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A landscape analysis of health technology assessment capacity in the Association of South-East Asian Nations region

Sharma M, Teerawattananon Y, Dabak SV, Isaranuwatchai W, Pearce F, Pilasant S, et al.

Health Res Policy Syst, 2021 Feb 11;19(1):19.
PMID: 33573676 DOI: 10.1186/s12961-020-00647-0

BACKGROUND: Progress towards achieving Universal Health Coverage and institutionalizing healthcare priority setting through health technology assessment (HTA) in the Association of South-East Asian Nations (ASEAN) region varies considerably across countries because of differences in healthcare expenditure, political support, access to health information and technology infrastructure. To explore the status and capacity of HTA in the region, the ASEAN Secretariat requested for member countries to be surveyed to identify existing gaps and to propose solutions to help countries develop and streamline their priority-setting processes for improved healthcare decision-making.
METHODS: A mixed survey questionnaire with open- and closed-ended questions relating to HTA governance, HTA infrastructure, supply and demand of HTA and global HTA networking opportunities in each country was administered electronically to representatives of HTA nodal agencies of all ASEAN members. In-person meetings or email correspondence were used to clarify or validate any unclear responses. Results were collated and presented quantitatively.
RESULTS: Responses from eight out of ten member countries were analysed. The results illustrate that countries in the ASEAN region are at different stages of HTA institutionalization. While Malaysia, Singapore and Thailand have well-established processes and methods for priority setting through HTA, other countries, such as Cambodia, Indonesia, Lao PDR, Myanmar, the Philippines and Vietnam, have begun to develop HTA systems in their countries by establishing nodal agencies or conducting ad-hoc activities.
DISCUSSION AND CONCLUSION: The study provides a general overview of the HTA landscape in ASEAN countries. Systematic efforts to mitigate the gaps between the demand and supply of HTA in each country are required while ensuring adequate participation from stakeholders so that decisions for resource allocation are made in a fair, legitimate and transparent manner and are relevant to each local context.
A novel automated diagnostic system for classification of myocardial infarction ECG signals using an optimal biorthogonal filter bank

Sharma M, Tan RS, Acharya UR

Comput Biol Med, 2018 11 01;102:341-356.
PMID: 30049414 DOI: 10.1016/j.compbiomed.2018.07.005

Myocardial infarction (MI), also referred to as heart attack, occurs when there is an interruption of blood flow to parts of the heart, due to the acute rupture of atherosclerotic plaque, which leads to damage of heart muscle. The heart muscle damage produces changes in the recorded surface electrocardiogram (ECG). The identification of MI by visual inspection of the ECG requires expert interpretation, and is difficult as the ECG signal changes associated with MI can be short in duration and low in magnitude. Hence, errors in diagnosis can lead to delay the initiation of appropriate medical treatment. To lessen the burden on doctors, an automated ECG based system can be installed in hospitals to help identify MI changes on ECG. In the proposed study, we develop a single-channel single lead ECG based MI diagnostic system validated using noisy and clean datasets. The raw ECG signals are taken from the Physikalisch-Technische Bundesanstalt database. We design a novel two-band optimal biorthogonal filter bank (FB) for analysis of the ECG signals. We present a method to design a novel class of two-band optimal biorthogonal FB in which not only the product filter but the analysis lowpass filter is also a halfband filter. The filter design problem has been composed as a constrained convex optimization problem in which the objective function is a convex combination of multiple quadratic functions and the regularity and perfect reconstruction conditions are imposed in the form linear equalities. ECG signals are decomposed into six subbands (SBs) using the newly designed wavelet FB. Following to this, discriminating features namely, fuzzy entropy (FE), signal-fractal-dimensions (SFD), and renyi entropy (RE) are computed from all the six SBs. The features are fed to the k-nearest neighbor (KNN). The proposed system yields an accuracy of 99.62% for the noisy dataset and an accuracy of 99.74% for the clean dataset, using 10-fold cross validation (CV) technique. Our MI identification system is robust and highly accurate. It can thus be installed in clinics for detecting MI.
Adductor accessorius - an unusual supernumerary adductor muscle of thigh

Goel S, Arora J, Mehta V, Sharma M, Suri RK, Rath G, et al.

Clin Ter, 2015;166(3):114-7.
PMID: 26152618 DOI: 10.7417/CT.2015.1840

The knowledge of variant anatomy of medial compartment of thigh is extremely important in surgical procedures requiring obturator nerve block. The nerve block is also recommended for providing additional analgesia following major knee surgeries and for relieving painful adductor muscle spasm. The interfascial injection technique is commonly followed in ultrasound guided obturator nerve block. For this procedure it is imperative to identify the adductor muscles on sonography to inject the anesthetic solution in the intermuscular fascial planes. The presence of an additional muscle can prove useful in myocutaneous flap surgeries for reconstruction especially of perineum. We hereby report a case of such an anomalous supernumerary adductor muscle present between adductor brevis and proximal part of adductor magnus, in an adult Indian male cadaver, recorded during routine dissection in Department of Anatomy, Vardhman Mahavir Medical College and Safdarjung Hospital. The muscle was innervated by the posterior division of obturator nerve. The morphology, embryological basis and clinical aspects are also discussed.
Fulltext Advanced drug delivery systems can assist in targeting coronavirus disease (COVID-19): A hypothesis

Mehta M, Prasher P, Sharma M, Shastri MD, Khurana N, Vyas M, et al.

Med Hypotheses, 2020 Nov;144:110254.
PMID: 33254559 DOI: 10.1016/j.mehy.2020.110254

The highly contagious coronavirus, which had already affected more than 2 million people in 210 countries, triggered a colossal economic crisis consequently resulting from measures adopted by various goverments to limit transmission. This has placed the lives of many people infected worldwide at great risk. Currently there are no established or validated treatments for COVID-19, that is approved worldwide. Nanocarriers may offer a wide range of applications that could be developed into risk-free approaches for successful therapeutic strategies that may lead to immunisation against the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) which is the primary causative organism that had led to the current COVID-19 pandemic. We address existing as well as emerging therapeutic and prophylactic approaches that may enable us to effectively combat this pandemic, and also may help to identify the key areas where nano-scientists can step in.
Advanced drug delivery systems targeting NF-κB in respiratory diseases

Prasher P, Sharma M, Chellappan DK, Gupta G, Jha NK, Singh SK, et al.

Future Med Chem, 2021 07;13(13):1087-1090.
PMID: 33947226 DOI: 10.4155/fmc-2021-0013
An accurate sleep stages classification system using a new class of optimally time-frequency localized three-band wavelet filter bank

Sharma M, Goyal D, Achuth PV, Acharya UR

Comput Biol Med, 2018 07 01;98:58-75.
PMID: 29775912 DOI: 10.1016/j.compbiomed.2018.04.025

Sleep related disorder causes diminished quality of lives in human beings. Sleep scoring or sleep staging is the process of classifying various sleep stages which helps to detect the quality of sleep. The identification of sleep-stages using electroencephalogram (EEG) signals is an arduous task. Just by looking at an EEG signal, one cannot determine the sleep stages precisely. Sleep specialists may make errors in identifying sleep stages by visual inspection. To mitigate the erroneous identification and to reduce the burden on doctors, a computer-aided EEG based system can be deployed in the hospitals, which can help identify the sleep stages, correctly. Several automated systems based on the analysis of polysomnographic (PSG) signals have been proposed. A few sleep stage scoring systems using EEG signals have also been proposed. But, still there is a need for a robust and accurate portable system developed using huge dataset. In this study, we have developed a new single-channel EEG based sleep-stages identification system using a novel set of wavelet-based features extracted from a large EEG dataset. We employed a novel three-band time-frequency localized (TBTFL) wavelet filter bank (FB). The EEG signals are decomposed using three-level wavelet decomposition, yielding seven sub-bands (SBs). This is followed by the computation of discriminating features namely, log-energy (LE), signal-fractal-dimensions (SFD), and signal-sample-entropy (SSE) from all seven SBs. The extracted features are ranked and fed to the support vector machine (SVM) and other supervised learning classifiers. In this study, we have considered five different classification problems (CPs), (two-class (CP-1), three-class (CP-2), four-class (CP-3), five-class (CP-4) and six-class (CP-5)). The proposed system yielded accuracies of 98.3%, 93.9%, 92.1%, 91.7%, and 91.5% for CP-1 to CP-5, respectively, using 10-fold cross validation (CV) technique.
Fulltext An international, multi-institution survey of the use of EUS in the diagnosis of pancreatic cystic lesions

Ge N, Brugge WR, Saxena P, Sahai A, Adler DG, Giovannini M, et al.

Endosc Ultrasound, 2019 9 26;8(6):418-427.
PMID: 31552915 DOI: 10.4103/eus.eus_61_19

Background and Objectives: Currently, pancreatic cystic lesions (PCLs) are recognized with increasing frequency and have become a more common finding in clinical practice. EUS is challenging in the diagnosis of PCLs and evidence-based decisions are lacking in its application. This study aimed to develop strong recommendations for the use of EUS in the diagnosis of PCLs, based on the experience of experts in the field.
Methods: A survey regarding the practice of EUS in the evaluation of PCLs was drafted by the committee member of the International Society of EUS Task Force (ISEUS-TF). It was disseminated to experts of EUS who were also members of the ISEUS-TF. In some cases, percentage agreement with some statements was calculated; in others, the options with the greatest numbers of responses were summarized.
Results: Fifteen questions were extracted and disseminated among 60 experts for the survey. Fifty-three experts completed the survey within the specified time frame. The average volume of EUS cases at the experts' institutions is 988.5 cases per year.
Conclusion: Despite the limitations of EUS alone in the morphologic diagnosis of PCLs, the results of the survey indicate that EUS-guided fine-needle aspiration is widely expected to become a more valuable method.
Application of an optimal class of antisymmetric wavelet filter banks for obstructive sleep apnea diagnosis using ECG signals

Sharma M, Agarwal S, Acharya UR

Comput Biol Med, 2018 09 01;100:100-113.
PMID: 29990643 DOI: 10.1016/j.compbiomed.2018.06.011

Obstructive sleep apnea (OSA) is a sleep disorder caused due to interruption of breathing resulting in insufficient oxygen to the human body and brain. If the OSA is detected and treated at an early stage the possibility of severe health impairment can be mitigated. Therefore, an accurate automated OSA detection system is indispensable. Generally, OSA based computer-aided diagnosis (CAD) system employs multi-channel, multi-signal physiological signals. However, there is a great need for single-channel bio-signal based low-power, a portable OSA-CAD system which can be used at home. In this study, we propose single-channel electrocardiogram (ECG) based OSA-CAD system using a new class of optimal biorthogonal antisymmetric wavelet filter bank (BAWFB). In this class of filter bank, all filters are of even length. The filter bank design problem is transformed into a constrained optimization problem wherein the objective is to minimize either frequency-spread for the given time-spread or time-spread for the given frequency-spread. The optimization problem is formulated as a semi-definite programming (SDP) problem. In the SDP problem, the objective function (time-spread or frequency-spread), constraints of perfect reconstruction (PR) and zero moment (ZM) are incorporated in their time domain matrix formulations. The global solution for SDP is obtained using interior point algorithm. The newly designed BAWFB is used for the classification of OSA using ECG signals taken from the physionet's Apnea-ECG database. The ECG segments of 1 min duration are decomposed into six wavelet subbands (WSBs) by employing the proposed BAWFB. Then, the fuzzy entropy (FE) and log-energy (LE) features are computed from all six WSBs. The FE and LE features are classified into normal and OSA groups using least squares support vector machine (LS-SVM) with 35-fold cross-validation strategy. The proposed OSA detection model achieved the average classification accuracy, sensitivity, specificity and F-score of 90.11%, 90.87% 88.88% and 0.92, respectively. The performance of the model is found to be better than the existing works in detecting OSA using the same database. Thus, the proposed automated OSA detection system is accurate, cost-effective and ready to be tested with a huge database.
Biobased natural deep eutectic system as versatile solvents: Structure, interaction and advanced applications

Usmani Z, Sharma M, Tripathi M, Lukk T, Karpichev Y, Gathergood N, et al.

Sci Total Environ, 2023 Jul 10;881:163002.
PMID: 37003333 DOI: 10.1016/j.scitotenv.2023.163002

The increasing emphasis on the development of green replacements to traditional organic solvents and ionic liquids (ILs) can be attributed to the rising concerns over human health and detrimental impacts of conventional solvents towards the environment. A new generation of solvents inspired by nature and extracted from plant bioresources has evolved over the last few years, and are referred to as natural deep eutectic solvents (NADES). NADES are mixtures of natural constituents like sugars, polyalcohols, sugar-based alcohols, amino acids and organic acids. Interest in NADES has exponentially grown over the last eight years, which is evident from an upsurge in the number of research projects undertaken. NADES are highly biocompatible as they can be biosynthesized and metabolized by nearly all living organisms. These solvents pose several noteworthy advantages, such as easy synthesis, tuneable physico-chemical properties, low toxicity, high biodegradability, solute sustainability and stabilization and low melting point. Research on the applicability of NADES in diverse areas is gaining momentum, which includes as - media for chemical and enzymatic reactions; extraction media for essential oils; anti-inflammatory and antimicrobial agent; extraction of bioactive composites; as chromatographic media; preservatives for labile compounds and in drug synthesis. This review gives a complete overview of the properties, biodegradability and toxicity of NADES which we propose can assist in further knowledge generation on their significance in biological systems and usage in green and sustainable chemistry. Information on applications of NADES in biomedical, therapeutic and pharma-biotechnology fields is also highlighted in the current article along with the recent progress and future perspectives in novel applications of NADES.
Can dextran-based nanoparticles mitigate inflammatory lung diseases?

Prasher P, Sharma M, R Wich P, Jha NK, Singh SK, Chellappan DK, et al.

Future Med Chem, 2021 12;13(23):2027-2031.
PMID: 34596425 DOI: 10.4155/fmc-2021-0218
Chitin and chitosan derived from crustacean waste valorization streams can support food systems and the UN Sustainable Development Goals

Amiri H, Aghbashlo M, Sharma M, Gaffey J, Manning L, Moosavi Basri SM, et al.

Nat Food, 2022 Oct;3(10):822-828.
PMID: 37117878 DOI: 10.1038/s43016-022-00591-y

Crustacean waste, consisting of shells and other inedible fractions, represents an underutilized source of chitin. Here, we explore developments in the field of crustacean-waste-derived chitin and chitosan extraction and utilization, evaluating emerging food systems and biotechnological applications associated with this globally abundant waste stream. We consider how improving the efficiency and selectivity of chitin separation from wastes, redesigning its chemical structure to improve biotechnology-derived chitosan, converting it into value-added chemicals, and developing new applications for chitin (such as the fabrication of advanced nanomaterials used in fully biobased electric devices) can contribute towards the United Nations Sustainable Development Goals. Finally, we consider how gaps in the research could be filled and future opportunities could be developed to make optimal use of this important waste stream for food systems and beyond.
Chromobacterium violaceum septicaemia from north India

Ray P, Sharma J, Marak RS, Singhi S, Taneja N, Garg RK, et al.

Indian J Med Res, 2004 Dec;120(6):523-6.
PMID: 15654137

Though Chromobacterium violaceum is a common inhabitant of soil and water in tropical and sub-tropical regions, human infections are rare but when they do occur result in high mortality. Since the first case from Malaysia in 1927, about 150 cases have been reported in world literature. Till date 6 cases have been reported from southern and eastern parts of India. We report here a case of C. violaceum septicaemia, probably the first case from north India. The patient, a 6 and a half year old boy was admitted with high fever. The patient had anaemia, neutrophilic leucocytosis and bilateral chest infiltrates. Routine and bacteriological investigations were carried out to establish the aetiological diagnosis. C. violaceum was isolated in pure culture from blood and pus. The patient was successfully treated with ciprofloxacin and amikacin. This is probably the first documented case report of C. violaceum infection from north India and the only Indian case with septicaemia which survived.
Fulltext Comparative Studies of Palmatine with Metformin and Glimepiride on the Modulation of Insulin Dependent Signaling Pathway In Vitro, In Vivo & Ex Vivo

Nwabueze OP, Sharma M, Balachandran A, Gaurav A, Abdul Rani AN, Małgorzata J, et al.

Pharmaceuticals (Basel), 2022 Oct 25;15(11).
PMID: 36355489 DOI: 10.3390/ph15111317

(1) Insulin resistance, a symptom of type 2 diabetes mellitus (T2DM), is caused by the inactivation of the insulin signaling pathway, which includes IRS-PI3K-IRS-1-PKC-AKT2 and GLUT4. Metformin (biguanide) and glimepiride (sulfonylurea) are both drugs that are derivatives of urea, and they are widely used as first-line drugs for the treatment of type 2 diabetes mellitus. Palmatine has been previously reported to possess antidiabetic and antioxidant properties. (2) The current study compared palmatine to metformin and glimepiride in a type 2 diabetes model for ADME and insulin resistance via the PI3K/Akt/GLUT4 signaling pathway: in vitro, in vivo, ex vivo, and in silico molecular docking. (3) Methods: Differentiated L6 skeletal muscle cells and soleus muscle tissue were incubated in standard tissue culture media supplemented with high insulin and high glucose as a cellular model of insulin resistance, whilst streptozotocin (STZ)-induced Sprague Dawley rats were used as the diabetic model. The cells/tissue/animals were treated with palmatine, while glimepiride and metformin were used as standard drugs. The differential gene expression of PI3K, IRS-1, PKC-α, AKT2, and GLUT4 was evaluated using qPCR. (4) Results: The results revealed that the genes IRS-PI3K-IRS-1-PKC-AKT2 were significantly down-regulated, whilst PKC-α was upregulated significantly in both insulin-resistant cells and tissue animals. Interestingly, palmatine-treated cells/tissue/animals were able to reverse these effects. (5) Conclusions: Palmatine appears to have rejuvenated the impaired insulin signaling pathway through upregulation of the gene expression of IRS-1, PI3K, AKT2, and GLUT4 and downregulation of PKC-expression, according to in vitro, in vivo, and ex vivo studies.
Comparing NAL-NL1 and DSL v5 in Hearing Aids Fit to Children with Severe or Profound Hearing Loss: Goodness of Fit-to-Targets, Impacts on Predicted Loudness and Speech Intelligibility

Ching TY, Quar TK, Johnson EE, Newall P, Sharma M

J Am Acad Audiol, 2015 Mar;26(3):260-74.
PMID: 25751694 DOI: 10.3766/jaaa.26.3.6

BACKGROUND: An important goal of providing amplification to children with hearing loss is to ensure that hearing aids are adjusted to match targets of prescriptive procedures as closely as possible. The Desired Sensation Level (DSL) v5 and the National Acoustic Laboratories' prescription for nonlinear hearing aids, version 1 (NAL-NL1) procedures are widely used in fitting hearing aids to children. Little is known about hearing aid fitting outcomes for children with severe or profound hearing loss.
PURPOSE: The purpose of this study was to investigate the prescribed and measured gain of hearing aids fit according to the NAL-NL1 and the DSL v5 procedure for children with moderately severe to profound hearing loss; and to examine the impact of choice of prescription on predicted speech intelligibility and loudness.
RESEARCH DESIGN: Participants were fit with Phonak Naida V SP hearing aids according to the NAL-NL1 and DSL v5 procedures. The Speech Intelligibility Index (SII) and estimated loudness were calculated using published models.
STUDY SAMPLE: The sample consisted of 16 children (30 ears) aged between 7 and 17 yr old.
DATA COLLECTION AND ANALYSIS: The measured hearing aid gains were compared with the prescribed gains at 50 (low), 65 (medium), and 80 dB SPL (high) input levels. The goodness of fit-to-targets was quantified by calculating the average root-mean-square (RMS) error of the measured gain compared with prescriptive gain targets for 0.5, 1, 2, and 4 kHz. The significance of difference between prescriptions for hearing aid gains, SII, and loudness was examined by performing analyses of variance. Correlation analyses were used to examine the relationship between measures.
RESULTS: The DSL v5 prescribed significantly higher overall gain than the NAL-NL1 procedure for the same audiograms. For low and medium input levels, the hearing aids of all children fit with NAL-NL1 were within 5 dB RMS of prescribed targets, but 33% (10 ears) deviated from the DSL v5 targets by more than 5 dB RMS on average. For high input level, the hearing aid fittings of 60% and 43% of ears deviated by more than 5 dB RMS from targets of NAL-NL1 and DSL v5, respectively. Greater deviations from targets were associated with more severe hearing loss. On average, the SII was higher for DSL v5 than for NAL-NL1 at low input level. No significant difference in SII was found between prescriptions at medium or high input level, despite greater loudness for DSL v5 than for NAL-NL1.
CONCLUSIONS: Although targets between 0.25 and 2 kHz were well matched for both prescriptions in commercial hearing aids, gain targets at 4 kHz were matched for NAL-NL1 only. Although the two prescriptions differ markedly in estimated loudness, they resulted in comparable predicted speech intelligibility for medium and high input levels.
Constraints on parton distribution functions and extraction of the strong coupling constant from the inclusive jet cross section in pp collisions at [Formula: see text][Formula: see text]

Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, et al.

Eur Phys J C Part Fields, 2015 06 26;75(6):288.
PMID: 26146483

The inclusive jet cross section for proton-proton collisions at a centre-of-mass energy of 7[Formula: see text] was measured by the CMS Collaboration at the LHC with data corresponding to an integrated luminosity of 5.0[Formula: see text]. The measurement covers a phase space up to 2[Formula: see text] in jet transverse momentum and 2.5 in absolute jet rapidity. The statistical precision of these data leads to stringent constraints on the parton distribution functions of the proton. The data provide important input for the gluon density at high fractions of the proton momentum and for the strong coupling constant at large energy scales. Using predictions from perturbative quantum chromodynamics at next-to-leading order, complemented with electroweak corrections, the constraining power of these data is investigated and the strong coupling constant at the Z boson mass [Formula: see text] is determined to be [Formula: see text], which is in agreement with the world average.
Constraints on the pMSSM, AMSB model and on other models from the search for long-lived charged particles in proton-proton collisions at [Formula: see text]

Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, et al.

Eur Phys J C Part Fields, 2015 07 17;75(7):325.
PMID: 26213486

Stringent limits are set on the long-lived lepton-like sector of the phenomenological minimal supersymmetric standard model (pMSSM) and the anomaly-mediated supersymmetry breaking (AMSB) model. The limits are derived from the results presented in a recent search for long-lived charged particles in proton-proton collisions, based on data collected by the CMS detector at a centre-of-mass energy of 8 TeV at the Large Hadron Collider. In the pMSSM parameter sub-space considered, 95.9 % of the points predicting charginos with a lifetime of at least 10 ns are excluded. These constraints on the pMSSM are the first obtained at the LHC. Charginos with a lifetime greater than 100 ns and masses up to about 800 GeV in the AMSB model are also excluded. The method described can also be used to set constraints on other models.
Fulltext Correction to: Review of global neurosurgery education: Horizon of Neurosurgery in the Developing Countries

Kato Y, Liew BS, Sufianov AA, Rasulic L, Arnautovic KI, Dong VH, et al.

Chinese neurosurgical journal, 2020;6:30.
PMID: 32925985 DOI: 10.1186/s41016-020-00209-x

[This corrects the article DOI: 10.1186/s41016-020-00194-1.].
Cysteine-rich antimicrobial peptides from plants: The future of antimicrobial therapy

Srivastava S, Dashora K, Ameta KL, Singh NP, El-Enshasy HA, Pagano MC, et al.

Phytother Res, 2021 Jan;35(1):256-277.
PMID: 32940412 DOI: 10.1002/ptr.6823

There has been a spurt in the spread of microbial resistance to antibiotics due to indiscriminate use of antimicrobial agents in human medicine, agriculture, and animal husbandry. It has been realized that conventional antibiotic therapy would be less effective in the coming decades and more emphasis should be given for the development of novel antiinfective therapies. Cysteine rich peptides (CRPs) are broad-spectrum antimicrobial agents that modulate the innate immune system of different life forms such as bacteria, protozoans, fungi, plants, insects, and animals. These are also expressed in several plant tissues in response to invasion by pathogens, and play a crucial role in the regulation of plant growth and development. The present work explores the importance of CRPs as potent antimicrobial agents, which can supplement and/or replace the conventional antibiotics. Different plant parts of diverse plant species showed the presence of antimicrobial peptides (AMPs), which had significant structural and functional diversity. The plant-derived AMPs exhibited potent activity toward a range of plant and animal pathogens, protozoans, insects, and even against cancer cells. The cysteine-rich AMPs have opened new avenues for the use of plants as biofactories for the production of antimicrobials and can be considered as promising antimicrobial drugs in biotherapeutics.
Development of solid dispersion systems of dapivirine to enhance its solubility

Gorajana A, Ying CC, Shuang Y, Fong P, Tan Z, Gupta J, et al.

Curr Drug Deliv, 2013 Jun;10(3):309-16.
PMID: 23360246

Dapivirine, formerly known as TMC 120, is a poorly-water soluble anti-HIV drug, currently being developed as a vaginal microbicide. The clinical use of this drug has been limited due to its poor solubility. The aim of this study was to design solid dispersion systems of Dapivirine to improve its solubility. Solid dispersions were prepared by solvent and fusion methods. Dapivirine release from the solid dispersion system was determined by conducting in-vitro dissolution studies. The physicochemical characteristics of the drug and its formulation were studied using Differential Scanning Calorimetry (DSC), powder X-ray Diffraction (XRD), Fourier-transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). A significant improvement in drug dissolution rate was observed with the solid dispersion systems. XRD, SEM and DSC results indicated the transformation of pure Dapivirine which exists in crystalline form into an amorphous form in selected solid dispersion formulations. FTIR and HPLC analysis confirmed the absence of drug-excipient interactions. Solid dispersion systems can be used to improve the dissolution rate of Dapivirine. This improvement could be attributed to the reduction or absence of drug crystallinity, existence of drug particles in an amorphous form and improved wettability of the drug.
Distributions of topological observables in inclusive three- and four-jet events in pp collisions at [Formula: see text][Formula: see text]

Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, Dragicevic M, et al.

Eur Phys J C Part Fields, 2015 07 01;75(7):302.
PMID: 26190937

This paper presents distributions of topological observables in inclusive three- and four-jet events produced in pp collisions at a centre-of-mass energy of 7[Formula: see text] with a data sample collected by the CMS experiment corresponding to a luminosity of 5.1[Formula: see text]. The distributions are corrected for detector effects, and compared with several event generators based on two- and multi-parton matrix elements at leading order. Among the considered calculations, MadGraph interfaced with pythia6 displays the overall best agreement with data.

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