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An integrated metabo-lipidomics profile of induced sputum for the identification of novel biomarkers in the differential diagnosis of asthma and COPD

J Transl Med. 2024 Mar 23;22(1):301. doi: 10.1186/s12967-024-05100-2.

ABSTRACT

BACKGROUND: Due to their complexity and to the presence of common clinical features, differentiation between asthma and chronic obstructive pulmonary disease (COPD) can be a challenging task, complicated in such cases also by asthma-COPD overlap syndrome. The distinct immune/inflammatory and structural substrates of COPD and asthma are responsible for significant differences in the responses to standard pharmacologic treatments. Therefore, an accurate diagnosis is of central relevance to assure the appropriate therapeutic intervention in order to achieve safe and effective patient care. Induced sputum (IS) accurately mirrors inflammation in the airways, providing a more direct picture of lung cell metabolism in comparison to those specimen that reflect analytes in the systemic circulation.

METHODS: An integrated untargeted metabolomics and lipidomics analysis was performed in IS of asthmatic (n = 15) and COPD (n = 22) patients based on Ultra-High-Pressure Liquid Chromatography-Mass Spectrometry (UHPLC-MS) and UHPLC-tandem MS (UHPLC-MS/MS). Partial Least Squares-Discriminant Analysis (PLS-DA) was applied to resulting dataset. The analysis of main enriched metabolic pathways and the association of the preliminary metabolites/lipids pattern identified to clinical parameters of asthma/COPD differentiation were explored. Multivariate ROC analysis was performed in order to determine the discriminatory power and the reliability of the putative biomarkers for diagnosis between COPD and asthma.

RESULTS: PLS-DA indicated a clear separation between COPD and asthmatic patients. Among the 15 selected candidate biomarkers based on Variable Importance in Projection scores, putrescine showed the highest score. A differential IS bio-signature of 22 metabolites and lipids was found, which showed statistically significant variations between asthma and COPD. Of these 22 compounds, 18 were decreased and 4 increased in COPD compared to asthmatic patients. The IS levels of Phosphatidylethanolamine (PE) (34:1), Phosphatidylglycerol (PG) (18:1;18:2) and spermine were significantly higher in asthmatic subjects compared to COPD.

CONCLUSIONS: This is the first pilot study to analyse the IS metabolomics/lipidomics signatures relevant in discriminating asthma vs COPD. The role of polyamines, of 6-Hydroxykynurenic acid and of D-rhamnose as well as of other important players related to the alteration of glycerophospholipid, aminoacid/biotin and energy metabolism provided the construction of a diagnostic model that, if validated on a larger prospective cohort, might be used to rapidly and accurately discriminate asthma from COPD.

PMID:38521955 | DOI:10.1186/s12967-024-05100-2

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HIV and hepatitis B, C co-infection and correlates of HIV infection among men who have sex with men in Rwanda, 2021: a respondent-driven sampling, cross-sectional study

BMC Infect Dis. 2024 Mar 23;24(1):347. doi: 10.1186/s12879-024-09206-2.

ABSTRACT

BACKGROUND: Men who have sex with men (MSM) are a key population group disproportionately affected by HIV and other sexually transmitted infections (STIs) worldwide. In Rwanda, the HIV epidemic remains a significant public health concern, and understanding the burden of HIV and hepatitis B and C coinfections among MSM is crucial for designing effective prevention and control strategies. This study aims to determine the prevalence of HIV, hepatitis B, and hepatitis C infections among MSM in Rwanda and identify correlates associated with HIV infection within this population.

METHODS: We used respondent-driven sampling (RDS) to recruit participants between November and December 2021. A face-to-face, structured questionnaire was administered. Testing for HIV infection followed the national algorithm using two rapid tests: Alere Combo and STAT PAK as the first and second screening tests, respectively. Hepatitis B surface antigen (HBsAg) and anti-HCV tests were performed. All statistics were adjusted for RDS design, and a multivariable logistic regression model was constructed to identify factors associated with HIV infection.

RESULTS: The prevalence of HIV among MSM was 6·9% (95% CI: 5·5-8·6), and among HIV-positive MSM, 12·9% (95% CI: 5·5-27·3) were recently infected. The prevalence of hepatitis B and C was 4·2% (95% CI: 3·0-5·7) and 0·7% (95% CI: 0·4-1·2), respectively. HIV and hepatitis B virus coinfection was 0·5% (95% CI: 0·2-1·1), whereas HIV and hepatitis C coinfection was 0·1% (95% CI: 0·0-0·5), and no coinfection for all three viruses was observed. MSM groups with an increased risk of HIV infection included those who ever suffered violence or abuse because of having sex with other men (AOR: 3·42; 95% CI: 1·87-6·25), those who refused to answer the question asking about ‘ever been paid money, goods, or services for sex’ (AOR: 10·4; 95% CI: 3·30-32·84), and those not consistently using condoms (AOR: 3·15; 95% CI: 1·31-7·60).

CONCLUSION: The findings suggest more targeted prevention and treatment approaches and underscore the importance of addressing structural and behavioral factors contributing to HIV vulnerability, setting interventions to reduce violence and abuse against MSM, promoting safe and consensual sexual practices, and expanding access to HIV prevention tools such as condoms and preexposure prophylaxis (PrEP).

PMID:38521947 | DOI:10.1186/s12879-024-09206-2

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“You cannot stay with one person once you begin having sex at a young age”: the prevalence, correlates and effects of early sexual debut among children in Ghana

Reprod Health. 2024 Mar 23;21(1):38. doi: 10.1186/s12978-024-01775-4.

ABSTRACT

BACKGROUND: Children’s initiation of early sex has several negative implications on their sexual and reproductive health, growth and development. In Ghana, few studies on early sexual debut have focused on adolescents. Therefore, this study examined the prevalence, causes, correlates and effects of early sexual debut among children aged 8 to 17 in Ghana using secondary data from the Department of Children of the Ministry of Gender, Children, and Social Protection.

METHODS: A convergent parallel mixed-method approach guided the study. Descriptive statistics and multivariable binary logistic regression were used to analyse the quantitative data, while thematic analysis was used to analyse the qualitative data.

RESULTS: The study found that the prevalence of early sexual debut among children was 13.2%, which is more predominant among female children. The main causes of early sexual debut include engaging in sex after watching pornography, self-desire to have sex, and being influenced by alcohol consumption. Also, age, sex, education, marital status, religion, ecological zone, living arrangements, and access to the Internet were significant correlates of early sexual debut. Early sexual debut increases children’s risk of unwanted pregnancy, which leads to the termination of children’s education or induced abortion. Also, early sexual debut had adverse impacts on the wellbeing of pregnant children and increased children’s risk of multiple lifetime sexual partners.

CONCLUSIONS: This study demonstrated that socio-demographic characteristics of children (e.g., age, sex, education, and marital status) were significant correlates of early sexual debut. Policymakers need to design appropriate interventions, considering the socio-demographic characteristics of children, to curb its occurrence in Ghana.

PMID:38521936 | DOI:10.1186/s12978-024-01775-4

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A systematic review of high impact CpG sites and regions for MGMT methylation in glioblastoma [A systematic review of MGMT methylation in GBM]

BMC Neurol. 2024 Mar 23;24(1):103. doi: 10.1186/s12883-024-03605-3.

ABSTRACT

BACKGROUND: MGMT (O 6 -methylguanine-DNA methyltransferase) promoter methylation is a commonly assessed prognostic marker in glioblastoma (GBM). Epigenetic silencing of the MGMT gene by promoter methylation is associated with greater overall and progression free survival with alkylating agent regimens. To date, there is marked heterogeneity in how MGMT promoter methylation is tested and which CpG sites are interrogated.

METHODS: To further elucidate which MGMT promoter CpG sites are of greatest interest, we performed comprehensive searches in PubMed, Web of Science, and Embase and reviewed 2,925 article abstracts. We followed the GRADE scoring system to assess risk of bias and the quality of the studies we included.

RESULTS: We included articles on adult glioblastoma that examined significant sites or regions within MGMT promoter for the outcomes: overall survival, progression free survival, and/or MGMT expression. We excluded systemic reviews and articles on lower grade glioma. fifteen articles met inclusion criteria with variable overlap in laboratory and statistical methods employed, as well as CpG sites interrogated. Pyrosequencing or BeadChip arrays were the most popular methods utilized, and CpG sites between CpG’s 70-90 were most frequently investigated. Overall, there was moderate concordance between the CpG sites that the studies reported to be highly predictive of prognosis. Combinations or means of sites between CpG’s 73-89 were associated with improved OS and PFS. Six studies identified CpG sites associated with prognosis that were closer to the transcription start site: CpG’s 8, 19, 22, 25, 27, 32,38, and CpG sites 21-37, as well as low methylation level of the enhancer regions.

CONCLUSION: The following systematic review details a comprehensive investigation of the current literature and highlights several potential key CpG sites that demonstrate significant association with OS, PFS, and MGMT expression. However, the relationship between extent of MGMT promoter methylation and survival may be non-linear and could be influenced by potential CpG hotspots, the extent of methylation at each CpG site, and MGMT enhancer methylation status. There were several limitations within the studies such as smaller sample sizes, variance between methylation testing methods, and differences in the various statistical methods to test for association to outcome. Further studies of high impact CpG sites in MGMT methylation is warranted.

PMID:38521933 | DOI:10.1186/s12883-024-03605-3

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The role of lung biopsy for diagnosis and prognosis of interstitial lung disease in systemic sclerosis: a systematic literature review

Respir Res. 2024 Mar 23;25(1):138. doi: 10.1186/s12931-024-02725-1.

ABSTRACT

BACKGROUND: The prognostic and theragnostic role of histopathological subsets in systemic sclerosis interstitial lung disease (SSc-ILD) have been largely neglected due to the paucity of treatment options and the risks associated with surgical lung biopsy. The novel drugs for the treatment of ILDs and the availability of transbronchial cryobiopsy provide a new clinical scenario making lung biopsy more feasible and a pivotal guide for treatment. The aim of our study was to investigate the usefulness of lung biopsy in SSc ILD with a systematic literature review (SLR).

METHODS: PubMed, Embase and Cochrane databases were searched up to June 30, 2023. Search terms included both database-specific controlled vocabulary terms and free-text terms relating to lung biopsy and SSc-ILD diagnostic and prognosis. The SLR was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Studies were selected according to the PEO (population, exposure, and outcomes) framework and Quality assessment of diagnostic accuracy studies (QUADAS) were reported.

RESULTS: We selected 14 articles (comprising 364 SSc-ILD patients). The paucity and heterogeneity of the studies prevented a systematic analysis. Diffuse cutaneous SSc was present in 30-100% of cases. Female predominance was observed in all studies (ranging from 64 to 100%). Mean age ranged from 42 to 64 years. Mean FVC was 73.98 (+/-17.3), mean DLCO was 59.49 (+/-16.1). Anti-Scl70 antibodies positivity was detected in 33% of cases (range: 0-69.6). All patients underwent surgical lung biopsies, and multiple lobes were biopsied in a minority of studies (4/14). Poor HRCT-pathologic correlation was reported with HRCT-NSIP showing histopathologic UIP in up to 1/3 of cases. Limited data suggest that SSc-UIP patients may have a worse prognosis and response to immunosuppressive treatment compared to other histopathologic patterns.

CONCLUSIONS: The data from this SLR clearly show the paucity and heterogeneity of the studies reporting lung biopsy in SSc ILD. Moreover, they highlight the need for further research to address whether the lung biopsy can be helpful to refine prognostic prediction and guide therapeutic choices.

PMID:38521926 | DOI:10.1186/s12931-024-02725-1

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An in vitro study elucidating the synergistic effects of aqueous cinnamon extract and an anti-TNF-α biotherapeutic: implications for a complementary and alternative therapy for non-responders

BMC Complement Med Ther. 2024 Mar 23;24(1):131. doi: 10.1186/s12906-024-04438-w.

ABSTRACT

BACKGROUND: Tumor necrosis factor-alpha (TNF-α) is a critical pro-inflammatory cytokine, and its abnormal production is associated with several immune mediated inflammatory diseases (IMID). Biological anti-TNF-α therapy includes treatment with monoclonal antibodies such as infliximab which have proven successful and are well-tolerated in most patients. Unfortunately, some patients may not respond to therapy (primary non-responders) or may lose sensitivity to the biological agent over time (early and late secondary non-responders). Natural products can reduce inflammation and act synergistically with small molecules or biologics, although evidence remains limited. This study aimed to investigate whether complementary and alternative medicine (CAM) could play a role in infliximab non-responders. Reportedly, cinnamon can help manage chronic inflammatory conditions owing to its anti-inflammatory properties.

METHODS: We studied the synergistic effects of cinnamon and infliximab in vitro using a two-step approach. First, we investigated whether cinnamon and infliximab act synergistically. Second, we selected conditions that supported statistically significant synergy with infliximab and studied the mRNA expression of several genes involved in non-response to infliximab. We used aqueous cinnamon extract (aCE) from Cinnamomum cassia, Cinnamomum zeylanicum, and Cinnamomum loureiroi and bioactive trans-cinnamaldehyde (TCA), cinnamic acid (CA), and eugenol to study the synergy between infliximab and aCE/bioactive compounds using bioassays in fibroblast (L929) and monocytic (U937) cell lines, followed by qPCR for molecular-level insights. TCA, C. cassia aCE, and C. zeylanicum aCE demonstrated a dose-dependent synergistic effect with infliximab. Moreover, we saw differential gene expression for adhesion molecules, apoptotic factors, signaling molecules, and matrix remodelers in presence and absence of aCE/bioactives.

RESULTS: CAM supplementation was most effective with C. cassia aCE, where a synergistic effect was observed for all the tested genes specifically for MMP-1, BcL-xL, Bax and JAK2, followed by TCA, which affected most of the tested genes except TLR-2, MMP1, MMP3, TIMP-1, and BAX, and C. zeylanicum aCE, which did not affect ICAM-1, VCAM-1, TLR-2, TLR-4, MMP1, MMP3, TIMP-1, and STAT3.

CONCLUSION: In conclusion, cinnamon acted synergistically with infliximab to mitigate inflammation when used as an extract. Purified bioactive TCA also showed synergistic activity. Thus, aCE, or cinnamon bioactive may be used as a CAM to improve patients’ quality of life.

PMID:38521924 | DOI:10.1186/s12906-024-04438-w

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Evaluation of the presence of gingivitis as confounding factor in assessing inflammatory status in serum and saliva of dogs with diabetes mellitus

BMC Vet Res. 2024 Mar 23;20(1):116. doi: 10.1186/s12917-024-03962-8.

ABSTRACT

The aim of this study was to evaluate the changes in the serum and salivary inflammatory markers induced by Diabetes mellitus (DM) in dogs and to assess the possible confounding effect of gingivitis. A panel of 13 cytokines was measured in the serum and saliva of dogs diagnosed with DM and compared with healthy dogs without gingivitis (control group 1; CG1) and dogs with gingivitis but otherwise healthy (control group 2; CG2). The results of the present study showed statistically significantly higher levels of IL-8, KC-like and MCP1 in the serum of dogs with DM compared to CG1 dogs. In the case of saliva, the DM group presented statistically higher GM-CSF, IL6, IL15, and MCP1 levels compared to CG1, and lower KC-like chemokine compared to CG2. Finally, gingivitis produced changes in saliva, with salivary levels of GM-CSF, IL-6, IL-7, IL-15, IP-10, KC-like, IL-10, IL-18, MCP1, TNFα being statistically significantly higher in the saliva of CG2 dogs compared to CG1. The results of the present study indicate that dogs with DM have altered cytokine levels in serum and saliva compared to healthy dogs. In addition, this study highlights the importance of taking oral health into account when determining cytokines in dogs, as gingivitis can significantly alter their concentrations. .

PMID:38521919 | DOI:10.1186/s12917-024-03962-8

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The association between physical activity and quality of life among people aged 60-89 living in own homes and nursing homes

BMC Geriatr. 2024 Mar 23;24(1):280. doi: 10.1186/s12877-024-04898-2.

ABSTRACT

BACKGROUND: The aim of the study was to obtain a response to the question of whether and how physical activity (PA) among people aged 60-89 years impacts quality of life and other sociodemographic characteristics (sex, age and place of living).

METHODS: Among 341 respondents aged 60 to 89, including 273 women (80%) and 68 men (20%) successfully completed IPAQ and WHOQOL AGE questionnaires. In the study were used International Physical Activity Questionnaire – IPAQ and World Health Organization Quality Of Life – Age – WHOQOL-AGE in Polish version.

RESULTS: The average total physical activity, including vigorous-intensity physical effort, moderate-intensity physical effort and walking amounts to 1381.87 ± 1978.60 MET-min/week. The average quality of life for the whole group of older people as evaluated with WHOQOL AGE scale was 64.79 (SD = 14.76; min:18.77-max: 98.07). Statistical analysis between physical activity and life quality proved significant dependence for the global life quality rating (p < 0.001).

CONCLUSIONS: Our research has shown that PA improves quality of life among older people. Higher scores of quality of life were obtained in the F1 subscale (satisfaction) than in the F2 subscale (meeting expectations) in both age groups. Age significantly affects quality of life for older people.

PMID:38521918 | DOI:10.1186/s12877-024-04898-2

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Developing an innovative national ACP-OSCE program in Taiwan: a mixed method study

BMC Med Educ. 2024 Mar 23;24(1):333. doi: 10.1186/s12909-024-05294-5.

ABSTRACT

OBJECTIVES: To evaluate the process and the comprehensiveness of advance care planning (ACP), we designed a national ACP-OSCE (Objective Structured Clinical Examination) program.

METHODS: The program was designed as a 40-minute OSCE test. Participants were categorized as different ACP team members to illustrate realistic scenarios. Preceptors were asked to observe ACP professionals’ actions, responses, and communication skills during ACP with standardized patients (SP) through a one-way mirror. Participants’ communication skills, medical expertise, legal knowledge, empathetic response and problem-solving skills of ACP were also self-evaluated before and after OSCE. Thematic analysis was used for qualitative analysis.

RESULTS: In Nov 2019, a total of 18 ACP teams with 38 ACP professionals completed the ACP-OSCE program, including 15 physicians, 15 nurses, 5 social workers, and 3 psychologists. After the ACP-OSCE program, the average score of communication skills, medical expertise, legal knowledge, empathetic response, ACP problem-solving all increased. Nurses felt improved in medical expertise, legal knowledge, and problem-solving skills, psychologists and social workers felt improved in legal knowledge, while physicians felt no improved in all domain, statistically. Thematic analysis showed professional skills, doctoral-patient communication, benefit and difficulties of ACP were the topics which participants care about. Meanwhile, most participants agreed that ACP-OSCE program is an appropriate educational tool.

CONCLUSION: This is the first national ACP-OSCE program in Asia. We believe that this ACP-OSCE program could be applied in other countries to improve the ACP process and quality.

PMID:38521917 | DOI:10.1186/s12909-024-05294-5

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Time to death and its predictors among adult patients on mechanical ventilation admitted to intensive care units in West Amhara comprehensive specialized hospitals, Ethiopia: a retrospective follow-up study

BMC Anesthesiol. 2024 Mar 23;24(1):114. doi: 10.1186/s12871-024-02495-9.

ABSTRACT

INTRODUCTION: Mechanical ventilation is the most common intervention for patients with respiratory failure in the intensive care unit. There is limited data from African countries, including Ethiopia on time to death and its predictors among patients on mechanical ventilators. Therefore, this study aimed to assess time to death and its predictors among adult patients on mechanical ventilation admitted in comprehensive specialized hospitals in West Amhara, Ethiopia.

METHODS: An institutional-based retrospective follow-up study was conducted from January 1, 2020, to December 31, 2022. A simple random sampling was used to select a total of 391 patients’ charts. Data were collected using data the extraction tool, entered into Epi-data version 4.6.0, and exported to STATA version 14 for analysis. Kaplan-Meier failure curve and the log-rank test were fitted to explore the survival difference among groups. The Cox regression model was fitted, and variables with a p-value < 0.25 in the bivariable Cox regression were candidates for the multivariable analysis. In the multivariable Cox proportional hazard regression, an adjusted hazard ratio with 95% confidence intervals were reported to declare the strength of association between mortality and predictors when a p value is < 0.05.

RESULTS: A total of 391 mechanically ventilated patients were followed for 4098 days at risk. The overall mortality of patients on mechanical ventilation admitted to the intensive care units was 62.2%, with a median time to death of 16 days (95% CI: 11, 22). Those patients who underwent tracheostomy procedure (AHR = 0.40, 95% CI: 0.20, 0.80), received cardio-pulmonary resuscitation (AHR = 8.78, 95% CI: 5.38, 14.35), being hypotensive (AHR = 2.96, 95% CI: 1.11, 7.87), and had a respiratory rate less than 12 (AHR = 2.74, 95% CI: 1.48, 5.07) were statistically significant predictors of time to death among mechanically ventilated patients.

CONCLUSION: The mortality rate of patients on mechanical ventilation was found to be high and the time to death was short. Being cardiopulmonary resuscitated, hypotensive, and had lower respiratory rate were significant predictors of time to death, whereas patients who underwent tracheostomy was negatively associated with time to death. Tracheostomy is needed for patients who received longer mechanical ventilation, and healthcare providers should give a special attention for patients who are cardiopulmonary resuscitated, hypotensive, and have lower respiratory rate.

PMID:38521916 | DOI:10.1186/s12871-024-02495-9