Search

This work aimed to enhance hemp seed oil encapsulation within a hemp seed protein-alginate complex by optimizing parameters in the solution-enhanced dispersion process, employing supercritical carbon dioxide (SEDS) without reliance on organic solvents or elevated temperatures. By response surface methodology (RSM), the microencapsulation efficacy (MEE), particle size (PS) and peroxide value (PV) was determined with respect to three parameters; temperature (°C), pressure (bar) and feed flow rate (mL/min). The optimum conditions were predicted at temperature (40 °C), pressure (150 bar) and feed flow rate (2 mL/min) to offer an MEE of 89.47%, PS of 7.81 μm and PV of 2.91 (meq/kg oil). In addition, the SEDS method was compared with spray- and freeze-drying for encapsulating hemp seed oil. The findings demonstrated SEDS' superiority, exhibiting exceptional attributes such as the highest MEE, smallest PS and the production of spherical, smooth microcapsules. This highlights its effectiveness in comparison to spray- and freeze-drying methods., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Chin Ping Tan reports financial support was provided by Malaysia Ministry of Higher Education. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Study Design: Multi-Ethnic Alignment Normative Study (MEANS) cohort: prospective, cross-sectional, multicenter., Objective: To analyze the distribution of GAP scores in the MEANS cohort and compare the spinal shape via stratification by GAP alignment category, age, and country., Summary of Background Data: The GAP score has been used to categorize spinal morphology and prognosticate adult spinal deformity surgical outcomes and mechanical complications. We analyzed a large, multiethnic, asymptomatic cohort to assess the distribution of GAP scores., Methods: Four hundred sixty-seven healthy volunteers without spinal disorders were recruited in five countries. Sagittal radiographic parameters were measured via the EOS imaging system. The GAP total and constituent factor scores were calculated for each patient. Kruskal-Wallis rank sum test was performed to compare variables across groups, followed by the post hoc Games-Howell test. Fisher exact test was used to compare categorical variables. The significance level was set to P <0.05., Results: In the MEANS cohort, 13.7% (64/467) of volunteers were ≥60 years old, and 86.3% (403/467) were <60 years old. 76.9% (359/467) was proportioned, 19.5% (91/467) was moderately disproportioned, and 3.6% (17/467) was severely disproportioned. There was no significant difference in the frequency of proportioned, moderately, or severely disproportioned GAP between subjects from different countries ( P =0.060). Those with severely disproportioned GAP alignment were on average 14.5 years older ( P =0.016), had 23.1° lower magnitude lumbar lordosis (LL) ( P <0.001), 14.2° higher pelvic tilt ( P <0.001), 13.3° lower sacral slope ( P <0.001), and 24.1° higher pelvic-incidence (PI)-LL mismatch ( P <0.001), 18.2° higher global tilt ( P <0.001) than those with proportioned GAP; thoracic kyphosis and PI were not significantly different ( P >0.05)., Conclusions: The GAP system applies to a large, multiethnic, asymptomatic cohort. Spinal alignment should be considered on a spectrum, as 19.5% of the asymptomatic volunteers were classified as moderately disproportioned and 3.6% severely disproportioned. Radiographic malalignment does not always indicate symptoms or pathology., Level of Evidence: 3., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This study presents a dataset of audio-visual soundscape recordings at 62 different locations in Singapore, initially made as full-length recordings over spans of 9-38 min. For consistency and reduction in listener fatigue in future subjective studies, one-minute excerpts were cropped from the full-length recordings. An automated method using pre-trained models for Pleasantness and Eventfulness (according to ISO 12913) in a modified partitioning around medoids algorithm was employed to generate the set of excerpts by balancing the need to encompass the perceptual space with uniformity in distribution. A validation study on the method confirmed its adherence to the intended design., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).)

Study Design: Prospective, cross-sectional study., Objective: In a geographically diverse population of asymptomatic volunteers, we sought to report the incidence of pelvic obliquity (PO), establish normative values of PO across patient factors, and assess the correlation of PO with radiographic parameters., Summary of Background Data: PO is defined as the misalignment of the pelvis and can be assessed through several anatomic landmarks. Significant PO, whether caused by leg-length discrepancy or not, can lead to coronal malalignment which causes severe pain and disability. Significant emphasis has been placed on achieving appropriate sagittal alignment in recent decades; however, a greater understanding of coronal alignment is needed, and PO is a crucial aspect of evaluating the coronal plane in adult spinal deformity patients., Methods: Asymptomatic adult volunteers, ages 18-80 years, enrolled patients from 5 countries (France, Japan, Singapore, Tunisia, and the United States) in the "multiethnic alignment normative study" cohort (IRB 201812144). The included volunteers had no known spinal disorder(s), no significant neck or back pain (Visual Analog Scale: ≤2; Oswestry Disability Index: ≤20), and no abnormal alignment (Cobb ≤20°). PO was measured in the frontal plane as the distance between the highest points of each acetabulum, calculated along the vertical axis in millimeters (mm). The incidence of PO was defined as PO ≥10 mm. Kruskal-Wallis, Wilcoxon rank-sum, Pearson correlation, and linear regression were used., Results: A total of 467 patients were included, and PO values by age, sex, body mass index, and country were provided. The overall incidence of PO ≥10 mm was 4.3%, and a nonsignificant trend toward increased PO with age was seen ( P = 0.077). No significant differences were seen in PO between sex, ethnicity, or body mass index groups. No significant correlation existed between PO and other commonly used coronal radiographic measurements., Conclusion: PO ≥10 mm occurred in 4.3% of asymptomatic volunteers. Despite the importance of recognizing PO in preventing coronal malalignment, PO did not seem to be associated with other radiographic and demographic information, which underscores the importance of intentionally assessing for any PO before surgery. These results in an asymptomatic population provide a foundation for studying PO in patients with spinal pathology., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: Cross-sectional cohort study., Objective: To classify spinal morphology using the "current" and "theoretical" Roussouly systems and assess sagittal alignment in an asymptomatic cohort., Methods: 467 asymptomatic volunteers were recruited from 5 countries. Radiographic parameters were measured via the EOS imaging system. "Current" and "theoretical" Roussouly classification was assigned with sagittal whole spine imaging using sacral slope (SS), pelvic incidence (PI), and the lumbar apex. One-way analysis of variance (ANOVA) was performed to compare subject characteristics across Roussouly types, followed by post hoc Bonferroni correction., Results: Volunteers were categorized into 4 groups (Types 1-4) and 1 subgroup (Type 3 AP) using the "current" and "theoretical" Roussouly systems. The mean PI in "current" Roussouly groups was 40.8° (Type 1), 43.6° (Type 2), 52.4° (Type 3), 62.4° (Type 4), and 43.7° (Type 3AP). The mean PI in "theoretical" Roussouly groups was 36.5° (Type 1), 39.1°(Type 2), 52.5° (Type 3), 67.3° (Type 4), and 51.0° (Type 3AP). The difference in PI between "current" and "theoretical" Roussouly types was significant for Type 1 ( P = .02), Type 2 ( P < .001), Type 4 ( P < .001), and Type 3AP ( P < .001). 34.7% of subjects had a "current" Roussouly type different from the "theoretical" type. Type 3 theoretical shape had the most frequent mismatch, constituting 61.1% of the mismatched subjects. 51.5% of mismatched Type 3 become "current" Type 4., Conclusion: The distribution of Roussouly types differs depending on whether the "current" or "theoretical" classification are employed. A sizeable proportion of volunteers exhibited current and theoretical type mismatch, highlighting the need to interpret sagittal alignment cautiously when utilizing the Roussouly system., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Modern microwave switches require high switching speeds to rapidly route data over multiple radio channels while minimizing the routing delay. This Letter proposes a novel, to the best of our knowledge, microwave frequency switching system using phase-locked Period-one (P1) dynamics of semiconductor lasers. When a semiconductor laser is optically injected by microwave-modulated optical signals, which carry two-tone input microwaves at 29 and 37 GHz, with proper injection power controlled by dual-voltage control signals, P1 dynamics are excited in the semiconductor laser and subsequently phase-locked by one of the input microwave tones. We have observed positive and negative switching delays in the switching process. For instance, a positive delay is observed when the system requires additional optical power to transition from a phase-locked state at 29 GHz to an unlocked state. Conversely, a negative delay occurs when the unlocked P1 dynamics approach but do not reach a 37-GHz frequency and then rapidly lock to the tone, thereby surpassing the speed of the control signals. These dual delays are instrumental in enhancing the switching speed of our system, enabling it to surpass the voltage switching time of the control signals by a factor of 3.6. In addition, by leveraging these dual delays, the duration of the microwave tones can be further extended in the switching process.

Background: Little is known about antioxidant efficacy of topical vitamin E on atopic dermatitis (AD) due to lack of controlled clinical studies., Aim: The study evaluates the effectiveness and safety of a topical moisturizer containing tocotrienol-rich composition over 12 weeks on patients aged between 1 month and 12 years with mild to moderate AD., Methods: We conducted a 12 weeks, prospective, open-label clinical study on the effect of tocotrienol as an adjunct to conventional treatment. This study was approved by the Ethics Committee for Research Involving Human Subject. JKEUPM-2019-274 (NMMR-19-1588-49234)., Results: Thirty AD patients with a mean age of 2.77 ± 3.05 were enrolled in the study. At week-12, significant reduction of investigator global assessment (63.4%), Patient-Oriented Scoring Atopic Dermatitis Index (PO-SCORAD) (65%), and SCORAD (52.3%) was noted (p < 0.05). There was also a significant decreased in pruritus intensity (46%, p < 0.05). Similarly at week-12, Infant's Dermatitis Quality of Life Index and Children's Dermatology Life Quality Index were found to improve significantly compared to baseline (p < 0.05). Instrumental assessment revealed improvement in TEWL and erythema index, 49.7% and 17.4%, respectively. No adverse reaction was observed. 95% of patients were satisfied with the moisturizer and 90% perceived it to be better than the one in the market. There was a 55.07% reduction in the use of hydrocortisone 1% cream toward the end of the study (p < 0.05)., Conclusions: The results suggested that tocotrienol-rich moisturizer is safe and effective in the management of AD in young children., (© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Bioretention systems are among the most popular stormwater best management practices (BMPs) for urban runoff treatment. Studies on plant performance using bioretention systems have been conducted, especially in developed countries with a temperate climate, such as the USA and Australia. However, these results might not be applicable in developing countries with tropical climates due to the different rainfall regimes and the strength of runoff pollutants. Thus, this study focuses on the performance of tropical plants in treating urban runoff polluted with greywater using a bioretention system. Ten different tropical plant species were triplicated and planted in 30 mesocosms with two control mesocosms without vegetation. One-way ANOVA was used to analyze the performance of plants, which were then ranked based on their performance in removing pollutants using the total score obtained for each water quality test. Results showed that vetiver topped the table with 86.4% of total nitrogen (TN) removal, 93.5% of total phosphorus (TP) removal, 89.8% of biological oxygen demand (BOD) removal, 90% of total suspended solids (TSS) removal, and 92.5% of chemical oxygen demand (COD) removal followed by blue porterweed, Hibiscus, golden trumpet, and tall sedge which can be recommended to be employed in future bioretention studies., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cryogenic milling, or cryomilling, involves the use of liquid nitrogen to lower the temperature of the biological material and/or the milling process. When applied to the study of subcellular or suborganellar structures and processes, it allows for their rapid extraction from whole cells frozen in the physiological state of choice. This approach has proven to be useful for the study of yeast mitochondrial ribosomes. Following cryomilling of 100 mL of yeast culture, conveniently tagged mitochondrial ribosomes can be immunoprecipitated and purified in native conditions. These ribosomes are suitable for the application of downstream approaches. These include mitoribosome profiling to analyze the mitochondrial translatome or mass spectrometry analyses to assess the mitoribosome proteome in normal growth conditions or under stress, as described in this method., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

The rearrangement hotspot (Rhs) repeat is an ancient giant protein fold found in all domains of life. Rhs proteins are polymorphic toxins that could either be deployed as an ABC complex or via a type VI secretion system (T6SS) in interbacterial competitions. To explore the mechanism of T6SS-delivered Rhs toxins, we used the gastroenteritis-associated Vibrio parahaemolyticus as a model organism and identified an Rhs toxin-immunity pair, RhsP-RhsP I . Our data show that RhsP-dependent prey targeting by V. parahaemolyticus requires T6SS2. RhsP can bind to VgrG2 independently without a chaperone and spontaneously self-cleaves into three fragments. The toxic C-terminal fragment (RhsP C ) can bind to VgrG2 via a VgrG2-interacting region (VIR). Our electron microscopy (EM) analysis reveals that the VIR is encapsulated inside the Rhs β barrel structure and that autoproteolysis triggers a dramatic conformational change of the VIR. This alternative VIR conformation promotes RhsP dimerization, which significantly contributes to T6SS2-mediated prey targeting by V. parahaemolyticus., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: The role of the craniocervical complex in spinal sagittal alignment has rarely been analyzed but it may play a fundamental role in postoperative mechanical complications. The aim of the study is to analyze the normative value of the cervical inclination angle (CIA) in an adult asymptomatic multiethnic population., Methods: Standing full-spine EOS of adult asymptomatic volunteers from 5 different countries were analyzed. The CIA was analyzed globally and then in each decade of life. Different ethnicities were compared. Comparisons between different groups was performed using a t-test and statistical significance was considered with a p-value < 0.05., Results: EOS of 468 volunteers were analyzed. The global mean CIA was 80.2° with a maximum difference of 9° between T1 and T12 (p < 0.001). The CIA remains constant until 60 years old then decreases significantly passing from a mean value before 20 years old of 82.25° to 73.65° after 70 years old. A statistically significant difference was found between the Arabics and other ethnicities with the formers having an inferior CIA: this was related to a mean older age (p < 0.05) and higher body mass index (p < 0.05) in the Arabics., Conclusion: The CIA remains constant until 60 years old and then reduces slightly but never under 70°. This angle is helpful to evaluate the lever arm at the upper instrumented vertebra after an adult spinal deformity surgery and could predict the occurrence of a proximal junctional kyphosis when its value is lower than normal. Further clinical studies must confirm this theory.

Study Design: Multicenter Cohort., Objective: Assess normative values of sagittal spinal and lower extremity alignment in asymptomatic volunteers stratified by age and gender., Summary of Background Data: Our understanding of ideal sagittal alignment is still evolving. The Multiethnic Alignment Normative Study (MEANS) investigated skeletal alignment of the largest multiethnic cohort of asymptomatic adult volunteers. We aim to assess normative values of sagittal spinal and lower extremity alignment in asymptomatic volunteers stratified by age and gender., Materials and Methods: Asymptomatic volunteers between the ages of 18-80 years were enrolled prospectively and then analyzed retrospectively from six different centers. Volunteers included reported no significant neck or back pain, nor any known spinal disorder(s). All volunteers underwent a standing full-body or full-spine low-dose stereoradiograph., Results: MEANS consisted of 468 volunteers with a mean age of 40.4±14.8 years. Thoracic kyphosis (TK) from T4 to T12 showed a mean of 37.4±10.9°. The average L1-S1 lumbar lordosis (LL) was -57.4±11.3°. LL did not show significant differences across the five age groups. TK showed a significant difference based on age ( P <0.0001). Sagittal vertical axis increased across age groups from -14.2 mm in young adults to 17.0 mm in patients >64. Similar trend was seen for T1 pelvic angle with a mean of 5.0° in young adults and 13.7° in those older than age 64. Knee flexion increased across age groups without a significant change in odontoid-knee distance which is a surrogate for the center of the head aligned over the knees., Conclusions: In asymptomatic volunteers, sagittal alignment parameters showed a slow and steady change across age groups exemplified by an increase in TK. However, LL did not show a significant decrease across age groups. Volunteers used compensatory mechanisms such as slight pelvis retroversion, knee flexion, and neck extension to maintain an aligned sagittal posture with their head centered over their knees (odontoid-knee)., Level of Evidence: 3., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Spinal alignment can have a significant impact on a patient's overall quality of life. Predicting the ideal sagittal spinal alignment of a specific individual is still a difficult task. The Multi-Ethnic Alignment Normative Study (MEANS) investigated skeletal alignment, including the spine and lower extremities, of the largest multi-ethnic cohort of asymptomatic adult volunteers. In this analysis, the authors aim to assess normative values of spinopelvic parameters and the regional cervical, thoracic, and lumbar spinal alignment in asymptomatic volunteers stratified by age and sex., Materials and Methods: Asymptomatic volunteers between ages 18 and 80 years were enrolled prospectively from centers in France, Japan, Singapore, Tunisia, and the United States. Volunteers included reported no significant neck or back pain (Visual Analog Scale ≤2), nor any known spinal disorder(s). All volunteers underwent a standing full-body or full-spine low-dose stereoradiograph., Results: MEANS consisted of 468 volunteers with a mean age of 40.4±14.8 years. Mean cervical lordosis from C2 to C7 was -0.4±12.7°. The T1-slope averaged 23.0±7.9° and showed strong correlation ( r =0.87) with the C7-slope mean of 19.8±8.6°. Thoracic kyphosis (TK) from T4 to T12 showed a mean of 37.4±10.9°. Average L1-S1 lumbar lordosis (LL) was -57.4±11.3°. The mean pelvic incidence (PI) measured 52.0±10.7° and pelvic tilt was 12.5±7.3°. Sacral slope averaged 39.5±8.2°. The average PI-LL was -5.4±10.7°. Approximately 60% of volunteers met the PI-LL criteria within ±10°, 8.3% were ≥10°, while 32.1% were ≤-10°. LL showed moderate correlation with PI ( r =0.53) and TK ( r =0.50), while there was no correlation between TK and PI. Multiple linear regression including PI, TK, and age resulted in the following equation LL=14.6+0.57 (PI)+0.57 (TK)-0.2 (age) ( r =0.75)., Conclusions: LL did not change with increasing age in asymptomatic volunteers. However, TK did increase with age leading to an increase in T1-slope and a compensatory increase in cervical lordosis. TK did not correlate with PI and was an independent variable in the prediction of LL., Level of Evidence: Level II-prospective cohort study., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Adult sporadic Burkitt lymphoma (BL) is a rare but highly aggressive subtype of lymphoma which lacks its own unique prognostic model. Systemic inflammatory biomarkers have been confirmed as prognostic markers in several types of malignancy. Our objective was to explore the predictive value of pretreatment inflammatory biomarkers and establish a novel, clinically applicable prognostic index for adult patients with sporadic BL., Methods: We surveyed retrospectively 336 adult patients with newly diagnosed sporadic BL at 8 Chinese medical centers and divided into training cohort (n = 229) and validation cohort (n = 107). The pretreatment inflammatory biomarkers were calculated for optimal cut-off value. The association between serum biomarkers and overall survival (OS) was analyzed by Kaplan-Meier curves and Cox proportional models. The risk stratification was defined based on normal LDH level, Ann Arbor stage of I and completely resected abdominal lesion or single extra-abdominal mass < 10 cm., Results and Conclusions: Univariate and multivariate analyses revealed that platelets< 254 × 10 9 /L, albumin< 40 g/L, lactate dehydrogenase≥334 U/L independently predicted unfavorable OS. We used these data as the basis for the prognostic index, in which patients were stratified into Group 1 (no or one risk factor), Group 2 (two risk factors), or Group 3 (three risk factors), which were associated with 5-year OS rates of 88.1, 72.4, and 45%, respectively. In the subgroup analysis for high-risk patients, our prognostic model results showed that high-risk patients with no more than one adverse factor presented a 5-year survival rate of 85.9%, but patients with three adverse factors had a 5-year survival rate of 43.0%. Harrell's concordance index (C-index) of the risk group score was 0.768. Therefore, the new prognostic model could be used to develop risk-adapted treatment approaches for adult sporadic BL., (© 2022. The Author(s).)

Objectives: The Integrated Care for Advanced REspiratory Disorders (ICARE) service is a stay-in, post-acute care program for hospitalized patients with chronic, nonmalignant lung diseases. It provides palliative rehabilitation-a novel model integrating functional rehabilitation with early palliative care. We compare reduction of health care utilization among ICARE participants vs matched controls receiving usual care., Design: This is a prospective, propensity score-matched study. Primary outcomes were reduction in hospital readmissions and length of stay and emergency department (ED) visits, comparing the period 6 months before and after ICARE, or 6 months before and after hospital discharge (for controls). Secondary outcomes included 6-minute walking distance (6MWD) and Modified Barthel Index (MBI)., Setting: Participants were matched 1:1 to controls by age, respiratory diagnosis, socioeconomic strata, index hospitalization length of stay, frailty, and recent admissions into intensive care unit or noninvasive ventilation units., Methods: Multidisciplinary interventions focused on symptom relief, functional rehabilitation, targeted comorbidity management, and postdischarge care coordination., Results: One hundred pairs of patients were matched. Participants were older adults (mean age 73.9 ± 8.2 years) with prolonged index hospitalization (median 12.0 days; interquartile range 7-18). Overall, 57% had high Hospital Frailty Risk Scores and 71% had overlapping respiratory diagnoses, the most common commonest being COPD (89%), followed by interstitial lung disease (54%) and bronchiectasis (28%). Small reductions in health care utilization were observed among controls. ICARE was associated with a further 9.1 ± 19.9 days' reduction in hospitalization length of stay (P < .001), 0.8 ± 1.9 lesser admission (P < .001), and 0.6 ± 2.2 fewer ED visits (P < .02). Participants with longest index hospitalization were observed to have greatest reduction in length of stay. 6MWD and MBI scores improved by 41.0 ± 60.2 m and 12.3 ± 11.6 points, respectively (both P < .001). Greater improvement was observed in patients with lower baseline 6MWD and MBI scores. Prescription of slow-release opioids rose from 9% to 49%. Treatment for anxiety and depression rose from 5% to 19%., Conclusions and Implications: Integrating palliative care with postexacerbation functional rehabilitation was associated with short-term reduction in health care utilization, improved functional capacity, and increased treatment of dyspnea, anxiety, and depression., (Copyright © 2021 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Throughout the past decade, Pickering emulsion has been increasingly utilized for the encapsulation of bioactive compounds due to its high stability and biocompatibility. In the present work, palm tocotrienols were initially encapsulated in a calcium carbonate Pickering emulsion, which was then subjected to alginate gelation and subsequent chitosan coating. The effects of wall material (alginate and chitosan) concentrations, gelation pH and time, and chitosan coating time on the encapsulation efficiency of palm tocotrienols were explored., Results: Our findings revealed that uncoated alginate microcapsules ruptured upon drying and exhibited low encapsulation efficiency (13.81 ± 2.76%). However, the addition of chitosan successfully provided a more complex and rigid external wall structure to enhance the stability of the microcapsules. By prolonging the crosslinking time from 5 to 30 min and increasing the chitosan concentration from 0.1% to 0.5%, the oil encapsulation efficiency was increased by 28%. Under the right gelation pH (pH 4), the extension of gelation time from 1 to 12 h resulted in an increase in alginate-Ca 2+ crosslinkings, thus strengthening the microcapsules., Conclusion: With the optimum formulation and process parameters, a high encapsulation efficiency (81.49 ± 1.75%) with an elevated oil loading efficiency (63.58 ± 2.96%) were achieved. The final product is biocompatible and can potentially be used for the delivery of palm tocotrienols. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

Calcium carbonate (CaCO 3 ) has been utilized as a pH-responsive component in various products. In this present work, palm tocotrienols-rich fraction (TRF) was successfully entrapped in a self-assembled oil-in-water (O/W) emulsion system by using CaCO 3 as the stabilizer. The emulsion droplet size, viscosity and tocotrienols entrapment efficiency (EE) were strongly affected by varying the processing (homogenization speed and time) and formulation (CaCO 3 and TRF concentrations) parameters. Our findings indicated that the combination of 5000 rpm homogenization speed, 15 min homogenization time, 0.75% CaCO 3 concentration and 2% TRF concentration resulted in a high EE of tocotrienols (92.59-99.16%) and small droplet size (18.83 ± 1.36 µm). The resulting emulsion system readily released the entrapped tocotrienols across the pH range tested (pH 1-9); with relatively the highest release observed at pH 3. The current study presents a potential pH-sensitive emulsion system for the entrapment and delivery of palm tocotrienols.

The Cervical Spine Research Society (CSRS) is dedicated to advancing the care of patients with cervical spine pathology. The authors present here highlights of the 2019 CSRS-Asia Pacific Traveling Fellowship.

Objective: To investigate the antioxidative and spermatogenesis-repairing effects of Shenjing Guben Pills (SGP), a Chinese medicine for invigorating the kidney and blood circulation, on the testis, epididymis and sperm in rats with oxidative stress injury (OSI) induced by cadmium chloride., Methods: Seventy-two male Wistar rats were equally randomized into six groups: normal control, OSI model control, Wuzi Yanzong Pills (WYP) and low-, medium- and high-dose SGP. The OSI model was made in the latter five groups by intraperitoneal injection of cadmium chloride at 1 mg/kg, and 24 hours later, the rats of the normal and model control groups treated intragastrically with 0.9% normal saline, those of the WYP group with WYP at 4.5 g/kg/d, and those of the low-, medium- and high-dose SGP groups with SGP at 2.8, 5.6 and 11.2 g/kg/d, respectively, all for 56 days. Then, all the animals were sacrificed for obtainment of the visceral indexes and histopathological changes of the testis, epididymis and seminal vesicle, measurement of sperm concentration and motility and the percentage of morphologically normal sperm (MNS) in the epididymis, and determination of the levels of glutathione perox-idase (GSH-PX), superoxide dismutase (SOD), malondial-dehyde aldehyde (MDA) and serum testosterone (T)., Results: Compared with the OSI model controls, the rats in the high-, medium- and low-dose SGP groups showed significantly higher visceral indexes of the testis (［0.237 ± 0.098］ vs ［0.403 ± 0.090］, ［0.357 ± 0.150］ and ［0.348 ± 0.140］ g/100 g, P < 0.05) and seminal vesicle (［0.241 ± 0.118］ vs ［0.347 ± 0.115］, ［0.336 ± 0.090］ and ［0.320 ± 0.065］ g/100 g, P < 0.05) and those of the high-dose SGP group in the epididymal index (［0.099 ± 0.088］ vs ［0.156 ± 0.030］ g/100 g, P < 0.05). In comparison with the OSI model controls, the animals of the high-, medium- and low-dose SGP groups exhibited significant increases in sperm concentration (［10.5 ± 17.7］ vs ［58.1 ± 32.2］, ［36.0 ± 36.2］ and ［31.9 ± 32.7］ ×10⁶/ml, P < 0.05) and serum T (［2.56 ± 0.75］ vs ［3.62 ± 0.96］, ［3.48 ± 1.33］ and ［3.24 ± 0.83］ nmol/L, P < 0.05 or P < 0.01), and those of the high- and medium-dose SCG groups in total sperm motility (［9.5 ± 13.0］% vs ［26.5 ± 15.5］% and ［18.9 ± 8.2］%, P < 0.05) and MNS (［36.2 ± 40.2］% vs ［85.3 ± 23.3］% and ［65.8 ± 28.1］%, P < 0.05) and the levels GSH-PX (［3.62 ± 2.22］ vs ［5.70 ± 1.73］ and ［5.42 ± 2.35］ U/mg prot, P < 0.05 ) and SOD (［41.3 ± 8.8］ vs ［52.7 ± 14.6］ and ［51.3 ± 14.7］ U/mg prot, P < 0.05). The MDA level, however, was markedly decreased in the high-, medium- and low-dose SGP groups (［0.41 ± 0.29］, ［0.44 ± 0.19］ and ［0.47 ± 0.20］ nmol/mg prot) as compared with that in the OSI model controls (［0.69 ± 0.28］ nmol/mg prot) (P < 0.05). Histopathological examinations manifested coagulative necrosis, calcification and disappearance of spermatogenic and Sertoli cells in the seminiferous tubules of the OSI model controls, with decreased intraluminal secretions and atrophic epithelial papillae in the seminal vesicles and non-sperm cells in the narrowed lumens of the atrophic epididymis. With the increased dose of SGP, the proportion of normal seminiferous tubules was enlarged, the epithelia of the seminal vesicle became column-shaped again, and the epididymal lumens grew lager with more sperm cells, which indicated a dose-dependent therapeutic efficacy. Medium- and high-dose SGP achieved a significantly better effect than WYP., Conclusions: Shenjing Guben Pills can antagonize oxidative stress, elevate the levels of testicular antioxidant enzymes and serum T, repair pathological injury of the testis, epididymis and seminal vesicle, and improve semen quality and spermatogenic function.

Purpose: To study the ability of a novel bovine serum albumin-angiotensin II (BSA-Ang II) conjugate to effect responses of the AT 1 angiotensin II receptor subtype mediated by the G-protein-coupled and the beta-arrestin pathways., Methods: Angiotensin II (Ang II) was conjugated with bovine serum albumin and compared with Ang II for competition binding to AT 1 receptors, to stimulate aldosterone release from adrenocortical cells, to promote beta-arrestin binding to AT 1 receptors, to promote calcium mobilization, and stimulate drinking of water and saline by rats., Results: The BSA-Ang II conjugate was less potent competing for AT 1 R binding, but was equally efficacious at stimulating aldosterone release from H295R adrenocortical cells. Both BSA-Ang II and Ang II stimulated calcium mobilization and beta-arrestin binding to AT 1 receptors. BSA-Ang II and Ang II stimulated water appetite equivalently but BSA-Ang II stimulated saline appetite more than Ang II. Both BSA-Ang II and Ang II were considerably more potent at causing calcium mobilization than β-arrestin binding., Conclusions: Addition of a high molecular weight molecule to Ang II reduced its AT 1 receptor binding affinity, but did not significantly alter stimulation of aldosterone release or water consumption. The BSA-Ang II conjugate caused a greater saline appetite than Ang II suggesting that it may be a more efficacious agonist of this beta-arrestin-mediated response than Ang II. The higher potency calcium signaling response suggests that the G-protein-coupled responses predominate at physiological concentrations of Ang II, while the beta-arrestin response requires pathophysiological or pharmacological concentrations of Ang II to occur.

Background: The relationship between survivin and extranodal, nasal-type natural killer/T cell lymphoma (ENKTCL) was unclearly established yet. We here studied the potential prognostic roles of survivin and its implication as a target in ENKTCL therapy., Methods: ENKTCL patients' peripheral blood were collected and tested by ELISA. ENKTCL cell lines were cultured with or without survivin inhibitor and tested by MTT and Flow cytometry. According to the gene expression profiles from the ArrayExpress Archive under E-TABM-702, survivin co-regulated cluster was established by Coupled Two-way Clustering Algorithm., Results: Seventeen point six percent of total 17 ENKTCL patients were serum survivin-positive. These patients had poorer outcome than that of negative cases (P<0.01). Analysis of survivin co-regulation genes in ENKTCL revealed that survivin was significantly involved in pluripotency, drug resistance, cell cycle and proliferation, indicating that it should be one of key regulators in ENKTCL and might be a latent therapeutic target. Our results just showed that YM155, a survivin inhibitor, had strong anti-tumor effect on ENKTCL cell lines in a dose dependent manner. It increased sub-G1 phase population and reduced G1- and G2-M phase populations (P<0.05). In addition, combining YM155 with DDP induced a larger decrease in cell viability than either agent alone and had a higher inhibition rate than Bliss index, suggesting their synergistic inhibition., Conclusions: We concluded that survivin was a potential prognostic marker and a critical regulatory molecule in the pathological process of ENKTCL. It would be a promising target in drugs discovery for ENKTCL therapy., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Male infertility (MI) is a complex multifactorial disease, and idiopathic infertility accounts for 30% of cases of MI. At present, the evidence for the effectiveness of empirical drugs is limited, and in vitro fertilization is costly and may increase the risk of birth defects and childhood cancers. Therefore, affected individuals may feel obliged to pursue natural remedies. Traditional Chinese medicine (TCM) may represent a useful option for infertile men. It has been demonstrated that TCM can regulate the hypothalamic-pituitary-testicular axis and boost the function of Sertoli cells and Leydig cells. TCM can also alleviate inflammation, prevent oxidative stress, reduce the DNA fragmentation index, and modulate the proliferation and apoptosis of germ cells. Furthermore, TCM can supply trace elements and vitamins, ameliorate the microcirculation of the testis, decrease the levels of serum anti-sperm antibody, and modify epigenetic markers. However, the evidence in favor of TCM is not compelling, which has hindered the development of TCM. This review attempts to elucidate the underlying therapeutic mechanisms of TCM. We also explore the advantages of TCM, differences between TCM and Western medicine, and problems in existing studies. Subsequently, we propose solutions to these problems and present perspectives for the future development of TCM., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2019 Korean Society for Sexual Medicine and Andrology.)

Bioretention systems have been implemented as stormwater best management practices (BMPs) worldwide to treat non-point sources pollution. Due to insufficient research, the design guidelines for bioretention systems in tropical countries are modeled after those of temperate countries. However, climatic factors and stormwater runoff characteristics are the two key factors affecting the capacity of bioretention system. This paper reviews and compares the stormwater runoff characteristics, bioretention components, pollutant removal requirements, and applications of bioretention systems in temperate and tropical countries. Suggestions are given for bioretention components in the tropics, including elimination of mulch layer and submerged zone. More research is required to identify suitable additives for filter media, study tropical shrubs application while avoiding using grass and sedges, explore function of soil faunas, and adopt final discharged pollutants concentration (mg/L) on top of percentage removal (%) in bioretention design guidelines.

Background: Metastasis remains the main cause of cancer-related death for gastric cancer (GC) patients, but the mechanisms are poorly understood. Using The Cancer Genome Atlas (TCGA) data base and bioinformatics analyses, we identified C12orf59 might act as a potential oncogenic protein in GC., Methods: We investigate the expression pattern and clinical significance of C12orf59 in two independent cohorts of GC samples. In the training cohort, we used the X-tile program software to generate the optimal cutoff value for C12orf59 expression in order to classify patients accurately according to clinical outcome. In the validation cohort, this derived cutoff score was applied to exam the association of C12orf59 expression with survival outcome. A series of in vivo and in vitro assays were then performed to investigate the function of C12orf59 in GC., Results: C12orf59 was significantly upregulated, and associated with poor survival outcome in two cohorts of GC samples. Gain- and loss of- function studies demonstrated C12orf59 promotes GC cell invasive and metastatic capacity both in vitro and in vivo, and induces epithelial-mesenchymal transition and angiogenesis. Mechanically, C12orf59 exerts oncogenic functions by up-regulating CDH11 expression via NF-κB signaling. Interesting, CDH11 could in turn promote NF-κB bind to C12orf59's promoter and form a positive feedback loop to sustain the metastatic ability of GC cells. Additionally, downregulation of miR-654-5p is another important mechanism for C12orf59 overexpression in GC., Conclusion: Our finding suggested the newly identified C12orf59/NF-κB/CDH11 feedback loop may represent a new strategy for GC treatment.

Background: Hoarding is a disorder characterized by excessive acquisition and persistent difficulty in discarding possessions. The behaviour has adverse emotional, physical, social, financial, and legal outcomes for the person with the disorder and family members, and might pose a significant public health problem. Hoarding has been included as a distinct disorder in the Diagnostic and Statistical Manual of Mental Disorders Fifth edition (DSM-5). The prevalence of hoarding disorder is approximately 2-6% globally. The current state of the evidence does not offer clear understanding of the causes of hoarding behaviours. A systematic review of the extant literature was carried out to determine the possible causal factors of hoarding behaviours., Methods: This review is conducted in line with PRISMA guidelines. The following electronic databases: Medline through Ovid, EMBASE and PsycINFO were searched for relevant articles published between January 2000 and November 2018. Only articles published in English language were included. Two reviewers independently scrutinized the studies and included them in this review., Results: Our search strategy returned a total of 396 references. Preliminary findings suggest that individuals with hoarding behaviours may have a genetic susceptibility; abnormal neural activity in the fronto-temporal, para-hippocampal gyrus and insular parts of the brain has also been identified. Traumatic life experiences have also been posited to predispose individuals to hoard., Conclusion: Although the understanding of hoarding disorder hasgrown in recent years, greater efforts are still needed to clarify the etiology and mechanisms of hoarding disorder as these may help in planning of more holistic interventions to treat the problem., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: A comparative survey from patients and radiographers of the new slump sitting flexion posture and the conventional standing forward bending posture. This study was performed to compare the technical and logistical aspects of the slump sitting versus the forward bending posture. Slump sitting flexes the lumbar spine more than the forward bending and increases the diagnosis rate of sagittal spinal instability up to 40% depending on the diagnostic criteria used. This should not come at the expense of patient safety and comfort nor burden the radiographers., Methods: Sixty patients were recruited from a single tertiary spine centre. Patients were block randomised into two groups with either the forward bending or the slump sitting being performed first. Feedback was obtained through self-administered questionnaires from patients regarding perceived safety, convenience and comfort, plus from radiographers regarding the imaging process, proxy measures of radiographer ability and scan difficulty., Results: There was no significant difference between the baseline characteristics in both groups. Majority (63%) of patients preferred slump sitting and felt that forward bending caused pain (P=0.025). Overall, slump sitting was equivalent in comfort, perceived safety and ease to forward bending. Despite requiring more logistics (P=0.031), more effort to set up (P=0.002) and explain (P=0.012), the majority of radiographers (83%) preferred slump sitting. This method was felt to be less dangerous (P=0.015) and easier to maintain (P<0.001)., Conclusions: This study showed that the superiority of slump sitting in allowing more lumbar flexion compared to the forward bending comes with patient safety or comfort. The technical demands of the learning curve can be offset with training. As such, slump sitting flexion views should be adopted as the standardized method for assessing spinal instability., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Dysregulation of non-coding RNAs, including miRNAs and lncRNAs has been reported to play vital roles in gastric cancer (GC) carcinogenesis, but the mechanism involved is largely unknown. Using the cancer genome atlas (TCGA) data set and bioinformatics analyses, we identified miR-532-5p as a potential tumor suppressor in GC, and found that lncRNA LINC01410 might be a negative regulator of miR-532-5p. We then conducted a series of in vivo and in vitro assays to explore the effect of LINC01410 on miR-532-5p-mediated GC malignancy and the underlying mechanism involved. MiR-532-5p overexpression inhibited GC metastasis and angiogenesis in vitro and in vivo, whereas miR-532-5p silencing had the opposite effect. Further study showed that miR-532-5p attenuated NF-κB signaling by directly inhibiting NCF2 expression, while miR-532-5p silencing in GC enhanced NF-κB activity. Furthermore, we demonstrated miR-532-5p down-regulation was caused by aberrantly high expression of LINC01410 in GC. Mechanistically, overexpression of LINC01410 promoted GC angiogenesis and metastasis by binding to and suppressing miR-532-5p, which resulted in up-regulation of NCF2 and sustained NF-κB pathway activation. Interestingly, NCF2 could in turn increase the promoter activity and expression of LINC01410 via NF-κB, thus forming a positive feedback loop that drives the malignant behavior of GC. Finally, high expression of LINC01410, along with low expression of miR-532-5p, was associated with poor survival outcome in GC patients. Our studies uncover a mechanism for constitutive LINC1410-miR-532-5p-NCF2-NF-κB feedback loop activation in GC, and consequently, as a potential therapeutic target in GC treatment.

Fish oil-in-water emulsions containing fish oil, thiol-modified β-lactoglobulin (β-LG) fibrils, chitosan and maltodextrin were fabricated using a high-energy method. The results showed that chitosan coating induced charge reversal; denoting successful biopolymers complexation. A significantly (p<0.05) larger droplet size and lower polydispersity index value, attributed to the thicker chitosan coating at the oil-water interface, were observed. At high chitosan concentrations, the cationic nature of chitosan strengthened the electrostatic repulsion between the droplets, thus conferring high oxidative stability and low turbidity loss rate to the emulsions. The apparent viscosity of emulsions stabilized using thiol-modified β-LG fibrils-chitosan complex was higher than those stabilized using β-LG fibrils alone, resulting in the former's higher creaming stability. Under thermal treatments (63°C and 100°C), emulsions stabilized using thiol-modified β-LG fibrils-chitosan complex possessed higher heat stability as indicated by the consistent droplet sizes observed. Chitosan provided a thicker protective layer that protected the oil droplets against high temperature. Bridging flocculation occurred at low chitosan concentration (0.1%, w/w), as revealed through microscopic observations which indicated the presence of large flocs. All in all, this work provided us with a better understanding of the application of protein fibrils-polysaccharide complex to produce stable emulsion., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Tocotrienol microcapsules (TM) were formed by firstly preparing Pickering emulsion containing tocotrienols, which was then gelled into microcapsules using alginate and chitosan. In this study, we examined the stability of TM during storage and when applied into a model food system, i.e. yogurt. During storage at 40°C, TM displayed remarkably lower tocotrienols loss (50.8%) as compared to non-encapsulated tocotrienols in bulk oil (87.5%). When the tocotrienols were incorporated into yogurt, the TM and bulk oil forms showed a loss of 23.5% and 81.0%, respectively. Generally, the tocotrienols were stable in the TM form and showed highest stability when these TM were added into yogurt. δ-Tocotrienol was the most stable isomer in both forms during storage and when incorporated into yogurt. The addition of TM into yogurt caused minimal changes in the yogurt's color and texture but slightly altered the yogurt's viscosity., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Considering the health benefits of tocotrienols, continuous works have been done on the encapsulation and delivery of these compounds. In this study, we encapsulated tocotrienols in chitosan-alginate microcapsules and evaluated their release profile. Generally, these tocotrienols microcapsules (TM) displayed high thermal stability. When subjected to pH adjustments (pH 1-9), we observed that the release of tocotrienols was the highest (33.78 ± 0.18%) under basic conditions. The TM were also unstable against the effect of ionic strength, with a high release (70.73 ± 0.04%) of tocotrienols even at a low sodium chloride concentration (50 mM). As for the individual isomers, δ-tocotrienol was the most sensitive to pH and ionic strength. In contrast, β-/γ-tocotrienols were the most ionic-stable isomers but more responsive toward thermal treatment. Simulated gastrointestinal model showed that the chitosan-alginate-based TM could be used to retain tocotrienols in the gastric and subsequently release them in the intestines for possible absorption.

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurological disease characterised by the degeneration of motor neurons, which are responsible for voluntary movement. There remains limited understanding of disease aetiology, with median survival of ALS of three years and no effective treatment. Identifying genes that contribute to ALS susceptibility is an important step towards understanding aetiology. The vast majority of published human genetic studies, including for ALS, have used samples of European ancestry. The importance of trans-ethnic studies in human genetic studies is widely recognised, yet a dearth of studies of non-European ancestries remains. Here, we report analyses of novel whole-exome sequencing (WES) data from Chinese ALS and control individuals., Methods: WES data were generated for 610 ALS cases and 460 controls drawn from Chinese populations. We assessed evidence for an excess of rare damaging mutations at the gene level and the gene set level, considering only singleton variants filtered to have allele frequency less than 5 × 10 -5 in reference databases. To meta-analyse our results with a published study of European ancestry, we used a Cochran-Mantel-Haenszel test to compare gene-level variant counts in cases vs controls., Results: No gene passed the genome-wide significance threshold with ALS in Chinese samples alone. Combining rare variant counts in Chinese with those from the largest WES study of European ancestry resulted in three genes surpassing genome-wide significance: TBK1 (p = 8.3 × 10 -12 ), SOD1 (p = 8.9 × 10 -9 ) and NEK1 (p = 1.1 × 10 -9 ). In the Chinese data alone, SOD1 and NEK1 were nominally significantly associated with ALS (p = 0.04 and p = 7 × 10 -3 , respectively) and the case/control frequencies of rare coding variants in these genes were similar in Chinese and Europeans (SOD1: 1.5%/0.2% vs 0.9%/0.1%, NEK1 1.8%/0.4% vs 1.9%/0.8%). This was also true for TBK1 (1.2%/0.2% vs 1.4%/0.4%), but the association with ALS in Chinese was not significant (p = 0.14)., Conclusions: While SOD1 is already recognised as an ALS-associated gene in Chinese, we provide novel evidence for association of NEK1 with ALS in Chinese, reporting variants in these genes not previously found in Europeans.

Cross-ethnic genetic studies can leverage power from differences in disease epidemiology and population-specific genetic architecture. In particular, the differences in linkage disequilibrium and allele frequency patterns across ethnic groups may increase gene-mapping resolution. Here we use cross-ethnic genetic data in sporadic amyotrophic lateral sclerosis (ALS), an adult-onset, rapidly progressing neurodegenerative disease. We report analyses of novel genome-wide association study data of 1,234 ALS cases and 2,850 controls. We find a significant association of rs10463311 spanning GPX3-TNIP1 with ALS (p = 1.3 × 10 -8 ), with replication support from two independent Australian samples (combined 576 cases and 683 controls, p = 1.7 × 10 -3 ). Both GPX3 and TNIP1 interact with other known ALS genes (SOD1 and OPTN, respectively). In addition, GGNBP2 was identified using gene-based analysis and summary statistics-based Mendelian randomization analysis, although further replication is needed to confirm this result. Our results increase our understanding of genetic aetiology of ALS.Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease. Here, Wray and colleagues identify association of the GPX3-TNIP1 locus with ALS using cross-ethnic meta-analyses.

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis in infancy, which is a major risk factor for recurrent wheezing and asthma. Orosomucoid 1-like protein 3 (ORMDL3) has been reported to associate with virus-triggered recurrent wheezing and asthma in children. However, little is known about how ORMDL3 is involved into RSV infection. In this study, we showed that the mRNA expression of ORMDL3 is significantly increased in the peripheral blood lymphocytes of infants with RSV-induced bronchiolitis compared with uninfected controls, also increased in bronchial epithelial cells and lung fibroblasts following RSV infection in vitro. To investigate the underlying mechanisms of RSV-induced ORMDL3 expression, we performed in silico analysis of the binding sites of several transcription factors in the ORMDL3 promoter. The proximal interferon-regulatory factor-3 (IRF-3) binding site positively regulated ORMDL3 transcription following exposure to RSV, as determined through mutational analysis. Overexpression and RNA interference experiments targeting IRF-3 showed that it regulates the expression of ORMDL3 following RSV exposure. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay showed that IRF-3 binds directly to the promoter of the ORMDL3 gene. Furthermore, we confirmed that expression of IRF-3 is significantly increased and shows a strong linear correlation with increased ORMDL3 in the peripheral blood lymphocytes from infants with RSV-induced bronchiolitis. Our results indicate that IRF-3 is an important regulator of ORMDL3 induction following RSV infection by binding directly to the promoter of ORMDL3, which may be implicated in the inflammatory and immune reactions involved in bronchiolitis and wheezing diseases., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Nasal-type, extranodal natural killer/T-cell lymphoma is a heterogeneous disorder with poor prognosis, requiring risk stratification in this population. The combined value of baseline absolute lymphocyte count and absolute monocyte count provided prognostic information in some malignancies. However, the evidence requires validation in extranodal natural killer/T-cell lymphoma. Aiming to investigate the prognostic significance of absolute lymphocyte count/absolute monocyte count ratio and absolute lymphocyte count/absolute monocyte count prognostic score for extranodal natural killer/T-cell lymphoma, a retrospective research was carried out. A total of 264 patients with newly diagnosed extranodal natural killer/T-cell lymphoma were analyzed in this study. The patients' absolute lymphocyte count and absolute monocyte count tested at initial diagnosis were collected. Receiver operating curve analysis showed that the optimal cut-off values for absolute lymphocyte count and absolute monocyte count were 1.0 × 10 9 and 0.5 × 10 9 L -1 , respectively, and for absolute lymphocyte count/absolute monocyte count ratio was 2.85. After a median follow-up of 27 months (range 1-87 months), the 3-year overall survival and progression-free survival was 75.4% and 67.6%, respectively. Patients with absolute lymphocyte count/absolute monocyte count ratio ≥ 2.85 had better 3-year overall survival and progression-free survival than those with absolute lymphocyte count/absolute monocyte count ratio <2.85 (p < 0.001). According to absolute lymphocyte count/absolute monocyte count prognostic score, significant difference has been noticed in 3-year overall survival and progression-free survival (p < 0.001) and high absolute lymphocyte count/absolute monocyte count prognostic score was associated with poorer survival. The International Prognostic Index and Korean Prognostic Index were used for prognosis and showed no significant difference. When adding absolute lymphocyte count/absolute monocyte count ratio and absolute lymphocyte count/absolute monocyte count prognostic score to the International Prognostic Index and Korean Prognostic Index model, additional prognostic information was found. These results suggest that absolute lymphocyte count/absolute monocyte count ratio and absolute lymphocyte count/absolute monocyte count prognostic score might be useful prognostic factors in extranodal natural killer/T-cell lymphoma.

Study Design: A retrospective, cohort study of 84 patients with deep spine infection managed at a major tertiary hospital over 14 years with a minimum follow up of 2 years., Objective: To determine the role of instrumentation in spines with deep infection., Summary of Background Data: It is often believed that implants should not be inserted in patients with deep spine infection because of the risk of persistent or recurrent infection. However, there are often concerns about spinal stability and a paucity of evidence to guide clinical practice in this field., Methods: We compared the mortality, reoperation, and reinfection rates in patients with spine infection treated with antibiotics alone, antibiotics with debridement, and antibiotics with debridement and instrumentation. Significant outcome predictors were determined using multivariable logistic regression model., Results: Forty-nine males and 35 females with a mean age was 62.0 years had spine infection affecting the lumbar spine predominantly. The most common form of infection was osteomyelitis and spondylodiscitis (69.4%). Staphylococcus aureus was the most common causative organism (61.2%).There was no difference in terms of reoperation or relapse for patients treated with antibiotics alone, antibiotics with debridement, or antibiotics with debridement and instrumentation. However, compared with antibiotics alone, the crude inhospital mortality was lower for patients treated with instrumentation (odds ratio, OR, 0.82; P = 0.01), and antibiotics with debridement (OR 0.80; P = 0.02)., Conclusion: Spinal instrumentation in an infected spine is safe and not associated with higher reoperation or relapse rates. Mortality is lower for patients treated with instrumentation., Level of Evidence: 3.

Nasal type, extranodal nature killer (NK)/T cell lymphoma-associated hemophagocytic syndrome (NK/T-LAHS) is a rare and fatal disorder with extremely poor prognosis. To investigate its clinical characteristics and risk factors, we retrospectively analyzed 295 patients with nasal type, extranodal nature killer/T cell lymphoma, of which 21 were diagnosed with hemophagocytic syndrome, with a cumulative incidence of 7.1%. The most frequently clinical characteristics were fever, lymphadenopathy, hepatosplenomegaly, pancytopenia, hyperferritinemia, liver dysfunction, hypertriglyceridemia, hypofibrinogenemia and evaluated lactate dehydrogenase (LDH) level. After a median follow-up of 27 months, the 2-year survival for the 295 patients was 74.6%. Significant difference for 2-year survival was found between patients with and without hemophagocytic syndrome (4.8% vs. 80.0%, P<0.001). After developing hemophagocytic syndrome, all patients survived no more than 3 months, with a median survival of 35 days. Risk factors for NK/T-LAHS were bone marrow (BM) involvement (P = 0.019; relative risk, 13.649; 95% confidence interval (CI): 1.538-121.103), hepatosplenomegaly (P = 0.003; relative risk, 9.616; 95%CI: 2.154-42.918), and elevated LDH level (>314U/L) (P = 0.038; relative risk, 6.293; 95%CI: 1.108-35.735). We conducted a risk model for all 295 patients based on the 3 adverse factors as follows: low risk (233 cases, 79.0%), no factor; intermediate risk (43 cases, 14.6%), one factor; high risk (19 cases, 6.4%), 2 or 3 factors. The probabilities for developing LAHS were 0.9% for low-, 14.0% for intermediate-, and 68.4% for high-risk group. Significant differences in the 3 risk groups were observed (P<0.001).

Lipopolysaccharide (LPS) might affect the central nervous system by causing neuroinflammation, which subsequently leads to brain damage and dysfunction. In this study, we evaluated the role of nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome activation in long-term behavioral alterations of 8-week-old male C57BL/6 mice injected intraperitoneally with LPS (5mg/kg). At different time points after injection, we assessed locomotor function with a 24-point neurologic deficit scoring system and the rotarod test; assessed recognition memory with the novel object recognition test; and assessed emotional abnormality (anhedonia and behavioral despair) with the tail suspension test, forced swim test, and sucrose preference test. We also assessed protein expression of NLRP3, apoptosis-associated speck-like protein (ASC), and caspase-1 p10 in hippocampus by Western blotting; measured levels of interleukin (IL)-1β, IL-18, tumor necrosis factor α (TNFα), and IL-10 in hippocampus; measured TNFα and IL-1β in serum by ELISA; and evaluated microglial activity in hippocampus by Iba1 immunofluorescence. We found that LPS-injected mice displayed long-term depression-like behaviors and recognition memory deficit; elevated expression of NLRP3, ASC, and caspase-1 p10; increased levels of IL-1β, IL-18, and TNFα; decreased levels of IL-10; and increased microglial activation. These effects were blocked by the NLRP3 inflammasome inhibitor Ac-Tyr-Val-Ala-Asp-chloromethylketone. The results demonstrate proof of concept that NLRP3 inflammasome activation contributes to long-term behavioral alterations in LPS-exposed mice, probably through enhanced inflammation, and that NLRP3 inflammasome inhibition might alleviate peripheral and brain inflammation and thereby ameliorate long-term behavioral alterations in LPS-exposed mice., (Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.)

Solute carrier family 34 member 2 (SLC34A2), a pH-sensitive sodium-dependent phosphate transporter, is associated with several human cancers. In this study, we investigate the clinical significance of SLC34A2 and its function in human bladder cancer (BC). The expression dynamics of SLC34A2 were examined in two independent cohorts of BC samples by quantitative PCR, western blotting and immunohistochemical staining. In the training cohort (156 cases), we applied the X-tile program software to assess the optimal cutoff points for biomarkers in order to accurately classify patients according to clinical outcome. In the validation cohort (130 cases), the cutoff score derived from X-title analysis was investigated to determine the association of SLC34A2 expression with survival outcome. A series of in vitro and in vivo assays were then performed to elucidate the function of SLC34A2 in BC and its underlying mechanisms. Results showed that SLC34A2 was significantly upregulated in BC cell lines and clinical samples. In both two cohorts of BC samples, high expression of SLC34A2 was associated with large tumor size, advanced T status and poor patients' survival. The depletion of SLC34A2 in BC suppressed cellular viability, colony formation and anchorage-independent growth in vitro, and inhibited xenograft tumor growth in vivo, whereas overexpression of SLC34A2 had the converse effect. Simultaneously, downregulation of SLC34A2 decreased the transcriptional activity and protein expression level of c-Myc in BC cells, whereas restoration of c-Myc expression could compromise the anti-proliferation effect of SLC34A2 depletion. Furthermore, miR-214 was proved as a negative regulator of SLC34A2. Our present study illustrated that SLC34A2 has an important role in promoting proliferation and tumorigenicity of BC, and may represent a novel therapeutic target for this disease.

Background: The development of chemoresistance and metastasis are the leading causes of death for gastric cancer (GC) patients, however, the molecular mechanisms involved remain unclear. Dysregulation of miRNAs is associated with a variety of disease, including GC. Recently, microarray profiling analysis revealed that miR-939 was dysregulated in human GC samples, but the role of miR-939 in GC has not been intensively investigated., Methods: In the present study, we firstly examined the expression pattern of miR-939 in two independent cohorts of clinical GC samples: one cohort of 112 GC patients with stage I-III disease who underwent surgery followed by adjuvant chemotherapy; and another cohort of 110 GC patients with stage IV disease who received palliative chemotherapy. A series of in vivo and in vitro assays were then performed to investigate the function of miR-939 in GC., Results: We detected that reduced expression of miR-939 was associated with chemoresistance and increased risk of tumor recurrence in GC patients. Further function study demonstrated that overexpression of miR-939 suppressed GC cell growth, and enhanced 5-fluorouracil-induced chemosensitivity by compromising cellular growth and inducing apoptosis in vitro and in vivo. Moreover, miR-939 repressed the migration and invasion of GC cells in vitro, and diminished the occurrence of lung metastasis in vivo. We further identified solute carrier family 34 member 2 (SLC34A2) was a novel target of miR-939. Mechanistically, we elucidated that miR-939 exerted its function mainly through inhibiting SLC34A2/Raf/MEK/ERK pathway, which is activated in GC. Multivariate analysis identified miR-939, SLC34A2, and their combination as independent indicators for poor prognosis and tumor recurrence in GC patients., Conclusion: Our data indicate that miR-939 acts as a tumor suppressor miRNA in GC, and miR-939/SLC34A2 axis represents a novel therapeutic strategy for future GC treatment.

Purpose: We previously reported the oncogenic role of paired-like homeodomain 2 (PITX2) in esophageal squamous cell carcinoma (ESCC). In this study, we aimed to identify the miRNA regulators of PITX2 and the mechanism underlying the pathogenesis of ESCC., Experimental Design: Using miRNA profiling and bioinformatics analyses, we identified miR-644a as a negative mediator of PITX2 in ESCC. A series of in vivo and in vitro assays were performed to confirm the effect of miR-644a on PITX2-mediated ESCC malignancy., Results: ESCC cells and tissues expressed less miR-644a than normal epithelial controls. In patient samples, lower expression of miR-644a in ESCC tissues was significantly correlated with tumor recurrence and/or metastasis, such that miR-644a, PITX2, and the combination of the two were independent prognostic indicators for ESCC patient's survival (P < 0.05). Gain- and loss-of-function studies demonstrated that miR-644a inhibited ESCC cell growth, migration, and invasion in vitro and suppressed tumor growth and metastasis in vivo In addition, miR-644a dramatically suppressed self-renewal and stem cell-like traits in ESCC cells. Furthermore, the effect of upregulation of miR-644a was similar to that of PITX2 knockdown in ESCC cells. Mechanistic studies revealed that miR-644a attenuates ESCC cells' malignancy and stem cell-associated phenotype, at least partially, by inactivation of the Akt/GSK-3β/β-catenin signaling pathway through PITX2. Furthermore, promoter hypermethylation caused downregulation of miR-644a in ESCC., Conclusions: Downregulation of miR-644a plays an important role in promoting both aggressiveness and stem-like traits of ESCC cells, suggesting that miR-644a may be useful as a novel prognostic biomarker or therapeutic target for the disease. Clin Cancer Res; 23(1); 298-310. ©2016 AACR., (©2016 American Association for Cancer Research.)

B-cell activating factor (BAFF) plays important roles in a variety of lymphoid malignancies. Compared with healthy adults, patients with non-Hodgkin lymphoma had higher level of serum BAFF, and it corresponded with disease severity, response for therapy and clinical outcome. Latent membrane protein 1 (LMP1) encoded by Epstein-Barr virus (EBV) which is a known agent of nasal, extranodal NK/T cell lymphoma (ENKTCL) can switch the BAFF activating promoter leading to higher expression of BAFF in EBV-related tumor cells. However, the relationship between BAFF and ENKTCL has not been reported. Here we proposed a hypothesis that BAFF might play a regulatory role in ENKTCL development and maintenance. Our results showed that serum BAFF in ENKTCL patients was significantly higher than that in control group and negatively correlated with patients' survival. It may be a valuable prognostic factor and deserved further study., (Copyright © 2016. Published by Elsevier Ltd.)

Study Design: A retrospective study of 180 patients with lung cancer spinal metastases, wherein prognostic score-predicted survival was compared with actual survival., Objective: To evaluate and compare the accuracy of prognostic scoring systems in lung cancer spinal metastases., Summary of Background Data: The modified Tokuhashi, Tomita, modified Bauer, and Oswestry scores are currently used to guide decisions regarding operative treatment of patients with spinal metastases. The best system for predicting survival in patients with lung cancer spinal metastases remains undetermined. The high incidence of spinal metastases from lung cancer and improved survival of patients treated with systemic therapy warrants evaluation of these scoring systems in this particular context., Methods: Patients with lung cancer spinal metastases treated at our institution between May 2001 and August 2012 were studied. Fifty-one patients were treated surgically. The primary outcome measure was survival from the time of diagnosis. Scoring-predicted survival was compared with actual survival. Potential prognostic factors were investigated using Cox regression analyses. Predictive values of each scoring system for 3- and 6-month survival were measured via receiver operating characteristic (ROC) curves., Results: Histological subtype (P = 0.015), sex (P = 0.001), Karnofsky performance scale (P = 0.001), extent of neurological palsy (P = 0.002), and visceral metastases (P = 0.037) are significant predictors of survival. Besides the Oswestry spinal risk index, no significant differences were found between different prognostic subgroups within the individual scoring systems. Although the modified Bauer score was most accurate, all four scoring systems had areas under the ROC curve 0.5 or less., Conclusion: Although better prognostic scores correlated with longer survival, all four scoring systems are inaccurate in prognosticating patients with lung cancer spinal metastases. Specific lung cancer histology appears prognostic and should be considered, especially given the increased survival of patients receiving new targeted therapies appropriate to their disease., Level of Evidence: 3.

Guanine nucleotide binding protein (G protein), alpha 13 (GNA13) has been implicated as an oncogenic protein in several human cancers. In this study, GNA13 was characterized for its role in gastric cancer (GC) progression and underlying molecular mechanisms. The expression dynamics of GNA13 were examined by immunohistochemistry (IHC) in two independent cohorts of GC samples. A series of in-vivo and in-vitro assays was performed to elucidate the function of GNA13 in GC and its underlying mechanisms. In both two cohorts of GC samples, we observed that GNA13 was markedly overexpressed in GC tissues and associated closely with aggressive magnitude of GC progression and poor patients' survival. Further study showed that upregulation of GNA13 expression increased the proliferation and tumorigenicity of GC cells in vitro and in vivo, by promoting cell growth rate, colony formation, and tumor formation in nude mice. By contrast, knockdown of GNA13 effectively suppressed the proliferation and tumorigenicity of GC cells in vitro and in vivo. Our results also demonstrated that the molecular mechanisms of the effect of GNA13 in GC included promotion of G1/S cell cycle transition through upregulation of c-Myc, activation of AKT and ERK activity, suppression of FOXO1 activity, upregulation of cyclin-dependent kinase (CDK) regulator cyclin D1 and downregulation of CDK inhibitor p21Cip1 and p27Kip1. Our present study illustrated that GNA13 has an important role in promoting proliferation and tumorigenicity of GC, and may represent a novel prognostic biomarker and therapeutic target for this disease.

In this study, changes in eight GSTs mRNA level including GST-α, GST-σ, GST-ω, GST-π, GST-μ, GST-ρ, GST-θ and microsomal GST (mGST) in the oyster Crassostrea ariakensis after exposure to Prorocentrum lima have been evaluated by quantitative real-time PCR. Additionally, the contents of five GST isoforms were detected by ELISA. After exposure to P. lima at density of 2 × 10(5) cells/L, mGST mRNA significantly increased in gill, while GST-σ was induced in digestive gland. After exposure to P. lima at density of 2 × 10(6) cells/L, GST-ω and mGST expressions increased in gill, whereas GST-α and GST-σ were induced in digestive gland. The GST content and activity in oysters exposed to P. lima also showed a different pattern when the different isoforms and organs were compared. After exposure to P. lima (2 × 10(6) cell/L), GST-π increased in gill but decreased in digestive gland. The total GST enzyme activity increased in gill, while remained unchanged in digestive gland. These various regulation of GST gene expressions indicated that the GSTs isoenzymes might play divergent physiological roles in the detoxification of DSP toxins in C. ariakensis., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

This meta-analysis sets out to systematically assess the efficacy of short course radiation (SRT) for rectal cancer patients based on randomized, controlled trials. Eight randomized controlled trials involving 6894 patients were ultimately included in this meta-analysis. Three trials (n = 2574) compared SRT with surgery alone. Local recurrence was improved (HR = 0.48, 95% CI 0.40 to 0.58). Overall survival was marginally improved with an HR of 0.90 (95% CI 0.81 to 1.00), but the magnitude of benefit was heterogeneous across trials. An additional three trials (n = 3682) compared SRT with selective postoperative radiation ± chemotherapy. A significant reduction of local recurrence (HR = 0.44, 95% CI 0.35 to 0.56) was also found after SRT. However, no benefit in overall survival was observed. Moreover, two trials (n = 638) compared SRT with long course chemoradiation. There was no statistically significant local recurrence or overall survival difference observed between the two strategies. Patients receiving SRT had lower grade 3 or 4 acute treatment related toxicity (RR 0.11, 95% CI 0.05 to 0.22) whereas no difference in late toxicity was observed. Overall, SRT is a reasonable alternative for resectable rectal cancer patients and should be part of an informed discussion of treatment options for this group of patients.