SCB-2019 protein vaccine as heterologous booster of neutralizing activity against SARS-CoV-2 Omicron variants after immunization with other COVID-19 vaccines.

We assessed the non-inferiority of homologous boosting compared with heterologous boosting with the recombinant protein vaccine, SCB-2019, in adults previously immunized with different COVID-19 vaccines. Three equal cohorts (N ~ 420) of Philippino adults (18-80 years) previously immunized with Comirnaty, CoronaVac or Vaxzevria COVID-19 vaccines were randomized 1:1 to receive homologous or heterologous (SCB-2019) boosters. Neutralizing antibodies against prototype SARS-CoV-2 (Wuhan-Hu-1) were measured in all participants and against Delta variant and Omicron sub-lineages in subsets (30‒50 per arm) 15 days after boosting. Participants recorded solicited adverse events for 7 days and unsolicited and serious adverse events until Day 60. Prototype SARS-CoV-2 neutralizing responses on Day 15 after SCB-2019 were statistically non-inferior to homologous Vaxzevria boosters, superior to CoronaVac, but lower than homologous Comirnaty. Neutralizing responses against Delta and Omicron BA.1, BA.2, BA.4 and BA.5 variants after heterologous SCB-2019 were higher than homologous CoronaVac or Vaxzevria, but lower than homologous Comirnaty. Responses against Omicron BF.7, BQ.1.1.3, and XBB1.5 following heterologous SCB-2019 were lower than after homologous Comirnaty booster but significantly higher than after Vaxzevria booster. SCB-2019 reactogenicity was similar to CoronaVac or Vaxzevria, but lower than Comirnaty; most frequent events were mild/moderate injection site pain, headache and fatigue. No vaccine-related serious adverse events were reported. Heterologous SCB-2019 boosting was well tolerated and elicited neutralizing responses against all tested SARS-COV-2 viruses including Omicron BA.1, BA.2, BA.4, BA.5, BF.7, BQ.1.1.3, and XBB1.5 sub-lineages that were non-inferior to homologous boosting with CoronaVac or Vaxzevria, but not homologous Comirnaty booster.

Superior Boosting of Neutralizing Titers Against Omicron SARS-CoV-2 Variants by Heterologous SCB-2019 Vaccine vs a Homologous Booster in CoronaVac-Primed Adults.

BACKGROUND: We compared homologous and heterologous boosting in adults in the Philippines primed with 2 or 3 doses of CoronaVac, with recombinant protein vaccine, SCB-2019. METHODS: CoronaVac-immunized adults (18-72 years) received a homologous or heterologous full or half dose SCB-2019 booster. We assessed all neutralizing antibody (NAb) responses against prototype SARS-CoV-2 after 15 days and NAb against SARS-CoV-2 Delta and Omicron variants in subsets (30‒50 per arm). Participants recorded adverse events. RESULTS: In 2-dose CoronaVac-primed adults prototype NAb geometric mean titers (GMT) were 203 IU/mL (95% confidence interval [CI], 182-227) and 939 IU/mL (95% CI, 841-1049) after CoronaVac and SCB-2019 boosters; the GMT ratio (4.63; 95% CI, 3.95-5.41) met predefined noninferiority and post-hoc superiority criteria. After 3-dose CoronaVac-priming prototype NAb GMTs were 279 IU/mL (95% CI, 240-325), 1044 IU/mL (95% CI, 898-1213), and 668 IU/mL (95% CI, 520-829) following CoronaVac, full and half-dose SCB-2019 boosters, respectively. NAb GMT ratios against Delta and Omicron comparing SCB-2019 with CoronaVac were all greater than 2. Mild to moderate reactogenicity was evenly balanced between groups. No vaccine-related serious adverse events were reported. CONCLUSIONS: Full or half dose SCB-2019 boosters were well tolerated with superior immunogenicity than homologous CoronaVac, particularly against newly emerged variants. Clinical Trials Registration. NCT05188677.

Heterologous boosting of neutralizing activity against Delta and Omicron SARS-CoV-2 variants in CoronaVac-primed adults; a randomized study with SCB-2019 vaccine

BackgroundThe global COVID-19 pandemic has peaked but some countries such as China are reporting serious infectious outbreaks due to SARS-CoV-2 variants. Waning vaccine-derived immunogenicity and mutations in variants allowing vaccine evasion require new booster immunization approaches. We compared homologous and heterologous boosting in adults previously fully primed with a whole-virus inactivated COVID-19 vaccine. MethodsAt multiple sites in the Philippines we enrolled 430 adults (18-72 years) immunized with two doses of CoronaVac at least 3 months previously and randomly assigned them to receive homologous (CoronaVac, n = 216) or heterologous (recombinant protein vaccine, SCB-2019, n = 214) booster doses. Non-inferiority/superiority of the neutralizing antibody (NAb) response 15 days after boosting was measured by microneutralization against prototype SARS-CoV-2, and Delta and Omicron variants in subsets (50 per arm). Participants recorded solicited local and systemic adverse events for 7 days, unsolicited AEs until Day 29, and serious adverse events until Day 60. ResultsNAb geometric mean titers (GMT) against prototype on Day 15 were 744 (95% CI: 669-828) and 164 (143-189) in heterologous and homologous groups, respectively, with a heterologous/homologous GMT ratio of 4.63 (3.95-5.41), meeting both pre-defined non-inferiority and superiority criteria. Similarly, geometric mean-fold rises for NAb against Delta and Omicron BA.1, BA.2, BA.4 and BA.5 variants were superior after heterologous SCB-2019 (range 3.01-4.66) than homologous CoronaVac (range 0.85-1.6) in an exploratory analysis. Reactogenicity and safety measures were evenly balanced between groups; the most frequent local reaction was mild or moderate injection site pain; mild or moderate headache and fatigue were the most frequent systemic adverse events. No vaccine-related serious adverse events were reported. ConclusionHeterologous boosting of CoronaVac-immunized adults with SCB-2019 was well tolerated with superior immunogenicity than homologous boosting, particularly for newly emerged variants, supporting use of SCB-2019 for booster vaccination.

OLA strategy for ARDS: Its effect on mortality depends on achieved recruitment (PaO2/FiO2) and mechanical power. Systematic review and meta-analysis with meta-regression / Estrategia OLA para el SDRA: su efecto en la mortalidad depende del reclutamiento alcanzado (PaO2/FiO2) y la potencia mecánica. Revisión sistemática y metaanálisis con metarregresión

Objective: The “Open Lung Approach” (OLA), that includes high levels of positive end-expiratory pressure coupled with limited tidal volumes, is considered optimal for adult patients with ARDS. However, many previous meta-analyses have shown only marginal benefits of OLA on mortality but with statistical heterogeneity. It is crucial to identify the most likely moderators of this effect. To determine the effect of OLA strategy on mortality of ventilated ARDS patients. We hypothesized that the degree of recruitment achieved in the control group (PaO2/FiO2 ratio on day 3 of ventilation), and the difference in Mechanical Power (MP) or Driving Pressure (DP) between experimental and control groups will be the most likely sources of heterogeneity. Design: A Systematic Review and Meta-analysis was performed according to PRISMA statement and registered in PROSPERO database. We searched only for randomized controlled trials (RCTs). GRADE guidelines were used for rating the quality of evidence. Publication bias was assessed. For the Meta-analysis, we used a Random Effects Model. Sources of heterogeneity were explored with Meta-Regression, using a priori proposed set of possible moderators. For model comparison, Akaike's Information Criterion with the finite sample correction (AICc) was used. Patients: Fourteen RCTs were included in the study. Results: Evidence of publication bias was detected, and quality of evidence was downgraded. Pooled analysis did not show a significant difference in the 28-day mortality between OLA strategy and control groups. Overall risk of bias was low. The analysis detected statistical heterogeneity. The two “best” explicative meta-regression models were those that used control PaO2/FiO2 on day 3 and difference in MP between experimental and control groups. The DP and MP models were highly correlated. Conclusions: There is no clear benefit of OLA strategy on mortality of ARDS patients, with significant heterogeneity among RCTs. ... (AU)

Objetivo: La Estrategia Open Lung (EOL), que incluye niveles elevados de presión positiva teleespiratoria junto con volumen corriente bajo, es considerada como el «patrón oro» para los pacientes adultos con SDRA. Sin embargo, varios metaanálisis previos han mostrado únicamente beneficios marginales de la EOL en la disminución de la mortalidad, aunque con gran heterogeneidad estadística. Es crucial identificar los moderadores más probables, así como determinar el efecto de la estrategia EOL en la mortalidad de los pacientes ventilados con SDRA. La hipótesis fue que el grado de reclutamiento alcanzado en el grupo control (cociente PaO2/FiO2 en el día3 de ventilación) y la diferencia en potencia mecánica (MP) o driving pressure (DP) entre el grupo experimental y el grupo control son la fuente más probable de heterogeneidad. Diseño Se realizó una revisión sistemática y metaanálisis de acuerdo con la declaración PRISMA, y se registró en la base de datos PROSPERO (N.° CRD42020179778). Se seleccionaron únicamente ensayos clínicos aleatorizados (ECA). Se estratificó la calidad de la evidencia de acuerdo con la metodología GRADE. Se evaluó el sesgo de publicación. Para el metaanálisis se utilizó el modelo de efectos aleatorios. Se exploraron las fuentes de heterogeneidad mediante metarregresión utilizando a priori un conjunto establecido de posibles moderadores. Para el modelo de comparación se utilizó el criterio de información de Akaike con la corrección para muestras pequeñas (AICc). Pacientes Se incluyeron 14 ECA en el estudio. Resultados Se detectó un sesgo de publicación, y la calidad fue degradada. El análisis combinado no mostró una diferencia estadísticamente significativa en la mortalidad en el día28 entre la estrategia EOL y los grupos control. El riesgo total de sesgo fue bajo. El análisis detectó heterogeneidad estadística. ... (AU)

OLA strategy for ARDS: Its effect on mortality depends on achieved recruitment (PaO2/FiO2) and mechanical power. Systematic review and meta-analysis with meta-regression.

OBJECTIVE: The "Open Lung Approach" (OLA), that includes high levels of positive end-expiratory pressure coupled with limited tidal volumes, is considered optimal for adult patients with ARDS. However, many previous meta-analyses have shown only marginal benefits of OLA on mortality but with statistical heterogeneity. It is crucial to identify the most likely moderators of this effect. To determine the effect of OLA strategy on mortality of ventilated ARDS patients. We hypothesized that the degree of recruitment achieved in the control group (PaO2/FiO2 ratio on day 3 of ventilation), and the difference in Mechanical Power (MP) or Driving Pressure (DP) between experimental and control groups will be the most likely sources of heterogeneity. DESIGN: A Systematic Review and Meta-analysis was performed according to PRISMA statement and registered in PROSPERO database. We searched only for randomized controlled trials (RCTs). GRADE guidelines were used for rating the quality of evidence. Publication bias was assessed. For the Meta-analysis, we used a Random Effects Model. Sources of heterogeneity were explored with Meta-Regression, using a priori proposed set of possible moderators. For model comparison, Akaike's Information Criterion with the finite sample correction (AICc) was used. SETTING: Not applicable. PATIENTS: Fourteen RCTs were included in the study. INTERVENTIONS: Not applicable. MAIN VARIABLES OF INTEREST: Not applicable. RESULTS: Evidence of publication bias was detected, and quality of evidence was downgraded. Pooled analysis did not show a significant difference in the 28-day mortality between OLA strategy and control groups. Overall risk of bias was low. The analysis detected statistical heterogeneity. The two "best" explicative meta-regression models were those that used control PaO2/FiO2 on day 3 and difference in MP between experimental and control groups. The DP and MP models were highly correlated. CONCLUSIONS: There is no clear benefit of OLA strategy on mortality of ARDS patients, with significant heterogeneity among RCTs. Mortality effect of OLA is mediated by lung recruitment and mechanical power.

OLA strategy for ARDS: Its effect on mortality depends on achieved recruitment (PaO2/FiO2) and mechanical power. Systematic review and meta-analysis with meta-regression.

OBJECTIVE: The "Open Lung Approach" (OLA), that includes high levels of positive end-expiratory pressure coupled with limited tidal volumes, is considered optimal for adult patients with ARDS. However, many previous meta-analyses have shown only marginal benefits of OLA on mortality but with statistical heterogeneity. It is crucial to identify the most likely moderators of this effect. To determine the effect of OLA strategy on mortality of ventilated ARDS patients. We hypothesized that the degree of recruitment achieved in the control group (PaO2/FiO2 ratio on day 3 of ventilation), and the difference in Mechanical Power (MP) or Driving Pressure (DP) between experimental and control groups will be the most likely sources of heterogeneity. DESIGN: A Systematic Review and Meta-analysis was performed according to PRISMA statement and registered in PROSPERO database. We searched only for randomized controlled trials (RCTs). GRADE guidelines were used for rating the quality of evidence. Publication bias was assessed. For the Meta-analysis, we used a Random Effects Model. Sources of heterogeneity were explored with Meta-Regression, using a priori proposed set of possible moderators. For model comparison, Akaike's Information Criterion with the finite sample correction (AICc) was used. SETTING: Not applicable. PATIENTS: Fourteen RCTs were included in the study. INTERVENTIONS: Not applicable. MAIN VARIABLES OF INTEREST: Not applicable. RESULTS: Evidence of publication bias was detected, and quality of evidence was downgraded. Pooled analysis did not show a significant difference in the 28-day mortality between OLA strategy and control groups. Overall risk of bias was low. The analysis detected statistical heterogeneity. The two "best" explicative meta-regression models were those that used control PaO2/FiO2 on day 3 and difference in MP between experimental and control groups. The DP and MP models were highly correlated. CONCLUSIONS: There is no clear benefit of OLA strategy on mortality of ARDS patients, with significant heterogeneity among RCTs. Mortality effect of OLA is mediated by lung recruitment and mechanical power.

Carbohydrate binding modules enhance cellulose enzymatic hydrolysis by increasing access of cellulases to the substrate.

Plant biomass is a low-cost and abundant source of carbohydrates for production of fuels, "green" chemicals and materials. Currently, biochemical conversion of the biomass into sugars via enzymatic hydrolysis is the most viable technology. Here, the role of carbohydrate binding modules (CBMs) in the disruption of insoluble polysaccharide structures and their capacity to enhance cellulase-promoted lignocellulosic biomass hydrolysis was investigated. We show that CBM addition promotes generation of additional reducing ends in the insoluble substrate by cellulases. On the contrary, bovine serum albumin (BSA), widely used in prevention of a non-specific protein binding, causes an increase in soluble reducing-end production, when applied jointly with cellulases. We demonstrate that binding of CBMs to cellulose is non-homogeneous, irreversible and leads to its amorphisation. Our results also reveal effects of CBM-promoted amorphogenesis on cellulose hydrolysis by cellulases.

Cross-plane heat transfer through single-layer carbon structures.

Graphene-based nano-structures have been recently proposed to function as additives to improve the conductivity of thermally sluggish phase change materials (PCMs). Based on the existing research studies, the improvement is dependent not only on the matrix material, but also on the geometry of the carbon structure. To gain more insight into the nano-scale thermal transport problem, we launched the current pilot research using water as the matrix material, to represent the hydroxyl-group-rich sugar alcohols as PCMs. We have found that the heat conduction across a graphene layer to water is much faster than the heat conduction to the graphene layer itself. Also, the high graphene-water thermal contact resistance fails to acknowledge the fast thermal kinetics of the low frequency phonons. In the investigation of the geometry effect, the cross-plane heat transfer coefficient is found to decrease with decreasing CNT diameter except CNT(9,9).

Fracture resistance and stress distribution of simulated immature teeth after apexification with mineral trioxide aggregate.

AIM: To evaluate the effect of adhesive restorations on fracture resistance and stress distribution in teeth with simulated immature apices and apical plugs of mineral trioxide aggregate (MTA). METHODOLOGY: Sixty bovine incisors were sectioned 8 mm above and 12 mm below the cemento-enamel junction (CEJ). The root canal was enlarged using a diamond bur, resulting in remaining root canal walls with 0.1-0.2 mm of thickness. A 5-mm apical plug of MTA was placed and the teeth were restored according to the following groups: GP--the root canal was filled with gutta-percha and endodontic sealer; CR--the root canal was filled with light-cured composite resin inserted incrementally; FP--a fibre post was cemented into the root canal; and RFP--the fibre post was relined with composite resin prior to the cementation into the root canal. A load was applied on the crown of all teeth at 135° to their long axis until fracture. Data was analysed by one-way anova and SNK tests (α = 0.05), whilst the fracture pattern was evaluated according to the position of the fracture. Stress distributions in the restored teeth were verified by finite element analysis. RESULTS: Teeth restored with fibre posts and relined fibre posts were associated with the highest fracture resistance, whilst the GP group had the lowest values. GP and RC groups had similar fracture resistance values (P = 0.109). All fractures types involved the cervical and middle thirds of roots. The GP model had high levels of stress concentration in the cervical and middle thirds of roots. No difference was found amongst the stress concentration in the RC, FP and RFP models. CONCLUSION: Restorative protocols alter the fracture resistance and stress distribution of immature teeth after placement of MTA apical plugs.

Normal standard for ventilatory function test in adult Filipinos

To establish reference values for lung function test in Filipinos, 283 (130 males and 153 females) normal non-smoking ( Multiple linear regressions with backward elimination was done. The data obtained was regressed against independent variables of age height, weight, and body surface area for each sex. Analysis of variance (ANOVA) of the regression equations for most parameters were significant at = 0.01. In a few parameters were significance was = 0.05. Only in Raw was the regression model not significant. The coefficient of determination (R) of our regression equations were low (

Operative procedures for unresectable pancreatic cancer: does operative bypass decrease requirements for postoperative procedures and in-hospital days?

BACKGROUND: The optimal surgical management of patients found to have unresectable pancreatic cancer at open exploration remains unknown. METHODS: Records of patients who underwent non-therapeutic laparotomy for pancreatic cancer during 2000-2009 and were followed until death at Memorial Sloan-Kettering Cancer Center, New York, were reviewed. RESULTS: Over the 10-year study period, 157 patients underwent non-therapeutic laparotomy. Laparotomy alone was performed in 21% of patients; duodenal bypass, biliary bypass and double bypass were performed in 11%, 30% and 38% of patients, respectively. Complications occurred in 44 (28%) patients. Three (2%) patients died perioperatively. Postoperative interventions were required in 72 (46%) patients following exploration. The median number of inpatient days prior to death was 16 (interquartile range: 8-32 days). Proportions of patients requiring interventions were similar regardless of the procedure performed at the initial operation, as were the total number of inpatient days prior to death. Patients undergoing gastrojejunostomy required fewer postoperative duodenal stents and those undergoing operative biliary drainage required fewer postoperative biliary stents. CONCLUSIONS: In this study, duodenal, biliary and double bypasses in unresectable patients were not associated with fewer invasive procedures following non-therapeutic laparotomy and did not appear to reduce the total number of inpatient hospital days prior to death. Continued effort to identify unresectability prior to operation is justified.

Burden of obstructive lung disease in a rural setting in the Philippines.

BACKGROUND AND OBJECTIVE: The aim of this study was to determine the prevalence of and risk factors associated with COPD in a rural setting in the Philippines. METHODS: The study was conducted in two municipalities in Nueva Ecija province in the Philippines. Using the Burden of Obstructive Lung Disease (BOLD) protocol and study design, non-hospitalized men or women, aged 40years or older, were recruited by multi-stage random sampling procedures. Participants completed questionnaires on respiratory symptoms and exposure to potential risk factors for COPD, including smoking, occupation and exposure to burning of biomass fuel. Spirometry was performed according to American Thoracic Society criteria. RESULTS: Of the 1188 individuals selected for recruitment, 722 had acceptable post-bronchodilator spirometry and were classified according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage. The overall prevalence of COPD for all stages was 20.8%. The prevalence of COPD at GOLD Stage I or higher was greater in men compared with women (26.5% vs 15.3%), and increased between the ages of 40 to >70years. Logistic regression analysis showed a significant association between all stages of COPD and farming for >40years (odds ratio (OR) 2.48, 95% confidence interval (CI): 1.43-4.30), use of firewood for cooking for >60years (OR 3.48, 95% CI: 1.57-7.71), a smoking history of ≥20 pack-years (OR 2.86; 95% CI: 1.78-4.60), and a history of tuberculosis (OR 6.31, 95% CI: 2.67-15.0). CONCLUSIONS: The prevalence COPD in a rural community in Nueva Ecija, Philippines was 20.8% for GOLD Stage I or higher, and 16.7% for GOLD Stage II or higher. In addition to smoking history, the use of firewood for cooking, working on a farm and a history of tuberculosis were significantly associated with fixed airflow obstruction, as assessed by spirometry.

Roflumilast in Asian patients with COPD: A randomized placebo-controlled trial.

BACKGROUND AND OBJECTIVE: Roflumilast, an oral, selective phosphodiesterase 4 inhibitor, has been shown to reduce exacerbations and improve pulmonary function in patients with COPD. This study examined the efficacy, safety and tolerability of roflumilast in Asian patients with COPD. METHODS: Patients with COPD were randomized 1:1 to enter a 12-week treatment period and receive either oral roflumilast, 500 µg once daily, or placebo, following a single-blind, 4-week baseline period in which all patients received placebo. The primary end point was mean change in FEV1 from baseline to each postrandomization visit during the treatment period. Other spirometric lung function measurements were evaluated as secondary end points. COPD exacerbations were monitored. Safety was assessed from clinical laboratory tests, vital signs, physical examination (including electrocardiogram) and monitoring of adverse events (AEs). RESULTS: Of 551 patients recruited, 410 were randomized and received at least one dose of study medication (roflumilast, n = 203; placebo, n = 207). Superiority of roflumilast over placebo was demonstrated by a statistically significant difference in postbronchodilator FEV1 (79 mL, P < 0.0001). Other spirometry end points, including prebronchodilator FEV1, pre-and postbronchodilator FEV6, forced vital capacity and peak expiratory flow significantly favoured roflumilast over placebo. AEs were more common with roflumilast than with placebo, but were comparable with those reported in previous studies. CONCLUSIONS: Roflumilast, 500 µg once daily, improves pulmonary function in Asian patients with COPD. The safety and tolerability of roflumilast in this population was similar to that in a Caucasian population.

Surface-relief gratings and photoinduced birefringence in layer-by-layer films of chitosan and an azopolymer.

Layer-by-layer (LBL) films of chitosan alternated with an azopolymer, PS119, have been used for optical storage and fabrication of surface-relief gratings. The optical properties stem from the trans-cis-trans isomerization cycles undergone by the azochromophore, with a kinetics for writing the birefringence pattern that is much slower than in the spin-coated or cast films of azopolymers. The long writing times, of the order of 100 s, are due to the electrostatic interactions between adjacent chitosan and PS119 layers. Such interactions are also responsible for other features in the LBL films, namely the increase in the amount of adsorbed material when the pH of the preparation solution is decreased and the large residual birefringence after the writing laser is switched off. Gratings could be inscribed with s-polarized but not with p-polarized light, indicating a mass transport process associated with photodegradation.

The gastroprotective effect of tannins extracted from duhat (Syzygium cumini Skeels) bark on HCl/ethanol induced gastric mucosal injury in Sprague-Dawley rats.

The gastroprotective effect of quantified tannins (13.4%) from Syzygium cumini was determined. Gastric mucosal damage was induced in sixty eight rats by oral gavage administration of HCl/ethanol solution. For macroscopic and microscopic studies, 30 rats were divided into three groups consisting of a negative control, an Omeprazole group and a Tannins group. There was no significant difference in the number, size and surface area of macroscopic lesions between the three groups. Microscopic examination using Best's Ulcer Staging Index showed that Tannins had a very significant decrease in gastric mucosal damage with p<0.01. Average lymphocyte populations in the three groups showed no significant difference, although both the Tannins and Omeprazole group had fewer lymphocytes. Thirty-eight rats were studied for the amount of free radicals present after induction of gastric damage. A dose which consisted of 20.0 g tannins/kg rat weight showed significantly lower stomach free radical concentrations. These findings suggest that tannins extracted from S. cumini have gastroprotective and anti-ulcerogenic effects.