administered alone or in conjunction with other treatment modalities.

Cefotaxime in Enteric Fever: Therapeutic Reappraisal.

Enteric fever is one of the most common infectious diseases in the economically developing world and this bacterial infection is the common most cause of fever in travelers to these endemic areas. Even after the availability and deployment of preventive measures like vaccination against Salmonella typhi (S. typhi) and sanitation practices; effective treatment is paramount to reduce the associated morbidity and mortality. Cephalosporins are antimicrobials belonging to the ß-lactam class with established efficacy, pharmacokinetic, and safety profile by virtue of which, they belong to the group of antibiotics most commonly utilized in clinical practice. They have a broadspectrum of activity against various gram-positive and gram-negative bacteria. Like penicillin, they belong to the ß-lactam class of drugs. Amid such a scenario of rising antimicrobial resistance, a broad-spectrum antibiotic like cefotaxime is a real bliss. Distinctive properties of cefotaxime like broad-spectrum of activity, bactericidal action, stability against the common resistance-causing mechanisms, and good safety profile make it a reliable choice in the therapy landscape of enteric fever. It delivers desired efficacy in such difficult-to-treat scenarios at a manageable tolerability profile. Cefotaxime and ceftriaxone have a comparable spectrum of antimicrobial activity, but both differ in terms of pharmacokinetics. Considering the published literature, cefotaxime seems to be a dependable option for the management of typhoid owing to its effectiveness against S. typhi bundled with an acceptable tolerability profile.

Inflammasome, Inflammation, Infection and Mefenamic Acid.

Nucleotide-binding oligomerization domain like receptors (NLRs) -intracellular proteins, are a recently discovered class of innate immune receptors that play a crucial role in initiating the inflammatory response following pathogen recognition. The dysregulation of NLRP3 inflammasome can cause uncontrolled inflammation and drive the development of a wide variety of human diseases. Mefenamic acid which belongs to fenamate group inhibits the NLRP3 inflammasome by inhibiting efflux of chloride ions and influx of calcium ions through blocking VRAC and TRPM2 respectively. Thus, Mefenamic acid provides a potentially practical pharmacological approach for treating NLRP3- driven diseases.

Medical Management and Diagnostic Testing among Stable Angina Patients in India: The STable Angina obseRvational (STAR) Registry.

OBJECTIVE: To study the practice pattern in the management of patients with stable angina (SA) in India. METHODS: The Stable Angina obseRvational Registry (STAR) prospectively enrolled patients provisionally diagnosed with SA by non-interventional practicing internists in India. Patients were followed for 3 months after enrollment to assess medical treatment, diagnostic management, and interventional treatment of coronary artery disease (CAD). At the study conclusion, a statistical analysis retrospectively categorized patients not at risk of CAD by the Morise-Jalisi scale though this was not part of the study protocol. RESULTS: Between January and May 2012, 2079 patients were enrolled at 131 centres. Mean age was 57 ± 11 years, 62% were men, and 40% had a history of diabetes. Over 90% of patients completed follow-up visit, >85% received statins and antiplatelet medications, >70% received beta blockers, and >60% received angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers. Diagnostic testing rates were low: 93% for electrocardiogram, 44% echocardiogram, 42% chest radiography, 12% stress test, and 8% underwent noninvasive CT or invasive coronary angiography, of which, 86% had abnormal results. After the study, the Morise-Jalisi probability of CAD was intermediate in 42% and high in 51% of patients. Only 3.4% of all patients had coronary revascularization. CONCLUSIONS: In a large cohort of Indian patients with SA, disease severity and probability of CAD were high. Clinicians used evidence-based care for medical management, but underutilized diagnostic testing. Patients with SA in India need to be risk-stratified for probability and severity of CAD and, if indicated, receive additional diagnostic testing.

The Serious Side of Supplements: An Ischemic Stroke in a Healthy 38-year-old Female.

The incidence of ischemic stroke in the young is on the rise. With young stroke victims, providers must consider both typical risk factors and other rare causes. We present a case of a healthy, 38-year-old female military dependent who presented with an ischemic right posterior central gyrus stroke in the setting of a patent foramen ovale and supplement diindolylmethane use. This case serves as a reminder of the hazards associated with supplement use and the importance of a thorough investigation of etiology in medical cases of ischemic stroke in the young.

Circuit analysis of the Drosophila brain using connectivity-based neuronal classification reveals organization of key communication pathways.

We present a functionally relevant, quantitative characterization of the neural circuitry of Drosophila melanogaster at the mesoscopic level of neuron types as classified exclusively based on potential network connectivity. Starting from a large neuron-to-neuron brain-wide connectome of the fruit fly, we use stochastic block modeling and spectral graph clustering to group neurons together into a common "cell class" if they connect to neurons of other classes according to the same probability distributions. We then characterize the connectivity-based cell classes with standard neuronal biomarkers, including neurotransmitters, developmental birthtimes, morphological features, spatial embedding, and functional anatomy. Mutual information indicates that connectivity-based classification reveals aspects of neurons that are not adequately captured by traditional classification schemes. Next, using graph theoretic and random walk analyses to identify neuron classes as hubs, sources, or destinations, we detect pathways and patterns of directional connectivity that potentially underpin specific functional interactions in the Drosophila brain. We uncover a core of highly interconnected dopaminergic cell classes functioning as the backbone communication pathway for multisensory integration. Additional predicted pathways pertain to the facilitation of circadian rhythmic activity, spatial orientation, fight-or-flight response, and olfactory learning. Our analysis provides experimentally testable hypotheses critically deconstructing complex brain function from organized connectomic architecture.

Online conversion of reconstructed neural morphologies into standardized SWC format.

Digital reconstructions provide an accurate and reliable way to store, share, model, quantify, and analyze neural morphology. Continuous advances in cellular labeling, tissue processing, microscopic imaging, and automated tracing catalyzed a proliferation of software applications to reconstruct neural morphology. These computer programs typically encode the data in custom file formats. The resulting format heterogeneity severely hampers the interoperability and reusability of these valuable data. Among these many alternatives, the SWC file format has emerged as a popular community choice, coalescing a rich ecosystem of related neuroinformatics resources for tracing, visualization, analysis, and simulation. This report presents a standardized specification of the SWC file format. In addition, we introduce xyz2swc, a free online service that converts all 26 reconstruction formats (and 72 variations) described in the scientific literature into the SWC standard. The xyz2swc service is available open source through a user-friendly browser interface ( https://neuromorpho.org/xyz2swc/ui/ ) and an Application Programming Interface (API).

Upper Gastrointestinal Manifestations of Crohn's Disease: Differential Diagnosis and Treatment of an Uncommon Presentation of Crohn's Disease.

Esophagogastroduodenoileal involvement of Crohn's disease (CD) is uncommon; less than 5% of adult patients will suffer from this condition, although this diagnosis is likely underestimated given the lack of routine evaluation of the upper gastrointestinal tract in the absence of symptoms. An interesting differential, including sarcoidosis, eosinophilic gastroenteritis, tuberculosis, and Brunner's gland hyperplasia, should be considered. The consequences of this diagnosis can have profound impacts on the military career of a soldier. Learning objectives of this case report include workup, differential, diagnosis, and treatment of esophagogastroduodenoileal involvement of CD, as well as discussing the psychological effects of this diagnosis and impact on an individual's military career.

Idiopathic Constrictive Bronchiolitis in an Active Duty Soldier.

Constrictive bronchiolitis is characterized by fibroproliferative thickening of the bronchiolar walls causing narrowing of the bronchiolar lumen, which may progress to the complete obliteration of bronchioles, resulting in progressive dyspnea and ultimately respiratory failure. Active duty service members returning from deployment with toxic exposures such as "burn pits" are known to be at risk for this condition. Other proposed etiologies for this condition include inhalation (nitrogen oxides, ammonia, welding fumes, aerosols [nicotine, diacetyl, and vitamin E acetate]), infection (respiratory syncytial virus, adenovirus, or Mycoplasma pneumoniae), rheumatic diseases, and graft-versus-host disease (lung or hematopoietic cell transplantation). Uncommonly, constrictive bronchiolitis can also be idiopathic. Here we present a case of a young active duty soldier with idiopathic constrictive bronchiolitis without any known risk factors for this disease. The goal of this case presentation is to help the military physician better understand this condition, including identification of this disease process, underlying etiologies, risk factors, and treatments available.

Neuronal classification from network connectivity via adjacency spectral embedding.

This work presents a novel strategy for classifying neurons, represented by nodes of a directed graph, based on their circuitry (edge connectivity). We assume a stochastic block model (SBM) in which neurons belong together if they connect to neurons of other groups according to the same probability distributions. Following adjacency spectral embedding of the SBM graph, we derive the number of classes and assign each neuron to a class with a Gaussian mixture model-based expectation maximization (EM) clustering algorithm. To improve accuracy, we introduce a simple variation using random hierarchical agglomerative clustering to initialize the EM algorithm and picking the best solution over multiple EM restarts. We test this procedure on a large (≈212-215 neurons), sparse, biologically inspired connectome with eight neuron classes. The simulation results demonstrate that the proposed approach is broadly stable to the choice of embedding dimension, and scales extremely well as the number of neurons in the network increases. Clustering accuracy is robust to variations in model parameters and highly tolerant to simulated experimental noise, achieving perfect classifications with up to 40% of swapped edges. Thus, this approach may be useful to analyze and interpret large-scale brain connectomics data in terms of underlying cellular components.

Comparative evaluation of thoracoscopy versus thoracotomy in the management of lung hydatid disease.

BACKGROUND: Lung hydatid disease is an endemic problem in Mediterranean countries, and the ideal surgical management for it is still debated. In this prospective study, we aimed to evaluate the feasibility and safety of thoracoscopy in patients with lung hydatid disease. We studied the advantages of thoracoscopic procedure over posterolateral thoracotomy. METHODS: A total of 32 patients with an uncomplicated, unilateral lung hydatid cyst were subjected to surgical treatment over a period of 5 years. Of the 32 patients, 18 were treated with thoracotomy and 14 with thoracoscopy. Observations were made with regard to duration and ease of operation, complications, hospital stay, return to activity, and recurrence. RESULTS: The mean operative duration in the thoracoscopy group was 95.21 min compared to 137.77 min in thoracotomy group (P < 0.0001). Postoperative analgesia requirement was less in the thoracoscopic group (mean 4.92 days) compared to that in the thoracotomy group (mean 13.94 days; P < 0.0001). The intercostal drain was removed earlier in the thoracoscopic group (mean 5 days) than in the thoracotomy group (mean 8.83 days; P < 0.0001). The postoperative hospital stay was 8.35 days (mean) in thoracoscopic group and 18.77 days in the thoracotomy group (P < 0.0001). The most serious morbidity was wound infection, with three cases (16.66%) in the thoracotomy group and one (7.11%) in the thoracoscopy group. There was no operative mortality and no recurrence during the follow-up period. CONCLUSIONS: We strongly recommend the use of thoracoscopy as a primary tool for the management of uncomplicated, unilateral lung hydatid disease. Thoracoscopy offers a great advantage over open thoracotomy in terms of very low morbidity.

Laser optoacoustic imaging system for detection of breast cancer.

We designed, fabricated and tested the laser optoacoustic imaging system for breast cancer detection (LOIS-64), which fuses optical and acoustic imaging techniques in one modality by utilizing pulsed optical illumination and ultrawide-band ultrasonic detection of resulting optoacoustic (OA) signals. The system was designed to image a single breast slice in craniocaudal or mediolateral projection with an arc-shaped array of 64 ultrawide-band acoustic transducers. The system resolution on breast phantoms was at least 0.5 mm. The single-channel sensitivity of 1.66 mVPa was estimated to be sufficient for single-pulse imaging of 6 to 11 mm tumors through the whole imaging slice of the breast. The implemented signal processing using the wavelet transform allowed significant reduction of the low-frequency (LF) acoustic noise, allowed localization of the optoacoustic signals from tumors, and enhanced the contrast and sharpened the boundaries of the optoacoustic images of the tumors. During the preliminary clinical studies on 27 patients, the LOIS-64 was able to visualize 18 out of 20 malignant lesions suspected from mammography and ultrasound images and confirmed by the biopsy performed after the optoacoustic tomography (OAT) procedure.

Quantifying Neuronal Information Flow in Response to Frequency and Intensity Changes in the Auditory Cortex.

Studies increasingly show that behavioral relevance alters the population representation of sensory stimuli in the sensory cortices. However, the mechanisms underlying this behavior are incompletely understood. Here, we record neuronal responses in the auditory cortex while a highly trained, awake, normal-hearing gerbil listens passively to target tones of high versus low behavioral relevance. Using an information theoretic framework, we model the overall transmission chain from acoustic input stimulus to recorded cortical response as a communication channel. To quantify how much information core auditory cortex carries about high versus low relevance sound, we then compute the mutual information of the multi-unit neuronal responses. Results show that the output over the stimulus-to-response channel can be modeled as a Poisson mixture. We derive a closed-form fast approximation for the entropy of a mixture of univariate Poisson random variables. A purely rate-code based model reveals reduced information transfer for high relevance compared to low relevance tones, hinting that changes in temporal discharge pattern may encode behavioral relevance.

Detection and visualization of defects in 3D unstructured models of nematic liquid crystals.

A method for the semi-automatic detection and visualization of defects in models of nematic liquid crystals (NLCs) is introduced; this method is suitable for unstructured models, a previously unsolved problem. The detected defects-also known as disclinations-are regions were the alignment of the liquid crystal rapidly changes over space; these defects play a large role in the physical behavior of the NLC substrate. Defect detection is based upon a measure of total angular change of crystal orientation (the director) over a node neighborhood via the use of a nearest neighbor path. Visualizations based upon the detection algorithm clearly identifies complete defect regions as opposed to incomplete visual descriptions provided by cutting-plane and isosurface approaches. The introduced techniques are currently in use by scientists studying the dynamics of defect change.

Superellipsoid-based, real symmetric traceless tensor glyphs motivated by nematic liquid crystal alignment visualization.

A glyph-based method for visualizing the nematic liquid crystal alignment tensor is introduced. Unlike previous approaches, the glyph is based upon physically-linked metrics, not offsets of the eigenvalues. These metrics, combined with a set of superellipsoid shapes, communicate both the strength of the crystal's uniaxial alignment and the amount of biaxiality. With small modifications, our approach can visualize any real symmetric traceless tensor.

Influence of methacrylic and acrylic acid polymers on the release performance of weakly basic drugs from sustained release hydrophilic matrices.

Weakly basic drugs and their salts exhibit a drop in aqueous solubility at high pH conditions, which can result in low and incomplete release of these drugs from sustained release formulations. The objective of this study is to modulate matrix microenvironmental pH by incorporation of acidic polymers and thus enhance the local solubility and release of basic drugs in high pH environment. Two weakly basic drugs, papaverine hydrochloride and verapamil hydrochloride with widely different pKa and aqueous solubilities at the pH of interest (6.8), were investigated for their release from hydrophilic matrices and the effect of a methacrylic (Eudragit L100-55) and an acrylic acid polymer (Carbopol 71G), were studied. For papaverine HCl, release increased with an increase in the levels of the acidic polymer used. Direct measurement of matrix pH using microelectrodes illustrated that the mechanism of release enhancement was based on modulation of microenvironmental pH. For verapamil HCl, incorporation of L100-55 resulted in release retardation due to an interaction between the anionic polymer and the cationic drug and the extent of retardation increased with an increase in the polymer level. The interaction product was characterized by NIR, FT-IR, and MTDSC techniques. Verapamil HCl release from Carbopol 71G based matrix tablets was higher than that from conventional hydroxypropyl methylcellulose (HPMC) based matrices, without any incorporated acidic additives.

Formulation of enterosoluble microparticles for an acid labile protein.

PURPOSE: A microencapsulation method that preserves the activity of an acid labile protein was developed. METHODS: Solvent evaporation technique that employed ICH class 2 and 3 solvents methanol and acetone, respectively to dissolve pH-sensitive Eudragit polymers was investigated. Total protein released and lactase activities were measured using the USP method A for enteric cores and optimized with respect to process parameters. RESULTS: The percentage yields and entrapment efficiencies were directly proportional to solid content. The mean percentage yield and entrapment efficiency of selected sample was 84 +/- 0.9% and 88 +/- 0.7%, respectively. The residual specific activity of lactase in the selected sample was 89% +/- 0.8 with a net activity loss of 2 +/- 0.28% and 4 +/- 0.52% under ambient and stressed storage, respectively. Dibutyl sebacate levels, lower processing temperatures and lower processing speeds were influential in modulating enzyme activity. The most important formulation factor affecting lactase stability was Eudragit type, followed in decreasing order by processing temperature, processing speed, and solid percentage. CONCLUSIONS: Reliable control of lactase release was achieved by microencapsulating the enzyme with pH-sensitive Eudragit L and S enteric polymers using either acetone- or methanol-based solvent but lactase activity was preserved only in acetone-based formulations.

Effect of fixed dose combinations of metoprolol and amlodipine in essential hypertension: MARS--a randomized controlled trial.

AIM: To compare two strengths of a fixed drug combination (FDC) containing metoprolol XL and amlodipine (metoprolol/amlodipine 50/5; and metoprolol/amlodipine 25/2.5) with its components in hypertension. METHODS: We conducted this multicentre, randomized, open-label, trial in Indian patients with hypertension (140-180 mmHg/90-114 mmHg) in 11 centres from nine cities. Eligible patients (n = 402) were randomized into one of five treatment groups (metoprolol XL 50 mg + amlodipine 5 mg, metoprolol XL 25 mg + amlodipine 2.5 mg, metoprolol XL 50 mg, metoprolol XL 25 mg or amlodipine 5 mg) and treated for 8 weeks with five follow-up visits to record blood pressure (BP) and clinical status. RESULTS: At baseline, treatment groups were well balanced; mean +/- SD BP was 154.87 +/- 11.91/96.63 +/- 6.97 mmHg. The greatest reduction in BP from baseline to 8 weeks was seen in the high-dose FDC group (23.61/14.91 mmHg; p<0.001). The remaining 4 groups too demonstrated a significant reduction (p< 0.001): low-dose FDC - 22.29/ - 14.66; metoprolol 50, - 23.17/ - 13.37; metoprolol 25,- 18.41/ 12.50 and amlodipine 5, - 23.01/- 13.08. BP reductions by FDCs, however, were not statistically superior to monotherapies. Responder rates (sitting diastolic BP< 90 mmHg or reduction > or =10 mmHg) were 93% in the high-dose FDC group and 97% in the low-dose FDC group, and control rates (sitting BP < 140/90 mmHg) were 66% and 58%, respectively. These rates were higher than that seen in individual components. There were no reports of serious adverse events related to study medications. One each from the low-dose FDC and metoprolol 25 mg group discontinued because of adverse events. CONCLUSIONS: FDCs of metoprolol and amlodipine are effective and safe in mild to moderate hypertension.