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OBJECTIVE: To evaluate the reliability, responsiveness, and validity of the Scale for the Assessment and Rating of Ataxia (SARA) in patients with lysosomal storage disorders (LSDs) who present with neurological symptoms, and quantify the threshold for a clinically meaningful change. METHODS: We analyzed data from three clinical trial cohorts (IB1001-201, IB1001-202, and IB1001-301) of patients with Niemann-Pick disease type C (NPC) and GM2 Gangliosidoses (Tay-Sachs and Sandhoff disease) comprising 122 patients and 703 visits. Reproducibility was described as re-test reliability between repeat baseline visits or baseline and post-treatment washout visits. Responsiveness was determined in relation to the Investigators, Caregivers, and Patients Clinical Global Impression of Improvement (CGI-I). The CGI-I data was also used to quantify a threshold for a clinically meaningful improvement on the SARA scale. Using a qualitative methods approach, patient/caregiver interviews from the IB1001-301 trial were further used to assess a threshold of meaningful change as well as the breadth of neurological signs and symptoms captured and evaluated by the SARA scale. RESULTS: The Inter-Class Correlation (ICC) was 0.95 or greater for all three trials, indicating a high internal consistency/reliability. The mean change in SARA between repeat baseline and post-treatment washout visit assessments in all trials was -0.05, SD 1.98, i.e., minimal, indicating no significant differences, learning effects or other systematic biases. For the CGI-I responses and change in SARA scores, Area Under the Curve (AUC) values were 0.82, 0.71, and 0.77 for the Investigators, Caregivers, and Patients CGI-I respectively, indicating strong agreement. Further qualitative analyses of the patient/caregiver interviews demonstrated a 1-point or greater change on SARA to be a clinically meaningful improvement which is directly relevant to the patients everyday functioning and quality of life. Changes captured by the SARA were also paralleled by improvement in a broad range of neurological signs and symptoms and beyond cerebellar ataxia. CONCLUSION: Qualitative and quantitative data demonstrate the reliability and responsiveness of the SARA score as a valid measure of neurological signs and symptoms in LSDs with CNS involvement, such as NPC and GM2 Gangliosidoses. A 1-point change represents a clinically meaningful transition reflecting the gain or loss of complex function.

Entamoeba histolytica, the causative agent of amebiasis, is one of the top three parasitic causes of mortality worldwide. However, no vaccine exists against amebiasis. Using a lead candidate vaccine containing the LecA fragment of Gal-lectin and GLA-3M-052 liposome adjuvant, we immunized rhesus macaques via intranasal or intramuscular routes. The vaccine elicited high-avidity functional humoral responses as seen by the inhibition of amebic attachment to mammalian target cells by plasma and stool antibodies. Importantly, antigen-specific IFN-γ-secreting peripheral blood mononuclear cells (PBMCs) and IgG/IgA memory B cells (BMEM) were detected in immunized animals. Furthermore, antigen-specific antibody and cellular responses were maintained for at least 8 months after the final immunization as observed by robust LecA-specific BMEM as well as IFN-γ+ PBMC responses. Overall, both intranasal and intramuscular immunizations elicited a durable and functional response in systemic and mucosal compartments, which supports advancing the LecA+GLA-3M-052 liposome vaccine candidate to clinical testing.

Previous research has found emotional colour connotations (red=negative, green=positive) to rapidly impact emotional judgements of faces presented in different colour contexts. However, it remains unclear whether this influence is reciprocal. We consider differences in processing speed and difficulty between perceptual (colour) and conceptual (emotion) stimuli to determine whether emotion information influences colour processing. We examined whether emotional face primes (angry/happy/neutral) influence red-green colour judgements and if this effect is greater under increased ambiguity of the colour stimuli. The findings suggest that primed emotional information can guide colour judgements. Specifically, happy face primes led to better categorisation accuracy for predominantly green stimuli, while angry face primes led to better categorisation accuracy for predominantly red stimuli. For ambiguous colour stimuli, a categorisation response bias was found for green following happy face primes. Our findings provide support for a reciprocal influence of emotional stimuli on colour judgements.

Background: Radiation therapy (RT) is an established palliative treatment for bone metastases; however, little is known about post-radiation survival and factors which impact it. The aim of this study was to assess a population-based sample of metastatic prostate cancer patients receiving palliative radiation therapy to bone metastases and contemporary palliative systemic therapy and identify factors that impact long-term survival. Materials/methods: This retrospective, population-based, cohort study assessed all prostate cancer patients receiving palliative RT for bone metastases at a Canadian provincial Cancer program during a contemporary time period. Baseline patient, disease, and treatment characteristics were extracted from the provincial medical physics databases and the electronic medical record. Post-RT Survival intervals were defined as the time interval from the first fraction of palliative RT to death from any cause or date of the last known follow-up. The median survival of the cohort was used to dichotomize the cohort into short- and long-term survivors following RT. Univariable and multivariable hazard regression analyses were performed to identify variables associated with post-RT survival. Results: From 1 January 2018 until 31 December 2019, 545 palliative RT courses for bone metastases were delivered to n = 274 metastatic prostate cancer patients with a median age of 76 yrs (Interquartile range (IQR) 39–83) and a median follow-up of 10.6 months (range 0.2 to 47.9). The median survival of the cohort was 10.6 months (IQR 3.5–25 months). The ECOG performance status of the whole cohort was ≤2 in n = 200 (73%) and 3–4 in n = 67 (24.5%). The most commonly treated sites of bone metastasis were the pelvis and lower extremities n = 130 (47.4%), skull and spine n = 114 (41.6%), and chest and upper extremities n = 30 (10.9%). Most patients had CHAARTED high volume disease n = 239 (87.2%). On multivariable hazard regression analysis, an ECOG performance status of 3–4 (p = 0.02), CHAARTED high volume disease burden (p = 0.023), and non-receipt of systemic therapy (p = 0.006) were significantly associated with worse post-RT survival. Conclusion: Amongst metastatic prostate cancer patients treated with palliative radiotherapy to bone metastases and modern palliative systemic therapies, ECOG performance status, CHAARTED metastatic disease burden, and type of first-line palliative systemic therapy were significantly associated with post-RT survival durations.

Ornithine transcarbamylase deficiency (OTCD) is an X-linked defect of ureagenesis and the most common urea cycle disorder. Patients present with hyperammonemia causing neurological symptoms, which can lead to coma and death. Liver transplantation (LT) is the only curative therapy, but has several limitations including organ shortage, significant morbidity and requirement of lifelong immunosuppression. This study aims to identify the characteristics and outcomes of patients who underwent LT for OTCD.We conducted a retrospective study for OTCD patients from 5 UK centres receiving LT in 3 transplantation centres between 2010 and 2022. Patients' demographics, family history, initial presentation, age at LT, graft type and pre- and post-LT clinical, metabolic, and neurocognitive profile were collected from medical records.A total of 20 OTCD patients (11 males, 9 females) were enrolled in this study. 6/20 had neonatal and 14/20 late-onset presentation. 2/20 patients had positive family history for OTCD and one of them was diagnosed antenatally and received prospective treatment. All patients were managed with standard of care based on protein-restricted diet, ammonia scavengers and supplementation with arginine and/or citrulline before LT. 15/20 patients had neurodevelopmental problems before LT. The indication for LT was presence (or family history) of recurrent metabolic decompensations occurring despite standard medical therapy leading to neurodisability and quality of life impairment. Median age at LT was 10.5 months (6–24) and 66 months (35–156) in neonatal and late onset patients, respectively. 15/20 patients had deceased donor LT (DDLT) and 5/20 had living related donor LT (LDLT). Overall survival was 95% with one patient dying 6 h after LT. 13/20 had complications after LT and 2/20 patients required re-transplantation. All patients discontinued dietary restriction and ammonia scavengers after LT and remained metabolically stable. Patients who had neurodevelopmental problems before LT persisted to have difficulties after LT. 1/5 patients who was reported to have normal neurodevelopment before LT developed behavioural problems after LT, while the remaining 4 maintained their abilities without any reported issues.LT was found to be effective in correcting the metabolic defect, eliminates the risk of hyperammonemia and prolongs patients' survival.

Abstract Synthetic biology has allowed for the industrial production of supply-limited sesquiterpenoids such as the antimalarial drug artemisinin and β-farnesene. One of the only unmodified animal products used in medicine is squalene, a triterpenoid derived from shark liver oil, which when formulated into an emulsion is used as a vaccine adjuvant to enhance immune responses in licensed vaccines. However, overfishing is depleting deep-sea shark populations, leading to potential supply problems for squalene. We chemically generated over 20 squalene analogues from fermentation-derived β-farnesene and evaluated adjuvant activity of the emulsified compounds compared to shark squalene emulsion. By employing a desirability function approach that incorporated multiple immune readouts, we identified analogues with enhanced, equivalent, or decreased adjuvant activity compared to shark squalene emulsion. Availability of a library of structurally related analogues allowed elucidation of structure-function relationships. Thus, combining industrial synthetic biology with chemistry and immunology enabled generation of sustainable terpenoid-based vaccine adjuvants comparable to current shark squalene-based adjuvants while illuminating structural properties important for adjuvant activity.

Purpose: Endobronchial electromagnetic transponder beacons (EMT) provide real-time, precise positional data of moving lung tumors. We report results of a phase 1/2, prospective, single-arm cohort study evaluating the treatment planning effects of EMT-guided SABR for moving lung tumors. Methods and Materials: Eligible patients were adults, Eastern Cooperative Oncology Group 0 to 2, with T1-T2N0 non-small cell lung cancer or pulmonary metastasis ≤4 cm with motion amplitude ≥5 mm. Three EMTs were endobronchially implanted using navigational bronchoscopy. Four-dimensional free-breathing computed tomography simulation scans were obtained, and end-exhalation phases were used to define the gating window internal target volume. A 3-mm expansion of gating window internal target volume defined the planning target volume (PTV). EMT-guided, respiratory-gated (RG) SABR was delivered (54 Gy/3 fractions or 48 Gy/4 fractions) using volumetric modulated arc therapy. For each RG-SABR plan, a 10-phase image-guided SABR plan was generated for dosimetric comparison. PTV/organ-at-risk (OAR) metrics were tabulated and analyzed using the Wilcoxon signed-rank pair test. Treatment outcomes were evaluated using RECIST (Response Evaluation Criteria in Solid Tumours; version 1.1). Results: Of 41 patients screened, 17 were enrolled and 2 withdrew from the study. Median age was 73 years, with 7 women. Sixty percent had T1/T2 non-small cell lung cancer and 40% had M1 disease. Median tumor diameter was 1.9 cm with 73% of targets located peripherally. Mean respiratory tumor motion was 1.25 cm (range, 0.53-4.04 cm). Thirteen tumors were treated with EMT-guided SABR and 47% of patients received 48 Gy in 4 fractions while 53% received 54 Gy in 3 fractions. RG-SABR yielded an average PTV reduction of 46.9% (P < .005). Lung V5, V10, V20, and mean lung dose had mean relative reductions of 11.3%, 20.3%, 31.1%, and 20.3%, respectively (P < .005). Dose to OARs was significantly reduced (P < .05) except for spinal cord. At 6 months, mean radiographic tumor volume reduction was 53.5% (P < .005). Conclusions: EMT-guided RG-SABR significantly reduced PTVs of moving lung tumors compared with image-guided SABR. EMT-guided RG-SABR should be considered for tumors with large respiratory motion amplitudes or those located in close proximity to OARs.

It is one thing for everyday phrases like “seeing red” to link some emotions with certain colours (e.g., anger with red), but can such links measurably bias information processing? We investigated whether emotional face information (angry/happy/neutral) held in visual working memory (VWM) enhances memory for shapes presented in a conceptually consistent colour (red or green) (Experiment 1). Although emotional information held in VWM appeared not to bias memory for coloured shapes in Experiment 1, exploratory analyses suggested that participants who physically mimicked the face stimuli were better at remembering congruently coloured shapes. Experiment 2 confirmed this finding by asking participants to hold the faces in mind while either mimicking or labelling the emotional expressions of face stimuli. Once again, those who mimicked the expressions were better at remembering shapes with emotion-congruent colours, whereas those who simply labelled them were not. Thus, emotion–colour associations appear powerful enough to guide attention, but—consistent with proposed impacts of “embodied emotion” on cognition—such effects emerged when emotion processing was facilitated through facial mimicry.

Arun Sivananthan1,2 &ast;, Victoria Nicholas3 &ast;, Georgina Kerry,4 Christopher Harlow,5 Pratyasha Saha,6 Helen-Cara Younan,7 Stephanie Williams,8 Lewis David,9 Clifford Lisk,10 Louise Schofield11 1Institute of Global Health Innovation, Imperial College London, London, UK; 2Department of Gastroenterology, Imperial College Healthcare NHS Trust, London, UK; 3Department of Medicine, Chelsea and Westminster NHS Foundation Trust, London, UK; 4Department of Gastroenterology, St George’s University Hospital NHS Foundation Trust, London, UK; 5Department of Cardiology, Epsom and St Heliers University Hospital, London, UK; 6Department of Rheumatology, University College London NHS Trust, London, UK; 7Department of Intensive Care Medicine, Imperial College Healthcare NHS Trust, London, UK; 8Department of Acute Medicine, Royal Free NHS Trust, London, UK; 9Department of Endocrinology, Bart’s Health NHS Trust, London, UK; 10Department of Geriatrics, Royal Free NHS Trust, London, UK; 11Department of Palliative Medicine, Royal Free NHS Trust, London, UK&ast;These authors contributed equally to this workCorrespondence: Arun Sivananthan, Institute of Global Health Innovation Imperial College London, 10th Floor QEQM Building, London, W2 1NY, UK, Tel +44 0203 3126666, Email a.sivananthan@nhs.netIntroduction: The Covid-19 pandemic brought significant disruption to post-graduate medical education. Lecture-based training days were rapidly converted to webinars. This study aims to assess the perceptions of digital training in internal medical trainees.Methods: IMTs (internal medicine trainees) nationally were surveyed on their perceptions of digital training, ease of access, engagement, and interactivity via a 10-item questionnaire. A mixed-method approach using qualitative and quantitative questions was used. Likert scales were analysed using a mean result of above 3 to indicate agreement.Results: 359 trainees responded. Trainees agreed that they preferred digital training to face-to-face teaching (mean 3.68); digital training was more engaging (mean 4.25), easier to access (mean 4.49), and as effective for learning as face-to-face teaching (mean 4.69). The most reported advantages were no travel (89%) and the ability to watch later on (88%). 63% of trainees reported loss of social interaction as a disadvantage.Discussion: This survey suggests that digital teaching has a potential role in IMT training beyond the pandemic.Keywords: medical education, digital training, IMT, webinar, post-graduate training

Background/Aims Colonoscopy is the gold standard diagnostic method for colorectal neoplasia, allowing detection and resection of adenomatous polyps; however, significant proportions of adenomas are missed. Computer-aided detection (CADe) systems in endoscopy are currently available to help identify lesions. Diminutive (≤5 mm) and nonpedunculated polyps are most commonly missed. This meta-analysis aimed to assess whether CADe systems can improve the real-time detection of these commonly missed lesions. Methods A comprehensive literature search was performed. Randomized controlled trials evaluating CADe systems categorized by morphology and lesion size were included. The mean number of polyps and adenomas per patient was derived. Independent proportions and their differences were calculated using DerSimonian and Laird random-effects modeling. Results Seven studies, including 2,595 CADe-assisted colonoscopies and 2,622 conventional colonoscopies, were analyzed. CADe-assisted colonoscopy demonstrated an 80% increase in the mean number of diminutive adenomas detected per patient compared with conventional colonoscopy (0.31 vs. 0.17; effect size, 0.13; 95% confidence interval [CI], 0.09–0.18); it also demonstrated a 91.7% increase in the mean number of nonpedunculated adenomas detected per patient (0.32 vs. 0.19; effect size, 0.05; 95% CI, 0.02–0.07). Conclusions CADe-assisted endoscopy significantly improved the detection of most commonly missed adenomas. Although this method is a potentially exciting technology, limitations still apply to current data, prompting the need for further real-time studies.

Introduction: We evaluated the association of pre-treatment immunologic biomarkers on the outcomes of early-stage non-small-cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT). Materials and methods: In this retrospective study, all newly diagnosed early-stage NSCLC treated with SBRT between January 2010 and December 2017 were screened and included for further analysis. The pre-treatment neutrophil-lymphocyte ratio (NLR), monocyte lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) were calculated. Overall survival (OS) and recurrence-free survival (RFS) were estimated by Kaplan–Meier. Multivariable models were constructed to determine the impact of different biomarkers and the Akaike information criterion (AIC), index of adequacy, and scaled Brier scores were calculated. Results: A total of 72 patients were identified and 61 were included in final analysis. The median neutrophil count at baseline was 5.4 × 109/L (IQR: 4.17–7.05 × 109/L). Median lymphocyte count was 1.63 × 109/L (IQR: 1.29–2.10 × 109/L), median monocyte count was 0.65 × 109/L (IQR: 0.54–0.83 × 109/L), median platelet count was 260.0 × 109/L (IQR: 211.0–302.0 × 109/L). The median NLR was 3.42 (IQR: 2.38–5.04), median MLR was 0.39 (IQR: 0.31–0.53), and median PLR was 156.4 (IQR: 117.2–197.5). On multivariable regression a higher NLR was associated with worse OS (p = 0.01; HR-1.26; 95% CI 1.04–1.53). The delta AIC between the two multivariable models was 3.4, suggesting a moderate impact of NLR on OS. On multivariable analysis, higher NLR was associated with poor RFS (p = 0.001; NLR^1 HR 0.36; 0.17–0.78; NLR^2 HR-1.16; 95% CI 1.06–1.26) with a nonlinear relationship. The delta AIC between the two multivariable models was 16.2, suggesting a strong impact of NLR on RFS. In our cohort, MLR and PLR were not associated with RFS or OS in multivariable models. Conclusions: Our study suggests NLR, as a biomarker of systemic inflammation, is an independent prognostic factor for OS and RFS. The nonlinear relationship with RFS may indicate a suitable immunological environment is needed for optimal SBRT action and tumoricidal mechanisms. These findings require further validation in independent cohorts.

Cement-based materials are increasingly and widely employed in infrastructure development; however, they pollute our environment by generating carbon dioxide, which is detrimental to our civilization. In self-cleaning concrete, photocatalysts accelerate the decomposition of organic particles; thus, photocatalytic degradation of gaseous pollutants could reduce pollution. The incorporation of photocatalytic components enhanced the mechanical self-cleaning properties of cement mortar. In this study, 4–6 percent by weight of rutile TiO2 was added to mortar, and the results were compared to those of a control sample. On the proposed mortar cubes, both fresh mortar and hardening mortar experiments were conducted. Because the initial and final setting times of TiO2 differ from those of conventional cement mortar, the surplus TiO2water-cement ratio had to be modified. The adaptability of the sol-gel method enables the use of various process parameters to influence the properties of the produced TiO2 nanoparticles. The compressive strength was calculated for 7, 14, 21, and 28 days, and an ultrasonic velocity test was performed after 28 days. On mortar samples, acid and sulfate attack experiments were performed. The M-3 mortar mixture containing 5% rutile exhibited the highest level of strength compared to the other mixtures. The M-3 exhibits a strength that is 10.96% greater than that of the control mix. The impact of acid and sulfate attack on the strength of mix M-2 is relatively modest in comparison to other mixtures. Using RhB (rhodamine color) discoloration under UV light, such as sunlight, the photocatalytic mortar is concentrated; a typical test for self-cleaning cementitious materials reveals the presence of more photocatalytic material, which yields the best results.

Epstein–Barr virus (EBV) reactivation in acute-phase of COVID-19 disease was recently discovered but it is not clear in terms of degree of mortality caused, and this was the aim of the current study. Six databases and three non‐databases were thoroughly searched, independently. The articles related to non‐human study (abstract, in vitro, in vivo, in silico, case study, poster, and review articles) were excluded for main analysis. Four articles related to mortality linked to EBV reactivation were systematically identified and included in the qualitative and quantitative analyses. Based on proportional meta-analysis of 4 studies, 34.3% or 0.343 (95% CI: 0.189–0.516; I2 = 74.6) mortality related to EBV reactivation was identified. To address high heterogeneity, subgroup meta-analysis was carried out. Based on subgroup analysis, 26.6% or 0.266 (95% CI: 0.191–0.348; I2 = 0) with no heterogeneity was identified. Interestingly, in comparative meta-analysis, EBV(−)/SARS-CoV-2(+) patients had statistically lesser mortality (9.9%) than EBV(+)/SARS-CoV-2(+) patients (23.6%) where RR = 2.31 (95% CI: 1.34–3.99; p=0.003; I2 = 6%). This finding is equivalent to the absolute mortality effect of 130 more per 1000 COVID-19 patients (95% CI: 34–296). Furthermore, based on statistical analysis, D-dimer was not statistically significantly different (p>0.05) between the groups although studies have shown that D-dimer was statistically significantly different (p

Abstract Androgen deprivation therapy (ADT) used for prostate cancer (PCa) management is associated with metabolic and anthropometric toxicity. Metformin given concurrent to ADT is hypothesized to counteract these changes. This planned interim analysis reports the gastrointestinal and genitourinary toxicity profiles of PCa patients receiving ADT and prostate/pelvic radiotherapy plus metformin versus placebo as part of a phase 2 randomized controlled trial. Men with intermediate or high-risk PCa were randomized 1:1 to metformin versus placebo. Both groups were given ADT for 18–36 months with minimum 2-month neoadjuvant phase prior to radiotherapy. Acute gastrointestinal and genitourinary toxicities were quantified using CTCAE v4.0. Differences in ≥ grade 2 toxicities by treatment were assessed by chi-squared test. 83 patients were enrolled with 44 patients randomized to placebo and 39 randomized to metformin. There were no significant differences at any time point in ≥ grade 2 gastrointestinal toxicities or overall gastrointestinal toxicity. Overall ≥ grade 2 gastrointestinal toxicity was low prior to radiotherapy (7.9% (placebo) vs. 3.1% (metformin), p = 0.39) and at the end of radiotherapy (2.8% (placebo) vs 3.1% (metformin), p = 0.64). There were no differences in overall ≥ grade 2 genitourinary toxicity between treatment arms (19.0% (placebo) vs. 9.4% (metformin), p = 0.30). Metformin added to radiotherapy and ADT did not increase rates of ≥ grade 2 gastrointestinal or genitourinary toxicity and is generally safe and well-tolerated.

Introduction: The implications of the COVID-19 pandemic are far reaching for persons living with dementia (PLWD) in the community and in long-term care (LTC), as they are among the most vulnerable. PLWD are at risk for severe COVID-19 and a disruption in accessing supportive and health care due to the confinement measures. Objectives: 1) To measure the impact of the pandemic on health and social services use, mortality, COVID-19 infection where possible of PLWD both in the community and in LTC facilities compared to before the pandemic; 2) To understand PLWDs’ and care partners’ perceived needs, behaviours related to health service use and the experiences of PLWD, care partners, and physicians with health and social services; 3) To generate and disseminate evidence-based and actionable recommendations on effective strategies to address the current pandemic and prepare for subsequent waves. Methods: A convergent mixed-methods design with a participatory approach in 4 Canadian provinces. Objective 1 will use a retrospective observational cohort design to examine administrative health data. Outcomes will include mortality (all-cause; COVID-19 related), health service use and, where possible, infection rates. Objective 2 will use an explanatory multiple case study, with surveys and semi-structured interviews to explore the experiences of PLWD and care partners using health and social services and the role of sociodemographic factors. The third, knowledge translation objective will integrate these results using a deliberative dialogue with key stakeholders (decision-makers, healthcare managers, PLWD, care partners, and clinicians) to develop and disseminate evidence-based recommendations for practice and policy. Impact and conclusion: This project will provide an understanding of the impact of the COVID-19 pandemic on PLWD and care partners in Canada and highlight areas for improvement.

Despite many publications related to the identification of new angiotensin-I-converting enzyme (ACE) inhibitors, especially peptides from natural products, the actual reason/s for why new ACE inhibitors need to be discovered are yet to be fully understood. New ACE inhibitors are pivotal to address serious side effects caused by commercially available ACE inhibitors in hypertensive patients. Despite the effectiveness of commercial ACE inhibitors, due to these side effects, doctors often prescribe angiotensin receptor blockers (ARBs). Recent evidence has shown the benefits of ACE inhibitors over ARBs in hypertensive patients and hypertensive–diabetes mellitus patients. In order to address these side effects, the somatic ACE’s enzyme structures need to be revisited. The peptides isolated from the natural products need to be verified for their stability against ACE and several important gastrointestinal enzymes. The stable peptides sequence with the presence of favourable ACE inhibitory-related amino-acids, such as tryptophan (W), at the C-terminal need to be subjected to molecular docking and dynamics analyses for selecting ACE inhibitory peptide/s with C-domain-specific inhibition instead of both C- and N-domains’ inhibition. This strategy will help to reduce the accumulation of bradykinin, the driving factor behind the formation of the side effects.

Chemotherapy-induced nausea and vomiting (CINV) continue to negatively influence the quality of life of both adult and pediatric cancer patients (Dupuis et al., 2010; Farrell et al., 2013; Russo et al., 2014; Hinds et al., 2009; Sommariva et al., 2016). Vomiting and retching are symptoms that can be assessed objectively while nausea, a subjective symptom, is more difficult to quantify. Adult cancer patients can usually describe the severity of the nausea they feel using self-report visual analog or adjectival rating scales. Instruments such as the Multinational Association of Supportive Care in Cancer Antiemesis Tool (available from www.mascc.org) have been validated for this purpose and are recommended by experts in the field (Hesketh et al., 2015).