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This research introduces a new variant of the two-echelon vehicle routing problem (2EVRP) called the two-echelon vehicle routing problem with transshipment nodes and occasional drivers (2EVRP-TN-OD). In addition to city freighters in the second-echelon network, a set of occasional drivers (ODs) is available to serve customers. ODs are the basis of a crowd-shipping system in which crowds with planned trips are willing to take detours to deliver packages in exchange for some compensation. To serve customers, ODs collect the assigned packages at either satellite served by first-echelon trucks or transshipment nodes served by city freighters. We formulate this problem as a mixed-integer nonlinear programming model and develop an adaptive large neighborhood search (ALNS) to solve it. New problem-specific destroy and repair operators and a tailored local search procedure are embedded into ALNS to deal with the problem’s unique characteristics. The experiments show that the proposed ALNS effectively solves 2EVRP-TN-OD by outperforming Gurobi in terms of both solution quality and computational time. Moreover, the experiments confirm that employing occasional drivers leads to lower operational costs. Sensitivity analyses on the characteristics of occasional drivers and the impact of transshipment nodes are presented as interesting managerial insights from 2EVRP-TN-OD.

The growing socioeconomic burden of musculoskeletal injuries and limitations of current therapies have motivated tissue engineering approaches to generate functional tissues to aid in defect healing. A readily implantable scaffold‐free system comprised of human bone marrow‐derived mesenchymal stem cells embedded with bioactive microparticles capable of controlled delivery of transforming growth factor‐beta 1 (TGF‐β1) and bone morphogenetic protein‐2 (BMP‐2) was engineered to guide endochondral bone formation. The microparticles were formulated to release TGF‐β1 early to induce cartilage formation and BMP‐2 in a more sustained manner to promote remodeling into bone. Cell constructs containing microparticles, empty or loaded with one or both growth factors, were implanted into rat critical‐sized calvarial defects. Micro‐computed tomography and histological analyses after 4 weeks showed that microparticle‐incorporated constructs with or without growth factor promoted greater bone formation compared to sham controls, with the greatest degree of healing with bony bridging resulting from constructs loaded with BMP‐2 and TGF‐β1. Importantly, bone volume fraction increased significantly from 4 to 8 weeks in defects treated with both growth factors. Immunohistochemistry revealed the presence of types I, II, and X collagen, suggesting defect healing via endochondral ossification in all experimental groups. The presence of vascularized red bone marrow provided strong evidence for the ability of these constructs to stimulate angiogenesis. This system has great translational potential as a readily implantable combination therapy that can initiate and accelerate endochondral ossification in vivo. Importantly, construct implantation does not require prior lengthy in vitro culture for chondrogenic cell priming with growth factors that is necessary for current scaffold‐free combination therapies. Stem Cells Translational Medicine 2017;6:1644–1659 A readily implantable scaffold‐free system comprised of human bone marrow‐derived mesenchymal stem cells (hMSCs) embedded with bioactive microparticles capable of controlled delivery of TGF‐β1 and bone morphogenetic protein‐2 was engineered to drive endochondral bone formation in rat calvarial defects. Micro‐computed tomography and histological analyses demonstrated that scaffold‐free hMSC constructs promoted bone bridging of the defects after 4 and 8 weeks.

This work discovered the influence of pretreatment methods (thermal drying and lyophilization (freeze-drying)) on the total phenolic content (TPC), the total flavonoid content (TFC), and the 1,1-diphenyl-2-picrylhydrazyl (DPPH) antioxidant activity of the berry extract of Cayratia trifolia L. of Ca Mau origin (Vietnam). With the assistance of microwave, the freeze-drying method showed higher TPC (9.68 ± 0.31 mg GAE/g), TFC (7.14 ± 0.51 mg QE/g), and DPPH scavenging activity (IC 50 of 24.96 ± 0.89 μg/mL) than those of thermal drying method, under the optimal conditions (an extraction time of 60 s, an ethanol concentration of 60% (%v/v), and a ratio of raw material-to-solvent of 1/500 g/mL).

This study examines the IGF serum profile (IGF-1, IGFBP-3 and the IGF Ratio) from 1633 women who undertook an Assessment Cycle prior to any treatment by assisted reproduction. The idea is to progressively study the IGF profile with a view to identify those women who may be classified as having adult growth hormone deficiency (AGHD) and who may benefit from specific dynamic endocrinological testing to identify a potential benefit from growth hormone adjuvant treatment. This first study evaluates the IGF profile on clinical parameters, namely age, body mass index (BMI) and stature. The study shows a significant linear reduction in IGF-1 levels across the four age groups (<35 years, 35–39 years, 40–44 years and ≥45 years; p < 0.001). However, there was no variation in IGFBP-3 levels but the IGF Ratio showed a progressive linear elevation with advancing age (p < 0.001). With respect to both BMI and stature, none of the IGF profile parameters showed any variation. We conclude that further studies are warranted to examine the notion of underlying AGHD in the causation of the well-known feature of age-related poor prognosis in assisted reproduction.

To assess the relationship between oocytes with smooth endoplasmic reticulum cluster (SERc) and embryological and birth outcomes in infertile couples. This was a descriptive study that included 231 infertile patients undergoing in vitro fertilization (IVF) with a total of 2447 mature oocytes (MII), of which 279 oocytes with SERc(+) from 100 patients, the remaining 2168 oocytes with SERc(-). Oocytes were evaluated for the presence or absence of the SERc simultaneously with intracytoplasmic sperm injection at 200x magnification using inverted microscopy - Observe D1. The mean age of patients was 32.05 ± 5.56 years. One hundred patients had at least one SERc(+) oocyte (with 279 SERc(+) and 956 SERc(-) oocytes). One hundred and thirty-one patients had 1212 SERc(-) oocytes. Fertilization outcomes and the rates of good-quality embryos on day 2 and day 5 did not differ between the SERc(+) and the SERc(-) groups. In the first frozen embryo transfer cycles, the clinical pregnancy rate in the group of patients with SERc(+) was not different with the SERc(-) group (61.1% vs 48.78%, p = 0.074, respectively). The live birth rate in the SERc(+) group was statistically significantly higher than the SERc(-) group (57.7% vs 43.9%, p = 0.045, respectively). The fertilization rate, the quality of embryos on days 2 and 5 from oocytes with SERc(+) are similar to those with SERc(-). The live birth rate in the patients with SERc(+) group is statistically significantly higher than the SERc(-) group. There is no difference in clinical pregnancy rate between patients with and without SERc. Therefore, the exclusion of oocytes with SERc should not be recommended.

Chronic low-grade inflammation (LGI) plays a role in the pathogenesis of gestational diabetes mellitus (GDM). LGI, on the one hand, promotes insulin resistance and at the same time, affects fetal development. The study aimed to use clinically feasible means to evaluate the association between maternal LGI and maternal insulin resistance and fetal growth indices by ultrasound in the third trimester. A crossectional and descriptive study on 248 first-time diagnosed GDM in Vietnam. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte (PLR) indices were significantly higher in GDM than in normal glucose-tolerant pregnancies (p = 0.048 and 0.016, respectively). GDM with LGI witnessed significantly higher systolic blood pressure, BMI, HbA1c, and significantly lower quantitative Insulin Sensitivity Check Index (QUICKI) than those without LGI. After adjusting for maternal BMI, fasting plasma glucose (FPG), age, and parity, C-reactive protein (CRP) was positively correlated with HOMA2-IR (B=0.13, p<0.01) and Mathews index (B=0.29, p<0.01). Regarding fetal characteristics, LGI was associated with fetal growth indices in the third trimester of GDM. NLR was negatively correlated with estimated fetal weight (EFW) (B=-64.4, p<0.05) after adjusting for maternal BMI and FPG. After adjusting for maternal BMI, FPG, age, and parity, PLR was negatively correlated with biparietal diameter (B=-0.02, p<0.01) and abdominal circumference (AC) (B=-0.16, p<0.05), and EFW (B=-1.1, p<0.01), and head circumference (HC) (B=-0.06, p<0.01); CRP was negatively correlated with AC (B=-0.16, p<0.001), EFW (B=-85.3, p<0.001), and HC (B=-5.0, p<0.001). In the third trimester, LGI was associated with maternal glucose and insulin resistance in GDM. Moreover, LGI was associated with fetal characteristics in ultrasonic images. There were negative correlations between LGI and fetal developmental characteristics.

ObjectivesWe examined impacts and interactions of COVID-19 response involvement, health-related behaviours and health literacy (HL) on anxiety, depression, and health-related quality of life (HRQoL) among healthcare workers (HCWs).DesignA cross-sectional study was conducted. Data were collected 6 April to 19 April 2020 using online-based, self-administered questionnaires.Setting19 hospitals and health centres in Vietnam.Participants7 124 HCWs aged 21–60 years.ResultsThe COVID-19 response-involved HCWs had higher anxiety likelihood (OR (95% CI)=4.41 (3.53 to 5.51)), higher depression likelihood (OR(95% CI)=3.31 (2.71 to 4.05)) and lower HRQoL score (coefficient, b(95% CI)=−2.14 (−2.89 to −1.38)), compared with uninvolved HCWs. Overall, HCWs who smoked or drank at unchanged/increased levels had higher likelihood of anxiety, depression and lower HRQoL scores; those with unchanged/healthier eating, unchanged/more physical activity and higher HL scores had lower likelihood of anxiety, depression and higher HRQoL scores. In comparison to uninvolved HCWs who smoked or drank at never/stopped/reduced levels, involved HCWs with unchanged/increased smoking or drinking had lower anxiety likelihood (OR(95% CI)=0.34 (0.14 to 0.83)) or (OR(95% CI)=0.26 (0.11 to 0.60)), and lower depression likelihood (OR(95% CI)=0.33 (0.15 to 0.74)) or (OR(95% CI)=0.24 (0.11 to 0.53)), respectively. In comparison with uninvolved HCWs who exercised at never/stopped/reduced levels, or with those in the lowest HL quartile, involved HCWs with unchanged/increased exercise or with one-quartile HL increment reported lower anxiety likelihood (OR(95% CI)=0.50 (0.31 to 0.81)) or (OR(95% CI)=0.57 (0.45 to 0.71)), lower depression likelihood (OR(95% CI)=0.40 (0.27 to 0.61)) or (OR(95% CI)=0.63 (0.52 to 0.76)), and higher HRQoL scores (b(95% CI)=2.08 (0.58 to 3.58)), or (b(95% CI)=1.10 (0.42 to 1.78)), respectively.ConclusionsPhysical activity and higher HL were found to protect against anxiety and depression and were associated with higher HRQoL. Unexpectedly, smoking and drinking were also found to be coping behaviours. It is important to have strategic approaches that protect HCWs’ mental health and HRQoL.

Background: The COVID-19 pandemic has been disseminating fear in the community, which has affected people’s quality of life, especially those with health problems. Health literacy (HL), eHealth literacy (eHEAL), and digital healthy diet literacy (DDL) may have potential impacts on containing the pandemic and its consequences. This study aimed to examine the association between the fear of COVID-19 scale (FCoV-19S) and the health-related quality of life (HRQoL), and to examine the effect modification by HL, eHEAL, and DDL on this association. Methods: A cross-sectional study was conducted in 11 hospitals across Vietnam from 7 April to 31 May 2020. Data were collected on 4348 outpatients, including demographic characteristics, HL, eHEAL, DDL, FCoV-19S, and HRQoL. Multiple linear regression and interaction models were used to explore associations. Results: Patients with higher FCoV-19S scores had lower HRQoL scores (unstandardized coefficient, B = −0.78, p < 0.001). HL (B = 0.20, p < 0.001), eHEAL (B = 0.24, p < 0.001), and DDL (B = 0.20, p < 0.001) were positively associated with higher HRQoL scores. The negative impact of FCoV-19S on HRQoL was significantly attenuated by higher eHEAL score groups (from one standard deviation (SD) below the mean, B = −0.93, p < 0.001; to the mean, B = −0.85, p < 0.001; and one SD above the mean, B = −0.77, p < 0.001); and by higher DDL score groups (from one SD below the mean, B = −0.92, p < 0.001; to the mean, B = −0.82, p < 0.001; and one SD above the mean, B = −0.72, p < 0.001). Conclusions: eHealth literacy and digital healthy diet literacy could help to protect patients’ health-related quality of life from the negative impact of the fear of COVID-19 during the pandemic.

Background. The optimal time to initiate antiretroviral therapy (ART) in human immunodeficiency virus (HIV)—associated tuberculous meningitis is unknown. Methods. We conducted a randomized, double-blind, placebo-controlled trial of immediate versus deferred ART in patients with HIV-associated tuberculous meningitis to determine whether immediate ART reduced the risk of death. Antiretroviral drugs (zidovudine, lamivudine, and efavirenz) were started either at study entry or 2 months after randomization. All patients were treated with standard antituberculosis treatment, adjunctive dexamethasone, and prophylactic co-trimoxazole and were followed up for 12 months. We conducted intention-to-treat, perprotocol, and prespecified subgroup analyses. Results. A total of 253 patients were randomized, 127 in the immediate ART group and 126 in the deferred ART group; 76 and 70 patients died within 9 months in the immediate and deferred ART groups, respectively. Immediate ART was not significantly associated with 9-month mortality (hazard ratio [HR], 1.12; 95% confidence interval [CI],.81-1.55; P = .50) or the time to new AIDS events or death (HR, 1.16; 95% CI,.87-1.55; P = .31). The percentage of patients with severe (grade 3 or 4) adverse events was high in both arms (90% in the immediate ART group and 89% in the deferred ART group; P = .84), but there were significantly more grade 4 adverse events in the immediate ART arm (102 in the immediate ART group vs 87 in the deferred ART group; P = .04). Conclusions. Immediate ART initiation does not improve outcome in patients presenting with HIV-associated tuberculous meningitis. There were significantly more grade 4 adverse events in the immediate ART arm, supporting delayed initiation of ART in HIV-associated tuberculous meningitis.

Background. Dengue is the most common arboviral infection of humans. There are currently no specific treatments for dengue. Balapiravir is a prodrug of a nucleoside analogue (called R1479) and an inhibitor of hepatitis C virus replication in vivo. Methods. We conducted in vitro experiments to determine the potency of balapiravir against dengue viruses and then an exploratory, dose-escalating, randomized placebo-controlled trial in adult male patients with dengue with <48 hours of fever. Results. The clinical and laboratory adverse event profile in patients receiving balapiravir at doses of 1500 mg (n = 10) or 3000 mg (n = 22) orally for 5 days was similar to that of patients receiving placebo (n = 32), indicating balapiravir was well tolerated. However, twice daily assessment of viremia and daily assessment of NS1 antigenemia indicated balapiravir did not measurably alter the kinetics of these virological markers, nor did it reduce the fever clearance time. The kinetics of plasma cytokine concentrations and the whole blood transcriptional profile were also not attenuated by balapiravir treatment. Conclusions. Although this trial, the first of its kind in dengue, does not support balapiravir as a candidate drug, it does establish a framework for antiviral treatment trials in dengue and provides the field with a clinically evaluated benchmark molecule. Clinical Trials Registration. NCT01096576.