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Rapid discovery of potentially vasodilative compounds from Uncaria by UHPLC/Q-Orbitrap-MS based metabolomics and correlation analysis

J Pharm Biomed Anal. 2021 Sep 21;206:114384. doi: 10.1016/j.jpba.2021.114384. Online ahead of print.

ABSTRACT

The genus Uncaria belongs to the family of Rubiaceae, which contains approximately 34 species. It has been widely used as a traditional Chinese medicine (TCM) in China to treat hypertension, fevers, headaches, gastrointestinal illness, epilepsy, wounds, and ulcers. Uncaria rhynchophylla. (Miq.) Miq. ex Hvail.(URM) and Uncaria hirsuta Havil.(UHH) are mainly used as remedies for hypertension, which both belong to the resource of “Gou-teng” in the Chinese Pharmacopoeia. However, the authentic antihypertensive components of Uncaria still have not been fully elucidated until now. In this work, we firstly explored and compared the vasorelaxation effect of URM and UHH on the isolated rat mesenteric artery ring. Then, the variations of metabolite profiles between URM and UHH samples were investigated by UHPLC/Q-Orbitrap-MS, and 16 different metabolites have been found through multivariate statistical analysis. Further, the potential vasodilative compounds which include corynoxeine, isocorynoxeine, isorhynchophylline, rhynchophylline, hirsuteine and hirsutine were screened through the correlation analysis between metabolites and anti-hypertension activities. And the relaxation effects of the six compounds on the mesenteric artery have verified. The results indicated that metabolomics combined with correlation analysis could be effective strategies to rapid explore the active compounds from TCM.

PMID:34607203 | DOI:10.1016/j.jpba.2021.114384

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Veliparib and nivolumab in combination with platinum doublet chemotherapy in patients with metastatic or advanced non-small cell lung cancer: A phase 1 dose escalation study

Lung Cancer. 2021 Sep 17;161:180-188. doi: 10.1016/j.lungcan.2021.09.004. Online ahead of print.

ABSTRACT

OBJECTIVES: Both combinations of the PARP inhibitor veliparib plus platinum doublet chemotherapy (CT), and the programmed death receptor-1 (PD-1) inhibitor nivolumab plus CT have demonstrated encouraging efficacy for treatment of non-small cell lung cancer (NSCLC). This phase 1 dose-escalation study (NCT02944396) evaluated the quadruple combination of veliparib with nivolumab and doublet CT in patients with unresectable advanced/metastatic NSCLC.

MATERIALS AND METHODS: Patients were enrolled into five dosing cohorts: patients received veliparib 120 mg twice daily (BID) combined with nivolumab 360 mg, carboplatin AUC 6 mg/mL∙min, and paclitaxel 200 mg/m2 (C/PAC) or veliparib 80/120/200/240 mg BID in combination with nivolumab 360 mg, carboplatin AUC 6 mg/mL∙min, and pemetrexed 500 mg/m2 (C/PEM). Primary objective was to identify the recommended phase 2 dose (RP2D) of veliparib + nivolumab + CT. Safety, tolerability, and efficacy of this combination were also assessed.

RESULTS: Twenty-five patients were enrolled: 6 patients received veliparib 120 mg BID + nivolumab + C/PAC and 19 received veliparib (80-240 mg BID) + nivolumab + C/PEM. No dose-limiting toxicities were reported, and the RP2Ds were veliparib 120 mg BID + nivolumab + C/PAC, and veliparib 240 mg BID + nivolumab + C/PEM. The most common any-grade adverse events (AEs) were fatigue (56%), nausea (52%), and anemia (48%). Grade 3/4 AEs included anemia (32%) and neutropenia (24%), and the most frequent serious AE was malignant neoplasm progression (12%). Veliparib exhibited approximately dose proportional kinetics in the dose range 80-240 mg BID combined with nivolumab and C/PEM, with no effects on pemetrexed pharmacokinetics. Overall, the confirmed objective response rate was 40%, and best overall response was 64%.

CONCLUSION: Veliparib combined with nivolumab and platinum doublet CT was tolerated in patients with advanced/metastatic NSCLC, and no evidence of drug-drug interaction was observed. Although preliminary, this quadruple therapy may have promising antitumor activity.

PMID:34607210 | DOI:10.1016/j.lungcan.2021.09.004

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Process Analytical Technologies – Advances in bioprocess integration and future perspectives

J Pharm Biomed Anal. 2021 Sep 25;207:114379. doi: 10.1016/j.jpba.2021.114379. Online ahead of print.

ABSTRACT

Process Analytical Technology (PAT) instruments include analyzers capable of measuring physical and chemical process parameters and key attributes with the goal of optimizing process controls. PAT in the form of a probe or sensor is designed to integrate within the pharmaceutical manufacturing line and is coupled with computing equipment to perform chemometric modeling for result interpretation and multilayer statistical control of processes. PAT solutions are intended for understanding bioprocesses with a goal to control quality at all stages of product manufacturing and achieve quality by design (QbD). The goal of PAT implementation is to promote real-time release of products to decrease the cycle time and cost of production. This review focuses on the applications of PAT solutions at different stages of the manufacturing process for vaccine production, the advantages, challenges at present state, and the vision of the future development of biopharmaceutical industries.

PMID:34607168 | DOI:10.1016/j.jpba.2021.114379

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Neuroaspis PLP10, a nutritional formula rich in omega-3 and omega-6 fatty acids with antioxidant vitamins including gamma-tocopherol in early Parkinson’s disease: A randomized, double-blind, placebo-controlled trial

Clin Neurol Neurosurg. 2021 Sep 17;210:106954. doi: 10.1016/j.clineuro.2021.106954. Online ahead of print.

ABSTRACT

In the present study, we investigated whether Neuroaspis PLP10™, a well-designed intervention, rich in omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) with specific antioxidant vitamins, may exert positive action in the improvement of Parkinson’s disease symptoms and perhaps delay the progression of the disease when used as an adjuvant to the conventional treatment. Forty patients were randomized 1:1 to receive either 20 ml dose, once daily, of control (pure virgin olive oil) or Neuroaspis PLP 10™, a formula containing a mixture of omega-3 (810 mg Eicosapentaenoic acid and 4140 mg Docosahexaenoic acid) and omega-6 fatty acids (1800 mg gamma-Linolenic acid and 3150 mg Linoleic acid) (1:1 w/w), with 0.6 mg vitamin A, vitamin E (22 mg) plus pure gamma (γ)-tocopherol (760 mg), for a total of 30 months in a randomized double-blind, placebo-controlled trial. Participants completed assessments based on the Hoehn and Yahr Staging Scale of Parkinson’s Disease (HY scale) and the Unified Parkinson’s Disease Rating Scale (UPDRS) III. Overall, for this small sample size clinical trial, Neuroaspis PLP10™ supplementation as an adjuvant treatment for 30 months in PD patients significantly delayed disease progression according to UPDRS (p ≤ 0.05) Vs placebo.

PMID:34607196 | DOI:10.1016/j.clineuro.2021.106954

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Management of congenital and acquired airway pathologies in newborns by a cross-disciplinary committee at a third level hospital

Cir Pediatr. 2021 Oct 1;34(4):180-185.

ABSTRACT

INTRODUCTION: Neonatal airway examination through flexible/rigid bronchoscopy has proved to be useful in the presence of persistent stridor and extubation failure, as well as to assess complications following cardiac surgery. At our institution, these examinations are carried out by a pulmonologist, a neonatologist, an otorhinolaryngologist, and a pediatric surgeon from the pediatric airway committee, established in 2014.

OBJECTIVE: To analyze the airway examinations performed in neonates during their stay at the neonatology/neonatal intensive care unit since the airway committee was established.

MATERIAL AND METHODS: A retrospective study of the airway examinations conducted in neonates from 2015 to 2019 was carried out. Clinical and demographic data, number of examinations, indications, findings, and complications were collected. Results are presented as mean and standard deviation. Statistical significance was established at p < 0.05.

RESULTS: 92 airway examinations were analyzed in 51 patients (54.9% of whom were female). 51% of the patients were premature. Extubation failure and persistent respiratory symptoms following successful extubation were the most frequent indications for airway examination (35.3%). Stratification by gestational age or weight at birth was not associated with an increased risk of pathological findings at examination (p > 0.05). The most frequent finding was vocal cord paralysis (n = 14; 27.5%). In 10 patients (19.6%), no pathological findings were observed.

CONCLUSION: Airway examination is useful in patients with stridor to identify vocal cord paralysis following extubation failure. It also allows congenital airway pathologies to be diagnosed and treated. The number of examinations with no pathological findings was similar to that reported in international series.

PMID:34606697

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Calculating the path of cancer

Scientists are using a new mathematical tool to predict how combinations of genetic mutations cause different types of tumors.
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A comparative study of efficacy and safety of autologous fat grafting versus Platelet-rich plasma in the treatment of post-acne scars

J Cosmet Dermatol. 2021 Oct 4. doi: 10.1111/jocd.14503. Online ahead of print.

ABSTRACT

BACKGROUND: Platelet-rich plasma is a useful adjuvant therapy in the treatment of acne scars. Fat is as ideal soft tissue filler.

AIMS: To compare the efficacy and safety of subcision with autologous fat grafting versus subcision with intradermal Platelet-rich plasma for the treatment of acne scars.

METHODS: Twenty-four patients were divided into two groups with 12 patients each. One group subjected to single session of subcision with autologous fat grafting. Second group treated with subcision followed by intradermal Platelet-rich plasma monthly once for 3 months. High resolution digital photographs taken before and after every session. Single blinded physician assessment was also done.

RESULTS: In quantitative acne scar assessment scoring, both group of patients showed significant percentage of improvement in acne scars, 61.23 ± 9.48% in patients treated with subcision followed by autologous fat grafting and 44.16 ± 7.28% in patients treated with subcision followed by intradermal PRP. At the time of enrolment, 33.3% (n = 8) of patients had Grade A (milder) scarring, 50% (n = 12) had Grade B (moderate) scarring while 16.7% (n = 4) had Grade C (severe) scarring. After the completion of the treatment, it was found that 75% (n = 18) of patients were in Grade A while 20.8% (n = 5) of patients were in Grade B (p < 0.05; significant).

CONCLUSION: Both the treatment modalities, i.e., autologous fat grafting and intradermal PRP were effective and safe for the treatment of acne scars and results in each group was significant (p < 0.001). But there were no statistically significant differences between the two treatment groups (p = 0.23).

PMID:34606674 | DOI:10.1111/jocd.14503

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SARS-CoV-2 prevalence and transmission in swimming activities: results from a retrospective cohort study

Scand J Med Sci Sports. 2021 Oct 4. doi: 10.1111/sms.14071. Online ahead of print.

ABSTRACT

There is an urgent need for research on the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing corona virus disease 2019 (COVID-19), as the transmissibility differs between settings and populations. Here we report on a questionnaire-based retrospective cohort study of the prevalence and transmission of SARS-CoV-2 among participants in swimming activities in Denmark in the last five months of 2020 during the COVID-19 pandemic. Eight of 162 swimming activities with a SARS-CoV-2 positive participant led to transmission to 23 other participants. Overall, the percentage of episodes leading to transmission was 4.9% (competitive swimming 8.9%; recreational swimming 1.3%). Overall, the incidence rate of transmission was 19.5 participants per 100,000 pool activity hours (corresponding values: 43.5 and 4.7 for competitive and recreational swimming, respectively). Compliance with precautionary restrictions was highest regarding hand hygiene (98.1%) and lowest in distancing personal sports bags (69.9%). As a result of low statistical power, the study showed no significant effect of restrictions. Insight into the risk of transmission of SARS-CoV-2 during indoor swimming is needed to estimate the efficiency of restrictive measures on this and other sports and leisure activities. Only when we know how the virus spreads through various settings, optimal strategies to handle the COVID-19 pandemic can be developed.

PMID:34606662 | DOI:10.1111/sms.14071

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A culturally targeted video to promote genetic counseling in a community sample of at-risk US Latina women: The role of the concrete mindset

J Community Psychol. 2021 Oct 4. doi: 10.1002/jcop.22718. Online ahead of print.

ABSTRACT

Latina women, who are at increased risk of hereditary breast and ovarian cancer (HBOC), have lower use of genetic counseling and testing (GCT) than non-Hispanic White women. In a recent study, culturally targeted video improved psychosocial outcomes related to GCT. Additional analyses examine whether the culturally targeted video improved positive reactions in women who focus on difficulties (concrete mindset) versus women who focus on the final goals (abstract mindset). Participants (N = 32) completed surveys before and immediately after watching the video. The surveys measured attitudes, emotions, and women’s mindset. Before watching the video, women with a concrete mindset reported more negative attitudes and negative emotions about GCT than women with an abstract mindset. After watching the video, women with a concrete mindset reported negative attitudes and feelings at levels comparable to those of women with an abstract mindset, reflecting a reduction in their negative attitudes and emotions. The sample size limits the power to find statistically significant differences. Results support the relevance of considering the audience’s mindset in the development and testing of public health messages to promote the use of GCT.

PMID:34606624 | DOI:10.1002/jcop.22718

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Reducing systematic errors due to deformation of organs at risk in radiotherapy

Med Phys. 2021 Oct 4. doi: 10.1002/mp.15262. Online ahead of print.

ABSTRACT

PURPOSE: In radiotherapy (RT), the planning CT (pCT) is commonly used to plan the full RT-course. Due to organ deformation and motion, the organ shapes seen at the pCT will not be identical to their shapes during RT. Any difference between the pCT organ shape and the organ’s mean shape during RT will cause systematic errors. We propose to use statistical shrinkage estimation to reduce this error using only the pCT and the population mean shape computed from training data.

METHODS: The method was evaluated for the rectum in a cohort of 37 prostate cancer patients that had a pCT and 7-10 treatment CTs with rectum delineations. Deformable registration was performed both within-patient and between patients, resulting in point-to-point correspondence between all rectum shapes, which enabled us to compute a population mean rectum. Shrinkage estimates were found by combining the pCTs linearly with the population mean. The method was trained and evaluated using leave-one-out cross validation. The shrinkage estimates and the patient mean shapes were compared geometrically using the Dice similarity index (DSI), Hausdorff distance (HD) and bidirectional local distance (BLD). Clinical dose/volume histograms, equivalent uniform dose (EUD) and minimum dose to the hottest 5% volume (D5%) were compared for the shrinkage estimate and the pCT.

RESULTS: The method resulted in moderate but statistically significant increase in similarity to the patient mean shape over the pCT. On average, the HD was reduced from 15.6 to 13.4 mm, while the DSI was increased from 0.74 to 0.78. Significant reduction in the bias of volume estimates were found in the DVH-range of 52.5 to 65 Gy, where the bias was reduced from -1.3 to -0.2 percentage points, but no significant improvement was found in EUD or D5%, CONCLUSIONS: The results suggest that shrinkage estimation can reduce systematic errors due to organ deformations in RT. The method has potential to increase the accuracy in RT of deformable organs and can improve motion modelling. This article is protected by copyright. All rights reserved.

PMID:34606630 | DOI:10.1002/mp.15262