scholarly journals Physiochemical Changes to TTCF Ensilication Investigated Using Time-Resolved SAXS

AppliedChem ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 4-13
Author(s):  
Aswin Doekhie ◽  
Rajeev Dattani ◽  
Yun-Chu Chen ◽  
Francoise Koumanov ◽  
Karen J. Edler ◽  
...  

Successful eradication or control of prevailing infectious diseases is linked to vaccine efficacy, stability, and distribution. The majority of protein-based vaccines are transported at fridge (2–8 °C) temperatures, cold chain, to retain potency. However, this has been shown to be problematic. Proteins are inherently susceptible to thermal fluctuations, occurring during transportation, causing them to denature. This leads to ineffective vaccines and an increase in vaccine-preventable diseases, especially in low-income countries. Our research utilises silica to preserve vaccines at room temperature, removing the need for cold chain logistics. The methodology is based upon sol–gel chemistry in which soluble silica is employed to encapsulate and ensilicate vaccine proteins. This yields a protein-loaded silica nanoparticle powder which is stored at room temperature and subsequently released using a fast chemical process. We have previously shown that tetanus toxin C fragment (TTCF) ensilication is a diffusion-limited cluster aggregation (DLCA)-based process using time-resolved small-angle x-ray scattering (SAXS). Here, we present our expanded investigation on the modularity of this system to further the understanding of ensilication via time-resolved SAXS. Our results show that variations in the ensilication process could prove useful in the transition from batch to in-flow manufacturing of ensilicated nanoparticles.

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 520
Author(s):  
Roberto Cárcamo-Calvo ◽  
Carlos Muñoz ◽  
Javier Buesa ◽  
Jesús Rodríguez-Díaz ◽  
Roberto Gozalbo-Rovira

Rotavirus is the leading cause of severe acute childhood gastroenteritis, responsible for more than 128,500 deaths per year, mainly in low-income countries. Although the mortality rate has dropped significantly since the introduction of the first vaccines around 2006, an estimated 83,158 deaths are still preventable. The two main vaccines currently deployed, Rotarix and RotaTeq, both live oral vaccines, have been shown to be less effective in developing countries. In addition, they have been associated with a slight risk of intussusception, and the need for cold chain maintenance limits the accessibility of these vaccines to certain areas, leaving 65% of children worldwide unvaccinated and therefore unprotected. Against this backdrop, here we review the main vaccines under development and the state of the art on potential alternatives.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Pandey U

Introduction: Postpartum haemorrhage is one of the leading causes of maternal death worldwide and it accounts for nearly one-quarter of all maternal deaths and almost half of all postpartum deaths in low-income countries. Primary postpartum haemorrhage (PPH) is the most common form of major obstetric haemorrhage. Materials and Methods: The study protocol was comprised of Consent, Measurement of Pre-delivery Hemoglobin, Administration of the Intervention, Measurement of postpartum blood loss and Measurement of Post-delivery (24-48 hours) Hemoglobin. Blood loss was measured using a calibrated drape. The drape was placed beneath the parturient buttocks and secured around her abdomen with ties. Blood loss was monitored for a minimum of one hour and was continued in the second hour in case of persistent bleeding. The drape with the collected blood was weighed on a scale. The weight of the drape and the container in which it is placed was deducted from the total recorded weight in order to obtain the weight of the blood collected in the drape. Blood loss weight in grams was converted to milliliters by dividing the figure in grams by 1.06 (blood density in grams per milliliter). Results: The cross tabulations were used to study the demographic, obstetrical and medical factors in women with obstetrical haemorrhage. Table 1 shows the selected sociodemographic characteristics of the study population. The mean age of cases and controls are 26.333.559 and 26.853.873 respectively. On comparison, they are statistically insignificant. (p=0.324). The educational, occupational and socioeconomic status was comparable between cases and controls (p >0.05). Table 2 shows Antenatal, intra-partum and post-partum data in cases and controls. Discussion & Conclusion: It is a study done in North India comparing the Oxytocin kept at room temperature with failure of maintenance of cold chain during transport and storage and the refrigerated Oxytocin. It is the common understanding and general training that Oxytocin must be stored in the refrigerator, failing which its efficacy reduces i.e. it, will not be effective in controlling PPH. During the study we compared the mean blood loss and change in hemoglobin levels in cases and control and despite the fact that major risk factor for PPH for example past history of PPH, past history of D&C, prolonged third stage labour duration, manual removal of placenta were comparable in both cases and controls, still the mean blood loss and change in hemoglobin values was more in cases than controls. This could be attributed to usage of market oxytocin which had failed cold chain maintenance resulted in less effective oxytocin in prevention of PPH, Hence causing more blood loss and drop in hemoglobin values. This shows the need of room temperature stable uterotonic drug in LMIC’s like ours. Recently room temperature stable carbetocin shows the potential as an effective uterotonic drug for the prevention of PPH. However according to various studies carbetocin cannot be used for induction or augmentation of labour so it cannot replace oxytocin fully, rather it acts as a part of collective PPH reduction strategy.


PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255807
Author(s):  
Haydee Miranda-Ortiz ◽  
Edith A. Fernández-Figueroa ◽  
Erika B. Ruíz-García ◽  
Anallely Muñoz-Rivas ◽  
Alejandra Méndez-Pérez ◽  
...  

The use of saliva for the diagnosis of SARS-CoV-2 has shown to be a good alternative to nasopharyngeal swabs (NPS), since it permits self-collection, avoids the exposure of healthy persons to infected patients, reduces waiting times, eliminates the need of personal protective equipment and is non-invasive. Yet current saliva testing is still expensive due to the need of specialized tubes containing buffers to stabilize the RNA of SARS-CoV-2 and inactivate the virus. These tubes are expensive and not always accessible in sufficient quantities. We now developed an alternative saliva testing method, using TRIzol for extraction, viral inactivation, and storage of SARS-CoV-2 RNA, combined with RT-qPCR, which was comparable in its performance to NPS. Paired saliva samples and NPS were taken from 15 asymptomatic healthcare workers and one patient with SARS-CoV-2. Further 13 patients with SARS-CoV-2 were only saliva-tested. All the tests were performed according to CDC 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel. Saliva (4 mL) was taken in sterile 50 mL tubes, 1.5 mL TRIzol were added and mixed. Our results show that 5 μL of saliva RNA extracted with TRIzol allow for an adequate detection of the virus in patients positive for SARS-CoV-2 and was equally sensitive to NPS in TRIzol. We conclude that saliva testing using TRIzol is a recommendable method for diagnosis of SARS-CoV-2 since it has several advantages over currently used saliva tests: it can be done with normal sterile tubes, does not need cold-chain handling, is stable at room temperature, is non-invasive and less costly, making it more accessible for low-income countries. Cheaper saliva testing using TRIzol is especially relevant for low-income countries to optimize diagnosis and help define quarantine durations for families, healthcare workers, schools, and other public workplaces, thus decreasing infections and mortality caused by SARS-CoV-2.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pawan Dulal ◽  
Robabeh Gharaei ◽  
Adam J. Berg ◽  
Adam A. Walters ◽  
Nicholas Hawkins ◽  
...  

AbstractAdenovirus vectors offer a platform technology for vaccine development. The value of the platform has been proven during the COVID-19 pandemic. Although good stability at 2–8 °C is an advantage of the platform, non-cold-chain distribution would have substantial advantages, in particular in low-income countries. We have previously reported a novel, potentially less expensive thermostabilisation approach using a combination of simple sugars and glass micro-fibrous matrix, achieving excellent recovery of adenovirus-vectored vaccines after storage at temperatures as high as 45 °C. This matrix is, however, prone to fragmentation and so not suitable for clinical translation. Here, we report an investigation of alternative fibrous matrices which might be suitable for clinical use. A number of commercially-available matrices permitted good protein recovery, quality of sugar glass and moisture content of the dried product but did not achieve the thermostabilisation performance of the original glass fibre matrix. We therefore further investigated physical and chemical characteristics of the glass fibre matrix and its components, finding that the polyvinyl alcohol present in the glass fibre matrix assists vaccine stability. This finding enabled us to identify a potentially biocompatible matrix with encouraging performance. We discuss remaining challenges for transfer of the technology into clinical use, including reliability of process performance.


2020 ◽  
Author(s):  
Pawan Dulal ◽  
Adam A Walters ◽  
Nicholas Hawkins ◽  
Tim DW Claridge ◽  
Katarzyna Kowal ◽  
...  

AbstractThe global network of fridges and freezers known as the “cold chain” can account for a significant proportion of the total cost of vaccination and is susceptible to failure. Cost-efficient techniques to enhance stability of vaccines could prevent such losses and improve vaccination coverage, particularly in low income countries. We have previously reported a novel, potentially less expensive thermostabilisation approach using a combination of simple sugars and glass micro-fibrous matrix, achieving an excellent recovery of vaccines after storage at supraphysiological temperatures. This matrix is, however, prone to fragmentation and currently not suitable for clinical translation.Here, we report an investigation of alternative, potentially GMP compatible, fibrous matrices. A number of commercially-available matrices permitted good protein recovery, quality of sugar glass and moisture content of the dried product but did not achieve the thermostabilisation performance of the original glass fibre matrix. We therefore further investigated physical and chemical characteristics of the glass fibre matrix and its components. Our investigation shows that the polyvinyl alcohol present in the glass fibre matrix assists vaccine stability. This finding enabled us to develop a custom-produced matrix with encouraging performance, as an initial step towards a biocompatible matrix for clinical translation. We discuss the path to transfer of the technology into clinical use, including potential obstacles.


2021 ◽  
Author(s):  
Caitlin L. Maikawa ◽  
Joseph L. Mann ◽  
Aadithya Kannan ◽  
Catherine M. Meis ◽  
Ben S. Ou ◽  
...  

ABSTRACTThere are 150 million people with diabetes worldwide who require insulin replacement therapy and the prevalence of diabetes is rising fastest in middle and low-income countries. Current formulations require costly refrigerated transport and storage to prevent loss of insulin integrity. This study shows the development of simple “drop-in” amphiphilic copolymer excipients to maintain formulation integrity, bioactivity, pharmacokinetics and pharmacodynamics for over 6 months when subjected to severe stressed aging conditions that cause current commercial formulation to fail in under 2 weeks. Further, when these copolymers are added to Humulin R (Eli Lilly) in original commercial packaging they prevent insulin aggregation for up to 4 days at 50 °C compared to less than 1 day for Humulin R alone. These copolymers demonstrate promise as simple formulation additives to increase the cold chain resilience of commercial insulin formulations, thereby expanding global access to these critical drugs for treatment of diabetes.


Author(s):  
Chinenye Mercy Nwankwo ◽  
Elizabeth Orua

Background: Low-income countries still have challenges with vaccine-preventable diseases, despite improvement in immunization coverage in Rwanda, cases of drop out and incomplete immunization persists.Methods: The study adopted descriptive cross-sectional approach with the use of quantitative and qualitative techniques on a population of 186 guardians/mothers with their under five children. Convenience sampling techniques was used to draw study sample size of 127 that attends the clinic and approval to participate in the study.  Data was obtained from validated study instruments and immunization records over a period of one month.Results: Study results showed that religion (p=0.01), gender (p=0.03), age (p=0.009) and educational status (p=0.04) influenced incomplete immunizations. About 78 (61.4%) respondents are unaware that vaccines prevents specific diseases, while 61 (48.0%) were too busy with other duty at the time of immunizations and 89 (70.1%) Participants do not see the need to complete the immunization. Furthermore, the age of the mother Knowledge of child immunization and hospital delivery were statistically significant with (p<0.05). Immunization cards and histories verified showed about 120 (94.4%) children were fully immunized, 46(24.5 %) were partially immunized and 67 (52.8%) children immunized before age one.Conclusions: A number of children were not fully immunized in their first year of life; others were inappropriately vaccinated. Emphasis made on completion of immunization schedule.


Author(s):  
Davor Petrović ◽  
Vida Čulić ◽  
Zofia Swinderek-Alsayed

AbstractJoubert syndrome (JS) is a rare congenital, autosomal recessive disorder characterized by a distinctive brain malformation, developmental delay, ocular motor apraxia, breathing abnormalities, and high clinical and genetic heterogeneity. We are reporting three siblings with JS from consanguineous parents in Syria. Two of them had the same homozygous c.2172delA (p.Trp725Glyfs*) AHI1 mutation and the third was diagnosed prenatally with magnetic resonance imaging. This pathogenic variant is very rare and described in only a few cases in the literature. Multinational collaboration could be of benefit for the patients from undeveloped, low-income countries that have a low-quality health care system, especially for the diagnosis of rare diseases.


2013 ◽  
pp. 121-136
Author(s):  
Duong Pham Bao

The objective of this article is to review the development of the rural financial system in Vietnam in recent years, especially, after Doi moi. There are two opposite schools of thought in the literature on rural credit policies in developing countries. One is the conventional supply-side (government-led) approach while the other is called “a new paradigm” that emphasizes the importance of the viability of financial providers and the well functioning of rural credit markets. Conventional theories of rural finance contend that rural finance in low-income countries is generally accompanied by many failures. Contrary to these theories, rural finance in Vietnam does not encounter the above-mentioned failures so far. Up to the present time, it is progressing well. Using a supply-side approach, methodologically, this study reviews the development of the rural financial system in Vietnam. The significance of this study is to challenge the extreme view of dichotomizing between the old and the new credit paradigms. Analysis in this study contends that a rural financial market that, (1) is initiated and spurred by government; (2) operates principally under market mechanisms; and (3) is strongly supported by rural organizations (semi-formal/informal institutions) can progress stably and well. Therefore, the extremely dichotomizing approach must be avoided.


EMJ Radiology ◽  
2020 ◽  

Retained foreign bodies have become very rare in countries where the safety rules in the operating theatre are very rigorous and follow precise guidelines. There are low-income countries where hospital structures are precarious, in which the implementation of surgical safety rules has only been effective recently. Surgical teams in these countries are not yet well trained in the observance of the guidelines concerning swab count, meaning that textilomas are not uncommon. Abdominal textiloma may be asymptomatic, or present serious gastrointestinal complications such as bowel obstruction, perforation, or fistula formation because of misdiagnosis. It may mimic abscess formation in the early stage or soft tissue masses in the chronic stage. This case report presents a 27-year-old female who underwent an emergency laparotomy in a rural surgical centre for an ectopic pregnancy. Two months later, a swelling had appeared on the left side of her abdomen, gradually increasing in size, which was not very painful but caused digestive discomfort and asthenia. Intermittent fever was described and treated with antibiotics. The patient was referred to a better equipped centre to benefit from a CT scan. A textiloma was strongly suspected on the CT but a left colic mass was not excluded. Laparotomy confirmed the diagnosis of textiloma and the postoperative course was uneventful. Prevention rules must be strengthened in these countries where patients can hardly bear the costs of iterative surgeries for complications that are avoidable.


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