The efficacy and tolerability of proteoglycan F in the treatment of knee osteoarthritis: A prospective, randomized, double-blind controlled trial.

Objective: To identify the efficacy and tolerability of Proteoglycan F in patients with primary knee OA.Design: A 24-week randomized, placebo-controlled, double-blind clinical trial with two arms: (1) Proteoglycan F (received 10 â€‹mg proteoglycan daily, for 24 weeks) and (2) control group (received placebo). Knee symptoms and joint cartilage status (evaluated by ultrasound and MRI of knee joints), quality of life, serum cytokine levels (IL-1ß and TNF-α), and safety evaluation were measured before, during, and after the treatment. Results: After 24-week treatment, pain reduction (in the KOOS pain score) of at least 20% and at least 50% (NRS scale) compared to baseline in the PGF group was significantly higher than those in the control group. The PGF group had greater reductions in the total scores of subchondral bone marrow edema, and bone cocoon under cartilage on knee MRI (classification according to WORMs), which were -2.27 (-4.0; -0.51) and -1.77 (-3.08; -0.46), respectively (p â€‹< â€‹0.05). The two groups had no statistically significant difference in knee ultrasound characteristics. After 4 weeks, 12, and 24 weeks compared to baseline, there was no statistically significant difference in levels of urea, creatinine, aspartate aminotransferase, and alanine aminotransferase within the group and between the two study groups. Conclusions: Salmon cartilage PG with 10 â€‹mg per day has potential to improve pain symptoms and subchondral bone marrow edema and bone cocoon under cartilage lesions in primary knee OA. However, the efficacy of PGF should be viewed with caution, and future studies are needed for more specific evaluation.

Translation and validation of Vietnamese version of the Birth Satisfaction Scale-Revised (BSS-R).

BACKGROUND: The 10-item Birth Satisfaction Scale-Revised (BSS-R) is a quick and easy survey instrument recommended by the International Consortium for Health Outcome Measures as the tool of choice for measuring women's birth satisfaction. AIM: To translate and validate a Vietnamese-language version of the BSS-R. METHOD: A quantitative cross-sectional method was used to gather data post translation and back-translation of a Vietnamese version of the BSS-R (VN-BSS-R). Data collected were psychometrically evaluated using key indices of validity and reliability. PARTICIPANTS: Vietnamese women who were within one month postpartum of birth (N = 383) took part in the study. RESULTS: Findings illustrate that a two-factor model offered excellent psychometric properties. With the two-factor VN-BSS-R, five items loaded onto a subscale 'Positive birth experiences' and the other five onto a second subscale 'Negative birth experiences'. This two-factor model offered a fit to data (root mean square error of approximation [RMSEA] = 0.07, 90% confidence interval [CI] [0.05, 0.09], root square mean residual [RMSE] = 0.04 and comparative fit index [CFI] = 0.97). Mean scores for the exploratory factor analysis [EFA]-derived 'positive' and 'negative' sub-scales were 17.12 (SD 2.34) and 8.40 (SD 4.18) respectively. CONCLUSION: The translated and validated VN-BSS-R is a psychometrically robust tool for measuring birth satisfaction in Vietnamese postpartum women.The VN-BSS-R is available for use to measure experiences and perceptions of intrapartum care received by Vietnamese women.

Advances in the Immunology of the Host-Parasite Interactions in African Trypanosomosis, including Single-Cell Transcriptomics.

Trypanosomes are single-celled extracellular parasites that infect mammals, including humans and livestock, causing global public health concerns and economic losses. These parasites cycle between insect vectors, such as tsetse flies and vertebrate hosts, undergoing morphological, cellular, and biochemical changes. They have remarkable immune evasion mechanisms to escape the host's innate and adaptive immune responses, such as surface coat antigenic variation and the induction of the loss of specificity and memory of antibody responses, enabling the prolongation of infection. Since trypanosomes circulate through the host body in blood and lymph fluid and invade various organs, understanding the interaction between trypanosomes and tissue niches is essential. Here, we present an up-to-date overview of host-parasite interactions and survival strategies for trypanosomes by introducing and discussing the latest studies investigating the transcriptomics of parasites according to life cycle stages, as well as host cells in various tissues and organs, using single-cell and spatial sequencing applications. In recent years, this information has improved our understanding of trypanosomosis by deciphering the diverse populations of parasites in the developmental process, as well as the highly heterogeneous immune and tissue-resident cells involved in anti-trypanosome responses. Ultimately, the goal of these approaches is to gain an in-depth understanding of parasite biology and host immunity, potentially leading to new vaccination and therapeutic strategies against trypanosomosis.

Mortality risk among Autistic children and young people: A nationwide birth cohort study.

LAY ABSTRACT: Existing literature indicates that Autistic people have shorter life expectancy, but little is known about the mortality risk among Autistic children and young people (0-24 years). We used a 15-year nationwide birth cohort study to estimate the mortality risk among Autistic children and young people in Aotearoa/New Zealand. The study included 895,707 children and 11,919 (1.4%) were Autistic. We found that autism was associated with a significantly higher mortality risk compared to the non-Autistic population. In addition, we found that this risk was significantly higher among females compared to males and for those with a co-occurring intellectual disability. Increased efforts are required to better meet the health needs of this population.

Associations between type 1 diabetes and educational outcomes: an Aotearoa/New Zealand nationwide birth cohort study using the Integrated Data Infrastructure.

AIMS/HYPOTHESIS: Type 1 diabetes is one of the most common chronic diseases of childhood. It is hypothesised that the metabolic and psychosocial consequences of type 1 diabetes may affect educational outcomes; however, existing literature presents conflicting results. This study aimed to assess whether educational outcomes differ for young people with and without type 1 diabetes in Aotearoa/New Zealand (NZ). METHODS: This was a nationwide 9 year birth cohort study of all people born in NZ from 1993 to 2001 using linked administrative data held within the Integrated Data Infrastructure, a national research database containing linked health and non-health data. Educational outcomes of high school attainment, high school attendance and university enrolment were measured from age 13 years until 20 years. Generalised linear regression models with log link and Gaussian distributions were used to compare educational outcomes between those with and those without type 1 diabetes, adjusting for sociodemographic and maternal characteristics. RESULTS: Of the 442,320 children in the birth cohort, type 1 diabetes was identified in 2058 (0.47%) (mean [SD] age of type 1 diabetes diagnosis 7.7 [3.4] years). Educational outcomes were significantly lower for children with type 1 diabetes than for those without type 1 diabetes, including for any high school qualification (RR 0.97 [95% CI 0.95, 0.99]), university entrance-level high school attainment (RR 0.88 [95% CI 0.84, 0.92]), regular high school attendance (RR 0.91 [95% CI 0.85, 0.97]) and university enrolment (RR 0.93 [95% CI 0.88, 0.98]), even after adjusting for sociodemographic and maternal factors. In addition, educational outcomes were substantially lower for those with post type 1 diabetes diagnosis hospitalisations for diabetic ketoacidosis and hypoglycaemia. CONCLUSIONS/INTERPRETATION: In this whole NZ birth cohort study, type 1 diabetes was associated with lower educational outcomes spanning secondary school and into university enrolment. Ongoing efforts to support students with type 1 diabetes are needed, particularly for those with a greater risk profile.

Associations between Ileal Juice Bile Acids and Colorectal Advanced Adenoma.

BACKGROUND: There is an urgent need to identify biomarkers for advanced adenoma, an important precursor of colorectal cancer (CRC). We aimed to determine alterations in ileal juice bile acids associated with colorectal advanced adenoma. METHODS: We quantified a comprehensive panel of primary and secondary bile acids and their conjugates using an ultraperformance liquid chromatography triple-quadrupole mass spectrometric assay in ileal juice collected at colonoscopy from 46 study subjects (i.e., 14 biopsy-confirmed advanced adenomas and 32 controls free of adenoma or cancer). Using analysis of covariance (ANCOVA), we examined the differences in bile acid concentrations by disease status, adjusting for age, sex, body mass index, smoking status and type 2 diabetes. RESULTS: The concentrations of hyodeoxycholic acid (HCA) species in ileal juice of the advanced adenoma patients (geometric mean = 4501.9 nM) were significantly higher than those of controls (geometric mean = 1292.3 nM, p = 0.001). The relative abundance of ursodeoxycholic acid (UDCA) in total bile acids was significantly reduced in cases than controls (0.73% in cases vs. 1.33% in controls; p = 0.046). No significant difference between cases and controls was observed for concentrations of total or specific primary bile acids (i.e., cholic acid (CA), chenodeoxycholic acid (CDCA) and their glycine- and taurine-conjugates) and total and specific major secondary bile acids (i.e., deoxycholic acid and lithocholic acid). CONCLUSIONS: Colorectal advanced adenoma was associated with altered bile acids in ileal juice. The HCA species may promote the development of colorectal advanced adenoma, whereas gut microbiota responsible for the conversion of CDCA to UDCA may protect against it. Our findings have important implications for the use of bile acids as biomarkers in early detection of colorectal cancer.

Association between Sleep Duration and Colorectal Adenomas: Findings from a Case-Control Study in Vietnam.

BACKGROUND: Colorectal cancer is one of the leading cancers worldwide and in Vietnam. Adenomas are important precursors of colorectal cancer. Study on the association between sleep duration and development of colorectal adenoma (CRA) is limited, particularly among Vietnamese population. METHODS: We conducted an individually matched case-control study of 870 CRA cases and 870 controls in a large-scale colorectal screening program involving 103,542 individuals ages ≥40 years old in Hanoi, Vietnam. Sleep duration was categorized in three groups: short: ≤6 hours/day, normal: 7 to 8 hours/day, and long: >8 hours/day. Conditional logistic regression was used to evaluate the association between sleep duration and adenomas risk after controlling for potential confounders. RESULTS: Overall, short-sleep duration was associated with increased risk of having CRA compared with normal duration [OR, 1.48; 95% confidence interval (CI), 1.12-1.97]. This pattern was present in both females (OR, 1.58; 95% CI, 1.14-2.18) and males (OR, 1.45; 95% CI, 1.08-1.93), with advanced adenomas (OR, 1.61; 95% CI, 1.09-2.38) and non-advanced adenomas (OR, 1.66; 95% CI, 1.19-2.32). Furthermore, the association between CRA development and short-sleep duration was more apparent among females who were nondrinker, nonobese, physically active, with proximal or both sided adenomas and with cardiometabolic disorder. Among males, the short-sleep duration was associated with CRA risk among never-smoking, cardiometabolic disorders, and obese. CONCLUSIONS: Short-sleep duration was associated with increased prevalence of both advanced and non-advanced CRAs among Vietnamese population. IMPACT: Findings from this study showed that maintaining an adequate sleep duration may have an important implication for colorectal adenoma prevention and control.

Endotracheal intubation performance at a large obstetric hospital delivery room, Hanoi, Vietnam.

Introduction: Intrapartum-related events account for nearly 700,000 neonatal deaths globally yearly. Endotracheal intubation is a cornerstone in preventing many of these deaths, but it is a difficult skill to acquire. Previous studies have described intubation performances in high-income countries, but data from low- and middle-income countries are lacking. We aimed to assess the performance of delivery room intubation in a lower middle-income country. Methods: This prospective observational study was conducted at the Phu San Hanoi Hospital, Vietnam, from September 2020 to January 2021. Video cameras were positioned above the resuscitation tables and data were extracted using adopted software (NeoTapAS). All neonates requiring positive pressure ventilation were included. Our main variables of interest were time to first intubation attempt, first intubation attempt duration, and successful first intubation attempt. Results: 18,107 neonates were born during the five months. Of these, 75 (0.4%) received positive pressure ventilation, and 36 (0.2%) required endotracheal intubation of whom 24 were captured on video. The median time to the first intubation attempt was 252 seconds (range 91-771 seconds), the median first attempt duration was 49 seconds (range 10-105 seconds), and the first attempt success rate was 75%. Conclusion: Incidences of positive pressure ventilation and endotracheal intubation were low in comparison to global estimates. Three out of four intubations were successful at the first attempt and the procedural duration was often longer than recommended. Future studies should focus on how to achieve and maintain intubation skills and could include considering alternative devices for airway management at birth.

Neonatal resuscitation monitoring: A low-cost video recording setup for quality improvement in the delivery room at the resuscitation table.

Background: The quality of neonatal resuscitation after delivery needs to be improved to reach the Sustainable Development Goals 3.2 (reducing neonatal deaths to <12/1,000 live newborns) by the year 2030. Studies have emphasized the importance of correctly performing the basic steps of resuscitation including stimulation, heart rate assessment, ventilation, and thermal control. Recordings with video cameras have previously been shown to be one way to identify performance practices during neonatal resuscitation. Methods: A description of a low-cost delivery room set up for video recording of neonatal resuscitation. The technical setup includes rechargeable high-definition cameras with two-way audio, NeoBeat heart rate monitors, and the NeoTapAS data collection tools for iPad with direct data export of data for statistical analysis. The setup was field tested at Mulago National Referral Hospital, Kampala, Uganda, and Phu San Hanoi Hospital, Hanoi, Vietnam. Results: The setup provided highly detailed resuscitation video footage including data on procedures and team performance, heart rate monitoring, and clinical assessment of the neonate. The data were analyzed with the free-of-charge NeoTapAS for iPad, which allowed fast and accurate registration of all resuscitative events. All events were automatically registered and exported to R statistical software for further analysis. Conclusions: Video analysis of neonatal resuscitation is an emerging quality assurance tool with the potential to improve neonatal resuscitation outcomes. Our methodology and technical setup are well adapted for low- and lower-middle-income countries settings where improving neonatal resuscitation outcomes is crucial. This delivery room video recording setup also included two-way audio communication that potentially could be implemented in day-to-day practice or used with remote teleconsultants.

Findings from the first colorectal cancer screening among 103 542 individuals in Vietnam with systematic review of colorectal cancer screening programs in Asia-Pacific region.

BACKGROUND: Colorectal cancer is a leading cancer incidence and cause of death worldwide and in Vietnam. Although screening is considered an effective measure to prevent and control colorectal cancer, there is no such effort in Vietnam. METHODS: Between 01 January 2018 and 31 October 2019, a population-based colorectal cancer screening program was conducted in Hanoi, Vietnam. A health advocacy campaign and follow-up phone calls were used to enroll residents aged ≥40 years old to complete an immunochemical-fecal occult blood testing. Positive immunochemical-fecal occult blood testing was followed by a colonoscopy. We also conducted a systematic review of the colorectal cancer screening programs in the Asia-Pacific region that used similar approach by searching Ovid Medline and PubMed databases. RESULTS: During study period, 103 542 individuals among 672 742 eligible residents attended the screening of whom 81.5% participants finished immunochemical-fecal occult blood testing test and the positive rate was 6.1%. The coverage rate for immunochemical-fecal occult blood testing test was 11.9%. Among 2278 individuals who underwent colonoscopy, 3.5% were histologically diagnosed with cancer, 17.8% with advanced adenomas, and 23.1% with non-advanced adenomas. Males had significantly higher detection rate of advanced adenomas, cancer or ≥ two polyps/tumor than females (P < 0.0001). The systematic review showed that in two-step modality (i.e. immunochemical-fecal occult blood testing/fecal immunochemical test and colonoscopy), the test positive was from 4.1 to 10.6%. Once colonoscopy was performed subsequently, the rate of cancer among positive participants was from 1.7 to 16.4% and that of advanced adenomas was from 7.1 to 23.1%. CONCLUSION: We showed that the two-step modality is a promising strategy for colorectal cancer screening in Vietnam that might apply to similar settings with limited resources.

Incidence of Intrapartum-Related Events at the Largest Obstetric Hospital in Hanoi, Vietnam: A Retrospective Study.

Every year, 2.4 million neonates die during their first month of life and even more suffer permanent injury. The main causes are intrapartum-related events, prematurity, and infection, with sub-Saharan Africa and southern Asia being the worst affected regions. With a focus on intrapartum-related events, we aimed to assess the neonatal demographic characteristics, clinical management, and outcomes among neonates born at the largest obstetric hospital in Hanoi, Vietnam. This was a retrospective cross-sectional study that included all the inborn neonates in November 2019, which was selected as a representative month. A total of 4554 neonates were born during the study period. Of these, 1.0% (n = 44) were stillbirths, 0.15% (n = 7) died in hospital, 0.61% (n = 28) received positive pressure ventilation at birth, and 0.15% (n = 7) were diagnosed with hypoxic ischemic encephalopathy. A total of 581 (13%) neonates were admitted to the neonatal unit, among which the most common diagnoses were prematurity (37%, n = 217) and infection (15%, n = 89). Except for the intrapartum-related events, our findings are consistent with the previously documented data on neonatal morbidity. The intrapartum-related events, however, were surprisingly low in number even in comparison to high-income countries. Research on the current clinical practice at Phu San Hanoi Hospital may bring further clarity to identify the success factors.

Looking Through the COVID-19 Window of Opportunity: Future Scenarios Arising From the COVID-19 Pandemic Across Five Case Study Sites.

The COVID-19 pandemic has caused (and continues to cause) severe disruption in global and local economies and has forced countries, societies, and individuals to adapt quickly to the unprecedented and unpredictable situations. Despite the obvious negative consequences of the pandemic, many have called for efforts to identify transformative opportunities for sustainable development throughout this disorderly time. In the present paper, we explore such potential opportunities in the context of an interdisciplinary, international research project, which is focusing on sustainable marine management in biosphere reserves and marine parks in Southeast Asia. During a virtual workshop conducted as part of the GCRF (Government's Global Challenges Research Fund) Blue Communities Project, future scenarios were developed depicting the potential effects of the COVID-19 pandemic on five case study sites. All of these sites are in areas of internationally recognized outstanding ecological value (Taka Bonerate Kepulauan-Selayar Biosphere Reserve, Indonesia; Tun Mustapha Park, Sabah, Malaysia; Palawan Biosphere Reserve, Philippines; North Devon Biosphere Reserve, United Kingdom; Cu Lao Cham-Hoi An Biosphere Reserve, Vietnam). At the macro-level, economies, governance structures, and societal norms are undergoing big changes. At the micro-level, the livelihoods, lifestyles, and backyards of local residents have to adapt. Collaboratively, we explored how COVID-19 posed challenges in our five case study sites, but we also focused on the potential COVID-19-related windows of opportunity for future sustainable development. Opportunities could be identified in all three pillars of sustainable development: the environment, the society, and the economy. Although remarkable similarities can be found across all five sites, we conclude that there cannot be a "one-size-fits-all" solution to turn the tide toward achieving sustainable development. Just as before the pandemic, sustainable development starts with engaging with and understanding local environments, challenges, and situations; building on local knowledge; and developing tailor-made solutions for the communities in situ.

Genome-Wide Association Mapping of Salinity Tolerance at the Seedling Stage in a Panel of Vietnamese Landraces Reveals New Valuable QTLs for Salinity Stress Tolerance Breeding in Rice.

Rice tolerance to salinity stress involves diverse and complementary mechanisms, such as the regulation of genome expression, activation of specific ion-transport systems to manage excess sodium at the cell or plant level, and anatomical changes that avoid sodium penetration into the inner tissues of the plant. These complementary mechanisms can act synergistically to improve salinity tolerance in the plant, which is then interesting in breeding programs to pyramidize complementary QTLs (quantitative trait loci), to improve salinity stress tolerance of the plant at different developmental stages and in different environments. This approach presupposes the identification of salinity tolerance QTLs associated with different mechanisms involved in salinity tolerance, which requires the greatest possible genetic diversity to be explored. To contribute to this goal, we screened an original panel of 179 Vietnamese rice landraces genotyped with 21,623 SNP markers for salinity stress tolerance under 100 mM NaCl treatment, at the seedling stage, with the aim of identifying new QTLs involved in the salinity stress tolerance via a genome-wide association study (GWAS). Nine salinity tolerance-related traits, including the salt injury score, chlorophyll and water content, and K+ and Na+ contents were measured in leaves. GWAS analysis allowed the identification of 26 QTLs. Interestingly, ten of them were associated with several different traits, which indicates that these QTLs act pleiotropically to control the different levels of plant responses to salinity stress. Twenty-one identified QTLs colocalized with known QTLs. Several genes within these QTLs have functions related to salinity stress tolerance and are mainly involved in gene regulation, signal transduction or hormone signaling. Our study provides promising QTLs for breeding programs to enhance salinity tolerance and identifies candidate genes that should be further functionally studied to better understand salinity tolerance mechanisms in rice.

Decreased APE-1 by Nitroxoline Enhances Therapeutic Effect in a Temozolomide-resistant Glioblastoma: Correlation with Diffusion Weighted Imaging.

Glioblastoma multiforme (GBM) is one of the most aggressive human tumors with poor survival rates. The current standard treatment includes chemotherapy with temozolomide (TMZ), but acquisition of resistance is a persistent clinical problem limiting the successful treatment of GBM. The purpose of our study was to investigate therapeutic effects of nitroxoline (NTX) against TMZ-resistant GBM in vitro and in vivo in TMZ-resistant GBM-bearing mouse model, which was correlated with diffusion-weighted imaging (DWI). For in vitro study, we used TMZ-resistant GBM cell lines and evaluated therapeutic effects of NTX by clonogenic and migration assays. Quantitative RT-PCR was used to investigate the expression level of TMZ-resistant genes after NTX treatment. For in vivo study, we performed 9.4 T MR imaging to obtain T2WI for tumor volume measurement and DWI for assessment of apparent diffusion coefficient (ADC) changes by NTX in TMZ-resistant GBM mice (n = 8). Moreover, we performed regression analysis for the relationship between ADC and histological findings, which reflects the changes in cellularity and apurinic/apyrimidinic endonuclease-1 (APE-1) expression. We observed the recovery of TMZ-induced morphological changes, a reduced number of colonies and a decreased rate of migration capacity in TMZ-resistant cells after NTX treatment. The expression of APE-1 was significantly decreased in TMZ-resistant cells after NTX treatment compared with those without treatment. In an in vivo study, NTX reduced tumor growth in TMZ-resistant GBM mice (P = 0.0122). Moreover, ADC was increased in the NTX-treated TMZ-resistant GBM mice compared to the control group (P = 0.0079), which was prior to a tumor volume decrease. The cellularity and APE-1 expression by histology were negatively correlated with the ADC value, which in turn resulted in longer survival in NTX group. The decreased expression of APE-1 by NTX leads to therapeutic effects and is inversely correlated with ADC in TMZ-resistant GBM. Therefore, NTX is suggested as potential therapeutic candidate against TMZ-resistant GBM.

A newly constructed Agrobacterium-mediated transformation system revealed the influence of nitrogen sources on the function of the LaeA regulator in Penicillium chrysogenum.

Penicillium chrysogenum is not only an industrially important filamentous fungus for penicillin production, but it also represents as a promising cell factory for production of natural products. Development of efficient transformation systems with suitable selection markers is essential for genetic manipulations in P. chrysogenum. In this study, we have constructed a new and efficient Agrobacterium tumefaciens-mediated transformation (ATMT) system with two different selection markers conferring the resistance to nourseothricin and phleomycin for P. chrysogenum. Under the optimized conditions for co-cultivation at 22 °C for 60 h with acetosyringone concentration of 200 µM, the transformation efficiency of the ATMT system could reach 5009 ± 96 transformants per 106 spores. The obtained transformants could be exploited as the T-DNA insertion mutants for screening genes involved in morphogenesis and secondary metabolism. Especially, the constructed ATMT system was applied successfully to generate a knockout mutant of the laeA regulatory gene and relevant complementation strains in a wild strain of P. chrysogenum. Our results indicated that the LaeA regulator controls growth, sporulation, osmotic stress response and antibiotic production in P. chrysogenum, but its function is reliant on nitrogen sources. Furthermore, we showed that the laeA orthologous genes from the citrus postharvest pathogen P. digitatum and from the industrial fungus Aspergillus niger could recover the phenotypic defects in the P. chrysogenum laeA deletion mutant. Conclusively, this work provides a new ATMT system, which can be employed for T-DNA insertional mutagenesis, heterologous gene expression or for molecular inspections of potential genes related to secondary metabolism in P. chrysogenum.

Increased Antiangiogenic Effect by Blocking CCL2-dependent Macrophages in a Rodent Glioblastoma Model: Correlation Study with Dynamic Susceptibility Contrast Perfusion MRI.

When glioblastoma multiforme (GBM) is treated with anti-vascular endothelial growth factor (VEGF) agents, it commonly exhibits tumor progression due to the development of resistance, which results in a dismal survival rate. GBM tumors contain a large number of monocytes/macrophages, which have been shown to be resistant to the effects of bevacizumab. It has been reported that tumor-associated macrophages (TAMs) promote resistance to bevacizumab treatment. Therefore, it is important to target TAMs in the GBM microenvironment. TAMs, which depend on chemokine ligand 2 (CCL2) for differentiation and survival, induce the expression of proangiogenic factors such as VEGF. Dynamic susceptibility contrast (DSC)-MR imaging is an advanced technique that provides information on tumor blood volume and can potentially predict the response to several treatments, including anti-angiogenic agents such as bevacizumab, in human GBM. In this study, we used a CCL2 inhibitor, mNOX-E36, to suppress the recruitment of TAMs in a CCL2-expressing rat GBM model and investigated the effect of combination therapy with bevacizumab using DSC-MR imaging. We demonstrated that the inhibition of CCL2 blocked macrophage recruitment and angiogenesis, which resulted in decreased tumor volume and blood volume in CCL2-expressing GBM in a rat model. Our results provide direct evidence that CCL2 expression can increase the resistance to bevacizumab, which can be assessed noninvasively with the DSC-MR imaging technique. This study shows that the suppression of CCL2 can play an important role in increasing the efficacy of anti-angiogenic treatment in GBM by inhibiting the recruitment of CCL2-dependent macrophages.

All-Trans Retinoic Acid Enhances Matrix Metalloproteinase 2 Expression and Secretion in Human Myeloid Leukemia THP-1 Cells.

All-trans retinoic acid (ATRA) is an effective drug for the induction therapy of acute promyelocytic leukemia. However, the treatment is associated with adverse events such as retinoic acid syndrome (RAS) in some patients, whose histologic characteristics included organ infiltration by leukemic cells. Matrix metalloproteinase 2 (MMP-2) is often upregulated in tumor cells and plays a role in tumor cell migration and invasion by degrading the extracellular matrix. In this study, we examined the possible modulatory effects of ATRA on MMP-2 expression and secretion in human myeloid leukemia cell line THP-1. The cells were treated with various concentrations of ATRA, and MMP-2 expression and secretion were examined. MMP-2 expression and secretion started to increase with ATRA concentration as low as 0.1 nM and gradually increased thereafter. Agonists of retinoic acid receptor (RAR) or retinoid X receptor (RXR) alone could enhance MMP-2 secretion, and RAR or RXR antagonists alone could reverse ATRA-induced MMP-2 secretion. ATRA increased intracellular calcium ion levels, and a calcium-channel blocker inhibited ATRA-induced MMP-2 secretion. Dexamethasone suppressed ATRA-induced MMP-2 secretion. Our results suggest that ATRA enhances MMP-2 expression and secretion in human myeloid leukemia THP-1 cells in a calcium ion dependent manner through RAR/RXR signaling pathways, and this enhanced expression and secretion may be associated with the possible mechanisms of RAS.

Flightin maintains myofilament lattice organization required for optimal flight power and courtship song quality in Drosophila.

The indirect flight muscles (IFMs) of Drosophila and other insects with asynchronous flight muscles are characterized by a crystalline myofilament lattice structure. The high-order lattice regularity is considered an adaptation for enhanced power output, but supporting evidence for this claim is lacking. We show that IFMs from transgenic flies expressing flightin with a deletion of its poorly conserved N-terminal domain (flnΔN62 ) have reduced inter-thick filament spacing and a less regular lattice. This resulted in a decrease in flight ability by 33% and in skinned fibre oscillatory power output by 57%, but had no effect on wingbeat frequency or frequency of maximum power output, suggesting that the underlying actomyosin kinetics is not affected and that the flight impairment arises from deficits in force transmission. Moreover, we show that flnΔN62 males produced an abnormal courtship song characterized by a higher sine song frequency and a pulse song with longer pulses and longer inter-pulse intervals (IPIs), the latter implicated in male reproductive success. When presented with a choice, wild-type females chose control males over mutant males in 92% of the competition events. These results demonstrate that flightin N-terminal domain is required for optimal myofilament lattice regularity and IFM activity, enabling powered flight and courtship song production. As the courtship song is subject to female choice, we propose that the low amino acid sequence conservation of the N-terminal domain reflects its role in fine-tuning species-specific courtship songs.

A review on sludge dewatering indices.

Dewatering of sludge from sewage treatment plants is proving to be a significant challenge due to the large amounts of residual sludges generated annually. In recent years, research and development have focused on improving the dewatering process in order to reduce subsequent costs of sludge management and transport. To achieve this goal, it is necessary to establish reliable indices that reflect the efficiency of sludge dewatering. However, the evaluation of sludge dewaterability is not an easy task due to the highly complex nature of sewage sludge and variations in solid-liquid separation methods. Most traditional dewatering indices fail to predict the maximum cake solids content achievable during full-scale dewatering. This paper reviews the difficulties in assessing sludge dewatering performance, and the main techniques used to evaluate dewatering performance are compared and discussed in detail. Finally, the paper suggests a new dewatering index, namely the modified centrifugal index, which is demonstrated to be an appropriate indicator for estimating the final cake solids content as well as simulating the prototype dewatering process.

Mutations of the Drosophila myosin regulatory light chain affect courtship song and reduce reproductive success.

The Drosophila indirect flight muscles (IFM) rely on an enhanced stretch-activation response to generate high power output for flight. The IFM is neurally activated during the male courtship song, but its role, if any, in generating the small amplitude wing vibrations that produce the song is not known. Here, we examined the courtship song properties and mating behavior of three mutant strains of the myosin regulatory light chain (DMLC2) that are known to affect IFM contractile properties and impair flight: (i) Dmlc2(Δ2-46) (Ext), an N-terminal extension truncation; (ii) Dmlc2(S66A,S67A) (Phos), a disruption of two MLC kinase phosphorylation sites; and (iii) Dmlc2(Δ2-46;S66A,S67A) (Dual), expressing both mutations. Our results show that the Dmlc2 gene is pleiotropic and that mutations that have a profound effect on flight mechanics (Phos and Dual) have minimal effects on courtship song. None of the mutations affect interpulse interval (IPI), a determinant of species-specific song, and intrapulse frequency (IPF) compared to Control (Dmlc2 (+) rescued null strain). However, abnormalities in the sine song (increased frequency) and the pulse song (increased cycles per pulse and pulse length) evident in Ext males are not apparent in Dual males suggesting that Ext and Phos interact differently in song and flight mechanics, given their known additive effect on the latter. All three mutant males produce a less vigorous pulse song and exhibit impaired mating behavior compared to Control males. As a result, females are less receptive to Ext, Phos, and Dual males when a Control male is present. These results open the possibility that DMLC2, and perhaps contractile protein genes in general, are partly under sexual selection. That mutations in DMLC2 manifest differently in song and flight suggest that this protein fulfills different roles in song and flight and that stretch activation plays a smaller role in song production than in flight.