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EBioMedicine Jun 2024Psoriasis (Pso) is a chronic inflammatory skin disease that poses both physical and psychological challenges. Dysbiosis of the skin microbiome has been implicated in...
BACKGROUND
Psoriasis (Pso) is a chronic inflammatory skin disease that poses both physical and psychological challenges. Dysbiosis of the skin microbiome has been implicated in Pso, yet a comprehensive multi-omics analysis of host-microbe interactions is still lacking. To bridge this gap, we conducted an exploratory study by adopting the integrated approach that combines whole metagenomic shotgun sequencing with skin transcriptomics.
METHODS
This was a cross-sectional study, adult patients with plaque-type Psoriasis (Pso) and healthy volunteers were included. Skin microbiota samples and biopsies were collected from both lesional and non-lesional skin areas on the lower back. Weighted Gene Correlation Network Analysis (WGCNA) was employed for co-expression network analysis, and cell deconvolution was conducted to estimate cell fractions. Taxonomic and functional features of the microbiome were identified using whole metagenomic shotgun sequencing. Association between host genes and microbes was analyzed using Spearman correlation.
FINDINGS
Host anti-viral responses and interferon-related networks were identified and correlated with the severity of psoriasis. The skin microbiome showed a greater prevalence of Corynebacterium simulans in the PASI severe-moderate groups, which correlated with interferon-induced host genes. Two distinct psoriatic clusters with varying disease severities were identified. Variations in the expression of cell apoptosis-associated antimicrobial peptides (AMPs) and microbial aerobic respiration I pathway may partly account for these differences in disease severity.
INTERPRETATION
Our multi-omics analysis revealed for the first time anti-viral responses and the presence of C. simulans associated with psoriasis severity. It also identified two psoriatic subtypes with distinct AMP and metabolic pathway expression. Our study provides new insights into understanding the host-microbe interaction in psoriasis and lays the groundwork for developing subtype-specific strategies for managing this chronic skin disease.
FUNDING
The research has received funding from the FP7 (MAARS-Grant 261366) and the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 821511 (BIOMAP). The JU receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. This publication reflects only the author's view and the JU is not responsible for any use that may be made of the information it contains. GAM was supported by a scholarship provided by CAPES-PRINT, financed by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES (Brazilian Government Agency). The authors thank all patients who participated in our study.
PubMed: 38924840
DOI: 10.1016/j.ebiom.2024.105222 -
PloS One 2024Ukraine has the second-largest HIV epidemic in Europe, with most new cases officially attributed to heterosexual transmission. Indirect evidence suggested substantial...
BACKGROUND
Ukraine has the second-largest HIV epidemic in Europe, with most new cases officially attributed to heterosexual transmission. Indirect evidence suggested substantial HIV transmission from people who inject drugs (PWID) to their sexual partners. This study examined the extent of heterosexual HIV transmission between PWID and non-drug-using adolescent girls and young women (AGYW).
METHODS
A cross-sectional survey recruited AGYW diagnosed with heterosexually-acquired HIV between 2016 and 2019 in nine regions of Ukraine. AGYW were asked to identify and refer their sexual partners ('Partners'), who subsequently underwent HIV testing, and, if positive, HCV testing. Both AGYW and Partners completed an interview assessing HIV risk behaviors prior to AGYW's HIV diagnosis.
RESULTS
In August-December 2020, we enrolled 321 AGYW and 64 Partners. Among the Partners, 42% either self-reported IDU or were HCV-positive, indicating an IDU-related mode of HIV transmission. PWID Partners were more likely to report sexually transmitted infections (STI) and had lower educational levels. Of the 62 women who recruited at least one Partner, 40% had a PWID Partner. Within this subgroup, there was a higher prevalence of STIs (52% vs. 24%) and intimate partner violence (36% vs. 3%). Condom use was less common (52% vs. 38% reporting never use), and frequent alcohol or substance use before sex was higher (48% vs 30%) among AGYW with PWID Partner, although this difference did not reach statistical significance. Notably, 52% of women were aware of their Partners' IDU.
CONCLUSION
At least 40% of heterosexual transmission among AGYW in Ukraine can be linked to PWID partners. Intensified, targeted HIV prevention efforts are essential for key and bridge populations (PWID and their sexual partners), addressing the biological and structural determinants of transmission between key and bridge populations, such as IDU- and HIV status disclosure, STIs, IPV, and stigma.
Topics: Humans; Female; Ukraine; Sexual Partners; HIV Infections; Adolescent; Young Adult; Cross-Sectional Studies; Adult; Substance Abuse, Intravenous; Male; Sexual Behavior; Risk-Taking; Heterosexuality; Hepatitis C
PubMed: 38923979
DOI: 10.1371/journal.pone.0305072 -
Current Oncology (Toronto, Ont.) Jun 2024Small cell bladder cancer (SCBC) is a rare and aggressive disease, often treated with platinum/etoposide-based chemotherapy. Key molecular drivers include the...
Small cell bladder cancer (SCBC) is a rare and aggressive disease, often treated with platinum/etoposide-based chemotherapy. Key molecular drivers include the inactivation of onco-suppressor genes (, ) and amplifications in proto-oncogenes (). We report a patient with SCBC who achieved an objective and prolonged response to lurbinectedin, which has been approved for metastatic small cell lung cancer, after developing disease progression on cisplatin/etoposide and nivolumab/ipilimumab. A genomic analysis of a metastatic biopsy prior to lurbinectedin initiation revealed a mutation and amplification of the cell cycle regulators and . A repeat biopsy following the development of lurbinectedin resistance showed a new actionable ERBB2 alteration without significant change in the tumor mutation burden (six mutations/Mb). The present report suggests that lurbinectedin may be active and should be further explored in SCBC harboring mutations and amplifications in E2F3 and MYC family complexes.
Topics: Humans; Carbolines; Urinary Bladder Neoplasms; Heterocyclic Compounds, 4 or More Rings; Mutation; Tumor Suppressor Protein p53; Male; Carcinoma, Small Cell; Heterocyclic Compounds, 3-Ring; Antineoplastic Agents; Middle Aged
PubMed: 38920737
DOI: 10.3390/curroncol31060254 -
Geriatrics (Basel, Switzerland) May 2024Self-disclosure is the attitude of communicating one's experiences and condition to others and is an indicator of mental health and an open personality. Frailty,...
Development of the Self-Assessment Self-Disclosure Questionnaire to Examine the Association between Self-Disclosure and Frailty among Community-Dwelling Older Adults in Japan.
Self-disclosure is the attitude of communicating one's experiences and condition to others and is an indicator of mental health and an open personality. Frailty, characterized by reduced physical and psychological resistance, predicts the incidence of dependency and mortality. Although low self-disclosure may be associated with frailty, there is no scale to measure older adults' self-disclosure. This cross-sectional study assessed the validity of a self-assessment self-disclosure questionnaire and examined the association between the content of self-disclosures to friends and acquaintances and frailty among community-dwelling older adults. A total of 237 adults aged ≥65 in Japan were surveyed using a mailed self-administered questionnaire in 2021. The self-disclosure scale consisted of 10 items and showed adequate validity. Participants were classified into a robust group ( = 117, women 57.3%) and a frailty group ( = 120, women 73.3%) using the Kihon Checklist. After adjusting for covariates, multivariate-adjusted logistic regression models revealed frailty was associated with lower self-disclosure of recent positive events, motivation and strengths (indicating strong points) in life, relationships with family and relatives, experiences of work and social activities, and financial status. The proposed questionnaire must still be further tested in other populations, but our initial results may contribute to preventing frailty and improving mental health among community-dwelling older adults.
PubMed: 38920423
DOI: 10.3390/geriatrics9030067 -
Clocks & Sleep May 2024Shift work, long work hours, and operational tasks contribute to sleep and circadian disruption in defence personnel, with profound impacts on cognition. To address...
Shift work, long work hours, and operational tasks contribute to sleep and circadian disruption in defence personnel, with profound impacts on cognition. To address this, a digital technology, the SleepSync app, was designed for use in defence. A pre-post design study was undertaken to examine whether four weeks app use improved sleep and cognitive fitness (high performance neurocognition) in a cohort of shift workers from the Royal Australian Air Force. In total, 13 of approximately 20 shift-working personnel from one base volunteered for the study. Sleep outcomes were assessed using the Insomnia Severity Index (ISI), the Patient-Reported Outcomes Measurement Information System (PROMIS), Sleep Disturbance and Sleep-Related Impairment Scales, the Glasgow Sleep Effort Scale, the Sleep Hygiene Index, and mental health was assessed using the Depression, Anxiety, and Stress Scale-21. Sustained attention was measured using the 3-min Psychomotor Vigilance Task (PVT) and controlled response using the NBack. Results showed significant improvements in insomnia (ISI scores 10.31 at baseline and 7.50 after app use), sleep-related impairments (SRI T-scores 53.03 at baseline to 46.75 post-app use), and healthy sleep practices (SHI scores 21.61 at baseline to 18.83 post-app use; all < 0.001). Trends for improvement were recorded for depression. NBack incorrect responses reduced significantly (9.36 at baseline; reduced by -3.87 at last week of app use, < 0.001), but no other objective measures improved. These findings suggest that SleepSync may improve sleep and positively enhance cognitive fitness but warrants further investigation in large samples. Randomised control trials with other cohorts of defence personnel are needed to confirm the utility of this intervention in defence settings.
PubMed: 38920420
DOI: 10.3390/clockssleep6020019 -
Health Affairs Scholar Jun 2024The Centers for Medicare & Medicaid Services (CMS) relies on public comments submitted in response to proposed national coverage determinations to assist the agency in...
The Centers for Medicare & Medicaid Services (CMS) relies on public comments submitted in response to proposed national coverage determinations to assist the agency in determining the coverage of items and services for Medicare beneficiaries. In a cross-sectional study, we characterized the cited evidence and what funding supported the cited evidence submitted in public comments to CMS for all therapeutic medical device national coverage determinations finalized between June 2019 and June 2022. Of 681 public comments, 159 (23%) cited at least 1 identifiable published scientific journal article. Within these 159 public comments, 198 unique articles were cited, 170 (86%) of which included funding statements or author disclosures. Among these, 96 (56%) disclosed funding from manufacturers that would benefit from Medicare coverage and/or were written by author(s) who received funding from these manufacturers. In summary, most public commenters for national coverage determinations did not cite published scientific journal articles to support their positions. Among those who did, more than half of articles were directly funded by manufacturers that would benefit from coverage. Greater funding of independent, non-industry-supported research may help provide unbiased evaluations of benefits and harms to support Medicare coverage decisions.
PubMed: 38919964
DOI: 10.1093/haschl/qxae064 -
Canadian Oncology Nursing Journal =... 2023To explore the impact of implementation of a symptom screening and supportive/palliative care referral pathway in patients newly referred to a Canadian gastrointestinal...
PURPOSE
To explore the impact of implementation of a symptom screening and supportive/palliative care referral pathway in patients newly referred to a Canadian gastrointestinal medical oncology clinic.
METHODS
Eighty-eight subjects were recruited in each study arm. Intervention subjects were assessed by a member of the supportive/palliative care team if they had a severity score of >3/10 on the Edmonton Symptom Assessment System. Controls received normal care, including discretionary referral. Symptom severity was assessed over the subsequent five months. Data on survival, care setting of death (home, hospice or hospital) and long-term resource use were also collected.
RESULTS
Screening led to 141 specialist supportive/palliative care visits in the intervention arm versus only nine in the control arm. There were, however, no subsequent significant differences in symptom severity or the long-term outcomes measured. Many patients identified by the >3/10 severity threshold did not need/want specialist supportive/palliative care referral, and those with severe distress were either identified by the oncology team already or were too unwell or overwhelmed to participate in the study. The specialist service was not overwhelmed. Important considerations on timing and mode of administration of screening tools were revealed.
CONCLUSION
Routine symptom screening can be burdensome for oncology patients and needs to be as simple as possible. Triaging positive screens is an important role for oncology nurses. Investment in training oncology teams to manage uncomplicated distress in the oncology clinic allows for optimal use of scarce supportive/palliative care specialist resources for patients with complex needs.
PubMed: 38919584
DOI: 10.5737/23688076334452 -
Frontiers in Nutrition 2024Human milk, due to its unique composition, is the optimal standard for infant nutrition. Osteopontin (OPN) is abundant in human milk but not bovine milk. The addition of... (Review)
Review
Human milk, due to its unique composition, is the optimal standard for infant nutrition. Osteopontin (OPN) is abundant in human milk but not bovine milk. The addition of bovine milk osteopontin (bmOPN) to formula may replicate OPN's concentration and function in human milk. To address safety concerns, we convened an expert panel to assess the adequacy of safety data and physiological roles of dietary bmOPN in infancy. The exposure of breastfed infants to human milk OPN (hmOPN) has been well-characterized and decreases markedly over the first 6 months of lactation. Dietary bmOPN is resistant to gastric and intestinal digestion, absorbed and cleared from circulation within 8-24 h, and represents a small portion (<5%) of total plasma OPN. Label studies on hmOPN suggest that after 3 h, intact or digested OPN is absorbed into carcass (62%), small intestine (23%), stomach (5%), and small intestinal perfusate (4%), with <2% each found in the cecum, liver, brain, heart, and spleen. Although the results are heterogenous with respect to bmOPN's physiologic impact, no adverse impacts have been reported across growth, gastrointestinal, immune, or brain-related outcomes. Recombinant bovine and human forms demonstrate similar absorption in plasma as bmOPN, as well as effects on cognition and immunity. The panel recommended prioritization of trials measuring a comprehensive set of clinically relevant outcomes on immunity and cognition to confirm the safety of bmOPN over that of further research on its absorption, distribution, metabolism, and excretion. This review offers expert consensus on the adequacy of data available to assess the safety of bmOPN for use in infant formula, aiding evidence-based decisions on the formulation of infant formula.
PubMed: 38919388
DOI: 10.3389/fnut.2024.1404303 -
The Iowa Orthopaedic Journal 2024Posterior cruciate ligament (PCL) tears in young children are rare and optimal treatment is poorly described. Diagnosis may prove challenging as young children may not... (Review)
Review
BACKGROUND
Posterior cruciate ligament (PCL) tears in young children are rare and optimal treatment is poorly described. Diagnosis may prove challenging as young children may not be able to verbalize a complete history of injury, may be difficult to examine, and plane film radiographs often appear within normal limits. Surgical treatment carries a risk of physeal arrest, but non-operative treatment may lead to recurrent instability and pain.
METHODS
We present a case report of a fouryear- old child with a PCL avulsion off the femoral insertion who received an open reduction and internal fixation (ORIF) with combined arthroscopic synovial debridement. We performed a literature review which compared the mechanism, location, concomitant injuries, work up and management of PCL injuries in children under the age of ten compared to adolescents and adults.
RESULTS
Nineteen months following surgery, physical examination revealed full knee range of motion and return to baseline function. Imaging studies confirmed there was no evidence of physeal arrest.
CONCLUSION
ORIF with arthroscopy can be an effective method to treat PCL avulsions in children under the age of 10 years. This is similar to other case reports which reported positive outcomes with ORIF in this population. Large studies are needed to best understand optimal treatment modalities for PCL injuries in very young children. .
Topics: Humans; Posterior Cruciate Ligament; Arthroscopy; Child, Preschool; Male; Debridement; Knee Injuries; Range of Motion, Articular; Treatment Outcome; Fracture Fixation, Internal; Female
PubMed: 38919372
DOI: No ID Found -
The Iowa Orthopaedic Journal 2024Fibular hemimelia is the most common congenital long bone deficiency. It is often associated with femoral and tibial deficiencies which result in a clinically evident...
BACKGROUND
Fibular hemimelia is the most common congenital long bone deficiency. It is often associated with femoral and tibial deficiencies which result in a clinically evident leg length discrepancy. The primary soft tissue concern is ACL/PCL deficiency. If treatment includes bony lengthening, joint stability is imperative to avoid complications. In this study, we detail a novel technique for long bone lengthening and ACL reconstruction in a single, cohesive surgery. This consolidates the need for multiple procedures and offers improved limb length symmetry and knee stability for this patient population. Clinical outcomes of pediatric patients with hemimelia who underwent either femoral or tibial lengthening with PRECICE® nail and concomitant ACL reconstruction are presented.
METHODS
After IRB approval, we identified five patients with complex fibular hemimelia who underwent ACL reconstruction and concomitant lengthening with at least two years of follow-up. Two patients (40%) presented with congenital short femur, and three (60%) with congenital short tibia. In each case, ACL reconstruction and either femoral or tibial guided growth via PRECICE® nail were performed. Operative techniques involving both soft tissue and bony methodology are described in detail.
RESULTS
All patients had objective improvement in knee stability as assessed both intra and post operatively, as well as successful intermedullary lengthening without complications related to joint stability. Three patients had minor complications unrelated to joint stability that did not interfere with overall result.
CONCLUSION
Fibular hemimelia associated with hypoplasia of bony and soft tissue structures can be successfully addressed with concomitant ligamentous reconstruction at the time of implantation of lengthening devices. This addresses knee instability and reduces both number of operative procedures and potential complications related to joint instability while pursuing bony lengthening. .
Topics: Humans; Retrospective Studies; Ectromelia; Male; Female; Fibula; Child; Anterior Cruciate Ligament Reconstruction; Bone Lengthening; Treatment Outcome; Adolescent; Tibia; Femur
PubMed: 38919371
DOI: No ID Found