Reaching the unreached through building trust: a mixed-method study on COVID-19 vaccination in rural Lao PDR.

INTRODUCTION: The global COVID-19 vaccine rollout has been impacted by socioeconomic disparities and vaccine hesitancy, but few studies examine reasons for changed attitudes. In Lao People's Democratic Republic (Lao PDR), a nationwide government-led initiative was developed in response to COVID-19, focused on community health ownership and trust in primary healthcare. The intervention team including health and governance sectors conducted capacity-building workshops with local staff and community representatives and visited villages for vaccination outreach. This study investigates the impact of this intervention on COVID-19 vaccine acceptance in rural communities. METHODS: Conducted in Xiengkhuang province, Lao PDR, from December 2022 to February 2023, the study employed a sequential mixed-methods research design. Data on vaccinated individuals from 25 villages were collected from 11 primary healthcare units; pre-post analysis was applied. Qualitative data, gathered through interviews and focus group discussions with villagers, village authorities, health staff and local government (n=102) in six villages, underwent inductive thematic analysis. RESULTS: First-dose vaccine uptake after the intervention increased significantly (6.9 times). Qualitative analysis identified key reasons for vaccination hesitancy: (1) mistrust due to rumours and past experiences; (2) poor communication and inconsistent messaging and (3) challenges in access for priority groups. Influencing factors during the intervention included (1) effective local-context communication; (2) leveraging existing community structures and influential individuals in a multisectoral approach and (3) increased community motivation through improved satisfaction, ownership and relationships. CONCLUSION: This study highlights the impact and methods of building trust with unreached populations in health interventions, emphasising locally led solutions. Successful reversal of vaccine hesitancy was achieved by addressing root causes and fostering ownership at community and local government levels through a 'positive approach'. This diverges from conventional supplemental immunisation activities and holds potential for systematically building trust between unreached populations and health systems. Further research could explore the impacts of routine vaccination for sustained improvements in health equity.

Venous thromboembolism among Asian populations with localized colorectal cancer undergoing curative resection: is pharmacological thromboprophylaxis required? A systematic review and meta-analysis.

PURPOSE: We compared the incidence of venous thromboembolism (VTE) among Asian populations with localized colorectal cancer undergoing curative resection with and without the use of pharmacological thromboprophylaxis (PTP). METHODS: A comprehensive literature search was undertaken to identify relevant studies published from January 1, 1980 to February 28, 2022. The inclusion criteria were patients who underwent primary tumor resection for localized nonmetastatic colorectal cancer; an Asian population or studies conducted in an Asian country; randomized controlled trials, case-control studies, or cohort studies; and the incidence of symptomatic VTE, deep vein thrombosis, and/or pulmonary embolism as the primary study outcomes. Data were pooled using a random-effects model. This study was registered in PROSPERO on October 11, 2020 (No. CRD42020206793). RESULTS: Seven studies (2 randomized controlled trials and 5 observational cohort studies) were included, encompassing 5,302 patients. The overall incidence of VTE was 1.4%. The use of PTP did not significantly reduce overall VTE incidence: 1.1% (95% confidence interval [CI], 0%-3.1%) versus 1.9% (95% CI, 0.3%-4.4%; P = 0.55). Similarly, PTP was not associated with significantly lower rates of symptomatic VTE, proximal deep vein thrombosis, or pulmonary embolism. CONCLUSION: The benefit of PTP in reducing VTE incidence among Asian patients undergoing curative resection for localized colorectal cancer has not been clearly established. The decision to administer PTP should be evaluated on a case-bycase basis and with consideration of associated bleeding risks.

A measles IgM rapid diagnostic test to address challenges with national measles surveillance and response in Malaysia.

INTRODUCTION: A lateral flow rapid diagnostic test (RDT) enables detection of measles specific immunoglobulin M (IgM) antibody in serum, capillary blood, and oral fluid with accuracy consistent with enzyme immunoassay (EIA). The objectives of the study were: 1) to assess measles RDT inter-reader agreement between two clinic staff; 2) to assess the sensitivity and specificity of the measles RDT relative to standard surveillance testing in a low transmission setting; 3) to evaluate the knowledge, attitudes, and practices of staff in clinics using the RDT; and 4) to assess the impact of RDT testing on the measles public health response in Malaysia. MATERIALS AND METHODS: The clinic-based prospective evaluation included all suspected measles cases captured by routine measles surveillance at 34 purposely selected clinics in 15 health districts in Malaysia between September 2019 and June 2020, following day-long regional trainings on RDT use. Following informed consent, four specimens were collected from each suspected case, including those routinely collected for standard surveillance [serum for EIA and throat swabs for quantitative reverse transcriptase polymerase chain reaction (RT-qPCR)] together with capillary blood and oral fluid tested with RDTs during the study. RDT impact was evaluated by comparing the rapidity of measles public health response between the pre-RDT implementation (December 2018 to August 2019) and RDT implementation periods (September 2019 to June 2020). To assess knowledge, attitudes, and practices of RDT use, staff involved in the public health management of measles at the selected sites were surveyed. RESULTS: Among the 436 suspect cases, agreement of direct visual readings of measles RDT devices between two health clinic staff was 99% for capillary blood (k = 0.94) and 97% for oral fluid (k = 0.90) specimens. Of the total, 45 (10%) were positive by measles IgM EIA (n = 44, including five also positive by RT-qPCR) or RT-qPCR only (n = 1), and 38 were positive by RDT (using either capillary blood or oral fluid). Using measles IgM EIA or RT-qPCR as reference, RDT sensitivity using capillary blood was 43% (95% CI: 30%-58%) and specificity was 98% (95% CI: 96%-99%); using oral fluid, sensitivity (26%, 95% CI: 15%-40%) and specificity (97%, 95% CI: 94%-98%) were lower. Nine months after training, RDT knowledge was high among staff involved with the public health management of measles (average quiz score of 80%) and was highest among those who received formal training (88%), followed by those trained during supervisory visits (83%). During the RDT implementation period, the number of days from case confirmation until initiation of public response decreased by about 5 days. CONCLUSION: The measles IgM RDT shows >95% inter-reader agreement, high retention of RDT knowledge, and a more rapid public health response. However, despite ≥95% RDT specificity using capillary blood or oral fluid, RDT sensitivity was <45%. Higher-powered studies using highly specific IgM assays and systematic RT-qPCR for case confirmation are needed to establish the role of RDT in measles elimination settings.

MiR-181a protects the heart against myocardial infarction by regulating mitochondrial fission via targeting programmed cell death protein 4.

Worldwide, myocardial infarction (MI) is the leading cause of death and disability-adjusted life years lost. Recent researches explored new methods of detecting biomarkers that can predict the risk of developing myocardial infarction, which includes identifying genetic markers associated with increased risk. We induced myocardial infarction in mice by occluding the left anterior descending coronary artery and performed TTC staining to assess cell death. Next, we performed ChIP assays to measure the enrichment of histone modifications at the promoter regions of key genes involved in mitochondrial fission. We used qPCR and western blot to measure expression levels of relative apoptotic indicators. We report that miR-181a inhibits myocardial ischemia-induced apoptosis and preserves left ventricular function after MI. We show that programmed cell death protein 4 (PDCD4) is the target gene involved in miR-181a-mediated anti-ischemic injury, which enhanced BID recruitment to the mitochondria. In addition, we discovered that p53 inhibits the expression of miR-181a via transcriptional regulation. Here, we discovered for the first time a mitochondrial fission and apoptosis pathway which is controlled by miR-181a and involves PDCD4 and BID. This pathway may be controlled by p53 transcriptionally, and we presume that miR-181a may lead to the discovery of new therapeutic and preventive targets for ischemic heart diseases.

A nonsymmetrical salamo-like fluorescence chemical sensor for selective identification of Cu2+ and B4O72- ions and practical applications.

An innovative salamo-like fluorescent chemical sensor H2L, has been prepared that can be utilized to selectively detect Cu2+ and B4O72- ions. Cu2+ ions can bind to oxime state nitrogen and phenol state oxygen atoms in the chemosensor H2L, triggering the LMCT effect leading to fluorescence enhancement. The crystal structure of the copper(II) complex, named as [Cu(L)], has been achieved via X-ray crystallography, and the sensing mechanism has been confirmed by further theoretical calculations with DFT. Besides, the sensor H2L recognizes B4O72- ions causing an ICT effect resulting in bright blue fluorescence. Moreover, the sensor has relatively high selectivity and sensitivity for Cu2+ and B4O72- ions, and the detection limits are 1.02 × 10-7 and 2.06 × 10-7 M, respectively. In addition, the good biocompatibility and excellent water solubility of the sensor H2L make it very advantageous in practical applications, using H2L powder for fingerprint visualization, using H2L to identify the phenomenon of B4O72- ions emitting bright blue fluorescence, making it an ink that can print encrypted messages on A4 paper, in addition to this, based on H2L, the real water sample was tested for Cu2+ ion recognition, and finally the test strip experiment was carried out.

Evaluation of the awareness of Western Australian SunSmart campaigns between 2008 and 2022.

ISSUE ADDRESSED: It is unknown whether SunSmart health promotion campaigns in Western Australia are still effectively reaching their target audience of young people (under 45 years). This study examined trends over time in awareness, relevancy and believability of SunSmart advertisements and identified socio-demographic characteristics and risk factors associated with campaign awareness. METHOD: Linear regression and log-binomial modelling were undertaken using data from the annual SunSmart post-campaign evaluation surveys between 2008/2009 and 2021/2022. SunSmart campaigns were analysed and categorised into the following themes: (1) personal real-life stories; (2) daily activities/sun exposure leads to skin cancer; or (3) cartoon/animated. RESULTS: Between 2008 and 2022, there were declines in total awareness (74.2% to 20.4%), unprompted awareness (33.7% to 4.9%) and relevancy (89.5% to 54.8%) of SunSmart advertisements (representing annual percent decreases of 3.6%, 3.1% and 1.8%, respectively). However, believability remained high over time (>94% in each annual survey). Trends were inconsistent between the awareness of campaign themes and socio-demographic characteristics and risk factors. Several campaigns had greater awareness in their subsequent years, compared with the first campaign year. CONCLUSION: In more recent years, SunSmart advertisements and campaigns may not have reached their target audience. In addition to socio-demographic characteristics, particularly age, advertisement factors may also affect the awareness of specific campaigns. SO WHAT?: Given the changing advertising landscape and its rising costs, ongoing funding is pertinent to increase the reach of future SunSmart campaigns. Increasing advertisements on alternative platforms and designing campaigns which separately target adolescents and adults need to be considered.

Nurses' knowledge of and attitude toward postoperative patient-controlled analgesia (PCA) and the associated factors.

BACKGROUND: Postoperative pain control is pivotal for surgical care; it facilitates patient recovery. Although patient-controlled analgesia (PCA) has been available for decades, inadequate pain control remains. Nurses' knowledge of and attitude toward PCA may influence the efficacy on clinic application. PURPOSE: The purpose of this study is to evaluate nurses' knowledge of and attitude toward postoperative PCA and investigate the associated factors. METHODS: This is a cross-sectional study. We enrolled registered nurses from a 2200-bed medical center in northern Taiwan within one year. The participants completed an anonymous self-reported PCA knowledge inventory and PCA attitude inventory. Data were analyzed descriptively and associated were tested using logistic regression. RESULTS: With 303 participants enrolled, we discovered that nurses had limited knowledge of and a negative attitude toward PCA. Under half of the participants know how to set up a bolus dose and lockout intervals. The majority held misconceptions regarding side effect management for opioids. The minority agree to increase the dose when a patient experienced persistent pain or suggested the use of PCA. Surprisingly, participants with a bachelor's or master's degree had lower knowledge scores than those with a junior college degree. Those with 6-10 years of work experience also are lower than those with under 5 years of experience. However, the participants with experience of using PCA for patient care had higher knowledge scores and a more positive attitude. CONCLUSIONS: Although postoperative PCA has been available for decades and education programs are routinely provided, nurses had limited knowledge of and a negative attitude toward PCA. A higher education level and longer work experience were not associated with more knowledge. The current education programs on PCA should be revised to enhance their efficacy in delivering up-to-date knowledge and situation training which may convey supportive attitude toward clinical application of PCA.

Sustaining essential health services in Lao PDR in the context of donor transition and COVID-19.

Lao People's Democratic Republic (Lao PDR) aims at graduating from least developed country status by 2026 and must increase the level of domestic financing for health. This paper examines how the government has prepared for the decline of external assistance and how donors have applied their transition approaches. Adapting a World Health Organization (WHO) framework, reflections and lessons were generated based on literature review, informal and formal consultations and focus group discussions with the Lao PDR government and development partners including budget impact discussion. The government has taken three approaches to transition from external to domestic funding: mobilizing domestic resources, increasing efficiency across programs and prioritization with a focus on strengthening primary health care (PHC). The government has increased gradually domestic government health expenditures as a share of the government expenditure from 2.6% in 2013 to 4.9% in 2019. The Ministry of Health has made efforts to design and roll out integrated service delivery of maternal, newborn, child, and adolescent health services, immunization and nutrition; integrated 13 information systems of key health programs into one single District Health Information Software 2; and prioritized PHC, which has led to shifting donors towards supporting PHC. Donors have revisited their aid policies designed to improve sustainability and ownership of the government. However, the government faces challenges in improving cross-programmatic efficiency at the operational level and in further increasing the health budget due to the economic crisis aggravated during Coronavirus disease 2019 (COVID-19). Working to implement donor transition strategies under the current economic situation and country challenges, calls into question the criteria used to evaluate transition. This criterion needs to include more appropriate indicators other than gross national income per capita, which does not reflect a country's readiness and capacity of the health system. There should be a more country-tailored strategy and support for considering the context and system-wide readiness during donor transition.

CaMKIIδ, Stabilized by RNA N6-Methyladenosine Reader IGF2BP2, Boosts Coxsackievirus B3-Induced Myocardial Inflammation via Interacting with TIRAP.

Calcium/calmodulin-dependent protein kinase II (CaMKII) has been demonstrated to be aberrantly activated in viral myocarditis (VMC), but the role of its subtype CaMKIIδ in VMC remains unclear.VMC mice and cardiomyocytes models were induced by Coxsackievirus B3 (CVB3) treatment. Mice that underwent sham surgery and saline-treated cardiomyocytes served as controls. Body weight, survival, left ventricular ejection fraction (LVEF), and fractional shortening (LVFS) were measured, and HE staining was performed to evaluate heart function in VMC mice model and sham control. Inflammation factors in serum or cell supernatant were detected by ELISA. Expressions of CaMKIIδ, Toll/interleukin-1 receptor domain containing adaptor protein (TIRAP), insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2), nuclear factor NF-kappaB (NF-κB) signals, and inflammation factors were examined by quantitative real time polymerase chain reaction (qRT-PCR) or western blot. CCK-8, EdU, and flow cytometry were used to evaluate cell behaviors. Co-immunoprecipitation (Co-IP), RNA immunoprecipitation (RIP), and RNA pull-down were utilized to validate molecule interaction. Methylated RNA immunoprecipitation (MeRIP) was performed to measure N6-methyladenosine (m6A) level of specific molecule.CaMKIIδ was upregulated in VMC mice and CVB3-treated primary cardiomyocytes, of which knockdown improved cell viability, proliferation, and suppressed cell apoptosis in vitro, thereby alleviating myocarditis in vivo. The stability of CaMKIIδ was attributed to the presence of IGF2BP2 through m6A modification. Loss of CaMKIIδ repressed NF-κB pathway via negatively and directly regulating TIRAP to be involved in inflammatory damage.CaMKIIδ, stabilized by m6A reader IGF2BP2, modulated NF-κB pathway via interacting with TIRAP to alter cell viability, proliferation, and apoptosis, thereby affecting VMC outcome.

Corosolic acid inhibits metastatic response of human renal cell carcinoma cells by modulating ERK/MMP2 signaling.

Corosolic acid (CA), a plant-derived pentacyclic triterpenoid, has potent anti-inflammatory, anti-metabolic, and anti-neoplastic actions against a variety of human cancers. However, the specific mechanism by which CA inhibits the progression of renal cell carcinoma (RCC) is yet unclear. We found that CA (≤8 µM) had no influence on either the growth or viability of RCC cell lines (786-O, ACHN, and Caki-1) or normal HK2 cells. However, in a dose-dependent manner, CA prevented the invasion and migration of RCC cells. Human protease array analysis showed that CA reduced MMP2 expression. At increasing concentrations of CA, the expression of MMP2 was dose-dependently reduced, as shown by western blot and RT-PCR analyses as well as immunofluorescence staining. CA also stimulated ERK1/2 phosphorylation in 786-O and Caki-1 cells. Transfection of CA-treated RCC cells with siRNA-ERK restored MMP2 protein expression and the motility and invasion capabilities of RCC cells. Molecular docking study results showed that CA and MMP2 interact strongly. These findings elucidate the mechanism by which CA prevents RCC cells from migrating and invading, and these findings indicate that CA may be a potential anti-metastatic therapy for RCC.

Transanal Total Mesorectal Excision With Delayed Coloanal Anastomosis (TaTME-DCAA) Versus Laparoscopic Total Mesorectal Excision (LTME) and Robotic Total Mesorectal Excision (RTME) for Low Rectal Cancer: A Propensity Score-Matched Analysis of Short-term Outcomes, Bowel Function, and Cost.

INTRODUCTION: Total mesorectal excision (TME) with delayed coloanal anastomosis (DCAA) is surgical option for low rectal cancer, replacing conventional immediate coloanal anastomosis (ICAA) with bowel diversion. This study aimed to assess the outcomes of transanal TME (TaTME) with DCAA versus laparoscopic TME (LTME) with ICAA versus robotic TME (RTME) with ICAA. METHODS: This was a retrospective propensity score-matched analysis of patients who underwent elective TaTME-DCAA between November 2021 and June 2022. Patients were propensity-score matched in a ratio of 1:3 to patients who underwent LTME-ICAA and RTME-ICAA from January 2019 to December 2020. Outcome measures were histopathologic results, postoperative morbidity, function, and inpatient costs. RESULTS: Twelve patients in the TaTME-DCAA group were compared with 36 patients in the LTME-ICAA and RTME-ICAA groups each after propensity score matching. Histopathologic results and postoperative morbidity rates were statistically similar. Overall stoma-related complication rates in the ICAA groups were 11%. Median total length of hospital stays for TME plus stoma reversal surgery was similar across all techniques (10 vs. 10 vs. 9 days; P =0.532). Despite a significantly shorter duration of follow-up, bowel function after TaTME-DCAA was comparable to that of LTME-ICAA and RTME-ICAA. Overall median inpatient costs of TaTME-DCAA were comparable to LTME-ICAA and significantly cheaper than RTME-ICAA ($31,087 vs. $29,927 vs. $36,750; P =0.002). CONCLUSIONS: TaTME with DCAA is a feasible and safe technique compared with other minimally invasive methods of TME, while avoiding bowel diversion and stoma-related complications, as well as comparing favorably in terms of overall hospitalization costs.

Backbone 1H, 15N and 13C resonance assignments for dengue NS2B without the NS3 protease cofactor region in detergent micelles.

Dengue virus is an important human pathogen affecting people especially in tropical and subtropical regions. Its genome encodes seven non-structural proteins that are important for viral assembly and replication. Dengue NS2B is a membrane protein containing four transmembrane helices and involved in protein-protein interactions. Its transmembrane helices are critical for location of NS2B on the cell membrane while one cytoplasmic region composed of approximately 40 amino acids serves as a cofactor of viral NS3 protease by forming a tight complex with the N-terminal region of NS3. Here, we report the backbone resonance assignments for a dengue NS2B construct referred to as mini-NS2B containing only the transmembrane regions without NS3 cofactor region in detergent micelles. Mini-NS2B exhibits well-dispersed cross-peaks in the 1H-15N-HSQC spectrum and contains four helices in solution. The available mini-NS2B and its assignment will be useful for determining the structure of NS2B and identifying small molecules binding to the transmembrane regions.

Construction of Ag/Ag2S/CdS Heterostructures through a Facile Two-Step Wet Chemical Process for Efficient Photocatalytic Hydrogen Production.

We have demonstrated a two-step wet chemical approach for synthesizing ternary Ag/Ag2S/CdS heterostructures for efficient photocatalytic hydrogen evolution. The CdS precursor concentrations and reaction temperatures are crucial in determining the efficiency of photocatalytic water splitting under visible light excitation. In addition, the effect of operational parameters (such as the pH value, sacrificial reagents, reusability, water bases, and light sources) on the photocatalytic hydrogen production of Ag/Ag2S/CdS heterostructures was investigated. As a result, Ag/Ag2S/CdS heterostructures exhibited a 3.1-fold enhancement in photocatalytic activities compared to bare CdS nanoparticles. Furthermore, the combination of Ag, Ag2S, and CdS can significantly enhance light absorption and facilitate the separation and transport of photogenerated carriers through the surface plasma resonance (SPR) effect. Furthermore, the Ag/Ag2S/CdS heterostructures in seawater exhibited a pH value approximately 2.09 times higher than in de-ionized water without an adjusted pH value under visible light excitation. The ternary Ag/Ag2S/CdS heterostructures provide new potential for designing efficient and stable photocatalysts for photocatalytic hydrogen evolution.

Using Machine Learning for the Risk Factors Classification of Glycemic Control in Type 2 Diabetes Mellitus.

Several risk factors are related to glycemic control in patients with type 2 diabetes mellitus (T2DM), including demographics, medical conditions, negative emotions, lipid profiles, and heart rate variability (HRV; to present cardiac autonomic activity). The interactions between these risk factors remain unclear. This study aimed to use machine learning methods of artificial intelligence to explore the relationships between various risk factors and glycemic control in T2DM patients. The study utilized a database from Lin et al. (2022) that included 647 T2DM patients. Regression tree analysis was conducted to identify the interactions among risk factors that contribute to glycated hemoglobin (HbA1c) values, and various machine learning methods were compared for their accuracy in classifying T2DM patients. The results of the regression tree analysis revealed that high depression scores may be a risk factor in one subgroup but not in others. When comparing different machine learning classification methods, the random forest algorithm emerged as the best-performing method with a small set of features. Specifically, the random forest algorithm achieved 84% accuracy, 95% area under the curve (AUC), 77% sensitivity, and 91% specificity. Using machine learning methods can provide significant value in accurately classifying patients with T2DM when considering depression as a risk factor.

Protective Effect of Hawthorn Fruit Extract against High Fructose-Induced Oxidative Stress and Endoplasmic Reticulum Stress in Pancreatic ß-Cells.

Hyperglycemia has deleterious effects on pancreatic ß-cells, causing dysfunction and insulin resistance that lead to diabetes mellitus (DM). The possible causes of injury can be caused by glucose- or fructose-induced oxidative and endoplasmic reticulum (ER) stress. Hawthorn (Crataegus pinnatifida) fruit has been widely used as a hypolipidemic agent in traditional herbal medicine. The study aimed to investigate whether high fructose-induced pancreatic ß-cell dysfunction could be reversed through amelioration of ER stress by the treatment of polyphenol-enriched extract (PEHE) from hawthorn fruit. The extract was partitioned using ethyl acetate as a solvent from crude water extract (WE) of hawthorn fruits, followed by column fractionation. The results showed that the contents of total polyphenols, flavonoids and triterpenoids in PEHE could be enhanced by 2.2-, 7.7- and 1.1-fold, respectively, in comparison to the original obtained WE from hawthorn fruit. In ER stress studies, a sharp increase in the inhibitory activity on the gene expression levels of GRP79, ATF6, IRE1α and CHOP involved in ER stress was evident when dosages of PEHE at 50-100 µg/mL were used against high-fructose (150 mM)-treated cells. HPLC-MS/MS analysis showed that polyphenols and flavonoids collectively accounted for 87.03% of the total content of PEHE.

Stenting as a bridge to surgery in obstructing colon cancer: Long-term recurrence pattern and competing risk of mortality.

BACKGROUND: Stenting as a bridge to curative surgery (SBTS) for obstructing colon cancer (OCC) has been associated with possibly worse oncological outcomes. AIM: To evaluate the recurrence patterns, survival outcomes, and colorectal cancer (CRC)-specific death in patients undergoing SBTS for OCC. METHODS: Data from 62 patients undergoing SBTS at a single tertiary centre over ten years between 2007 and 2016 were retrospectively examined. Primary outcomes were recurrence patterns, overall survival (OS), cancer-specific survival (CSS), and CRC-specific death. OS and CSS were estimated using the Kaplan-Meier curves. Competing risk analysis with cumulative incidence function (CIF) was used to estimate CRC-specific mortality with other cause-specific death as a competing event. Fine-Gray regressions were performed to determine prognostic factors of CRC-specific death. Univariate and multivariate subdistribution hazard ratios and their corresponding Wald test P values were calculated. RESULTS: 28 patients (45.2%) developed metastases after a median period of 16 mo. Among the 18 patients with single-site metastases: Four had lung-only metastases (14.3%), four had liver-only metastases (14.3%), and 10 had peritoneum-only metastases (35.7%), while 10 patients had two or more sites of metastatic disease (35.7%). The peritoneum was the most prevalent (60.7%) site of metastatic involvement (17/28). The median follow-up duration was 46 mo. 26 (41.9%) of the 62 patients died, of which 16 (61.5%) were CRC-specific deaths and 10 (38.5%) were deaths owing to other causes. The 1-, 3-, and 5-year OS probabilities were 88%, 74%, and 59%; 1-, 3-, and 5-year CSS probabilities were 97%, 83%, and 67%. The highest CIF for CRC-specific death at 60 mo was liver-only recurrence (0.69). Liver-only recurrence, peritoneum-only recurrence, and two or more recurrence sites were predictive of CRC-specific death. CONCLUSION: The peritoneum was the most common metastatic site among patients undergoing SBTS. Liver-only recurrence, peritoneum-only recurrence, and two or more recurrence sites were predictors of CRC-specific death.

Long-Term Immunogenicity and In Vitro Prophylactic Protective Efficacy of M. tuberculosis Fusion Protein DR2 Combined with Liposomal Adjuvant DIMQ as a Boosting Vaccine for BCG.

The resuscitation of dormant Mycobacterium tuberculosis is an important cause of adult tuberculosis (TB) transmission. According to the interaction mechanism between M. tuberculosis and the host, the latency antigen Rv0572c and region of difference 9 (RD9) antigen Rv3621c were selected in this study to prepare the fusion protein DR2. Stimulating clinically diagnosed active tuberculosis infections (i.e., TB patients), latent tuberculosis infections, and healthy controls confirmed that T lymphocytes could recognize DR2 protein in the peripheral blood of TB-infected individuals more than subcomponent protein. The DR2 protein was then emulsified in the liposome adjuvant dimethyl dioctadecyl ammonium bromide, and imiquimod (DIMQ) was administered to C57BL/6 mice immunized with Bacillus Calmette-Guérin (BCG) vaccine to evaluate their immunogenicity. Studies have shown that DR2/DIMQ, a booster vaccine for BCG primary immunization, can elicit robust CD4+ Th1 cell immune response and predominant IFN-γ+ CD4+ effector memory T cells (TEM) subsets. Furthermore, the serum antibody level and the expression of related cytokines increased significantly with the extension of immunization time, with IL2+, CD4+, or CD8+ central memory T cells (TCM) subsets predominant in the long term. This immunization strategy showed matched prophylactic protective efficacy by performing in vitro challenge experiment. This result provides robust evidence that the novel subunit vaccine prepared by fusion protein DR2 combined with liposomal adjuvant DIMQ is a promising TB vaccine candidate for further preclinical trials as a booster vaccine for BCG.

Dynamics of immune responses are inconsistent when trauma patients are grouped by injury severity score and clinical outcomes.

The injury severity score (ISS) is used in daily practice to evaluate the severity of trauma patients; however, the score is not always consistent with the prognosis. After injury, systemic inflammatory response syndrome (SIRS) and compensatory anti-inflammatory response syndrome (CARS) are related to the prognosis of trauma patients. We aimed to evaluate the associations between the immune response and prognosis in trauma patients. Patients who admitted to the Trauma Intensive Care Unit (ICU) were eligible. Whole blood samples were collected at admission, and then 6, 12, 24, 48 and 72 h after admission. Natural killer (NK) cells, lymphocyte subset population and cytokines release were identified using flow cytometry. We grouped patients by their ISS (≤ 25 and > 25 as very severe injury) and ICU stay (≤ 10 days as a short ICU stay and > 10 days as a long ICU stay) for evaluation. Fifty-three patients were enrolled. ICU stay but not ISS was close correlated with activity daily living (ADL) at discharge. Patients with a long ICU stay had an immediate increase in NK cells followed by lymphopenia which persisted for 48 h. Immediate activation of CD8+ T cells and then exhaustion with a higher programmed cell death-1 (PD-1) expression and suppression of CD4+ T cells with a shift to an anti-inflammatory Th2 phenotype were also observed in the patients with a long ICU stay. When the patients were grouped by ISS, the dynamics of immune responses were inconsistent to those when the patients were grouped by ICU stay. Immune responses are associated with the prognosis of trauma patients, however the currently used clinical parameters may not accurately reflect immune responses. Further investigations are needed to identify accurate predictors of prognosis in trauma patients.

Laser hemorrhoidoplasty versus conventional hemorrhoidectomy for grade II/III hemorrhoids: a systematic review and meta-analysis.

PURPOSE: This study compared the short- and long-term clinical outcomes of laser hemorrhoidoplasty (LH) vs. conventional hemorrhoidectomy (CH) in patients with grade II/III hemorrhoids. METHODS: PubMed/Medline and the Cochrane Library were searched for randomized and nonrandomized studies comparing LH against CH in grade II/III hemorrhoids. The primary outcomes included postoperative use of analgesia, postoperative morbidity (bleeding, urinary retention, pain, thrombosis), and time of return to work/daily activities. RESULTS: Nine studies totaling 661 patients (LH, 336 and CH, 325) were included. The LH group had shorter operative time (P<0.001) and less intraoperative blood loss (P<0.001). Postoperative pain was lower in the LH group, with lower postoperative day 1 (mean difference [MD], -2.09; 95% confidence interval [CI], -3.44 to -0.75; P=0.002) and postoperative day 7 (MD, -3.94; 95% CI, -6.36 to -1.52; P=0.001) visual analogue scores and use of analgesia (risk ratio [RR], 0.59; 95% CI, 0.42-0.81; P=0.001). The risk of postoperative bleeding was also lower in the LH group (RR, 0.18; 95% CI, 0.12- 0.28; P<0.001), with a quicker return to work or daily activities (P=0.002). The 12-month risks of bleeding (P>0.999) and prolapse (P=0.240), and the likelihood of complete resolution at 12 months, were similar (P=0.240). CONCLUSION: LH offers more favorable short-term clinical outcomes than CH, with reduced morbidity and pain and earlier return to work or daily activities. Medium-term symptom recurrence at 12 months was similar. Our results should be verified in future well-designed trials with larger samples.

Concurrent outbreaks of circulating vaccine-derived poliovirus types 1 and 2 affecting the Republic of the Philippines and Malaysia, 2019-2021.

Concurrent outbreaks of circulating vaccine-derived poliovirus serotypes 1 and 2 (cVDPV1, cVDPV2) were confirmed in the Republic of the Philippines in September 2019 and were subsequently confirmed in Malaysia by early 2020. There is continuous population subgroup movement in specific geographies between the two countries. Outbreak response efforts focused on sequential supplemental immunization activities with monovalent Sabin strain oral poliovirus vaccine type 2 (mOPV2) and bivalent oral poliovirus vaccines (bOPV, containing Sabin strain types 1 and 3) as well as activities to enhance poliovirus surveillance sensitivity to detect virus circulation. A total of six cVDPV1 cases, 13 cVDPV2 cases, and one immunodeficiency-associated vaccine-derived poliovirus type 2 case were detected, and there were 35 cVDPV1 and 31 cVDPV2 isolates from environmental surveillance sewage collection sites. No further cVDPV1 or cVDPV2 have been detected in either country since March 2020. Response efforts in both countries encountered challenges, particularly those caused by the global COVID-19 pandemic. Important lessons were identified and could be useful for other countries that experience outbreaks of concurrent cVDPV serotypes.