Forecasting the Anti-Rabies Vaccine Demand at Jawaharlal Medical College and Hospital, Ajmer, Rajasthan: A Comparative Analysis based on Time Series Model

Background: In India, high mortality and morbidity rates of human rabies is observed. Hence, a structured surveillance system is yet to be put in place for public health discussion. At the tertiary care hospital and all public health centres, requirement of anti-rabies vaccine is needed in advance to predict the upcoming months coverage so that wastage of vaccine is minimum. Objective: To find a suitable model for forecasting the appropriate stock of anti-rabies vaccines to avoid shortage and over-supply at anti rabies clinic. Methods and Material: This was a record based cross sectional study, conducted at anti rabies clinic of Jawaharlal Nehru Medical College and Hospital, Ajmer. Data of used anti rabies vaccine was taken from immunization inventory during the period from 2017 to 2020. Time series analysis based on Holt-Winter and Box-Jenkins methods were carried out to predict the need of vaccine. Results: Study series was not stationary and stationarity was observed by taken difference in the observation between two consequent months. Residuals of the series were normally distributed and independent to each other. ARIMA(0, 1, 1) was the best model in comparison to Holt-Winter model for prediction because of low value of model selection criterion.  The forecasted value for anti-rabies vaccine was done for the year 2021. Conclusions: The following study concluded that time series can be used as a tool to forecast anti-rabies vaccine coverage and will help the policy makers to formulate appropriate plans and strategies and improve the management of vaccination resources and inventory

Efficacy of IGFBP7 for treatment of metastatic melanoma and other cancers in mouse models and human cell lines

We recently identified the secreted protein IGFBP7 as a factor required for an activated BRAF oncogene to induce senescence or apoptosis in primary human cells. In human melanomas containing an activating BRAF mutation (BRAF-positive melanomas), IGFBP7 is epigenetically silenced, which seems to be a critical step in melanoma genesis. Restoration of IGFBP7 function by the addition of recombinant IGFBP7 (rIGFBP7) induces apoptosis in BRAF-positive human melanoma cell lines, and systemically administered rIGFBP7 markedly suppresses the growth of BRAF-positive primary tumors in xenografted mice. Here we further evaluate the role of IGFBP7 in the treatment of BRAF-positive melanoma and other malignancies. We find that in human metastatic melanoma samples IGFBP7 is epigenetically silenced and at an even higher frequency than that found in primary melanomas. Using a murine experimental metastasis assay, we show that systemic administration of rIGFBP7 markedly suppresses the growth of metastatic disease and prolongs survival. An analysis of the NCI60 panel of human cancer cell lines reveals that in addition to melanoma, IGFBP7 induces apoptosis in several other cancer types, in particular colorectal cancer cell lines. In general, IGFBP7 induces apoptosis in human cancer cell lines that have an activating mutation in BRAF or RAS, and that are sensitive to chemical inhibition of BRAF-MEK-ERK signaling. Significantly, systemically administered rIGFBP7 blocks the growth of colorectal tumors containing an activating RAS or BRAF mutation in mouse xenografts. The results presented here, in conjunction with those from previous studies, justify the further development of IGFBP7 as an anticancer agent

ACCELERATED STABILITY STUDY OF CHITRAK HARITAKI AVALEHA

Objective: Accelerated stability study of Chitrak Haritaki avaleha was done for six months to know the stability of formulation in reference of its phyto-constituents and microbial growth therein.Methods: Chitrak Haritaki avaleha was made in laboratory following classical method [Sample lab (SL)] as per AFI part-1(The Ayurvedic formulary of India, part-1) and two samples were collected from local market [Market Sample-1(MK-1) & Market sample-2 (MK-2)] of reputed brand. These three samples were put in controlled condition following ICH (International Conference on Harmonization) guidelines for accelerated stability study for six months. The intermediate samplings were done at starting, after one, three and six month respectively. These samples were investigated for reducing sugar, phyto-constituents (Total tannins, piperine, vitamin C and total polyphenols contents), microbial load and their organoleptic characteristics. Results: All the results were calculated and compared for variation during course of time. Variation in the result of samples was evaluated against Arrhenius equation which ensured that formulation was stable over two years and no significant variation was found over six month of accelerated stability condition.Conclusion: Since it is traditional avalehakalpana, the shelf life period was about one year (Sharangdhar Samhita) and updated to three year in Drug and cosmetic rule 1945, 161B. The presented study reflect that Chitrak Haritaki avaleha was stable over two year (by taking inference from Arrhenious equation) and more sophisticated packing may improve the shelf life period.Keywords: Avaleha, Shelf life, Accelerated stability, Chitrak Haritaki avaleha

CTCF-mediated topological boundaries during development foster appropriate gene regulation

The genome is organized into repeating topologically associated domains (TADs), each of which is spatially isolated from its neighbor by poorly understood boundary elements thought to be conserved across cell types. Here, we show that deletion of CTCF (CCCTC-binding factor)-binding sites at TAD and sub-TAD topological boundaries that form within the HoxA and HoxC clusters during differentiation not only disturbs local chromatin domain organization and regulatory interactions but also results in homeotic transformations typical of Hox gene misregulation. Moreover, our data suggest that CTCF-dependent boundary function can be modulated by competing forces, such as the self-assembly of polycomb domains within the nucleus. Therefore, CTCF boundaries are not merely static structural components of the genome but instead are locally dynamic regulatory structures that control gene expression during development

Does mobile phone instructional video demonstrating sputum expectoration improve the sputum sample quality and quantity in presumptive pulmonary TB cases? Protocol for a prospective pragmatic non-randomised controlled trial in Karnataka state, India.

INTRODUCTION: Sputum smear microscopy is the cornerstone of tuberculosis (TB) diagnosis under the Revised National Tuberculosis Control Programme (RNTCP) in India. Instructions on how to produce a good sputum sample are a part of RNTCP training manuals, but its assessment is not emphasised. Healthcare provider's instruction to expectorate a good sputum sample has limitations. Presumptive TB patients often submit inadequate (in quantity and/or quality) sputum samples, which may result in false-negative results. Objectives of the study are, among the selected RNTCP designated microscopy centres in Dakshina Kannada district, Karnataka, India, (a) to assess the effectiveness of mobile phone instructional video demonstrating sputum expectoration on sputum quality and quantity and (b) to explore the mobile phone video implementation challenges as perceived by the healthcare providers. METHODS AND ANALYSIS: This is a pragmatic, prospective, non-randomised controlled trial in two pairs of RNTCP Designated Microscopy Centres (located at secondary and primary healthcare facilities) of Dakshina Kannada district, India. Presumptive pulmonary TB patients aged ≥18 years will be included. We will exclude who are severely ill, blind, hearing impaired, patients who have already brought their sputum for examination, and transported sputum. In the intervention group, participants will watch a mobile phone instructional video demonstrating submission of an adequate sputum sample. The control group will follow the usual ongoing procedure for sputum submission. This study would require 406 participants for each group to achieve a power of 90% for detecting a difference of 15% between the two groups. The participant enrolment started in December 2019. ETHICS AND DISSEMINATION: Yenepoya University Ethics Committee, Mangaluru, India, has approved the study protocol (YEC-1/158/2019). It complies with the Declaration of Helsinki, local laws, and the International Council for Harmonization-good clinical practices. Investigators will present the results in scientific forums, publish in a scientific journal, and share with RNTCP officers. TRIAL REGISTRATION NUMBER: Clinical Trial Registry of India (CTRI/2019/06/019887)

DISCRIMINATORY POTENTIAL OF BIPHASIC MEDIUM OVER COMPENDIAL AND BIORELEVANT MEDIUM FOR ASSESSMENT OF DISSOLUTION BEHAVIOR OF TABLETS CONTAINING MELOXICAM NANOPARTICLES

ABSTRACTObjective: Dissolution test serves as a quality control tool for assessment of drug release from dosage form as well as a research tool to optimize newformulations. The existing guidelines by FDA, EMA, ICH, USP, etc., describe specifications for the dissolution of immediate release as well as modifiedrelease oral dosage form. However, none of them have discussed about the discriminatory potential of the medium to differentiate release profile of twoor more products that are pharmaceutically equivalent. It is pertinent to add here that the pharmaceutical equivalents are not always bioequivalent.Hence, a discriminatory dissolution procedure is a must requirement to differentiate the release behavior of drug from a pharmaceutically equivalentproduct that contains different types and amount of excipient in the formulation. This also becomes more cumbersome when it is desirable forprediction of in vivo behavior of a drug when it is converted into a novel delivery system like nanoparticles. The reason could be the presence ofexcipients used to formulate drug nanoparticles into solid oral dosage form, may change the drug disintegration as well as dissolution behavior, whichultimately may lead to altered bioavailability.Methods: In this study, the nanoparticles of meloxicam were prepared using wet media milling and the milled samples were dried using spray drier.The dried nanoparticles were converted into tablet dosage form by varying the type of diluent. To one batch lactose was used and another one wascontaining dicalcium phosphate (DCP). The assessment of release of meloxicam from these two batches was evaluated in various dissolution media.Results: The study revealed that in all the cases the nanoparticulate tablets of Batch 1 have given increased dissolution profile as compared tomarketed formulation (Muvera), Batch 2 and controlled tablets of meloxicam. This proved that the excipients also play a major role in the releasebehavior of drug otherwise if it was not so, the nanoparticulate tablets of Batch 1 and Batch 2 would have given the same dissolution profile in all thetried media. Batch 1 containing lactose with a higher surface area provided more and rapid wetting of the drug by the dissolution media compared toBatch 2 that contained DCP as a major diluent.®Conclusion: Among all the dissolution media tried to evaluate the discriminatory power and simulation with a biorelevant medium, the biphasicmedium of pH 1.8, 4.8 and 6.8 has promised to simulate with biorelevant media. However, the medium of pH 6.8 has shown the best dissolution profile.Keywords: Solubility, Compendial media, Biphasic media, Dissolution, Meloxicam

INFLUENCE OF FORMULATION PARAMETERS ON DISSOLUTION RATE ENHANCEMENT OF PIROXICAM USING LIQUISOLID TECHNIQUE

ABSTRACTObjective: This study revealed formulation of a liquisolid system of poorly soluble piroxicam to enhance its dissolution rate. To formulate a liquisolidsystem loaded with piroxicam, solubility study was carried out in various non-volatile liquids.Methods: In 1 ml of polyethylene glycol (PEG) 600, 100 mg piroxicam was added and stirred with gentle heating. To the above liquid medication, 1 gmicrocrystalline cellulose (MCC) 102 (as MCC has given better results), 1 g Syloid 244 FP, 2 g PEG 4000, 500 mg aerosil 200, and 0.255 g sodium starchglycolate (SSG) (5%) were added and mixed properly. The blend was compressed and subjected for quality control parameters.Results: Among all the non-volatile liquids evaluated, piroxicam was most soluble in PEG 600. Using this as liquid medication, several liquisolid compactswere prepared by varying the ratios of MCC PH 102 as carrier and Syloid 244FP as coating material and evaluated for precompression studies. To furtheraccelerate the release of drug, various additives were added in the formulation. Among them, PEG 4000 has shown better flow as well as compressionproperties. Hence, the final formulation (LS-16B) was prepared using a combination of MCC PH 102, Syloid 244 FP, PEG 4000 and SSG as superdisintegrant.The dissolution studies revealed that about 92.18% drug got released from liquisolid compacts in 120 minutes, whereas only 68.16% release wasobserved for pure piroxicam. X-ray diffraction and scanning electron microscopy images revealed the successful formation of liquisolid system.Conclusion: It was concluded that dissolution rate of poorly soluble piroxicam could be enhanced using liquisolid technique.Keywords: Piroxicam, Polyethylene glycol 600, Microcrystalline cellulose PH 102, Syloid 244 FP, Polyethylene glycol 4000

FORMULATION, SYSTEMATIC OPTIMIZATION, IN VITRO, EX VIVO, AND STABILITY ASSESSMENT OF TRANSETHOSOME BASED GEL OF CURCUMIN

Objectives: The current work presents a formulation of curcumin-loaded transethosome (CRM-TE) in the form of a gel and its characterization.Methods: Thirteen formulations were prepared by varying the concentration of Phospholipon 90G as lipid, ethanol, and ratio of lipid: Span using Box- Behnken Design. The optimized formulation was characterized by vesicle size, entrapment efficiency, drug retention, drug permeation through skin, and morphology. Parameters of CRM-TE were compared to other vesicular systems that include liposomes, ethosomes, and transfersomes. Optimized CRM-TE was incorporated into gels, and comparative evaluation was performed. CRM-TE gel was kept at 5±3°C, 25±3°C, and 40±3°C for 180 days, further evaluated for entrapment efficacy and vesicle size.Results: CRM-TE showed 286.4 nm vesicle size, 61.2% entrapment efficiency, 19.8% drug retention, and 71.3% drug permeation at 24 h in the skin. It was found superior in terms of all the parameters as compared to other vesicular formulations. CRM-TE gel also exhibited best characteristics in terms of entrapment efficiency, drug retention, and drug permeation. CRM-TE gel exhibited better stability at 5±3°C in terms of vesicle size and entrapment efficiency as compared to other storage conditions.Conclusion: CRM-TE gel could offer efficient delivery of curcumin through topical route

INVESTIGATION AND OPTIMIZATION OF FORMULATION PARAMETERS FOR SELFNANOEMULSIFYING DELIVERY SYSTEM OF TWO LIPOPHILIC AND GASTROINTESTINAL LABILE DRUGS USING BOX-BEHNKEN DESIGN

Objective: Present research work aims toward codelivery of two hydrophobic drugs, curcumin (CRM) and duloxetine hydrochloride (DXH) through self-nanoemulsifying drug delivery systems (SNEDDS).Methods: Initially, binary mixture in the ratio of 1:1 was prepared and then loaded into SNEDDS. Box-Behnken design (BBD) was adopted to develop SNEDDS. As per the optimal design, 13 SNEDDS prototypes were prepared. Castor oil, tween-80 and Transcutol P® were used as oil, surfactant, and cosurfactant, respectively. To 1 mL of SNEDDS, 30 mg each of CRM and DXH was loaded (CRM-DXH- SNEDDS).Results: The design revealed that for mean droplet size, polydispersity index (PDI), as well as percentage drug loading, all the three factors, i.e. ratio of oil (a), surfactant (b), and cosurfactant (c) were found to give significant effect. Factor B showed the most significant effect on mean droplet size (y1). In case of PDI (y2), factors B and C exerted maximum influence, whereas, Factor A has shown non-significant effect. For percentage drug loading of drugs (y3 and y4), all the three factors were found to have the most significant effect. The optimized batch of CRM-DXH- SNEDDS having composition castor oil, tween-80, and Transcutol P® in the ratio: 2.17:5.22:2.61, revealed that the mean drug loading (%) of CRM and DXH in an optimized batch of SNEDDS was found to be 87.22±1.87 and 92.32±0.19%, respectively. The mean droplet size, PDI, and zeta potential of formed SNEDDS were observed as 113.14±1.14 nm, 0.20±0.026, and −13.2 mV, respectively.Conclusion: BBD provided optimal formula composition for SNEDDS for obtaining desirable drug loading, emulsion droplet size, and zeta potential

A comprehensive evaluation of multicategory classification methods for microbiomic data

BACKGROUND: Recent advances in next-generation DNA sequencing enable rapid high-throughput quantitation of microbial community composition in human samples, opening up a new field of microbiomics. One of the promises of this field is linking abundances of microbial taxa to phenotypic and physiological states, which can inform development of new diagnostic, personalized medicine, and forensic modalities. Prior research has demonstrated the feasibility of applying machine learning methods to perform body site and subject classification with microbiomic data. However, it is currently unknown which classifiers perform best among the many available alternatives for classification with microbiomic data. RESULTS: In this work, we performed a systematic comparison of 18 major classification methods, 5 feature selection methods, and 2 accuracy metrics using 8 datasets spanning 1,802 human samples and various classification tasks: body site and subject classification and diagnosis. CONCLUSIONS: We found that random forests, support vector machines, kernel ridge regression, and Bayesian logistic regression with Laplace priors are the most effective machine learning techniques for performing accurate classification from these microbiomic data