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1.
Cell ; 186(21): 4632-4651.e23, 2023 10 12.
Article in English | MEDLINE | ID: mdl-37776858

ABSTRACT

The dynamics of immunity to infection in infants remain obscure. Here, we used a multi-omics approach to perform a longitudinal analysis of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in infants and young children by analyzing blood samples and weekly nasal swabs collected before, during, and after infection with Omicron and non-Omicron variants. Infection stimulated robust antibody titers that, unlike in adults, showed no sign of decay for up to 300 days. Infants mounted a robust mucosal immune response characterized by inflammatory cytokines, interferon (IFN) α, and T helper (Th) 17 and neutrophil markers (interleukin [IL]-17, IL-8, and CXCL1). The immune response in blood was characterized by upregulation of activation markers on innate cells, no inflammatory cytokines, but several chemokines and IFNα. The latter correlated with viral load and expression of interferon-stimulated genes (ISGs) in myeloid cells measured by single-cell multi-omics. Together, these data provide a snapshot of immunity to infection during the initial weeks and months of life.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Child , Infant , Humans , Child, Preschool , SARS-CoV-2/metabolism , Multiomics , Cytokines/metabolism , Interferon-alpha , Immunity, Mucosal
2.
Breast Cancer Res Treat ; 196(1): 1-15, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36085533

ABSTRACT

PURPOSE: Circulating microRNAs (miRNAs) are potential diagnostic biomarkers for breast cancer (BC). The application of miRNA panels could improve the performance of screening tests. Here, we integrated bioinformatic tools and meta-analyses to select circulating miRNAs with high diagnostic accuracy and combined these markers to develop diagnostic panels for BC. METHODS: Analyses across databases were performed to identify potential BC-related circulating miRNAs. Next, a comprehensive meta-analysis was conducted for each miRNA following the PRISMA guidelines. An electronic and manual search for relevant literature was carried out by two reviewers through PubMed, ScienceDirect, Biomed Central, and Google Scholar. The quality of the included studies was assessed using the QUADAS-2, and the statistical analyses were performed using R software 4.1.1. Finally, the accurate biomarkers confirmed through meta-analyses were combined into diagnostic models for BC. RESULTS: Twenty-seven circulating miRNAs were identified as BC-related by bioinformatic tools. After screening, only 10 miRNAs presented in 45 studies were eligible for meta-analyses. By assessing pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio, 8 miRNAs (miR-21, miR-30b, miR-125b, miR-145, miR221 miR-222, and miR-335) were revealed as promising BC diagnostic biomarkers. Two panels constructed from these miRNAs showed excellent diagnostic accuracy for BC, with areas under the SROC curve of 0.917 and 0.944. CONCLUSION: We identified 8 potential circulating miRNAs and 2 diagnostic models that are useful for diagnosing BC. However, the established miRNA panels have not been tested in any experimental studies and thus should be validated in large case-control studies for clinical use.


Subject(s)
Breast Neoplasms , Circulating MicroRNA , MicroRNAs , Biomarkers , Biomarkers, Tumor/genetics , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Female , Humans , MicroRNAs/genetics , Odds Ratio
3.
Surg J (N Y) ; 8(2): e123-e126, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35712051

ABSTRACT

Primary breast tuberculosis (TB) is a rare extrapulmonary TB mainly affecting young women of childbearing age from endemic countries. Its incidence is increasing in immunocompromised and HIV-infected people and with the emergence of drug-resistant strains of Mycobacterium tuberculosis (MTB). There are no specific clinical signs suggestive of this disease, it often presents as a hard mass or breast abscess. There is an overlap of features with other inflammatory, infectious, benign lesions, fat necrosis and malignant neoplasms of the breast. The detection of MTB remains the gold standard for diagnosis. Several other diagnostic modalities are used, with varying lack of sensitivity and specificity, and with a range of false negatives. A quarter of cases were treated solely on the basis of clinical, imaging or histological suspicion, without confirmation of the diagnosis. Therefore, we report the case of a young Vietnamese woman, presented for a nonhealing breast abscess, and diagnosed with breast TB based on the patient's ethnicity, histological findings, lack of clinical response to conventional antibiotic therapy, and a good clinical response to anti-TB treatment.

4.
Article in English | MEDLINE | ID: mdl-32021973

ABSTRACT

OBJECTIVES: To evaluate the safety, feasibility and efficacy of trans-vaginal fractional micro-ablative CO2 laser therapy in combination with platelet rich plasma (PRP) for the treatment of stress urinary incontinence (SUI) in women. STUDY DESIGN: Participants with SUI underwent three sessions of transvaginal CO2 laser and PRP treatment, administered at 4-6-week intervals. Outcomes were assessed using the bladder function section of the Australian Pelvic Floor Questionnaire (APFQ). The primary outcome was changes in the participants' symptoms of SUI. Secondary outcomes were related to general bladder function. Outcome differences from baseline (T1) to 3 months (T2) and 12 months (T3) were analysed using Wilcoxon signed-rank tests. Subjective verbal scales were used to assess the degree of pain associated with PRP injections and laser treatment. RESULTS: Sixty-two women with SUI were enrolled into this study. There were 66% (41/62) of participants who reported improved SUI symptoms from T1 to T2 (p < 0.001) and at T3, 62% (23/37) of patients reported improved SUI symptoms (p < 0.001). From T1 to T2, all bladder function variables were improved significantly (p < 0.002). At T3, significant improvements (p < 0.03) were maintained for all bladder function variables, except pad usage (p = 0.073). CONCLUSIONS: Combining transvaginal fractional CO2 laser with PRP might be a beneficial treatment for SUI. It may have the potential to be a minimally-invasive and low-risk alternative to surgery, with reduced recovery time.

5.
Article in English | MEDLINE | ID: mdl-31396591

ABSTRACT

OBJECTIVES: To evaluate the impact of trans-vaginal fractional CO2 laser treatment on symptoms of stress urinary incontinence (SUI) in women. STUDY DESIGN: Women clinically diagnosed with SUI preferring non-surgical treatment were recruited to the study. Fractional CO2 laser system (MonaLisa T, DEKA) treatments were administered trans-vaginally every 4-6 weeks for a total of three treatments. Response to treatment was assessed at baseline (T1), at 3 months after treatment completion (T2) and at 12-24-month follow-up (T3) using the Australian Pelvic Floor Questionnaire (APFQ). The primary outcome was changes in reported symptoms of SUI. Secondary outcomes assessed included bladder function, urgency, urge urinary incontinence (UUI), pad usage, impact of urinary incontinence on quality of life (QOL) and degree of bothersome bladder. RESULTS: Fifty-eight women were recruited and received the study treatment protocol. Eighty-two percent of participants reported an improvement in symptoms of SUI at completion of treatment (mild to no SUI) (p = <0.01). Treatment effect waned slightly when assessed at follow-up. Nevertheless, 71% of participants reported ongoing improvement in SUI symptoms at 12-24 months (p < 0.01). All secondary outcome measures were improved after treatment compared to baseline. CONCLUSIONS: This study suggests that fractional CO2 laser is a safe, feasible, and beneficial treatment for SUI and may have a role as a minimally-invasive alternative to surgical management.

6.
Aust N Z J Obstet Gynaecol ; 59(1): 117-122, 2019 02.
Article in English | MEDLINE | ID: mdl-29920645

ABSTRACT

OBJECTIVE: To compare current practice in the management of female pelvic organ prolapse in Australia and New Zealand with that in 2007, and assess the impact on practice of the withdrawal of Prolift® and Prosima® mesh kits in 2015. MATERIALS AND METHODS: In early 2015, two invitations to participate in a survey, including a link to Surveymonkey, were emailed to 2506 Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) trainees and fellows. The online survey closely resembled a printed survey that was posted to RANZCOG trainees and fellows in 2007 and had additional questions relating to the impact of withdrawal of Prolift® and Prosima® products. RESULTS: Four-hundred-and-three doctors participated, giving a response rate of 16%. Native tissue repair was the procedure of choice for primary and recurrent prolapse of the anterior and posterior vaginal wall. An implant was used to treat 45% of anterior recurrences and 25% of posterior recurrences. Vaginal hysterectomy and repair were the procedures of choice for uterovaginal prolapse. Sacrospinous hysteropexy was the uterine preservation procedure of choice, preferred by 41%. For post-hysterectomy vault prolapse, sacrospinous colpopexy and vaginal repair was preferred by 65% of respondents. Between 2007 and 2015, there was a substantial decrease in respondents' usage of implants across all indications except for midurethral slings and sacrocolpo/hysteropexy. Forty-two percent of respondents changed their practice as a result of Prolift® and Prosima® being withdrawn. CONCLUSION: There is a trend toward increasing use of various native tissue prolapse repair procedures and midurethral slings, and less utilisation of transvaginal mesh for prolapse.


Subject(s)
Pelvic Organ Prolapse/surgery , Practice Patterns, Physicians'/trends , Aged , Australia , Female , Gynecologic Surgical Procedures/trends , Humans , Hysterectomy, Vaginal/trends , Middle Aged , New Zealand , Suburethral Slings/trends , Surgical Mesh/trends , Surveys and Questionnaires , Suture Techniques
7.
Psychiatry Res ; 209(3): 684-90, 2013 Oct 30.
Article in English | MEDLINE | ID: mdl-23561490

ABSTRACT

Stigmatisation towards depression has previously been reported amongst medical students from a variety of backgrounds. This study explored personal and perceived stigmas associated with depression, and their relationship with demographics, knowledge of depression, levels of personal stress and history of medical illness amongst Australian-trained medical students. A cross-sectional survey was undertaken amongst students enroled June-to-August 2009 across four Australian medical schools. In total, 1010 students completed the survey, a response rate of 29.6%. Approximately 25% of students reported a past history of depression. Higher stress (K-10 scores) was reported by females and those with a past history of depression. On a scale of 0-to-5, the mean (±S.D.) personal and perceived stigma depression scores were 1.83±1.49 and 4.05±1.42 respectively. In multivariate analysis, higher perceived stigma and K-10 scores, a past history of anxiety and Year 3 of medical school indicated higher personal stigma scores. Perceived stigma was positively associated with K-10 scores, personal stigma scores, and a Caucasian background. Our findings suggest a high level of personal and particularly perceived stigma associated with depression amongst medical students, especially those displaying higher levels of stress. Adequate support and screening for psychological stress may de-stigmatise depression and improve mental health amongst future Australian doctors.


Subject(s)
Attitude to Health , Depression/psychology , Social Stigma , Stereotyping , Stress, Psychological/psychology , Students, Medical/psychology , Adult , Australia , Cross-Sectional Studies , Female , Health Surveys , Humans , Male , Predictive Value of Tests , Young Adult
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