Metamorphosis of Twin Screw Extruder-Based Granulation Technology: Applications Focusing on Its Impact on Conventional Granulation Technology.

In order to be at pace with the market requirements of solid dosage forms and regulatory standards, a transformation towards systematic processing using continuous manufacturing (CM) and automated model-based control is being thought through for its fundamental advantages over conventional batch manufacturing. CM eliminates the key gaps through the integration of various processes while preserving quality attributes via the use of process analytical technology (PAT). The twin screw extruder (TSE) is one such equipment adopted by the pharmaceutical industry as a substitute for the traditional batch granulation process. Various types of granulation techniques using twin screw extrusion technology have been explored in the article. Furthermore, individual components of a TSE and their conjugation with PAT tools and the advancements and applications in the field of nutraceuticals and nanotechnology have also been discussed. Thus, the future of granulation lies on the shoulders of continuous TSE, where it can be coupled with computational mathematical studies to mitigate its complications.

Crosstalk between Vaginal Microbiome and Female Health: A review.

Microbiota plays a fundamental role in the overall development and defences of human beings. The majority of indigenous microbiota exists in a mutually beneficial relationship with their hosts, while few of these are opportunistic pathogens that can lead to life-threatening diseases and chronic infections. These microbial communities constitute the primary defence against infections induced by non-indigenous invasive organisms. Female vaginal ecosystem thought to have been shaped over the years by co-evolutionary processes occurring between the particular microbial partners and the human host. Vaginal secretions contain numerous microorganisms and the host provides them nutrients for their growth and development. Disruptions in vaginal association with the microbiomes lead to the change in the vaginal environment, which enhanced the risk of acquiring diseases including sexually transmitted infections, bacterial vaginosis, fungal infections, preterm birth etc. The focus of this review is on the detailed analysis of vaginal microbiome interplay and its overall impact on female health. The mutualistic relationship between the vagina and residing microbial species has been well described. Finally, the recent advancements in the detection of microbiome interactions with the vaginal environment have been presented.

Immobilization alters heparin cleaving properties of heparinase I.

We report here a novel observation that immobilization of heparinase I on CNBr-activated Sepharose results in heparin degradation properties that are different from heparinase I in the free solution form. Studies over a range of pHs (5-8) and temperatures (5-50°C) as well as under batch and flow conditions show that immobilized heparinase 1 displays altered pH and temperature optima, and a higher propensity for generation of longer chains (hexa- and octa-) with variable sulfation as compared to that in the free form, which is known to yield disaccharides. The immobilized enzyme retained good eliminase activity over at least five cycles of reuse. In combination, results suggest that heparinase I immobilization may offer a more productive route to longer, variably sulfated sequences.

Potential of biosynthesized titanium dioxide nanoparticles towards wastewater treatment and antimicrobial activity.

This study reports a green, sustainable, reliable, and cost-effective method for the biosynthesis of titanium dioxide nanoparticles (TiO2NPs) using the leaf and stem extracts of Carissa opaca. The newly synthesized biogenic TiO2NPs were confirmed and characterized using various analytical techniques, such as Fourier transform infrared spectroscopy (FTIR), high-resolution transmission electron microscopy (HRTEM), dynamic light scattering (DLS), zeta potential, X-ray diffraction (XRD), inductively coupled plasma analysis (ICP), and scanning electron microscopy (SEM). Both the electron microscopy, i.e., SEM and HRTEM confirmed the spherical/hexagonal crystalline structure of TiO2NPs with an average particle size range from 72.8 to 84.11 nm. These nanoparticles (NPs) exhibited aggregation and possessed a diverse array of functional groups on their surface. Biosynthesized TiO2NPs showed excellent photocatalytic activity against methylene blue (MB) with decolorizing efficiency of 87.8% and 91.95%, whereas in case of methyl violet (MV), the decolorizing efficiency of 82.1% and 71.9% was observed with nanoparticles synthesized using leaf and stem extract, respectively. The newly synthesized NPs have also shown good antibacterial potential against Klebsiella pneumoniae and Staphylococcus aureus. This new biomimetic approach offers an economical and environmentally benign alternative for the removal of hazardous dyes and may find a place for antimicrobial applications.

Role of vaginal microbiota in idiopathic infertility: a prospective study.

OBJECTIVE: The causes of idiopathic infertility are still not known; however, it may be associated with microbial etiologies. The present study examines the vaginal microbiota of infertile as well as fertile women longitudinally. METHODOLOGY: The study was presented and accepted by the Institutional Ethical Committee of Shri Mata Vaishno Devi University, Katra, Jammu and Kashmir (India). An observational, prospective, multicenteric investigation was conducted at the Department of Obstetrics and Gynecology, Government Medical College Jammu, and its affiliated hospitals in Jammu and Kashmir (India). In order to examine the microbial composition, a cohort of 80 female individuals were involved in the screening process. The investigation involved sequencing of the V3-V4 region of 16S rRNA gene, which was subsequently analyzed using the Mothur pipeline. RESULTS: The study revealed that the vaginal microbiota of infertile women differed from that of healthy women who had previously given birth without any complications. Both populations have variations in their alpha as well as beta diversity and taxonomical composition. The microbial profiles in the cases of infertility are characterized by elevated levels of Gardnerella, Prevotella, Atopobium, and Enterococcus whereas a higher level of Lactobacillus iners was observed in case of fertile women. CONCLUSION: In conclusion, it can be inferred that the composition of the vaginal microbiome potentially exerts a significant influence on females afflicted with idiopathic infertility.

Vaginal microbiome: considerations for reproductive health.

The microbial communities are an indispensable part of the human defense system and coexist with humans as symbionts, contributing to the metabolic functions and immune defense against pathogens. An ecologically stable vaginal microbiota is dominated by Lactobacillus species, which plays an important role in the prevention of genital infections by controlling the vaginal pH, reducing glycogen to lactic acid, and stimulating bacteriocins and hydrogen peroxide. In contrast, an abnormal vaginal microbial composition is associated with an increased risk of bacterial vaginosis, trichomoniasis, sexually transmitted diseases, preterm labor and other birth defects. This microbial diversity is affected by race, ethnicity, pregnancy, hormonal changes, sexual activities, hygiene practices and other conditions. In the present review, we discuss the changes in the microbial community of the vaginal region at different stages of a female's life cycle and its influence on her reproductive health and pathological conditions.

Degradation of synthetic dyes using nanoparticles: a mini-review.

The industrial revolution has marked a strong impact on financial upgradation of several countries, and increase in the industrial establishment globally has direct impact on environment because of the release of unwanted product in air and inside the water bodies. The use of dyes has increased tremendously in various industries ranging from food, leather, textile, paper, cosmetic, pharmaceuticals, etc. The problem has emerged due to disposing of the dyes in the open environment, and mostly it is disposed along with the industrial wastes into the water bodies, which becomes harmful for animals, aquatic life and human health. This review highlights the role of the nanoparticles particularly biosynthesized nanoparticles for eliminating the dyes from the industrial wastewater. There are several methods for the synthesis of nanoparticle including physical, chemical and green synthesis of nanoparticles commonly known as biological method. Among all, the biological method is considered as the rapid, easy, eco-friendly and is being performed at mild conditions. The uses of nanoparticles for removal of dyes from water minimize the hazardous impact and thus considered to be the best approach as far as water quality and safety of environment is concerned.

Reducing Financial Barriers for Households Due to COVID-19: The Case in India.

As countries all over the world grapple with containing the COVID-19 outbreak, Low- and Middle-Income Countries (LMICs) are particularly hard-pressed because on the one hand, the pandemic has created unforeseen high demand for health services which requires increased spending. On the other hand, the contagion and the public health measures taken to curb it have disrupted economies whilst creating additional spending pressures as well. This constrains the policy options available for LMICs to ensure an adequate and sustainable financing for the health sector's COVID-19 response whilst maintaining routine supply of essential health services. Despite this, as demonstrated by India, many LMICs are undertaking many reform efforts to address both the health and economic hardships caused by the pandemic. In this commentary, we describe the policy tools that one such LMIC, India, has used to enable financing for the outbreak.

Health financing reforms for Universal Health Coverage in five emerging economies.

BACKGROUND: Many countries have committed to achieving Universal Health Coverage. This paper summarizes selected health financing themes from five middle-income country case studies with incomplete progress towards UHC. METHODS: The paper focuses on key flagship UHC programs in these countries, which exist along other publicly financed health delivery systems, reviewed through the lens of key health financing functions such as revenue raising, pooling and purchasing as well as governance and institutional arrangements. RESULTS: There is variable progress across countries. Indonesia's Jaminan Kesehatan Nasional (JKN) reforms have made substantial progress in health services coverage and health financing indicators though challenges remain in its implementation. In contrast, Ghana has seen reduced funding levels for health and achieved less than 50% in the UHC service coverage index. In India, despite Ayushman Bharat (PM-JAY) reforms having provided important innovations in purchasing and public-private mix, out of pocket spending remains high and the public health financing level low. Kenya still has a challenge to use public financing to enhance coverage for the informal sector, while South Africa has made little progress in strategic purchasing. CONCLUSIONS: Despite variations across countries, therefore, important challenges include inadequate financing, sub-optimal pooling, and unmet expectations in strategic purchasing. While complex federal systems may complicate the path forward for most of these countries, evidence of strong political commitment in some of these countries bodes well for further progress.

An Insight into Vaginal Microbiome Techniques.

There is a unique microbial community in the female lower genital tract known as the vaginal microbiota, which varies in composition and density and provides significant benefits during pregnancy, reproductive cyclicity, healthy newborn delivery, protection from preterm birth, infections such as UTIs, bacterial vaginosis, and so on, and improves the efficacy of treatments for vaginal cancers. Methods: It is necessary to know how the vaginal microbiome is composed in order to make an accurate diagnosis of the diseases listed above. A microbiome's members are difficult to classify, and the way microbial communities function and influence host-pathogen interactions are difficult to understand. More and more metagenomic studies are able to unravel such complexities due to advances in high-throughput sequencing and bioinformatics. When it comes to vaginal microbiota research, we'll be looking at the use of modern techniques and strategies that can be used to investigate variations in vaginal microbiota in order to detect diseases earlier, better treat vaginal disorders, and boost women's health. Discussion: The discussed techniques and strategies may improve the treatment of vaginal disorders and may be beneficial for women's overall health.

Bioactive compounds and probiotics-a ray of hope in COVID-19 management.

The use of bioactive compounds and probiotic bacteria against the viral diseases in human is known for a long time. Anti-viral, anti-inflammatory and anti-allergic properties of bioactive compounds and bacteria with probiotic properties in respiratory viral diseases may have significance to enhance immunity. This review highlights some of the important bioactive compounds and probiotic bacteria, suggesting them as a ray of hope in the milieu of the COVID-19 management.

Enantioselective resolution of 2-arylpropionic acid derivatives employing immobilization of lipase from Bacillus subtilis strain Kakrayal_1 (BSK-L).

This work studied the enantioselective resolution of 2-arylpropionic acid derivatives employing immobilization of lipase produced by Bacillus subtilis strain Kakrayal_1 (BSK-L). The efficient immobilization of lipase on modified silica gel was confirmed by Fourier transform infrared spectroscopy. Tethering of lipase facilitated the enhancement of physiochemical properties and stability of enzyme. Covalently immobilized enzyme retained 85% of residual activity even on reuse after 10th reaction cycle. Validation of immobilized lipase for enantioselective resolution of 2-arylpropionic acid derivatives led to 47.8% conversion efficiency with 87% enantiomeric excess (ee) for ketoprofen, and 27.3% conversion efficiency with 75% ee for flurbiprofen. The enantioselective resolution using immobilized lipase (BSK-L) was superior to free and commercially procured lipase, which suggest a potential application of immobilized lipase in the pharmaceutical/chemical industry.

Production and purification of an alkaline lipase from Bacillus sp. for enantioselective resolution of (±)-Ketoprofen butyl ester.

The present study was conducted to purify lipase from indigenous Bacillus subtilis strain Kakrayal_1 (BSK-L) for enantioselective resolution of racemic-ketoprofen. The production of lipase (BSK-L) was optimized using Plackett-Burman and central composite design of response surface methodology (RSM). The optimized media containing olive oil (3.5%), MnSO4 (8 mM), CaCl2 (5 mM), peptone (20 g/l), pH (8), agitation (180 rpm) and temperature (37 °C) resulted in maximum lipase production of 7500 U/g of cell biomass. The lipase was purified using sequential method to an overall purification fold of 13% with 20% recovery, 882 U/mg specific activity and a molecular weight of 45 kDa. Optimal pH and temperature of purified lipase were found to be 8 and 37 °C, respectively. Furthermore, BSK-L displayed good stability with various organic solvents, surfactants and metal ions. K m and V max values of lipase were observed to be 2.2 mM and 6.67  mmoles of product formed/min/mg, respectively. The racemic ketoprofen butyl ester was hydrolyzed using lipase with 49% conversion efficiency and 69% enantiomeric excess (ee) which was superior to the commercially procured lipase (Candida antarctica lipase). Thus, this enzyme could be considered as a promising candidate for the pharmaceutical industry.

Heparin depolymerization by immobilized heparinase: A review.

Heparin is a member of the glycosaminoglycan (GAG) family composed of glucosamine and uronic acid units containing O-sulfo, N-acetyl and N-sulfo groups, which are alternating in the chain and linked by 1→4 manner. It is a naturally occurring anticoagulant that prevents the formation of clots and their growth within blood. Certain low molecular weight heparins (LMWHs) are considered as better therapeutic agents than natural heparin because of the reduced side effects and smaller risk of bleeding. LMWHs can be produced from heparin by chemical or enzymatic depolymerizations. Heparinases catalyze the cleavage of glycosidic linkage between amino sugars and uronic acids in heparin. There are three kinds of heparinases which are frequently used for depolymerization of heparin. Despite wide range of applications of heparinases in health care, their use still has been hampered due to poor stability and high cost. To overcome this problem heparinases are recommended for immobilization to reduce the cost of product and enhance stability. Heparinases have been successfully immobilized using various methods and supports, mostly for deheparinization of blood through extracorporeal devices. The focus of this review is to present the current status of heparinase immobilization including various supports and methods used, stability and applications.

Evaluation of alkali and thermotolerant lipase from an indigenous isolated Bacillus strain for detergent formulation

Background: Lipases are used in detergent industries to minimise the use of phosphate-based chemicals in detergent formulations. The use of lipase in household laundry reduces environmental pollution and enhances the ability of detergent to remove tough oil or grease stains. Results: A lipase-producing indigenous Bacillus subtilis strain [accession no. KT985358] was isolated from the foothills of Trikuta mountain in Jammu and Kashmir, India. The lipase (BSK-L) produced by this strain expressed alkali and thermotolerance. Lipase has an optimal activity at pH 8.0 and temperature 37°C, whereas it is stable at pH 6.0­9.0 and showed active lipolytic activity at temperatures 30 to 60°C. Furthermore, lipase activity was found to be stimulated in the presence of the metal ions Mn2+, K+, Zn2+, Fe2+ and Ca2+. This lipase was resistant to surfactants, oxidising agents and commercial detergents, suggesting it as a potential candidate for detergent formulation. BSK-L displayed noticeable capability to remove oil stains when used in different washing solutions containing buffer, lipase and commercial detergent. The maximum olive oil removal percentage obtained was 68% when the optimum detergent concentration (Fena) was 0.3%. The oil removal percentage from olive oil-soiled cotton fabric increased with 40 U/mL of lipase. Conclusions: This BSK-L enzyme has the potential for removing oil stains by developing a pre-soaked solution for detergent formulation and was compatible with surfactants, oxidising agents and commercial detergents.

Development and validation of highly sensitive method for determination of misoprostol free acid in human plasma by liquid chromatography-electrospray ionization tandem mass spectrometry: application to a clinical pharmacokinetic study.

A highly sensitive, selective and evaporation free SPE extraction, ESI-LC-MS/MS method has been developed for estimation of misoprostol free acid in human plasma using misoprostol acid-d(5) as an internal standard (IS). The analyte was separated using isocratic mobile phase on reverse phase column and analyzed by MS/MS in the multiple reaction monitoring mode using the respective [M-H] anions, m/z 367-249 for misoprostol acid and m/z 372-249 for the IS. The total run time was 5.0 min and the elution of misoprostol acid and misoprostol acid-d(5) (IS) occurred at 3.6 min. The developed method was validated in human plasma with a lower limit of quantification of 2.5 pg/mL. A linear response function was established for the range of concentrations 2.5-1200 pg/mL (r>0.998) for misoprostol acid in human plasma. The intra and inter-day precision values for misoprostol acid met the acceptance as per FDA guidelines. Misoprostol acid was stable in the battery of stability studies viz., bench-top, auto-sampler and freeze/thaw cycles. The developed assay method was applied to an oral pharmacokinetic study in humans.

Incidence and correlates of 'catastrophic' maternal health care expenditure in India.

Using data from the 60(th) round of the National Sample Survey of India (2004), the study investigates the incidence and correlates of 'catastrophic' maternal expenditure (ME) in India. Data on ME come from 6879 births that took place during 365 days prior to the survey. The study adapts earlier definitions and methods for catastrophic total health care expenditure to measure 'catastrophic' ME as: (i) maternal health care expenditure more than 10% of the annual normative household consumption expenditure (ME-1), and (ii) maternal health care expenditure more than 40% of the annual 'capacity to pay' (ME-2). The 'capacity to pay' was derived by subtracting state-wise poverty-line household expenditure from household consumption expenditure. The average maternal expenditure varied by place of delivery: US dollar 9.5, US dollar 24.7 and US dollar 104.3 for birth at home, in a public facility and in a private facility, respectively. Sixteen per cent of households incurred ME of more than 10% of total household consumption expenditure (ME-1), while 51% households incurred ME of more than 40% of household 'capacity to pay' (ME-2). While incidence of ME-1 increased with income decile, the reverse was observed for ME-2, reflecting higher non-utilization of institutional maternal care and its non-affordability among poorer households. All the households from the poorest decile and 99% from the second poorest decile paid more than 40% of their capacity to pay. Multivariate regression results indicate that antenatal care and delivery care in private facilities increased the chances of ME-1 and ME-2 (P < 0.001). Measuring maternal expenditure against 'capacity to pay' (ME-2) may be better than measuring it as a proportion of overall household expenditure when assessing financial constraints in the use of maternal services. Improving the performance of the public sector, appropriate regulation of and partnership with the private sector, and effective direct cash transfers to pregnant women in the poorest households may increase utilization of maternal services and reduce the financial distress associated with ME.

Child immunization in Vietnam: situation and barriers to coverage.

This paper addresses the overall performance and inequalities in the immunization of children in Vietnam. Descriptive and logistic analysis of cross-national demographic and health data was used to examine inequality in immunization, identify the most vulnerable groups in immunization coverage, and identify the gap in coverage between hard-to-access people and the remainder of the population. The gap in the coverage was found to occur primarily in vulnerable groups such as the poor minority or poor rural children. No evidence was found of a difference in immunization coverage because of sex or birth order. However, the age of children showed a significant influence on the rate of immunization. Mother's education and regular watching of television had a significant influence on child immunization. In order to improve child immunization coverage in Vietnam, efforts should be concentrated on poor children from minority groups and those living in rural areas, especially remote ones. Community development, investment for immunization and re-organization of immunization services at the grassroots level are also key factors to remove the barriers to immunization for vulnerable populations in Vietnam.