Standardization and validation of a new atomic absorption spectroscopy technique for determination and quantitation of Aluminium adjuvant in immunobiologicals

In the present study, Aluminium quantification in immunobiologicals has been described using atomic absorption spectroscopy (AAS) technique. The assay was found to be linear in 25-125 microg/ml Aluminium range. The procedure was found to be accurate for different vaccines with recoveries of external additions ranging between 93.26 and 103.41%. The mean Limit of Variation (L.V.) for both intra- and inter-assay precision was calculated to be 1.62 and 2.22%, respectively. Further the procedure was found to be robust in relation to digestion temperature, alteration in acid (HNO(3) and H(2)SO(4)) ratio used for sample digestion and storage of digested vaccine samples up to a period of 15 days. After validation, AAS method was compared for its equivalency with routinely used complexometric titration method. On simultaneously applying on seven different groups of both bacterial and viral vaccines, viz., DPT, DT, TT, Hepatitis-A and B, Antirabies vaccine (cell culture) and tetravalent DPT-Hib, a high degree of positive correlation (+0.85-0.998) among AAS and titration methods was observed. Further AAS method was found to have an edge over complexometric titration method that a group of vaccines, viz., ARV (cell culture, adsorbed) and Hepatitis-A, in which Aluminium estimation is not feasible by pharmacopoeial approved complexometric titration method (possibly due to some interference in the sample matrix), this newly described and validated AAS assay procedure delivered accurate and reproducible results.     

Molecular regulation of santalol biosynthesis in Santalum album L.

Santalum album L. commonly known as East-Indian sandal or chandan is a hemiparasitic tree of family santalaceae. Santalol is a bioprospecting molecule present in sandalwood and any effort towards metabolic engineering of this important moiety would require knowledge on gene regulation. Santalol is a sesquiterpene synthesized through mevalonate or non-mevalonate pathways. First step of santalol biosynthesis involves head to tail condensation of isopentenyl pyrophosphate (IPP) with its allylic co-substrate dimethyl allyl pyrophosphate (DMAPP) to produce geranyl pyrophosphate (GPP; C10 — a monoterpene). GPP upon one additional condensation with IPP produces farnesyl pyrophosphate (FPP; C15 — an open chain sesquiterpene). Both the reactions are catalyzed by farnesyl diphosphate synthase (FDS). Santalene synthase (SS), a terpene cyclase catalyzes cyclization of open ring FPP into a mixture of cyclic sesquiterpenes such as α-santalene, epi-β-santalene, β-santalene and exo bergamotene, the main constituents of sandal oil. The objective of the present work was to generate a comprehensive knowledge on the genes involved in santalol production and study their molecular regulation. To achieve this, sequences encoding farnesyl diphosphate synthase and santalene synthase were isolated from sandalwood using suppression subtraction hybridization and 2D gel electrophoresis technology. Functional characterization of both the genes was done through enzyme assays and tissue-specific expression of both the genes was studied. To our knowledge, this is the first report on studies on molecular regulation, and tissue-specific expression of the genes involved in santalol biosynthesis.     

IL-12 enhances the antitumor actions of trastuzumab via NK cell IFN-γ production

The antitumor effects of therapeutic mAbs may depend on immune effector cells that express FcRs for IgG. IL-12 is a cytokine that stimulates IFN-γ production from NK cells and T cells. We hypothesized that coadministration of IL-12 with a murine anti-HER2/neu mAb (4D5) would enhance the FcR-dependent immune mechanisms that contribute to its antitumor activity. Thrice-weekly therapy with IL-12 (1 μg) and 4D5 (1 mg/kg) significantly suppressed the growth of a murine colon adenocarcinoma that was engineered to express human HER2 (CT-26(HER2/neu)) in BALB/c mice compared with the result of therapy with IL-12, 4D5, or PBS alone. Combination therapy was associated with increased circulating levels of IFN-γ, monokine induced by IFN-γ, and RANTES. Experiments with IFN-γ-deficient mice demonstrated that this cytokine was necessary for the observed antitumor effects of therapy with IL-12 plus 4D5. Immune cell depletion experiments showed that NK cells (but not CD4(+) or CD8(+) T cells) mediated the antitumor effects of this treatment combination. Therapy of HER2/neu-positive tumors with trastuzumab plus IL-12 induced tumor necrosis but did not affect tumor proliferation, apoptosis, vascularity, or lymphocyte infiltration. In vitro experiments with CT-26(HER2/neu) tumor cells revealed that IFN-γ induced an intracellular signal but did not inhibit cellular proliferation or induce apoptosis. Taken together, these data suggest that tumor regression in response to trastuzumab plus IL-12 is mediated through NK cell IFN-γ production and provide a rationale for the coadministration of NK cell-activating cytokines with therapeutic mAbs.     

Diversity among health care leaders in Canada: a cross-sectional study of perceived gender and race

Background:Diverse health care leadership teams may improve health care experiences and outcomes for patients. We sought to explore the race and gender of hospital and health ministry executives in Canada and compare their diversity with that of the populations they serve.Methods:This cross-sectional study included leaders of Canada’s largest hospitals and all provincial and territorial health ministries. We included individuals listed on institutional websites as part of the leadership team if a name and photo were available. Six reviewers coded and analyzed the perceived race and gender of leaders, in duplicate. We compared the proportion of racialized health care leaders with the race demographics of the general population from the 2016 Canadian Census.Results:We included 3056 leaders from 135 institutions, with reviewer concordance on gender for 3022 leaders and on race for 2946 leaders. Reviewers perceived 37 (47.4%) of 78 health ministry leaders as women, and fewer than 5 (< 7%) of 80 as racialized. In Alberta, Saskatchewan, Prince Edward Island and Nova Scotia, provinces with a centralized hospital executive team, reviewers coded 36 (50.0%) of 72 leaders as women and 5 (7.1%) of 70 as racialized. In British Columbia, New Brunswick and Newfoundland and Labrador, provinces with hospital leadership by region, reviewers perceived 120 (56.1%) of 214 leaders as women and 24 (11.5%) of 209 as racialized. In Manitoba, Ontario and Quebec, where leadership teams exist at each hospital, reviewers perceived 1326 (49.9%) of 2658 leaders as women and 243 (9.2%) of 2633 as racialized. We calculated the representation gap between racialized executives and the racialized population as 14.5% for British Columbia, 27.5% for Manitoba, 20.7% for Ontario, 12.4% for Quebec, 7.6% for New Brunswick, 7.3% for Prince Edward Island and 11.6% for Newfoundland and Labrador.Interpretation:In a study of more than 3000 health care leaders in Canada, gender parity was present, but racialized executives were substantially under-represented. This work should prompt health care institutions to increase racial diversity in leadership.

Race and gender-based disparities in health care leadership^1–4 may negatively affect the health of marginalized patients.^5,6 Diverse leadership is an integral step in establishing equitable health care institutions that serve the needs of all community members.⁷ Many barriers prevent racialized people, women and gender nonbinary individuals from attaining leadership positions, including reduced access to networking opportunities, ^8–10 discrimination from patients and colleagues^2,11–13 and an institutional culture that views white, male leaders as most effective. ^14,15 The intersectional effects of discrimination may intensify these barriers for racialized women and nonbinary people.^16,17 Fundamentally, diversity and inclusion in our institutions is important on the basis of basic human rights for all people.¹⁸Health care leadership in Europe and the United States is thought to lack gender and racial diversity.^19–22 The degree to which these imbalances exist across Canadian health care institutions is not clear. Despite past evidence that men hold a disproportionate number of health care leadership positions in Canada,^23,24 a recent study noted gender parity among leaders of provincial and territorial ministries of health.²⁵ Among university faculty^26,27 and administration, ²⁸ racialized individuals appear to be under-represented, suggesting that a similar trend may exist in health care leadership.Race and gender can be studied in many ways.²⁹ Perceived race is a measure of “the race that others believe you to be,” and these assessments “influence how people are treated and form the basis of racial discrimination including nondeliberate actions that nonetheless lead to socioeconomic inequities.”²⁹ Similarly, perceived gender refers to an observer’s assumptions about a person’s gender, which can lead to differential and unfair treatment. ³⁰ Assessing perceived race and gender provides crucial insights into the ways in which social inequalities are informed and produced.²⁹ In this study, we sought to identify the perceived race and gender of hospital executive leaders in Canada and of nonelected leaders of the provincial and territorial health ministries. Furthermore, we wanted to analyze how the perceived racial composition of health care leadership compares with the racial composition of the population in the geographic areas that these leaders serve.     

Urogenital schistosomiasis during pregnancy is associated with low birth weight delivery: analysis of a prospective cohort of pregnant women and their offspring in Gabon

An estimated 40 million women of childbearing age suffer from schistosomiasis. Animal models indicate a deleterious effect of maternal schistosomiasis on pregnancy outcomes. To date there is a lack of epidemiological evidence evaluating schistosomiasis-related morbidity in pregnancy. This study was designed to describe the impact of urogenital schistosomiasis on pregnancy outcomes in a highly endemic region of central Africa. Pregnant women attending antenatal clinics in Fougamou and Lambaréné, Gabon, were consecutively screened for the presence of Schistosoma haematobium eggs in diurnal urine samples. Maternal and newborn characteristics assessed at delivery were compared between infected and uninfected mothers. The impact of maternal schistosomiasis on low birth weight and preterm delivery was assessed using logistic regression analysis. Urogenital schistosomiasis was diagnosed in 103 (9%) of 1115 pregnant women. Maternal age was inversely associated with the prevalence of urogenital schistosomiasis, with a higher burden amongst nulliparous women. Low birth weight was more common amongst infants of S. haematobium-infected mothers. This association was unaffected by controlling for demographic characteristics, gestational age and Plasmodium infection status (adjusted Odds Ratio 1.93; 95% confidence interval: 1.08–3.42). Other risk factors associated with low birth weight delivery were underweight mothers (adjusted Odds Ratio 2.34; 95% confidence interval: 1.12–4.92), peripheral or placental Plasmodium falciparum infection (adjusted Odds Ratio 2.04; 95% confidence interval: 1.18–3.53) and preterm birth (adjusted Odds Ratio 3.12; 95% confidence interval: 1.97–4.96). Preterm delivery was not associated with S. haematobium infection (adjusted Odds Ratio 1.07 95% confidence interval: 0.57–1.98). In conclusion, this study indicates that pregnant women with urogenital schistosomiasis are at an increased risk for low birth weight deliveries. Further studies evaluating targeted treatment and prevention programmes for urogenital schistosomiasis in pregnant women and their impact on delivery outcomes are warranted.     

A comparative review towards potential of microbial cells for heavy metal removal with emphasis on biosorption and bioaccumulation

The threat of heavy metal pollution to environmental health is getting worldwide attention due to their persistence and non-biodegradable nature. Ineffectiveness of various physicochemical methods due to economical and technical constraints resulted in the search for a cost-effective and eco-friendly biological technique for heavy metal removal from the environment. The two effective biotic methods used are biosorption and bioaccumulation. A comparison between these two processes demonstrated that biosorption is a better heavy metal removal process than bioaccumulation. This is due to the intoxication of heavy metal by inhibiting their entry into the microbial cell. Genes and enzymes related to bioremoval process are also discussed. On comparing the removal rate, bacteria are surpassed by algae and fungi. The aim of this review is to understand the biotic processes and to compare their metal removal efficiency.     

In vitro liver model using microfabricated scaffolds in a modular bioreactor

Hepatocyte function on 3-D microfabricated polymer scaffolds realised with the pressure-activated microsyringe was tested under static and dynamic conditions. The dynamic cell culture was obtained using the multicompartment modular bioreactor system. Hepatocyte cell density, glucose consumption, and albumin secretion rate were measured daily over a week. Cells seeded on scaffolds showed an increase in cell density compared with monolayer controls. Moreover, in dynamic culture, cell metabolic function increased three times in comparison with static monolayer cultures. These results suggest that cell density and cell-cell interactions are mediated by the architecture of the substrate, while the endogenous biochemical functions are regulated by a sustainable supply of nutrients and interstitial-like flow. Thus, a combination of 3-D scaffolds and dynamic flow conditions are both important for the development of a hepatic tissue model for applications in drug testing and regenerative medicine.     

Drug Interactions Involving Antifungal Drugs: Time Course and Clinical Significance

The antifungal armamentarium has expanded greatly over the past two decades. This expansion, along with the pharmacologically complex therapeutic regimens used in treating many patients with systemic fungal disease, enhances the risk of clinically significant drug–drug interactions. This review examines the drug–drug interaction potential of antifungal agents by pharmacologic class and attempts to provide perspective on the time course and clinical significance of these events.