Preconditioning-Induced Facilitation of Lactate Release from Astrocytes Is Essential for Brain Ischemic Tolerance.

A sublethal ischemic episode [termed preconditioning (PC)] protects neurons in the brain against a subsequent severe ischemic injury. This phenomenon is known as brain ischemic tolerance and has received much attention from researchers because of its robust neuroprotective effects. We have previously reported that PC activates astrocytes and subsequently upregulates P2X7 receptors, thereby leading to ischemic tolerance. However, the downstream signals of P2X7 receptors that are responsible for PC-induced ischemic tolerance remain unknown. Here, we show that PC-induced P2X7 receptor-mediated lactate release from astrocytes has an indispensable role in this event. Using a transient focal cerebral ischemia model caused by middle cerebral artery occlusion, extracellular lactate levels during severe ischemia were significantly increased in mice who experienced PC; this increase was dependent on P2X7 receptors. In addition, the intracerebroventricular injection of lactate protected against cerebral ischemic injury. In in vitro experiments, although stimulation of astrocytes with the P2X7 receptor agonist BzATP had no effect on the protein levels of monocarboxylate transporter (MCT) 1 and MCT4 (which are responsible for lactate release from astrocytes), BzATP induced the plasma membrane translocation of these MCTs via their chaperone CD147. Importantly, CD147 was increased in activated astrocytes after PC, and CD147-blocking antibody abolished the PC-induced facilitation of astrocytic lactate release and ischemic tolerance. Taken together, our findings suggest that astrocytes induce ischemic tolerance via P2X7 receptor-mediated lactate release.

Antimicrobial Resistance Patterns of Staphylococcus Aureus Isolated at a General Hospital in Vietnam Between 2014 and 2021.

Purpose: Staphylococcus aureus is a commensal bacteria species that can cause various illnesses, from mild skin infections to severe diseases, such as bacteremia. The distribution and antimicrobial resistance (AMR) pattern of S. aureus varies by population, time, geographic location, and hospital wards. In this study, we elucidated the epidemiology and AMR patterns of S. aureus isolated from a general hospital in Vietnam. Methods: This was a cross-sectional study. Data on all S. aureus infections from 2014 to 2021 were collected from the Microbiology department of Military Hospital 103, Vietnam. Only the first isolation from each kind of specimen from a particular patient was analyzed using the Cochran-Armitage and chi-square tests. Results: A total of 1130 individuals were diagnosed as S. aureus infection. Among them, 1087 strains were tested for AMR features. Most patients with S. aureus infection were in the age group of 41-65 years (39.82%). S. aureus isolates were predominant in the surgery wards, and pus specimens were the most common source of isolates (50.62%). S. aureus was most resistant to azithromycin (82.28%), erythromycin (82.82%), and clindamycin (82.32%) and least resistant to teicoplanin (0.0%), tigecycline (0.16%), quinupristin-dalfopristin (0.43%), linezolid (0.62%), and vancomycin (2.92%). Methicillin-resistant S. aureus (MRSA) and multidrug-resistant (MDR) S. aureus were prevalent, accounting for 73.02% and 60.90% of the total strains respectively, and the strains isolated from the intensive care unit (ICU) had the highest percentage of multidrug resistance (77.78%) among the wards. Conclusion: These findings highlight the urgent need for continuous AMR surveillance and updated treatment guidelines, particularly considering high resistance in MRSA, MDR strains, and ICU isolates. Future research focusing on specific resistant populations and potential intervention strategies is crucial to combat this rising threat.

Economic costs associated with unhealthy weight control behaviors among Australian adolescents.

OBJECTIVE: This study explored the relationship between unhealthy weight control behaviors (UWCBs) and their associated economic costs among adolescents using the 2014-2018 Longitudinal Study of Australian Children (LSAC). METHODS: LSAC data in Wave 6 (n = 3538 adolescents aged 14-15 years), Wave 7 n = 3089 adolescents aged 16-17 years), and Wave 8 (n = 3037 adolescents aged 18-19 years) were derived from a representative sample of Australian adolescents. UWCBs were measured using the self-reported Branched Eating Disorder Test questionnaire. UWCBs were sub-classified into having fasting behaviors, using weight loss supplements or purging behaviors. Economic costs include healthcare and productivity costs to caregivers. Healthcare costs were measured using data from the Medicare and Pharmaceutical Benefits, which includes both medical and pharmaceutical costs. Productivity losses were measured using caregivers' lost leisure time due to UWCBs among adolescents. RESULTS: The mixed effect model identified statistically significant higher economic costs (mean difference = $453, 95% CIs $154, $752), higher health care costs (mean difference = $399, 95% CIs $102, $695), and higher productivity costs (mean difference = $59, 95% CIs $29, $90) for adolescents with UWCBs compared to their peers with no UWCBs. Subgroup analysis revealed that higher costs were associated with fasting and purging behaviors. DISCUSSION: UWCBs were associated with increased economic costs during adolescence. Our finding suggests there should be a policy focus on tackling UWCBs to reduce the economic burden on the healthcare system and society. PUBLIC SIGNIFICANCE: The study contributes to existing knowledge by investigating the direct healthcare costs and productivity losses associated with unhealthy weight control behaviors in Australian adolescents (14-18 years old) using a dataset that follows Australian adolescents over time. We found that engaging in unhealthy weight control behaviors such as fasting, using weight loss supplements, and purging was linked to higher costs among adolescents, suggesting policies should focus on addressing these behaviors.

Characterisation of polycyclic aromatic hydrocarbons associated with indoor PM0.1 and PM2.5 in Hanoi and implications for health risks.

Polycyclic aromatic hydrocarbons (PAHs) associated with indoor PM pose a high risk to human health because of their toxicity. A total of 160 daily samples of indoor PM2.5 and PM0.1 were collected in Hanoi and analysed for 15 PAHs. In general, the concentrations of carcinogenic PAHs (car-PAHs) accounted for 21% ± 2%, 19.1% ± 2%, and 26% ± 3% of the concentrations of 15 PAHs in PM2.5, PM0.1-2.5, and PM0.1, respectively. Higher percentages of car-PAHs were found in smaller fractions (PM0.1), which can be easily deposited deep in the pulmonary regions of the human respiratory tract. The concentrations of 15 PAHs were higher in winter than in summer. The most abundant PAH species were naphthalene and phenanthrene, accounting for 11%-21% and 19%-23%, respectively. The PAH content in PM0.1 was almost twice as high as those in PM2.5 and PM0.1-2.5. Principal component analysis found that vehicle emissions and the combustion of biomass and coal were the main outdoor sources of PAHs, whereas indoor sources included cooking activities, the combustion of incense, scented candles, and domestic uses in houses. According to the results, 60%-90% of the PM0.1-bound BaP(eq) was deposited in the alveoli region, whereas 63%-75% of the PM2.5-bound BaP(eq) was deposited in head airways (HA), implying that most of the particles deposited in the HA region were PM0.1-2.5. The contributions of dibenz[a,h]anthracene and benzo[a]pyrene were dominant and contributed from 36% to 51% and 31%-50%, respectively, to the carcinogenic potential, whereas benzo[a]pyrene contributed from 30% to 49% to the mutagenic potential for both size fractions. The incremental lifetime cancer risk, simulated by Monte Carlo simulation, was within the limits set by the US EPA, indicating an acceptable risk for the occupants. These results provide an additional scientific basis for protecting human health from exposure to indoor PAHs.

Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer.

BACKGROUND: Neoadjuvant or adjuvant immunotherapy can improve outcomes in patients with resectable non-small-cell lung cancer (NSCLC). Perioperative regimens may combine benefits of both to improve long-term outcomes. METHODS: We randomly assigned patients with resectable NSCLC (stage II to IIIB [N2 node stage] according to the eighth edition of the AJCC Cancer Staging Manual) to receive platinum-based chemotherapy plus durvalumab or placebo administered intravenously every 3 weeks for 4 cycles before surgery, followed by adjuvant durvalumab or placebo intravenously every 4 weeks for 12 cycles. Randomization was stratified according to disease stage (II or III) and programmed death ligand 1 (PD-L1) expression (≥1% or <1%). Primary end points were event-free survival (defined as the time to the earliest occurrence of progressive disease that precluded surgery or prevented completion of surgery, disease recurrence [assessed in a blinded fashion by independent central review], or death from any cause) and pathological complete response (evaluated centrally). RESULTS: A total of 802 patients were randomly assigned to receive durvalumab (400 patients) or placebo (402 patients). The duration of event-free survival was significantly longer with durvalumab than with placebo; the stratified hazard ratio for disease progression, recurrence, or death was 0.68 (95% confidence interval [CI], 0.53 to 0.88; P = 0.004) at the first interim analysis. At the 12-month landmark analysis, event-free survival was observed in 73.4% of the patients who received durvalumab (95% CI, 67.9 to 78.1), as compared with 64.5% of the patients who received placebo (95% CI, 58.8 to 69.6). The incidence of pathological complete response was significantly greater with durvalumab than with placebo (17.2% vs. 4.3% at the final analysis; difference, 13.0 percentage points; 95% CI, 8.7 to 17.6; P<0.001 at interim analysis of data from 402 patients). Event-free survival and pathological complete response benefit were observed regardless of stage and PD-L1 expression. Adverse events of maximum grade 3 or 4 occurred in 42.4% of patients with durvalumab and in 43.2% with placebo. Data from 62 patients with documented EGFR or ALK alterations were excluded from the efficacy analyses in the modified intention-to-treat population. CONCLUSIONS: In patients with resectable NSCLC, perioperative durvalumab plus neoadjuvant chemotherapy was associated with significantly greater event-free survival and pathological complete response than neoadjuvant chemotherapy alone, with a safety profile that was consistent with the individual agents. (Funded by AstraZeneca; AEGEAN ClinicalTrials.gov number, NCT03800134.).

Ipilimumab plus nivolumab in patients with symptomatic melanoma brain metastasis requiring corticosteroids.

STUDY AIM: To investigate the efficacy of PD-1-directed antibody-based therapy in patients with symptomatic melanoma brain metastases (MBM) and concurrent treatment with corticosteroids. METHODS: This retrospective cohort study included patients with cutaneous melanoma with symptomatic MBM and concurrent treatment with corticosteroids who received PD-1-directed antibody-based treatment at the Royal Marsden Hospital London between 2016 and 2021. The primary outcome was overall survival (OS), secondary outcomes were intracranial response rate (ORR) and duration of response (DOR). We used the Kaplan-Meier method to describe survival. RESULTS: Between 2016 and 2021, 256 patients presented with metastatic melanoma, of whom 29 were eligible with symptomatic MBM requiring corticosteroids and receiving ipilimumab plus nivolumab. Median age was 54 (interquartile range 44, 66). Median OS was 5.45months (95% confidence interval (CI) 2.89, 29.40), with 21% of patients (95% CI 9%, 47%) alive after 3years. ORR was 28% (8/29) and DOR was 7.85months (95% CI 7.85, not estimably [NE]). Responding patients had a median OS of 56.4months (95% CI 46.03, NE). Elevated lactate dehydrogenase and Eastern Cooperative Oncology Group PS> 2 were associated with poorer outcomes (median OS 29.4 versus 3.12months and 6.44 versus 5.13months), no such association was observed for corticosteroid dose, number of lesions, or line of treatment. CONCLUSION: Patients with symptomatic MBM derive only modest benefit from combination immunotherapy treatment. Nevertheless, those with disease response have the potential to derive long-term benefit, justifying ipilimumab plus nivolumab in this group in the absence of other more effective treatment options.

Adverse drug reactions associated with immune checkpoint inhibitors: An exploratory nested case-control study in a historical cohort.

INTRODUCTION: Data on adverse drug reactions (ADRs) of immune checkpoint inhibitors (ICIs) used in oncology are mainly derived from clinical trials or cancer-specific reviews. We aim to analyze ADRs that occurred in patients treated with ICIs in real life. MATERIALS AND METHODS: We conducted an observational study on a historical cohort of the University Hospitals of Lyon. All patients who initiated an ICI treatment for any cancer in 2017 were included. Patients were followed from the first infusion until 90 days after the last one, death, date of last news or end of the study period (28 February 2019), whichever came first. Two pharmacovigilance specialists assessed the accountability and the severity of each ADR using Naranjo algorithm and common terminology criteria for adverse events (CTCAE) classification, respectively. RESULTS: 248 patients were included. They were treated with anti-PD-(L)-1, mainly nivolumab (70.6%) and pembrolizumab (25.8%). Lung cancer (62.1%) and melanoma (20.2%) were the most represented cancers. 139 ADRs occurred in 93 patients (37.5%), on average at the 6th cure (±6.8). ADRs mainly concerned skin (29.5%), endocrine (19.4%) and digestive (10.8%) systems. 17.3% of ADRs were grades III-V and two patients died because of ADRs. By comparing patients with (N=93) or without (N=155) ADRs, all characteristics appeared similar except for age, number of infusions received and death status. The spontaneous notification rate found in this study was 5.8% for all grade ADRs (N = 8) but raised to 23.8% when only grades higher than III were considered (N = 5). DISCUSSION/CONCLUSION: Our results are consistent with literature data in frequency and type of serious ADRs. We found a lower frequency of ADRs of any grade, which could be explained by a fairer causality assessment in our study than in clinical trials.

Silymarin-Functionalized Selenium Nanoparticles Prevent LPS-Induced Inflammatory Response in RAW264.7 Cells through Downregulation of the PI3K/Akt/NF-κB Pathway.

Silymarin exhibits an anti-inflammatory property in various cancers and inflammatory diseases. In our previous work, silymarin-mediated selenium nanoparticles (SeNPs) (Si-SeNPs) were developed using a green synthesis technique, and its potential as an anticancer agent was confirmed. In order to further examine the extended comprehensive potential of Si-SeNPs, this investigation focuses on studying the enhanced anti-inflammatory effect of Si-SeNPs in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Enzyme-linked immunosorbent assay and quantitative reverse transcription-polymerase chain reaction were used to evaluate the expression of pro-inflammatory mediators and cytokines. Western blotting and immunofluorescence assays were conducted to assess the protein expression of p-PI3K, p-Akt, p-NF-κB, and p-IκBα. Compared to silymarin, Si-SeNPs exhibited a significantly increased inhibitory effect on LPS-induced release of nitric oxide and the expression of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin 1ß (IL-1ß) in RAW264.7 cells. A western blot assay indicated that Si-SeNPs downregulated the PI3K/Akt and NF-κB signaling pathways. The immunofluorescence assay suggested that Si-SeNPs inhibited the nuclear translocation and the activation of NF-κB. In addition, 740 Y-P (PI3K agonist) was used to demonstrate that activating the PI3K/Akt signal could partially reverse the inflammatory response, suggesting a causal role of the PI3K/Akt signaling pathway in the anti-inflammatory effect of Si-SeNPs. Consequently, these findings indicate that Si-SeNPs could be a functional agent of the attenuation of LPS-induced inflammatory responses in RAW264.7 macrophages through inhibiting the PI3K/Akt/NF-κB signaling pathway. In addition, biosynthesized Si-SeNPs could be more effective at reducing inflammation than only silymarin extracts. Thus, this study lays an experimental foundation for the clinical application of using biosynthesized SeNPs as a novel candidate in the field of inflammation-associated diseases.

Differential hemodynamics between arteriovenous fistulas with or without intervention before successful use.

A significant number of arteriovenous fistulas (AVFs) fail to maturate for dialysis. Although interventions promote maturation, functional primary patency loss is higher for AVFs with interventions (assisted maturation) than AVFs without interventions (un-assisted maturation). Although blood flow-associated hemodynamics have long been proposed to affect AVF remodeling, the optimal hemodynamic parameters for un-assisted maturation are unclear. Additionally, AVF maturation progress is generally not investigated until 6 weeks after AVF creation, and the examination is focused on the AVF's venous limb. In this exploratory study, patients (n = 6) underwent magnetic resonance imaging (MRI) at 1 day, 6 weeks, and 6 months after AVF creation surgery. Before successful use for hemodialysis, three AVFs required intervention and three did not. MRI of the AVFs were used to calculate lumen cross-sectional area (CSA) and perform computational fluid dynamics (CFD) to analyze hemodynamics, including velocity, wall shear stress (WSS), and vorticity. For the venous limb, the no-intervention group and intervention group had similar pre-surgery vein diameter and 1-day post-surgery venous CSA. However, the no-intervention group had statistically larger 1-day venous velocity (0.97 ± 0.67 m/s; mean ± SD), WSS (333 ± 336 dyne/cm2) and vorticity (1709 ± 1290 1/s) than the intervention group (velocity = 0.23 ± 0.10 m/s; WSS = 49 ± 40 dyne/cm2; vorticity = 493.1 ± 227 1/s) (P < 0.05). At 6 months, the no-intervention group had statistically larger venous CSA (43.5 ± 27.4 mm2) than the intervention group (15.1 ± 6.2 mm2) (P < 0.05). Regarding the arterial limb, no-intervention AVF arteries also had statistically larger 1-day velocity (1.17 ± 1.0 m/s), WSS (340 ± 423 dyne/cm2), vorticity (1787 ± 1694 1/s), and 6-month CSA (22.6 ± 22.7 mm2) than the intervention group (velocity = 0.64 ± 0.36 m/s; WSS = 104 ± 116 dyne/cm2, P < 0.05; vorticity = 867 ± 4551/s; CSA = 10.7 ± 6.0 mm2, P < 0.05). Larger venous velocity, WSS, and vorticity immediately after AVF creation surgery may be important for later lumen enlargement and AVF maturation, with the potential to be used as a tool to help diagnose poor AVF maturation earlier. However, future studies using a larger cohort are needed to validate this finding and determine cut off values, if any.

Urinary neutrophil gelatinase-associated lipocalin predicted to contrast-associated acute kidney injury after planned percutaneous coronary intervention in elderly patients.

AIM: To determine the proportion of contrast-associated acute kidney injury (CA-AKI) after percutaneous coronary intervention (PCI) and the predictive value of urine neutrophil gelatinase-associated lipocalin (uNGAL) for CA-AKI in elderly patients with chronic coronary artery disease. METHODS: A total of 509 patients who had planned percutaneous coronary intervention (mean age was 63.58 ± 11.63 years and 63.3% of males) were divided into two groups: group 1 (n = 153; elderly patients) with ≥70 years old and group 2 (n = 356) with <70 years old. Urine NGAL was measured by the ELISA method. Clinical and laboratory data were collected on the day before intervention. CA-AKI was defined based on Kidney Disease: Improving Global Outcomes criteria. RESULTS: The ratio of CA-AKI in group 1 was 23.5% which was higher than that of group 2 (8.7%) with a p-value < 0.001. Urine NGAL level in group 1 was significantly higher than that of group 2 [31.3 (19.16-55.13) ng/ml vs. 19.86 (13.21-29.04) ng/ml, p < 0.001]. At a cut-off value of 44.43 ng/ml, uNGAL had a predictive value for CA-AKI in all patients (AUC = 0.977, p < 0.001). Especially at a cut-off value of 44.14 ng/ml, uNGAL had a predictive value for CA-AKI in elderly patients (AUC = 0.979, p < 0.001). CONCLUSIONS: The rate of CA-AKI after PCI in elderly patients was 23.5%. Urine NGAL before PCI had a good predictive value for CA-AKI in elderly patients with chronic coronary artery disease.

All-inside arthroscopic anterior cruciate ligament reconstruction with internal brace Ligament Augmentation using semitendinosus tendon autograft: A case series.

Introduction and importance: Anterior Cruciate Ligament (ACL) reconstruction surgery has been proven to be closely related to the graft healing process, which can last up to 12 months after surgery. In recent years, through various biomechanical and clinical studies, Internal Brace Ligament Augmentation (IBLA) has been shown to protect the graft during these early postoperative stages and improve the outcome of ACL reconstruction. We present this case series of all-inside arthroscopic anterior cruciate ligament reconstruction with IBLA using semitendinosus tendon autografts, with the goal of evaluating postoperative clinical and patient-reported outcomes. Case presentation: A total of 37 patients who underwent all-inside arthroscopic anterior cruciate ligament reconstruction with IBLA using only semitendinosus tendon autografts, were evaluated, in terms of patient reported outcome and clinical assessment, during the 3, 6 and 12 months post-operative follow-up. Results: The mean Lysholm Knee score at the final follow-up was 94,03 +- 3,65 with a difference of 34,59 +- 5,52 to the baseline level. International Knee Documentation Committee (IKDC) classification rated 30 cases of grade A and 7 cases of grade B. In terms of clinical tests and knee's range of motion, all patients have returned to normal, and no cases of re-rupture or other severe complications were found. Clinical discussion: Early follow-up patient reported outcomes have provided good to great results for the 37 patients who underwent all-inside arthroscopic anterior cruciate ligament reconstruction with IBLA using semitendinosus tendon autografts and no cases of graft failure or other notable complication has been discovered. Clinical findings suggest improved knee's integrity and range of movement during the early stages, which may promote early rehabilitation, however future long-term comparative studies are needed. Conclusion: IBLA with all-inside ACL reconstructions using only semitendinosus autograft has provided good to great results however, future long-term comparative studies are needed.

Effect of Photobiomodulation Therapy on Reducing Acute Pain and Inflammation Following Surgical Removal of Impacted Mandibular Third Molars: A Randomized, Split-Mouth Clinical Trial.

Objective: This study aimed to compare the effects of photobiomodulation therapy (PBMT) on analgesic and inflammatory reduction with that of ibuprofen following surgical removal of impacted mandibular third molars (IMTMs). Methods: A randomized, split-mouth clinical trial was performed on patients undergoing bilateral IMTM removal. PBMT [gallium aluminum arsenide (GaAlAs) laser] with specific parameters (wavelength of 810 nm, power of 0.5% ± 20% W, and energy density of 4 J/cm2) was applied randomly on one side of the mouth immediately after surgery and 1 and 2 days after surgery. The pain level was self-rated with a Likert scale at 2, 4, 6, 24, and 48 h postoperatively. Swelling and trismus were measured on the first and second day after surgery. Saliva was collected for measuring pre- and postoperative salivary immunoglobulin A (sIgA) concentrations with the sandwich ELISA test. Results: The study sample included 25 patients (average age of 22.88 years) with 50 bilateral symmetrical IMTMs. Pain level was highest at 2 h after surgery in both groups and gradually decreased over time (p < 0.01). Swelling and trismus at 48 h were higher than at 24 h (p < 0.01). Within the first 48 h postoperatively, pain level, swelling, and trismus were significantly lower in the PBMT group (p < 0.05). Postoperative sIgA was also significantly lower in the PBMT group (p < 0.05). Conclusions: In short-term and specific conditions of this study, it was found that PBMT helped promote postoperative pain relief and anti-inflammation after surgical removal of IMTMs. The results suggested that there may be a link between a decrease in salivary sIgA levels and decrease in inflammatory processes after PBMT. Trial Registration No. NCT04280809 at ClinicalTrials.gov.

Prevalence and Determinants of Vaginal Infection With Human Papillomavirus Among Female University Students in Vietnam.

BACKGROUND/AIM: Cervical cancer is the second most common malignancy among women in Vietnam, but the country is yet to introduce a national human papillomavirus (HPV) vaccine programme targeted at adolescents. We determined HPV prevalence and HPV vaccine knowledge among female university students in Vietnam. PATIENTS AND METHODS: We surveyed and screened 1,491 female university students in Hanoi, Hue, and Ho Chi Minh City for their sexual behaviours, HPV knowledge and low- and high-risk HPV infection. RESULTS: The prevalence of any HPV infection and any high-risk HPV infection were 4.2% (95%CI=3.3%-5.4%) and 3.4% (95%CI=2.5%-4.4%), respectively. Being sexually active [adjusted prevalence ratio (aPR): 6.22; 95%CI=3.4-11.37] and having ever been pregnant (aPR: 4.82; 95%CI=1.93-12.04) were positively associated with high-risk HPV infection. Whilst 60% of participants had heard of HPV vaccine, only 4.6% had received the vaccine. CONCLUSION: The low HPV prevalence found in university students in Vietnam indicates that they can benefit from HPV vaccination, along with a well-designed HPV health promotion programme.

Prevalence and risk factors for human papillomavirus infection among female sex workers in Hanoi and Ho Chi Minh City, Viet Nam: a cross-sectional study.

Objective: Female sex workers (FSWs) are at high risk of human papillomavirus (HPV) infections and cervical cancer due to their high number of sexual partners. The objectives of this study were to determine the prevalence of HPV and identify risk factors for high-risk HPV infection among FSWs in Hanoi and Ho Chi Minh City (HCMC), Viet Nam. Methods: A cross-sectional study was conducted in Hanoi and HCMC between December 2017 and May 2018. We surveyed and screened 699 FSWs aged 318 years for HPV infection and abnormal cytology. A multivariable modified Cox regression model was used to determine risk factors for high-risk HPV infection. Results: The overall prevalence of any HPV, high-risk HPV and HPV-16/18 infection in the 699 FSWs was 26.3%, 17.6% and 4.0%, respectively, and were similar in both cities. Multiple infections were identified in 127 participants (69.0%). HPV-52 was the most prevalent (7%), followed by HPV-58 (6%). Abnormal cytology was detected in 91 participants (13.0%). FSWs who are divorced (adjusted prevalence ratio [aPR]: 1.96, 95% confidence interval [CI]: 1.01-3.81), widowed (aPR: 3.26, 95% CI: 1.49-7.12) or living alone (aPR: 1.85, 95% CI: 1.01-3.39) were associated with a higher prevalence of high-risk HPV infection. Discussion: Almost one in five FSWs in Viet Nam are infected with high-risk HPV. This highlights the importance of prevention strategies such as HPV vaccination and screening in this high-risk group.

Anal human papillomavirus prevalence and risk factors among men who have sex with men in Vietnam.

OBJECTIVES: Men who have sex with men (MSM) are at risk of human papillomavirus (HPV)-related cancers, while published data are scarce. This study determined HPV prevalence and risk factors in MSM in Vietnam to inform HPV prevention strategies in this key population. METHODS: A cross-sectional study of 799 MSM aged 16-50 years was conducted in Vietnam in 2017-2018. Information was collected on risk behaviours, and knowledge of HPV and anal cancer; rectal swabs were taken to detect anal HPV infection. An in-house polymerase chain reaction and Genoflow HPV array test kit were used for HPV detection and genotyping. RESULTS: The median age of the study participants was 25 years (range 18-52). Overall prevalence of any HPV and HPV16/18 infection was 32.3% and 11.0%, respectively. A higher prevalence of high-risk HPV infection to all 14 types tested was found in Ho Chi Minh City (30.9%) than in Hanoi (18.4%). High-risk HPV infection was associated with inconsistent condom use and history of engaging in sex under the influence of drugs (adjusted odds ratio (aOR), 2.27; 95% CI, 1.48-10.67), as well as having multiple sexual partners (aOR, 1.01; 95% CI, 1.00-1.02). CONCLUSIONS: High-risk anal HPV infections in Vietnamese MSM were significantly associated with risky sexual behaviours. A targeted HPV vaccination strategy would have substantial benefit for MSM in Vietnam.

Liquid biopsy uncovers distinct patterns of DNA methylation and copy number changes in NSCLC patients with different EGFR-TKI resistant mutations.

Targeted therapy with tyrosine kinase inhibitors (TKI) provides survival benefits to a majority of patients with non-small cell lung cancer (NSCLC). However, resistance to TKI almost always develops after treatment. Although genetic and epigenetic alterations have each been shown to drive resistance to TKI in cell line models, clinical evidence for their contribution in the acquisition of resistance remains limited. Here, we employed liquid biopsy for simultaneous analysis of genetic and epigenetic changes in 122 Vietnamese NSCLC patients undergoing TKI therapy and displaying acquired resistance. We detected multiple profiles of resistance mutations in 51 patients (41.8%). Of those, genetic alterations in EGFR, particularly EGFR amplification (n = 6), showed pronounced genome instability and genome-wide hypomethylation. Interestingly, the level of hypomethylation was associated with the duration of response to TKI treatment. We also detected hypermethylation in regulatory regions of Homeobox genes which are known to be involved in tumor differentiation. In contrast, such changes were not observed in cases with MET (n = 4) and HER2 (n = 4) amplification. Thus, our study showed that liquid biopsy could provide important insights into the heterogeneity of TKI resistance mechanisms in NSCLC patients, providing essential information for prediction of resistance and selection of subsequent treatment.

Association between the school physical activity environment, measured and self-reported student physical activity and active transport behaviours in Victoria, Australia.

BACKGROUND: Environments within schools including the physical, social-cultural and policy/practice environments have the potential to influence children's physical activity (PA) behaviours and weight status. This Australian first study comprehensively examined the association(s) of physical, social-cultural and policy/practice environments with PA, active transport (AT) and weight status among regional primary school children. METHODS: Data were from two childhood obesity monitoring systems in regional Victoria, Australia. Measured height and weight were collected from students in Year 2 (aged approx. 7-8 years), Year 4 (9-10 years), and Year 6 (11-12 years). Self-reported PA behaviour, including AT were collected from students in Year 4 and 6 and a sub-sample wore an ActiGraph (wGT3X-BT) accelerometer for 7-days. A school physical activity environment audit was completed by the school principal and responses were used to calculate school physical activity environment scores (PAES) and active transport environment scores (ATES). Mixed effects logistic regression was used to assess the relationship between the proportion of students meeting the PA guidelines (≥60mins/day of moderate-to-vigorous PA) and PAES tertiles (low, medium, high) and those using AT and school ATES tertiles, controlling for gender, school size/type and socioeconomic composition. RESULTS: The analysed sample included 54/146 (37%) schools and 3360/5376 (64%) students. In stratified analysis, girls in schools with a medium PAES score were more likely to meet the objectively measured PA guideline compared to low PAES score (OR 2.3, 95%CI 1.27, 4.16). Similarly, students in schools with a medium or high ATES score had higher odds of self-reported AT (medium OR 3.15, 95%CI 1.67, 5.94; high OR 3.71, 95%CI: 1.80, 7.64). No association between PAES or ATES and weight status were observed. Self-reported AT among boys (OR 1.59, 95%CI 1.19, 2.13) and girls (OR 1.56, 95%CI 1.08, 2.27) was associated with higher odds of meeting self-reported PA guidelines on all 7-days than those who did not report using AT. CONCLUSIONS: In this study of regional Victorian primary schools, PA environments were only associated with girls' adherence to PA guidelines. School AT environments were strongly associated with students' AT behaviours and with increased likelihood of students being physically active.

Eccrine Porocarcinoma: A Challenging Diagnostic and Therapeutic Tumoral Entity.

Eccrine porocarcinoma is a rare malignant cutaneous tumor with high rates of extracutaneous spread, and its diagnosis and management can be quite challenging. This is a case of an 82-year-old woman presenting with an asymptomatic and chronic pubic skin lesion for whom the work-up required many investigations and procedures to confirm the diagnosis of metastatic eccrine porocarcinoma. Indeed, the patient underwent a wide local excision of the skin lesion, imaging with an FDG-PET scan, a colonoscopy, and two inguinal node dissections. As illustrated in this case, surgery should always be considered to achieve disease remission. Other treatments such as chemotherapy and radiotherapy have also been reported in the literature without clear standard guidelines.

Comparison of the Quality of Life of Patients with Breast or Colon Cancer with an Arm Vein Port (TIVAD) Versus a Peripherally Inserted Central Catheter (PICC).

INTRODUCTION: Venous access is a crucial element in chemotherapy delivery. It remains unclear whether cancer patients prefer a port to a peripherally inserted central catheter (PICC). Our study aimed to assess cancer patients' satisfaction with their venous access device and to compare the quality of life (QoL) of subjects with a PICC to those with a port. METHODS: In this prospective cohort study, EORTC QLQ-C30, and a locally developed quality of life survey (QLAVD), designed to assess satisfaction with venous access devices, were administered to breast or colorectal cancer patients over a one-year period following the device insertion. Mixed effects models were used to assess changes on mean scores at different time points. RESULTS: A total of 101 patients were recruited over a three-year period, (PICC group, n = 50; port group, n = 51). Survey response rates for months one and three were 72% and 48%, respectively. Overall, no significant differences were noted between the two groups in relation to EORTC QOL. At three months, the mean pain scores were 3.5 ± 2.3 for the port and 1.3 ± 0.75 for PICC (<0.001). The mean score for a negative effect of the venous access device on psychosocial well-being was 6.0 ± 4.1 for PICC and 3.0 ± 2.7 for the port (p = 0.005). Complications related to PICCs occurred in 38% patients versus 41% with a port (p > 0.24). CONCLUSIONS: Although subjects with a port experienced more pain during the device insertion or access for chemotherapy, it had a smaller negative impact on psychosocial scores than the PICC. No significant differences in complications rates were observed between the two devices.

The historic oil price fluctuation during the Covid-19 pandemic: What are the causes?

On 20 April 2020, the West Texas Intermediate (WTI) crude oil price dropped to negative levels for the first time in history. This study examines the factors underlying the historic oil price fluctuation during the Covid-19 pandemic. The autoregressive distributed lag (ARDL) bounds testing approach incorporating a structural break is applied to the daily series from 17 January to 14 September 2020 to analyze long-run relationships and short-run dynamics. The results reveal that increases in Covid-19 pandemic cases, US economic policy uncertainty, and expected stock market volatility contributed to the fall in the WTI crude oil price, whereas the fall in the global stock markets appears to significantly reduce the fall. Furthermore, the Russia-Saudi Arabia oil price war and speculation on oil futures are shown to play a critical part in the collapse of the oil markets. The findings are consistent with our expectations. Although it is reasonable to assume that the solution to this oil crisis is a pick-up in global oil demand, which will occur only when the novel coronavirus is defeated, this study proposes policy recommendations to cope with the current oil price crash.