Modeling the impact of biolarvicides on malaria transmission.

Biolarvicides are in use in several parts of the world for malaria vector control. We propose a five compartment dynamical systems model to study malaria transmission when biolarvicides are administered, to study the impact of this environmentally safe method on malaria spread. A comprehensive analysis of the model is presented. Model analysis shows that the basic reproductive rate R is larger in the absence of biolarvicides as compared to their presence. Theoretical analysis is corroborated by data from field studies. We show that there exist intermediate parameter regimes that separate disease-free and endemic states, which can in turn be modulated by biolarvicide use. Using Latin hypercube sampling we study the sensitivity of the model to parameter value changes. Calibration of our model to mosquito population and biolarvicide data for indoor and outdoors scenarios, yield parameter values hitherto not available or measurable. We validate our model with malaria incidence data from a region in India and provide predictions for malaria incidence in the presence and absence of biolarvicide. This model provides a prognostic tool to field work involving biolarvicide use in control of malaria.

To study the occurrence of risk factors for pulmonary tuberculosis in the homeless population in areas of Delhi, India.

BACKGROUND: In India, there are only a few studies done in the area of assessing the risk factors of Tuberculosis (TB) among the homeless population. The homeless population has quite a higher chance of developing Pulmonary Tuberculosis (PTB) as compared with the general population due to the presence of an inappropriate environment and high prevalence of risk factors. METHODS: This study was done among the homeless population in both males and females aged 18 years and above in areas of Delhi (Yamuna Pusta and Mansarovar Park). The participants were screened for TB symptoms and risk factors to diagnose active PTB in them. RESULTS: Out of 200 participants, 17 were diagnosed with active PTB. The overall occurrence of Tuberculosis among the studied homeless population was found to be 85 cases per 1000 population. The occurrence of behavioral habits such as smoking was found to be 41.2% (7/17), tobacco chewing at 47.1% (8/17), and alcohol at 47.1% (8/17) among the cases. The occurrence of HIV coinfection was 5.9% (1/17) and diabetes was 5.9% (1/17). The prevalence of TB among homeless females was 1.5 times higher than homeless males but out of 17 diagnosed patients, males had a higher prevalence of TB as compared to females. CONCLUSION: The occurrence of PTB in the homeless population is quite high as it is also reported in a study in the United States that the national incidence of tuberculosis in the homeless population was 36 cases/100,000 and it needs to be addressed to eliminate tuberculosis.7 Moreover, the risk factors such as tobacco, smoking, alcohol, coinfections, etc. might have played a major role in the development of PTB. Also, there is a need for larger studies with large sample sizes to provide evidence against the same.

Infection control and preventing the transmission of tuberculosis in high-risk centres - recovery shelter for homeless people.

The term "infection control" refers to the policies and practices used in hospitals and other healthcare facilities to limit the spread of illnesses with the primary goal of lowering infection rates. The objective is to reduce the chance of infection in patients and Healthcare workers (HCWs). This may be achieved by making all the HCWs to follow and practice the infection prevention and control (IPC) guidelines and by providing safe and quality healthcare. Because of more exposure to TB patients and insufficient TB infection prevention and control (TBIPC) procedures in a healthcare facility, healthcare workers (HCWs) working in TB centers are at an elevated risk of contracting TB. Although there are a number of TBIPC guidelines, there is limited knowledge of their contents, if they are applicable in the given situation, and whether they are being properly applied in TB centers. The purpose of this study was to observe the TBIPC guidelines' implementation in CES (Centre of equity studies) recovery shelters well as the elements that affect it. The percentage of public health care personnel who used proper TBIPC practices was low. The execution of TBIPC guidelines in tuberculosis (TB) centers was poor. It was impacted because TB treatment institutions and centers have unique health systems and TB disease burdens.

Clinicopathological Challenges in Tumors of the Nasal Cavity and Paranasal Sinuses: Our Experience.

Background and objective Nasal and paranasal lesions are one of the most common otorhinolaryngological presentations encountered in clinical practice. Common presenting symptoms of these lesion range from nasal blockades, facial swellings, pain, nasal discharge, and epistaxis to orbital and ear symptoms. Diagnosis can be tricky as these symptoms are common in inflammatory conditions and tumors. The aim of our study was to observe the epidemiology and clinical pathological findings in patients with nasal and paranasal masses presenting to our institute and discuss the challenges in proper diagnosis and management due to similar presentations, and the role of histopathological examination (HPE) and immunohistochemistry (IHC) in overcoming these challenges. Methods The IPD records of 396 patients were taken up for the study. All the specimens were sent in 10% neutral buffered formalin for examination as biopsy for diagnosis or after surgical excision. After adequate fixation, the biopsy specimen was submitted for routine processing, followed by paraffin embedding, and stained with hematoxylin and eosin (H&E). Special stains like periodic acid-Schiff (PAS) and Ziehl-Neelsen (ZN) stains for acid-fast bacilli (AFB) were used as required. IHC was performed in the required samples. IHC markers were performed on representative paraffin-embedded sections according to the streptavidin-biotin immunoperoxidase technique as needed. The findings were noted, and histology was correlated with clinical presentations and investigations, tabulated, and statistically analyzed using SPSS Statistics (IBM, Armonk, NY). Results Of note, 67.92%% were non-neoplastic lesions whereas 18.18% came out to be benign neoplasms and 13.88% were malignant lesions on HPE. Nasal obstruction was the most common presenting symptom (73.23% of patients) followed by nasal mass (64.14% of cases). Inflammatory sinonasal polyps were the most prominent cases in our study, accounting for 41.16% of all lesions; 18.68% fungal RS (mucormycosis) were seen in our study and 4.54% were cases of juvenile nasopharyngeal angiofibroma (JNA). The majority of benign neoplasms encountered were Schneiderian papilloma or inverted papilloma (06.81%). Eighteen (4.54%) cases of squamous cell carcinomas (SCC) were seen in our study and 2.77% (n=11) cases were of adenoid cystic carcinoma. Of 18 cases of SCC, moderately differentiated SCC carcinoma accounted for 10 cases followed by poorly differentiated SCC (5/18) and nonkeratinizing SCC (3/18). IHC for p40 was performed in all the cases of nonkeratinizing SCC, which showed strong and diffuse nuclear positivity. Conclusion The nasal cavity is the site of the most varied presentation of tumors in the upper respiratory tract. Mass in the nose and paranasal sinus (PNS) form a heterogeneous group of lesions with varied histopathological features. The proximity of the area to the eyes and brain warrants early definitive diagnosis so that the lesion is treated before it can involve important and vital centers. Even though malignant nasal tumors have a very low incidence, they cause a lot of morbidity due to their long course and frequent local recurrences. Nasal tumors tend to become polypoidal. Epithelioid papilloma of the nasal cavity often resembles a nasal polyp. Clinical diagnosis can be challenging due to similar presentations and appearances, and hence histological examination is a vital tool for the timely diagnosis of such patients.

Is Chemical Cauterization Safe on Septal Cartilage in Treatment of Recurrent Epistaxis?

Epistaxis is one of the most common emergencies. Topical agents such as silver nitrate, is known to be a strong oxidizing agent and have been widely used, especially in recurrent and refractory cases. The extent of depth of coagulative necrosis is dependent on time of exposure and concentration. 2 mm wide bar of nasal septum from 30 patients was taken and AgNO3 was applied for 10, 20, 40 s. H&E staining was then performed to see depth of penetration and intensity of stain deposits. It was observed that with increase time of application, depth of penetration and density of deposits were increased for both 75% and 100% concentration of solution. Distribution in depth of penetration was significant when 75% concentration was applied for more than 20 s. But when 100% concentration was used, similar findings were found even after 10 s in young age group. Our study shows that when silver nitrate is used for chemical cauterization in different concentrations and for different times, their penetration is different. Moreover, the depth of penetration depends more on the time of contact than concentration of silver nitrate. We would recommend using 75% solution for use with a contact time not more than 20 s in adults and 10 s in children.

Nivalenol Mycotoxin Concerns in Foods: An Overview on Occurrence, Impact on Human and Animal Health and Its Detection and Management Strategies.

Mycotoxins are secondary metabolites produced by fungi that infect a wide range of foods worldwide. Nivalenol (NIV), a type B trichothecene produced by numerous Fusarium species, has the ability to infect a variety of foods both in the field and during post-harvest handling and management. NIV is frequently found in cereal and cereal-based goods, and its strong cytotoxicity poses major concerns for both human and animal health. To address these issues, this review briefly overviews the sources, occurrence, chemistry and biosynthesis of NIV. Additionally, a brief overview of several sophisticated detection and management techniques is included, along with the implications of processing and environmental factors on the formation of NIV. This review's main goal is to offer trustworthy and current information on NIV as a mycotoxin concern in foods, with potential mitigation measures to assure food safety and security.

Optimization, modeling, and characterization study for the physicochemical properties of raw banana and defatted soy composite extrudates.

Novel raw banana and defatted soy composite extrudates were formulated to combat celiac enteropathy. The influence of four independent parameters viz. barrel temperature (BT: 60-80 °C), screw speed (SS: 200-300 rpm), moisture content (MC: 10-20%, wb), and defatted soy flour content (SFC: 0-32%) on physicochemical properties of extrudates were evaluated. Response surface methodology (RSM) identified the optimum extrusion conditions (80 °C BT, 200 rpm SS, 10% MC, and 32% SFC). Compared to RSM (R2:0.379-0.918), artificial neural network (R2:0.909-0.991) proved as a better tool for response prediction. Scanning electron microscopy confirmed the antagonistic effect of SFC addition on extrudate porosity. The addition of SFC decreased the crystallinity of the starch granules (71 to 49%), whereas, storage time had a positive effect (49 to 53%) on crystallinity of the composite extrudates. Fourier transform infrared spectroscopy analysis elucidated the secondary structures of protein in the composite flour which were degraded during the extrusion cooking.

De-novo Drug Design, Molecular Docking and In-Silico Molecular Prediction of AChEI Analogues through CADD Approaches as Anti-Alzheimer's Agents.

BACKGROUND: There are over 44 million persons who suffer with Alzheimer's disease (AD) worldwide, no existence of cure and only symptomatic treatments are available for it. The aim of this study is to evaluate the anti-Alzheimer potential of designed AChEI analogues using computer simulation docking studies. AChEIs are the most potential standards for treatment of AD, because they have proven efficacy. Among all AChEIs donepezil possesses lowest adverse effects, it can treat mildmoderate- severe AD and only once-daily dosing is required. Therefore, donepezil is recognized as a significant prototype for design and development of new drug molecule. METHODS: In this study the Inhibitory potential of the design compounds on acetylcholinesterase enzyme has been evaluated. Docking studies has been performed which further analyzed by in-silico pharmacokinetic evaluation through pharmacopredicta after that Interaction modes with enzyme active sites were determined. Docking studies revealed that there is a strong interaction between the active sites of AChE enzyme and analyzed compounds. RESULTS: As a result 26 compounds have been indicates better inhibitory activity on AChE enzyme and all the screening parameters have also been satisfied by all 26 compounds. From these 26 compounds, six compounds 17, 18, 24, 30, 36 and 56 are found to be the most potent inhibitors of this series by insilico study through INVENTUS v 1.1 software, having highest bio-affinities i.e. - 8.51, - 7.67, - 8.30, - 7.59, - 8.71 and -7.62 kcal/mol respectively, while the standard or reference drug donepezil had binding affinity of - 6.32 kcal/mol. CONCLUSION: Computer aided drug design approach has been playing an important role in the design and development of novel anti- AD drugs. With the help of structure based drug design some novel analogues of donepezil have been designed and the molecular docking studies with structure based ADME properties prediction studies is performed for prediction of AChE inhibitory activity. The binding mode of proposed compounds with target protein i.e. AChE has been evaluated and the resulting data from docking studies explains that all of the newly designed analogues had significantly high affinity towards target protein compared to donepezil as a reference ligand.

A TB model: Is disease eradication possible in India?

Tuberculosis (TB) is returning to be a worldwide global public health threat. It is estimated that 9.6 million cases occurred in 2014, of which just two-thirds notified to public health authorities. The "missing cases" constitute a severe challenge for TB transmission control. TB is a severe disease in India, while, worldwide, the WHO estimates that one third of the entire world population is infected. Nowadays, incidence estimation relies increasingly more on notifications of new cases from routine surveillance. There is an urgent need for better estimates of the load of TB, in high-burden settings. We developed a simple model of TB transmission dynamics, using a dynamical system model, consisting of six classes of individuals. It contains the current medical epidemiologists' understanding of the spread of the Mycobacterium tuberculosis in humans, which is substantiated by field observations at the district level in India. The model incorporates the treatment options provided by the public and private sectors in India. Mathematically, an interesting feature of the system is that it exhibits a backward, or subcritical, bifurcation. One of the results of the investigation shows that the discrepancy between the diagnosis rates of the public and private sector does not seem to be the cause of the endemicity of the disease, and, unfortunately, even if they reached 100% of correct diagnosis, this would not be enough to achieve disease eradication. Several other approaches have been attempted on the basis of this model to indicate possible strategies that may lead to disease eradication, but the rather sad conclusion is that they unfortunately do not appear viable in practice.

Feasibility of achieving the 2025 WHO global tuberculosis targets in South Africa, China, and India: a combined analysis of 11 mathematical models.

BACKGROUND: The post-2015 End TB Strategy proposes targets of 50% reduction in tuberculosis incidence and 75% reduction in mortality from tuberculosis by 2025. We aimed to assess whether these targets are feasible in three high-burden countries with contrasting epidemiology and previous programmatic achievements. METHODS: 11 independently developed mathematical models of tuberculosis transmission projected the epidemiological impact of currently available tuberculosis interventions for prevention, diagnosis, and treatment in China, India, and South Africa. Models were calibrated with data on tuberculosis incidence and mortality in 2012. Representatives from national tuberculosis programmes and the advocacy community provided distinct country-specific intervention scenarios, which included screening for symptoms, active case finding, and preventive therapy. FINDINGS: Aggressive scale-up of any single intervention scenario could not achieve the post-2015 End TB Strategy targets in any country. However, the models projected that, in the South Africa national tuberculosis programme scenario, a combination of continuous isoniazid preventive therapy for individuals on antiretroviral therapy, expanded facility-based screening for symptoms of tuberculosis at health centres, and improved tuberculosis care could achieve a 55% reduction in incidence (range 31-62%) and a 72% reduction in mortality (range 64-82%) compared with 2015 levels. For India, and particularly for China, full scale-up of all interventions in tuberculosis-programme performance fell short of the 2025 targets, despite preventing a cumulative 3·4 million cases. The advocacy scenarios illustrated the high impact of detecting and treating latent tuberculosis. INTERPRETATION: Major reductions in tuberculosis burden seem possible with current interventions. However, additional interventions, adapted to country-specific tuberculosis epidemiology and health systems, are needed to reach the post-2015 End TB Strategy targets at country level. FUNDING: Bill and Melinda Gates Foundation.

Cost-effectiveness and resource implications of aggressive action on tuberculosis in China, India, and South Africa: a combined analysis of nine models.

BACKGROUND: The post-2015 End TB Strategy sets global targets of reducing tuberculosis incidence by 50% and mortality by 75% by 2025. We aimed to assess resource requirements and cost-effectiveness of strategies to achieve these targets in China, India, and South Africa. METHODS: We examined intervention scenarios developed in consultation with country stakeholders, which scaled up existing interventions to high but feasible coverage by 2025. Nine independent modelling groups collaborated to estimate policy outcomes, and we estimated the cost of each scenario by synthesising service use estimates, empirical cost data, and expert opinion on implementation strategies. We estimated health effects (ie, disability-adjusted life-years averted) and resource implications for 2016-35, including patient-incurred costs. To assess resource requirements and cost-effectiveness, we compared scenarios with a base case representing continued current practice. FINDINGS: Incremental tuberculosis service costs differed by scenario and country, and in some cases they more than doubled existing funding needs. In general, expansion of tuberculosis services substantially reduced patient-incurred costs and, in India and China, produced net cost savings for most interventions under a societal perspective. In all three countries, expansion of access to care produced substantial health gains. Compared with current practice and conventional cost-effectiveness thresholds, most intervention approaches seemed highly cost-effective. INTERPRETATION: Expansion of tuberculosis services seems cost-effective for high-burden countries and could generate substantial health and economic benefits for patients, although substantial new funding would be required. Further work to determine the optimal intervention mix for each country is necessary. FUNDING: Bill & Melinda Gates Foundation.