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AnteayerPLOS ONE Medicine&Health

Allogeneic limbo-deep anterior lamellar keratoplasty (Limbo-DALK)—A novel surgical technique in corneal stromal disease and limbal stem cell deficiency

by Verena Schöneberger, Volkan Tahmaz, Mario Matthaei, Sigrid Roters, Simona L. Schlereth, Friederike Schaub, Claus Cursiefen, Björn O. Bachmann

Purpose

To describe a novel corneal surgical technique combining Deep Anterior Lamellar Keratoplasty (DALK) with grafting of allogeneic limbus (Limbo-DALK) for the treatment of eyes with corneal stromal pathology and limbal stem cell deficiency (LSCD).

Methods

Clinical records of six Limbo-DALKs performed in five patients diagnosed with LSCD and corneal stromal pathology requiring keratoplasty were retrospectively reviewed. All patients were diagnosed with LSCD due to various pathologies including thermal and chemical burns, congenital aniridia or chronic inflammatory ocular surface disease. Parameters analysed included demographics, diagnoses, clinical history, thickness measurements using anterior segment OCT, visual acuity, and epithelial status. Regular follow-up visits were scheduled at 6 weeks as well as 3, 6, 9, and 12 and 18 months postoperatively. Main outcome measures were time to graft epithelialisation and the occurrence of corneal endothelial decompensation.

Results

Two grafts showed complete epithelial closure at 2 days, two at 14 days. In one eye, complete epithelial closure was not achieved after the first Limbo-DALK, but was achieved one month after the second Limbo-DALK. No endothelial decompensation occurred except in one patient with silicone oil associated keratopathy. Endothelial graft rejection was not observed in any of the grafts.

Conclusion

Based on the data from this pilot series, limbo-DALK appears to be a viable surgical approach for eyes with severe LSCD and corneal stromal pathology, suitable for emergency situations (e.g. corneal ulceration with impending corneal perforation), while minimising the risk of corneal endothelial decompensation.

Diagnostics of preeclampsia based on Congo red binding to urinary components: Rationales and limitations

by Sergei A. Fedotov, Maria S. Khrabrova, Elena S. Vashukova, Andrey S. Glotov, Anastasia O. Anpilova, Vladimir A. Dobronravov, Maria E. Velizhanina, Aleksandr A. Rubel

Preeclampsia is a disorder that can occur during pregnancy and is one of the leading causes of death among pregnant women. This disorder occurs after the 20th week of pregnancy and is characterized by arterial hypertension, proteinuria, fetoplacental, and multiple organ dysfunctions. Despite the long history of studying preeclampsia, its etiology and pathogenesis remain poorly understood, and therapy is symptomatic. One of the factors of the disorder is believed to be misfolded proteins that are prone to form amyloid aggregates. The CRD tests, utilizing the binding of the amyloid-specific dye Congo red to urine components, demonstrate high efficiency in diagnosing preeclampsia. However, these tests have also been found to be positive in other disorders with proteinuria, presumably associated with concomitant amyloidosis. To assess the limitations of the CRD tests, we examined urine congophilia and protein components mediating Congo red positivity in patients with proteinuria, including preeclampsia, amyloid and non-amyloid nephropathies. We stained the urine samples and calculated congophilia levels. We also assessed the contribution of large protein aggregates to congophilia values using ultracentrifugation and determined the molecular weights of congophilic urinary proteins using centrifugal concentrators. All proteinuric groups demonstrate positive results in the CRD tests and congophilia levels were more than two times higher compared with the control non-proteinuric groups (p rs = 0.76), non-amyloid nephropathies (rs = 0.90), and preeclampsia (rs = 0.90). Removal of large aggregates from urine did not affect the congophilia levels. Separation of urine protein fractions revealed congophilic components in the range of 30–100 kDa, including monomeric serum albumin. Our results indicate limitations of CRD tests in preeclampsia diagnostics in women with renal disorders and underscore the need for further research on the mechanisms of Congo red binding with urine components.

Cross-sectional study of attitudes toward online continuing dental education in Libya during the COVID-19 pandemic

by Ranya F. Elemam, Jamal M. El Swiah, Abduallah O. Durda, Nagwa N. Hegazy

During the COVID-19 pandemic, many educational institutions switched to e-learning educational platforms. This approach was essential but raised challenges, particularly in training practitioners for medical emergencies. This approach not only led to global challenges and a need for rapid adaptation, but also raised inequities across countries, with some facing far more technical challenges than others. In Libya, low investment in education technology and unpredictable internet connectivity limited its integration into schools and universities even before the pandemic. The current study reports feedback from an online continuing dental education (CDE) course for dental practitioners that was developed emergently during the pandemic and aimed to address the challenges posed by Libya’s internet environment. Participants were recruited through social media and received an 8-hour online CDE course consisting of three modules. Participants were invited to complete a pre-course demographic/informational survey on a Google form. After passing all modules, students were prompted to complete a post-course survey consisting of 23, five-point Likert scale questions. Respondents included 43 females (74.1%) and 15 males (25.9%). For ~50% of the cohort (n = 32), this was their first online clinical course. 87.9% of post-course participants rated the course as a positive learning experience, while 90.9% agreed their learning outcomes had been achieved. Most participants (97%) agreed the course instructor explained all concepts clearly. In total, 81.8% agreed that the technology effectively supported their learning. Most agreed that a clear demarcation between each course module existed and that the language and depth of the material were adequate. Some students reported technical difficulties, and 33.3% saw repetitions in the modules. However, all post-course respondents said they would recommend the online course to colleagues. Libyan dental practitioners showed high satisfaction levels towards the e-learning process, course content, instructors’ attitudes, and overall e-learning experience despite the inherent e-learning challenges posed in this country.

Risk of sexually transmitted infections among U.S. military service members in the setting of HIV pre-exposure prophylaxis use

by Jason M. Blaylock, Evan C. Ewers, Elizabeth J. Bianchi, David B. King, Rosemary O. Casimier, Hector Erazo, Stephen Grieco, Jenny Lay, Sheila A. Peel, Kayvon Modjarrad, Charmagne G. Beckett, Jason F. Okulicz, Paul T. Scott, Shilpa Hakre

Background

The evidence for an increased incidence of sexually transmitted infections (STIs) among patients utilizing HIV pre-exposure prophylaxis (PrEP) has been inconsistent. We assessed the risk of incident STI while on PrEP compared to periods off PrEP among military service members starting PrEP.

Methods

Incidence rates of chlamydia, gonorrhea, syphilis, hepatitis C virus, and HIV were determined among military service members without HIV prescribed daily oral tenofovir disoproxil fumarate and emtricitabine for HIV PrEP from February 1, 2014 through June 10, 2016. Hazard ratios for incident STIs were calculated using an Anderson-Gill recurrent event proportional hazard regression model.

Results

Among 755 male service members, 477 (63%) were diagnosed with incident STIs (overall incidence 21.4 per 100 person-years). Male service members had a significantly lower risk of any STIs (adjusted hazard ratio (aHR) 0.21, 95% CI 0.11–0.40) while using PrEP compared to periods off PrEP after adjustment for socio-demographic characteristics, reasons for initiating PrEP, surveillance period prior to PrEP initiation, and the effect of PrEP on site and type of infection in multivariate analysis. However, when stratifying for anatomical site and type of infection, the risk of extragenital gonorrhea infection (pharyngeal NG: aHR 1.84, 95% CI 0.82–4.13, p = 0.30; rectal NG: aHR 1.23, 95% CI 0.60–2.51, p = 1.00) and extragenital CT infection (pharyngeal CT: aHR 2.30, 95% CI 0.46–11.46, p = 0.81; rectal CT: aHR 1.36, 95% CI 0.81–2.31, p = 0.66) was greater on PrEP compared to off PrEP although these values did not reach statistical significance.

Conclusions

The data suggest entry into PrEP care reduced the overall risk of STIs following adjustment for anatomical site of STI and treatment. Service members engaged in PrEP services also receive more STI prevention counseling, which might contribute to decreases in STI risk while on PrEP.

Characterization of Type VI secretion system in <i>Edwardsiella ictaluri</i>

by Safak Kalindamar, Hossam Abdelhamed, Adef O. Kordon, Hasan C. Tekedar, Lesya Pinchuk, Attila Karsi

Edwardsiella ictaluri is a Gram-negative facultative intracellular fish pathogen causing enteric septicemia of catfish (ESC). While various secretion systems contribute to E. ictaluri virulence, the Type VI secretion system (T6SS) remains poorly understood. In this study, we constructed 13 E. ictaluri T6SS mutants using splicing by overlap extension PCR and characterized them, assessing their uptake and survival in channel catfish (Ictalurus punctatus) peritoneal macrophages, attachment and invasion in channel catfish ovary (CCO) cells, in vitro stress resistance, and virulence and efficacy in channel catfish. Among the mutants, EiΔevpA, EiΔevpH, EiΔevpM, EiΔevpN, and EiΔevpO exhibited reduced replication inside peritoneal macrophages. EiΔevpM, EiΔevpN, and EiΔevpO showed significantly decreased attachment to CCO cells, while EiΔevpN and EiΔevpO also displayed reduced invasion of CCO cells (p EiΔevpA, EiΔevpH, EiΔevpM, EiΔevpN, and EiΔevpO were susceptible to oxidative stress in both nutrient-rich and minimal medium. In fish challenges, EiΔevpD, EiΔevpE, EiΔevpG, EiΔevpJ, and EiΔevpK exhibited attenuation and provided effective protection against E. ictaluri wild-type (EiWT) infection in catfish fingerlings. However, their attenuation and protective efficacy were lower in catfish fry. These findings shed light on the role of the T6SS in E. ictaluri pathogenesis, highlighting its significance in intracellular survival, host cell attachment and invasion, stress resistance, and virulence. The attenuated T6SS mutants hold promise as potential candidates for protective immunization strategies in catfish fingerlings.

Impact of San Francisco’s New Street crisis response Team on Service use among people experiencing homelessness with mental and substance use disorders: A mixed methods study protocol

by Matthew L. Goldman, Megan McDaniel, Deepa Manjanatha, Monica L. Rose, Glenn-Milo Santos, Starley B. Shade, Ann A. Lazar, Janet J. Myers, Margaret A. Handley, Phillip O. Coffin

Mobile crisis services for people experiencing distress related to mental health or substance use are expanding rapidly across the US, yet there is little evidence to support these specific models of care. These new programs present a unique opportunity to expand the literature by utilizing implementation science methods to inform the future design of crisis systems. This mixed methods study will examine the effectiveness and acceptability of the Street Crisis Response Team (SCRT), a new 911-dispatched multidisciplinary mobile crisis intervention piloted in San Francisco, California. First, using quantitative data from electronic health records, we will conduct an interrupted time series analysis to quantitatively examine the impacts of the SCRT on people experiencing homelessness who utilized public behavioral health crisis services in San Francisco between November 2019 and August 2022, across four main outcomes within 30 days of the crisis episode: routine care utilization, crisis care reutilization, assessment for housing services, and jail entry. Second, to understand its impact on health equity, we will analyze racial and ethnic disparities in these outcomes prior to and after implementation of the SCRT. For the qualitative component, we will conduct semi-structured interviews with recipients of the SCRT’s services to understand their experiences of the intervention and to identify how the SCRT influenced their health-related trajectories after the crisis encounter. Once complete, the quantitative and qualitative findings will be further analyzed in tandem to assist with more nuanced understanding of the effectiveness of the SCRT program. This evaluation of a novel mobile crisis response program will advance the field, while also providing a model for how real-world program implementation can be achieved in crisis service settings.

Maternal exposure to SSRIs or SNRIs and the risk of congenital abnormalities in offspring: A systematic review and meta-analysis

by Weiyi Huang, Robin L. Page, Theresa Morris, Susan Ayres, Alva O. Ferdinand, Samiran Sinha

Background

The association of maternal exposure to selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) with the risk of system-specific congenital malformations in offspring remains unclear. We conducted a meta-analysis to examine this association and the risk difference between these two types of inhibitors.

Methods

A literature search was performed from January 2000 to May 2023 using PubMed and Web of Science databases. Cohort and case-control studies that assess the association of maternal exposure to SSRIs or SNRIs with the risk of congenital abnormalities were eligible for the study.

Results

Twenty-one cohort studies and seven case-control studies were included in the meta-analysis. Compared to non-exposure, maternal exposure to SNRIs is associated with a higher risk of congenital cardiovascular abnormalities (pooled OR: 1.64 with 95% CI: 1.36, 1.97), anomalies of the kidney and urinary tract (pooled OR: 1.63 with 95% CI: 1.21, 2.20), malformations of nervous system (pooled OR: 2.28 with 95% CI: 1.50, 3.45), anomalies of digestive system (pooled OR: 2.05 with 95% CI: 1.60, 2.64) and abdominal birth defects (pooled OR: 2.91 with 95%CI: 1.98, 4.28), while maternal exposure to SSRIs is associated with a higher risk of congenital cardiovascular abnormalities (pooled OR: 1.25 with 95%CI: 1.20, 1.30), anomalies of the kidney and urinary tract (pooled OR: 1.14 with 95%CI: 1.02, 1.27), anomalies of digestive system (pooled OR: 1.11 with 95%CI: 1.01, 1.21), abdominal birth defects (pooled OR: 1.33 with 95%CI: 1.16, 1.53) and musculoskeletal malformations (pooled OR: 1.44 with 95%CI: 1.32, 1.56).

Conclusions

SSRIs and SNRIs have various teratogenic risks. Clinicians must consider risk-benefit ratios and patient history when prescribing medicines.

Healthcare professionals’ views on the most important outcomes for non-infectious uveitis of the posterior segment: A qualitative study

by Mohammad O. Tallouzi, David J. Moore, Nicholas Bucknall, Philip I. Murray, Melanie J. Calvert, Alastair K. Denniston, Jonathan Mathers

Background

Uveitis comprises a range of conditions that result in intraocular inflammation. Most sight-threatening uveitis falls into the broad category known as Non-infectious Posterior Segment-Involving Uveitis (PSIU). To evaluate treatments, trialists and clinicians must select outcome measures. The aim of this study was to understand healthcare professionals’ perspectives on what outcomes are important to adult patients with PSIU and their carers.

Methods

Twelve semi-structured telephone interviews were undertaken to understand the perspectives of healthcare professionals. Interviews were audio recorded, transcribed and thematically analysed. Findings were compared with the views of patients and carers and outcomes abstracted from a previously published systematic review.

Results

Eleven core domains were identified as important to healthcare professionals: (1) visual function, (2) symptoms, (3) functional ability, (4) impact on relationships, (5) financial impact, (6) psychological morbidity and emotional well-being (7) psychosocial adjustment to uveitis, (8) doctor / patient / interprofessional relationships and access to health care, (9) treatment burden, (10) treatment side effects, (11) disease control. Healthcare professionals recognised a similar range of domains to patients and carers but placed more emphasis on certain outcomes, particularly in the disease control domain. In contrast the range of outcomes identified via the systematic review was limited.

Conclusion

Healthcare professionals recognise all of the published outcome domains as patients/carers in the previous publication but with subtly differing emphasis within some domains and with a priority for certain types of measures. Healthcare professionals discussed the disease control and side effects/complications to a greater degree than patients and carers in the focus groups

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