Influence of Heating Temperature and pH on Acid Gelation of Micellar Calcium Phosphate-Adjusted Skim Milk.

Micellar calcium phosphate (MCP) plays an important role in maintaining the structure and stability of the casein micelle and its properties during processing. The objective of this study was to investigate how heating (10 min at 80 or 90 °C) at different pH levels (6.3, 6.6, 6.9, or 7.2) impacted the acid-induced gelation of MCP-adjusted milk, containing 67 (MCP67), 100 (MCP100), or 113 (MCP113) % of the original MCP content. The unheated sample MCP100 at pH 6.6 was considered the control. pH acidification to pH 4.5 at 30 °C was achieved with glucono delta-lactone while monitoring viscoelastic behaviour by small-amplitude oscillatory rheology. The partitioning of calcium and proteins between colloidal and soluble phases was also examined. In MCP-depleted skim milk samples, the concentrations of non-sedimentable caseins and whey proteins were higher compared to the control and MCP-enriched skim milk samples. The influence of MCP adjustment on gelation was dependent on pH. Acid gels from sample MCP67 exhibited the highest storage modulus (G'). At other pH levels, MCP100 resulted in the greatest G'. The pH of MCP-adjusted skim milk also impacted the gel properties after heating. Overall, this study highlights the substantial impact of MCP content on the acid gelation of milk, with a pronounced dependency of the MCP adjustment effect on pH variations.

Structural Properties of Casein Micelles with Adjusted Micellar Calcium Phosphate Content.

Micellar calcium phosphate (MCP) content of skim milk was modified by pH adjustment followed by dialysis. Turbidity, casein micelle size and partitioning of Ca and caseins between the colloidal and soluble phases of milk were determined. Protein structure was characterised by Fourier transform infrared (FTIR) spectroscopy and proton nuclear magnetic resonance (1H NMR), whereas organic and inorganic phosphorus were studied by phosphorus-31 nuclear magnetic resonance (31P NMR). The sample with the lowest MCP content (MCP7) exhibited the smallest particle size and turbidity, measuring 83 ± 8 nm and 0.08 ± 0.01 cm-1, respectively. Concentrations of soluble caseins increased with decreasing MCP levels. At ~60% MCP removal, FTIR analysis indicated a critical stage of structural rearrangement and 31P NMR analysis showed an increase in signal intensity for Ca-free Ser-P, which further increased as MCP concentration was further reduced. In conclusion, this study highlighted the importance of MCP in maintaining micellar structure and its impact on the integrity of casein micelle.

Influence of pH on Heat-Induced Changes in Skim Milk Containing Various Levels of Micellar Calcium Phosphate.

The present study investigated the effect of micellar calcium phosphate (MCP) content and pH of skim milk on heat-induced changes in skim milk. Four MCP-adjusted samples, ranging from 67 to 113% of the original MCP content, were heated (90 °C for 10 min) at different pH values (6.3, 6.6, 6.9, and 7.2), followed by determining changes in particle size, turbidity, protein distribution, and structure. The results demonstrate a strong effect of MCP level and pH on heat-induced changes in milk, with the MCP67 samples revealing the greatest thermal stability. Specifically, decreasing MCP content by 33% (MCP67) led to a smaller increase in non-sedimentable κ-casein and a lower decrease in αs2-casein concentrations after heating compared to other samples. Lower MCP content resulted in a moderate rise in the average particle size and turbidity, along with lower loading of ß-turn structural component after heating at low pH (pH 6.3). Notably, MCP113 exhibited instability upon heating, with increased particle size, turbidity, and a significant decrease in non-sedimentable αs2-casein concentration, along with a slight increase in non-sedimentable κ-casein concentration. The FTIR results also revealed higher loading of intermolecular ß-sheet, ß-turn, and random coil structures, as well as lower loading of α-helix and ß-sheet structures in MCP-enhanced skim milk samples. This suggests significant changes in the secondary structure of milk protein and greater formation of larger aggregates.

The benefit of intravenous immune globulin in the treatment of delayed radiation myelopathy.

Delayed radiation myelopathy (DRM) is a rare yet severe complication of radiotherapy. This condition has a progressive pattern that is often irreversible. Several therapeutic strategies have been introduced to alleviate disease complications, including corticosteroids, hyperbaric oxygen, anticoagulants, and antivascular endothelial growth factor (VEGF) agents. However, despite their beneficial effect, they have not been the definitive treatments for DRM. Here we present the case of a 55-year-old woman with a history of multiple myeloma who developed neurological complications 11 months after radiation therapy. As her radiologic findings demonstrated transverse myelitis, based on the DRM diagnostic criteria, the diagnosis of delayed radiation myelitis was reached. Therefore, methylprednisolone pulse therapy was initiated, resulting in the complete resolution of her neurological symptoms. However, on her follow-up examination, although she did not have new neurological complications, magnetic resonance imaging (MRI) demonstrated a residual enhancement in the thoracic spinal cord area. Hence, due to the possibility of myelitis progression and spinal cord atrophy, intravenous immune globulin (IVIG) was administered, resulting in the resolution of lesion enhancement. Considering this outcome and the immunomodulatory properties of IVIG, it could be regarded as a potential therapeutic option in the case of DRM activity.

Identifying and Mitigating Potential Biases in Predicting Drug Approvals.

INTRODUCTION: Machine learning models are increasingly applied to predict the drug development outcomes based on intermediary clinical trial results. A key challenge to this task is to address various forms of bias in the historical drug approval data. OBJECTIVE: We aimed to identify and mitigate the bias in drug approval predictions and quantify the impacts of debiasing in terms of financial value and drug safety. METHODS: We instantiated the Debiasing Variational Autoencoder, the state-of-the-art model for automated debiasing. We trained and evaluated the model on the Citeline dataset provided by Informa Pharma Intelligence to predict the final drug development outcome from phase II trial results. RESULTS: The debiased Debiasing Variational Autoencoder model achieved better performance (measured by the [Formula: see text] score 0.48) in predicting the drug development outcomes than its un-debiased baseline ([Formula: see text] score 0.25). It had a much higher true-positive rate than baseline (60% vs 15%), while its true-negative rate was slightly lower (88% vs 99%). The Debiasing Variational Autoencoder distinguished between drugs developed by large pharmaceutical firms and those by small biotech companies. The model prediction is strongly influenced by multiple factors such as prior approval of the drug for another indication, whether the trial meets the positive/negative endpoints, and the year when the trial is completed. We estimate that the debiased model generates financial value for the drug developer in six major therapeutic areas, with a range of US$763-1,365 million. CONCLUSIONS: Our analysis shows that debiasing improves the financial efficiency of late-stage drug development. From the pharmacovigilance perspective, the debiased model is more likely to identify drugs that are both safe and effective. Meanwhile, it may predict a higher probability of success for drugs with potential adverse effects (because of its lower true-negative rate), thus it must be used with caution to predict the development outcomes of drug candidates currently in the pipeline.

The Persistence Time of SARS-CoV-2 RNA in Hospitalized COVID-19 Patients: A Prospective Study.

BACKGROUND: In late December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), the causative agent of coronavirus disease 2019 (COVID-19), spread to almost all countries worldwide. The outbreak of this virus has been confirmed on 19th February, 2020, in Iran. OBJECTIVE: The aim of this study was to investigate the time of viral RNA clearance in swab and serum samples of COVID-19 patients having received different medications. We also evaluated different factors that may affect viral RNA persistence in patients infected by SARS-CoV-2. METHODS: In March 2020, twenty-one hospitalized COVID-19 patients participated in this prospective study. All patients received antiviral agents in their routine care. Throat swabs and blood samples were obtained from all patients in different intervals, including day 3 or 5, day 7, day 10, and finally, 14 days after the first positive real-time RT-PCR (rRT-PCT) test. RESULTS: The median time from the symptom onset (SO) to the first negative rRT-PCR results for throat swabs and serum samples of COVID-19 patients was 18 and 14 days, respectively. These times were more significant in patients with lymphopenia, oxygen saturation ≤ 90%, and comorbidity. CONCLUSION: This preliminary study highlights that SASR-CoV-2 RNA was not detectable in the upper respiratory tract for longer than three weeks. In addition, SARS-CoV-2 may persist for a long period of time in the respiratory than in the serum samples. This study supports the idea that in limited resource settings, the patients should be tested earlier than three weeks for discharge management.

The effect of a semi-rigid thoracolumbosacral orthosis (TLSO) on foot pressure in elderly subjects presenting with spinal hyperkyphosis.

Purpose: The ageing process can be accompanied by a degeneration of the spine and increase the risk of thoracic hyperkyphosis (excessive spinal forward curvature) amongst elderly people. This condition can in turn impair mobility, reduce balance, and increase the risk of falling and mortality in affected individuals. The use of corrective orthotic bracing has been shown to improve spinal posture, and increase stability and balance amongst the elderly. However, there is little evidence that evaluates the use of corrective braces on foot pressure changes in these subjects.Methods: In this study, we evaluated the use of a thoracolumbosacral orthosis (TLSO) on 19 subjects over 60 years old who presented with hyperkyphosis. We measured foot pressure using the Pedar-X system before (without brace) and after (with brace) immediate using a TLSO in both static (quite standing) and dynamic (walking on a 5 meters freeway) scenarios.Results: The results demonstrated that using a TLSO immediately decreases forefoot pressures in stasis, and around the first metatarsal, as well as pressures relating to the second to fifth metatarsals under dynamic conditions. Hindfoot pressures were increased, but not significantly.Conclusion: This study showed that using a TLSO can be beneficial for elderly people with hyperkyphosis.Implications for rehabilitationThe ageing process can be accompanied by a degeneration of the spine and increase the risk of thoracic hyperkyphosis.The use of corrective orthotic bracing has been shown to improve spinal posture, and increase stability and balance amongst the elderly.Using a TLSO decreases forefoot pressures in stasis, and around the first metatarsal, as well as pressures relating to the second to fifth metatarsals under dynamic conditions.

Development of a validated algorithm for the diagnosis of paediatric asthma in electronic medical records.

An accurate estimation of the prevalence of paediatric asthma in Alberta and elsewhere is hampered by uncertainty regarding disease definition and diagnosis. Electronic medical records (EMRs) provide a rich source of clinical data from primary-care practices that can be used in better understanding the occurrence of the disease. The Canadian Primary Care Sentinel Surveillance Network (CPCSSN) database includes cleaned data extracted from the EMRs of primary-care practitioners. The purpose of the study was to develop and validate a case definition of asthma in children 1-17 who consult family physicians, in order to provide primary-care estimates of childhood asthma in Alberta as accurately as possible. The validation involved the comparison of the application of a theoretical algorithm (to identify patients with asthma) to a physician review of records included in the CPCSSN database (to confirm an accurate diagnosis). The comparison yielded 87.4% sensitivity, 98.6% specificity and a positive and negative predictive value of 91.2% and 97.9%, respectively, in the age group 1-17 years. The algorithm was also run for ages 3-17 and 6-17 years, and was found to have comparable statistical values. Overall, the case definition and algorithm yielded strong sensitivity and specificity metrics and was found valid for use in research in CPCSSN primary-care practices. The use of the validated asthma algorithm may improve insight into the prevalence, diagnosis, and management of paediatric asthma in Alberta and Canada.

Efficacy of probiotic use in acute rotavirus diarrhea in children: A systematic review and meta-analysis.

BACKGROUND: Probiotic therapies with different strains demonstrated some beneficial effects, although some studies did not show any significant effects. This study assessed systematically the current knowledge on the effect of probiotic bacteria on duration of acute rotavirus diarrhea in children compared with control. METHODS: The PubMed, Cochrane Controlled Trial Register (CCTR) and Ovid (Wolters Kluwer Health) were searched between 1980 to June 15, 2013. Randomized controlled trials including the administration of probiotics for treatment of rotavirus diarrhea in infants and children were reviewed. RESULTS: A total number of 1244 articles were found through the aforementioned search. 203 articles were selected after the first screening of title and abstract. The intervention group included subjects who received probiotic strains and dosage in any conditions. Placebo or any similar vehicle without probiotic was used in the controlled trials. Finally, 14 articles were selected. The outcomes from each study were considered in the duration of diarrhea. Statistical analyses were performed with Stata software. The pooled estimate of efficacy of probiotics in prevention or treatment of disease yielded in all studies a mean difference of 0.41 (CI 95%: -0.56 to -0.25; p<0.001). The pooled estimate of efficacy of lactobacillus rhamnosus GG and other probiotics significantly reduced the duration of diarrhea. Among trials, the overall reduction of LGG was 0.47 (CI 95%: -0.80 to -0.14; P= 0.020). CONCLUSION: In conclusion, probiotics exert positive effect in reducing the duration of acute rotavirus diarrhea compared with control.