Optimisation of phenolic compounds and antioxidant capacity of Trigona honey and propolis using response surface methodology from fermented food products

Honey and propolis are honeybee products that are becoming increasingly common as a result of their ability to improve human health. The optimal combination of honey and propolis for total phenolic content (TPC), total flavonoid content (TFC), and antioxidant capacity were analysed for Trigona honey and propolis aqueous extracts using response surface methodology and a central composite design. The effect of honey (X1: 15 - 16.5 g) and propolis (X2: 13.5 - 15 g) on the total phenolic content (TPC, Y1), total flavonoid content (TFC, Y2), antioxidant capacity (DPPH, Y3; ABTS, Y4), and FRAP (Y5) were tested. The experimental outcomes were adequately fitted into a second-order polynomial model regarding TPC (R2 = 0.9539, p = 0.0002), TFC (R2 = 0.9209, p = 0.0010), antioxidant activity (DPPH, R2 = 0.9529, p = 0.0002; ABTS, R2 = 0.9817, p < 0.0001), and FRAP (R2 = 0.9363, p = 0.0005). The optimal percentage compositions of honey and propolis were 15.26 g (50.43%) and 15 g (49.57%), respectively. The predicted results for TPC, TFC, DPPH (IC50), ABTS, and FRAP were 162.46 mg GAE/100 g, 2.29 mgQE/g, 14.52 mg/mL, 564.27 µMTE/g, and 3.56 mMTE/g, respectively. The experimental outcomes were close to the predicted results: 152.06 ± 0.55 mg GAE/100 g, 2.21 ± 0.05 mg QE/g, 13.85 ± 0.34 mg/mL, 555.22 ± 36.84 µMTE/g, and 3.71 ± 0.02 mMTE/g, respectively. It was observed that the optimal combination of honey and propolis provided the highest antioxidant yield and can be used as functional foods, cosmetics, and medical and pharmacological ingredients

Optimization of extraction temperature and time on phenolic compounds and antioxidant activity of Malaysian propolis Trigona spp. aqueous extract using response surface methodology

Propolis is a natural product with rich bioactive constituents for medicinal, pharmaceutical, food, and cosmetic uses. It is considered a diet supplement to enhance health and prevent disease. The optimum extraction conditions used to obtain the highest yield of total phenolic content (TPC), total flavonoid content (TFC), and antioxidant capacities for Trigona propolis aqueous extract was analyzed using response surface methodology and the central composite design. The effects of extraction temperature (X1: 30-60 °C) and extraction time (X2: 24-72 hours) on TPC (Y1), TFC (Y2), and antioxidant activities (DPPH (Y3), ABTS •+ radical scavenging assay (Y4), and ferric reducing antioxidant power (Y5) were investigated. The experimental data were satisfactorily fitted into a second-order polynomial model with regard to TPC (R 2 = 0.9461, p = 0.0003), TFC (R 2 = 0.9110, p = 0.0015), DPPH (R 2 = 0.9482, p <0.0001), ABTS (R 2 = 0.9663, p <0.0001), and FRAP (R 2 = 0.9058, p = 0.0018). The optimum extraction temperature and time were 43.75 °C and 52.85 hours. The predicted response values for TPC, TFC, DPPH, ABTS, and FRAP were 104.30 mg GAE/100g, 6.95 mg QE/g, 3.24 mMTE/g, 2.59 mMTE/g, and 4.34 mMTE/g, respectively. The experimental values were close to the predicted values 100.41 ± 2.74 mg GAE/100g, 6.74 ± 0.08 mg QE/g, 3.17 ± 0.08 mMTE/g, 2.76 ± 0.14 mMTE/g, and 4.60 ± 0.14 mMTE/g. As a result, the models generated are suitable, and RSM was successful in optimizing the extraction conditions. Consequently, in this study, it was observed that the optimum extraction temperature and time provided the highest antioxidant yield of aqueous propolis extract which can be used as functional food ingredients

The antioxidant activity and induction of apoptotic cell death by Musa paradisiaca and Trigona sp. honey jelly in ORL115 and ORL188 cells

Background: Head and neck cancer patients usually need nutritional support due to difficulties in swallowing and chewing. Therefore, this study aimed to formulate Musa paradisiaca and Trigona sp. honey jelly (MTJ) as a convenient functional food. Methods: The antioxidant properties were analysed using 2,2′-diphenyl-1 picrylhydrazyl (DPPH), ferric reducing antioxidant potential (FRAP) and 2,2′-azinodi 3-ethylbenthiazolinesulfonate (ABTS) assays. Cytotoxicity was assayed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test and the induction of apoptosis was observed via caspase-3/7 activity assay. The identification of phenolic compounds was done via ultra-high-performance-liquid chromatography coupled to mass spectrometer (UHPLC-MS/MS). Results: The antioxidant analysis exhibited: the half inhibitory concentration (IC50) of DPPH inhibition, 54.10 (SD = 4.51) µg/mL; the FRAP value, 30.07 (SD = 0.93) mM TEQ/100 g; and the ABTS value, 131.79 (SD = 8.73) mg TEQ/100 g. Cinnamic acid was the most abundant phenolic compound, followed by maleic acid and salicylic acid. The IC50 for ORL115 and ORL188 were 35.51 mg/mL and 43.54 mg/mL, respectively. The cells became rounded and dissymmetrical which reduced in number and size. The apoptotic cell death in ORL115 and ORL188 was deduced as caspase-3/7 activities that significantly increased (P &lt; 0.05). Conclusion: The study evidenced that the antioxidant activity of MTJ could influence the induction of apoptosis in ORL115 and ORL188 in future investigations and verifications

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

AbstractDevelopmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy.</jats:p

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Mortality of emergency abdominal surgery in high-, middle- and low-income countries

Background: Surgical mortality data are collected routinely in high-income countries, yet virtually no low- or middle-income countries have outcome surveillance in place. The aim was prospectively to collect worldwide mortality data following emergency abdominal surgery, comparing findings across countries with a low, middle or high Human Development Index (HDI). Methods: This was a prospective, multicentre, cohort study. Self-selected hospitals performing emergency surgery submitted prespecified data for consecutive patients from at least one 2-week interval during July to December 2014. Postoperative mortality was analysed by hierarchical multivariable logistic regression. Results: Data were obtained for 10 745 patients from 357 centres in 58 countries; 6538 were from high-, 2889 from middle- and 1318 from low-HDI settings. The overall mortality rate was 1⋅6 per cent at 24 h (high 1⋅1 per cent, middle 1⋅9 per cent, low 3⋅4 per cent; P < 0⋅001), increasing to 5⋅4 per cent by 30 days (high 4⋅5 per cent, middle 6⋅0 per cent, low 8⋅6 per cent; P < 0⋅001). Of the 578 patients who died, 404 (69⋅9 per cent) did so between 24 h and 30 days following surgery (high 74⋅2 per cent, middle 68⋅8 per cent, low 60⋅5 per cent). After adjustment, 30-day mortality remained higher in middle-income (odds ratio (OR) 2⋅78, 95 per cent c.i. 1⋅84 to 4⋅20) and low-income (OR 2⋅97, 1⋅84 to 4⋅81) countries. Surgical safety checklist use was less frequent in low- and middle-income countries, but when used was associated with reduced mortality at 30 days. Conclusion: Mortality is three times higher in low- compared with high-HDI countries even when adjusted for prognostic factors. Patient safety factors may have an important role. Registration number: NCT02179112 (http://www.clinicaltrials.gov)

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone