Groundnut Meal and Carrot Fortified Pasta: Optimization of Ingredients Level Using RSM

The present study was undertaken to optimize the level of groundnut meal, carrot juice and refined wheat flour for the development of pasta using response surface methodology. Different experimental combinations were designed using box-benken design of experiments considering 10–20 g groundnut meal, 14–30 mL carrot juice and 80–90 g refined wheat flour. Pasta samples with higher level of groundnut meal and carrot juice showed higher antioxidant activity and overall sensory acceptability. The samples with higher groundnut meal resulted in higher protein content. Pasta samples with higher amount of carrot juice showed higher rehydration ratio and lesser cooking time with low solid loss in cooking water. The food materials were optimized to obtain the best experimental combination for development of groundnut meal and carrot fortified pasta. Different levels of groundnut meal, carrot juice and wheat flour significantly affected the colour as well as cooking quality of pasta. The protein and antioxidant activity of pasta were increased with increasing level of groundnut meal and carrot juice in the sample. Optimized groundnut meal and carrot fortified pasta consisted of 17.64 % groundnut meal and 82.36 % wheat flour with 27.45 mL per 100 g formulation of carrot juice showing overall desirability as 0.849. This pasta sample required 3.49 min to cook with 4.71 % solid loss and rehydration ratio as 4.15 having 17.32 % protein content, 10.63 % antioxidant activity, 301.32 mg/100 g total phenols and overall sensory acceptability score as 8.7.     

Essential role of plasminogen activator inhibitor type-1 in radiation enteropathy

Intestinal radiation injury is a dose-limiting factor in radiation therapy for abdominal and pelvic cancers. Because transforming growth factor-beta1 is a key mediator involved in radiation-induced damage, we hypothesized that its target gene, plasminogen activator inhibitor type 1 (PAI-1), is an essential mediator of intestinal radiation toxicity. In a model of radiation enteropathy, survival was monitored and intestinal radiation injury was assessed in both wild-type (Wt) and PAI-1 knockout mice. Immunohistochemical labeling of PAI-1 was also assessed in patients treated with preoperative radiotherapy for rectal adenocarcinoma. Finally, the molecular mechanisms involved in radiation-induced PAI-1 expression were investigated. We found that PAI-1 -/- mice exhibited increased survival and better intestinal function compared with Wt mice. Intestinal radiation injury was attenuated in irradiated PAI-1 -/- mice compared with irradiated Wt mice, and irradiation increased blood cell-endothelial cell interactions in Wt but not PAI-1 -/- mice. In vivo, radiation-induced intestinal damage in mice, as well as in patients treated with radiotherapy, was associated with the up-regulation of PAI-1 in the endothelium. In vitro, irradiation increased PAI-1 expression in endothelial cells by a p53/Smad3-dependent mechanism. Together, these data demonstrate that PAI-1 plays a critical role in radiation-induced intestinal damage, suggesting that PAI-1 is an attractive target for preventing or reducing the side effects of radiation therapy.     

Prospective study evaluating the use of nasal glucagon for the treatment of moderate to severe hypoglycaemia in adults with type 1 diabetes in a real‐world setting

In the present multicentre, open‐label, prospective, phase III study, we evaluated the real‐world effectiveness and ease of use of nasal glucagon (NG) in the treatment of moderate/severe hypoglycaemic events (HEs) in adults with type 1 diabetes (T1D). Patients and caregivers were taught how to use NG (3 mg) to treat moderate/severe HEs, record the time taken to awaken or return to normal status, and measure blood glucose (BG) levels over time. Questionnaires were used to collect information about adverse events and ease of use of NG. In the efficacy analysis population, 69 patients experienced 157 HEs. In 95.7% patients, HEs resolved within 30 minutes of NG administration. In all the 12 severe HEs, patients awakened or returned to normal status within 15 minutes of NG administration without additional external medical help. Most caregivers reported that NG was easy to use. Most adverse events were local and of low to moderate severity. In this study, a single, 3‐mg dose of NG demonstrated real‐life effectiveness in treating moderate and severe HEs in adults with T1D. NG was well tolerated and easy to use.     

Acute reversible monoparesis in multiple neurocysticercosis: A case report and review of literature

Focal neurological deficit like monoparesis due to cortical lesions is a rare entity. In spite of the common presentations like seizures and headaches in neurocysticercosis, occurrence of reversible monoparesis is an atypical phenomenon. Even in the absence of infarct or hemorrhages, manifestation of neural deficit due to compressive effect only is an interesting finding. And on top of that, reversible nature of the deficit in space occupying lesion is a rare occurrence in the existing literature. Here, we describe a known case of neurocysticercosis with reversible acute monoparesis secondary to multiple neurocysticercosis. The variations with which neurocysticercosis can present broaden our understanding in its pathophysiology and management protocol.     

A highly efficacious live attenuated mumps virus–based SARS-CoV-2 vaccine candidate expressing a six-proline stabilized prefusion spike

With the rapid increase in SARS-CoV-2 cases in children, a safe and effective vaccine for this population is urgently needed. The MMR (measles/mumps/rubella) vaccine has been one of the safest and most effective human vaccines used in infants and children since the 1960s. Here, we developed live attenuated recombinant mumps virus (rMuV)–based SARS-CoV-2 vaccine candidates using the MuV Jeryl Lynn (JL2) vaccine strain backbone. The soluble prefusion SARS-CoV-2 spike protein (preS) gene, stablized by two prolines (preS-2P) or six prolines (preS-6P), was inserted into the MuV genome at the P–M or F–SH gene junctions in the MuV genome. preS-6P was more efficiently expressed than preS-2P, and preS-6P expression from the P–M gene junction was more efficient than from the F–SH gene junction. In mice, the rMuV-preS-6P vaccine was more immunogenic than the rMuV-preS-2P vaccine, eliciting stronger neutralizing antibodies and mucosal immunity. Sera raised in response to the rMuV-preS-6P vaccine neutralized SARS-CoV-2 variants of concern, including the Delta variant equivalently. Intranasal and/or subcutaneous immunization of IFNAR1^−/− mice and golden Syrian hamsters with the rMuV-preS-6P vaccine induced high levels of neutralizing antibodies, mucosal immunoglobulin A antibody, and T cell immune responses, and were completely protected from challenge by both SARS-CoV-2 USA-WA1/2020 and Delta variants. Therefore, rMuV-preS-6P is a highly promising COVID-19 vaccine candidate, warranting further development as a tetravalent MMR vaccine, which may include protection against SARS-CoV-2.

The current pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused tremendous damage to all aspects of our society (1–3). As of 1 June 2022, nearly 528 million cases have been reported worldwide, with nearly 6.3 million deaths (∼1.20% mortality). Symptoms of SARS-CoV-2 infection are primarily respiratory although increasing numbers of other syndromes such as cognitive deficits are being reported. As of June 2022, several SARS-CoV-2 vaccines based on messenger RNA (mRNA), inactivated virus, and adenovirus vectors (Ad26.COV2.S and ChAdOx1) have been approved for vaccination in humans over the age of 5 (4). These vaccines are highly efficacious, reaching 70 to 95% effectiveness against SARS-CoV-2 infection (4).Despite the high success of the current SARS-CoV-2 vaccines, there are several limitations. Protection provided by current vaccines begins to decline after 3 mo (5), which has required a third or fourth dose to boost the immune response. Current vaccines are less effective against recently emergent SARS-CoV-2 variants of concern (VoCs) (6–9). More and more evidence has shown that vaccine-induced neutralizing antibodies were significantly weakened or insufficient to neutralize VoCs such as the Delta variant (7–9), which spreads much faster and causes more severe illness than the earlier strains. In addition, the current vaccines neutralize the most recently emerged variant, Omicron, ∼40 times less efficiently compared with early SARS-CoV-2 isolates (10, 11). The mRNA vaccines are expensive to produce, hard to transport internationally, and difficult to store in many countries because of the requirement for expensive −80 °C freezers.A safe and efficacious pediatric SARS-CoV-2 vaccine is needed to halt the current pandemic. Pfizer’s mRNA vaccine is 90.7% effective in preventing COVID-19 symptoms in children 5 to 11 y old (12, 13). On 17 June 2022, Food and Drug Administration (FDA) authorized emergency use of the Moderna and Pfizer mRNA vaccines for children down to 6 mo of age. As of 23 June 2022, a total of 13.7 million COVID-19 cases have occurred in children, representing 18.8% of the total COVID-19 cases in the United States. Notably, COVID-19 cases in children have increased significantly after the reopening of schools. Therefore, development of other vaccine platforms and strategies to enhance durability, reduce cost, and enhance stability are essential for terminating the pandemic.Historically, the MMR (measles/mumps/rubella) vaccine has been one of the safest and most effective human vaccines ever developed (14–16). The application in children started in the 1960s and provides long-lasting protection against these three viruses (14, 16). Among the three MMR components, measles virus (MeV) and mumps virus (MuV) are nonsegmented negative-sense (NNS) RNA viruses, belonging to the family Paramyxoviridae in the order Mononegavirales. The MuV genome is 15,384 nt in length, and it encodes seven structural proteins arranged in the order 3′-leader-N-P-M-F-SH-HN-L-trailer-5′ (17). The limited number of discrete genes of the NNS RNA genome and the intergenic regions available for inserting additional genes facilitates the development of live vectored vaccines. MuV is an excellent viral vector for delivery of vaccines against other highly pathogenic viruses, primarily because of its high safety and efficacy, well-established good manufacturing practices, induction of long-lived immunity, and the potential for the development of a quadrivalent vaccine against four major pediatric diseases (18, 19).In this study, we developed a suite of safe and highly efficacious recombinant MuV (rMuV)–based SARS-CoV-2 vaccine candidates expressing a stabilized prefusion spike with two prolines (preS-2P) or six prolines (preS-6P) at different gene junctions in the MuV genome. Among them, the rMuV-based preS-6P vaccine induces a broad neutralizing antibody against VoCs and T cell immunity, and provides complete protection against SARS-CoV-2 WA1 and the Delta variant challenge in animal models.     

Expanding the spectrum of ADNP-related disorder-Antenatally diagnosed congenital diaphragmatic hernia and a novel de novo mutation in ADNP gene

De novo heterozygous ADNP variants have been associated with a complex neurological phenotype characterized primarily by neurodevelopmental delay. Cardiac and renal anomalies have additionally been observed in a few patients. All reported cases to date have been ascertained postnatally. Congenital diaphragmatic hernia (CDH) has been previously observed in one child diagnosed with a de novo ADNP-related neurodevelopmental disorder. We report a fetus who presented with syndromic CDH associated with a de novo heterozygous ADNP variant.