Spontaneous Pupillary Recovery of Urrets-Zavalia Syndrome Following Descemet’s Membrane Endothelial Keratoplasty

To report a case of Urrets-Zavalia syndrome (UZS) with spontaneous pupillary recovery following Descemet's membrane endothelial keratoplasty (DMEK). This was an interventional case report with literature review. A 37-year-old female phakic patient presented to our clinic with bilateral decreased vision secondary to worsening Fuch’s endothelial dystrophy. She underwent bilateral inferior peripheral iridotomies prior to undergoing left DMEK surgery under general anaesthesia. The DMEK surgery was uncomplicated but she had a large fixed and dilated left pupil on the following day despite a normal examination with a normal intraocular pressure. A diagnosis of UZS was made. The pupil remained fixed and dilated until 4 months postoperatively, which anisocoria started to improve by time. At 6 months postoperative, anisocoria had fully resolved with normal pupillary reactions and complete resolution of photopic symptoms. UZS is a rare complication of DMEK surgery and, to our best knowledge, only one case has been reported in the literature. Surgeons and patients should be aware of this potential phenomenon following uneventful DMEK surgery. Conservative measures should be considered for initial management of UZS in young patients as spontaneous recovery may sometimes ensue, as occurred in our case

Strategies in Translating the Therapeutic Potentials of Host Defense Peptides

The golden era of antibiotics, heralded by the discovery of penicillin, has long been challenged by the emergence of antimicrobial resistance (AMR). Host defense peptides (HDPs), previously known as antimicrobial peptides, are emerging as a group of promising antimicrobial candidates for combatting AMR due to their rapid and unique antimicrobial action. Decades of research have advanced our understanding of the relationship between the physicochemical properties of HDPs and their underlying antimicrobial and non-antimicrobial functions, including immunomodulatory, anti-biofilm, and wound healing properties. However, the mission of translating novel HDP-derived molecules from bench to bedside has yet to be fully accomplished, primarily attributed to their intricate structure-activity relationship, toxicity, instability in host and microbial environment, lack of correlation between in vitro and in vivo efficacies, and dwindling interest from large pharmaceutical companies. Based on our previous experience and the expanding knowledge gleaned from the literature, this review aims to summarize the novel strategies that have been employed to enhance the antimicrobial efficacy, proteolytic stability, and cell selectivity, which are all crucial factors for bench-to-bedside translation of HDP-based treatment. Strategies such as residues substitution with natural and/or unnatural amino acids, hybridization, L-to-D heterochiral isomerization, C- and N-terminal modification, cyclization, incorporation with nanoparticles, and “smart design” using artificial intelligence technology, will be discussed. We also provide an overview of HDP-based treatment that are currently in the development pipeline

Amniotic Membrane Transplantation for Infectious Keratitis: A Systematic Review and Meta-Analysis

Infectious keratitis (IK) is the 5th leading cause of blindness globally. Broad-spectrum topical antimicrobial treatment is the current mainstay of treatment for IK, though adjuvant treatment or surgeries are often required in refractory cases of IK. This systematic review aimed to examine the effectiveness and safety of adjuvant amniotic membrane transplantation (AMT) for treating IK. Electronic databases, including MEDLINE, EMBASE and Cochrane Central, were searched for relevant articles. All clinical studies, including randomized controlled trials (RCTs), non-randomized controlled studies and case series (n>5), were included. Primary outcome measure was time to complete corneal healing and secondary outcome measures included corrected-distance-visual-acuity (CDVA), uncorrected-distance-visual-acuity (UDVA), corneal vascularization and adverse events. A total of twenty-eight studies (including four RCTs) with 861 eyes were included. When compared to standard antimicrobial treatment (SAT) alone, adjuvant AMT resulted in shorter mean time to complete corneal healing (-4.08 days; 95% CI, -6.27 to -1.88;

Photoactivated chromophore for infectious keratitis – Corneal cross-linking (PACK-CXL): A systematic review and meta-analysis

Purpose: To examine the efficacy of adjuvant photoactivated chromophore for infectious keratitis–corneal cross-linking (PACK-CXL) for the treatment of infectious keratitis (IK). / Methods: Electronic databases, including MEDLINE, EMBASE and Cochrane Central, were searched for articles related to PACK-CXL. All clinical studies, including randomized controlled trials (RCTs), non-randomized controlled studies, case series and case reports, were included. A meta-analysis was further performed when there were sufficient similarities in the included RCTs. Primary outcome measure was time to complete corneal healing and secondary outcome measures included size of epithelial defect and infiltrate, corrected-distance-visual-acuity (CDVA), and adverse events. / Results: Forty-six eligible studies (including four RCTs) with 435 patients were included. When compared to standard antimicrobial treatment (SAT) alone, adjuvant PACK-CXL resulted in shorter mean time to complete corneal healing (−7.44 days; 95% CI, −10.71 to −4.16) and quicker resolution of the infiltrate at 7 days (−5.49 mm2; 95% CI, −7.44 to −3.54) and at 14–30 days (−5.27 mm2; 95% CI, −9.12 to −1.41). There was no significant difference in the size of epithelial defect, CDVA and risk of adverse events. Evidence on the use of PACK-CXL in acanthamoeba and mixed IK was insufficient. / Conclusions: Our study demonstrates that adjuvant PACK-CXL expedites the healing of IK when compared to SAT alone (low-quality evidence). Further adequately powered, high-quality RCTs are required to fully ascertain the therapeutic effect of PACK-CXL

Characterization of aldehyde dehydrogenase isozymes in ovarian cancer tissues and sphere cultures

BACKGROUND: Aldehyde dehydrogenases belong to a superfamily of detoxifying enzymes that protect cells from carcinogenic aldehydes. Of the superfamily, ALDH1A1 has gained most attention because current studies have shown that its expression is associated with human cancer stem cells. However, ALDH1A1 is only one of the 19 human ALDH subfamilies currently known. The purpose of the present study was to determine if the expression and activities of other major ALDH isozymes are associated with human ovarian cancer and ovarian cancer sphere cultures. METHODS: Immunohistochemistry was used to delineate ALDH isozyme localization in clinical ovarian tissues. Western Blot analyses were performed on lysates prepared from cancer cell lines and ovarian cancer spheres to confirm the immunohistochemistry findings. Quantitative reverse transcription-polymerase chain reactions were used to measure the mRNA expression levels. The Aldefluor® assay was used to measure ALDH activity in cancer cells from the four tumor subtypes. RESULTS: Immunohistochemical staining showed significant overexpression of ALDH1A3, ALDH3A2, and ALDH7A1 isozymes in ovarian tumors relative to normal ovarian tissues. The expression and activity of ALDH1A1 is tumor type-dependent, as seen from immunohistochemisty, Western blot analysis, and the Aldefluor® assay. The expression was elevated in the mucinous and endometrioid ovarian epithelial tumors than in serous and clear cell tumors. In some serous and most clear cell tumors, ALDH1A1 expression was found in the stromal fibroblasts. RNA expression of all studied ALDH isozymes also showed higher expression in endometrioid and mucinous tumors than in the serous and clear cell subtypes. The expression of ALDH enzymes showed tumor type-dependent induction in ovarian cancer cells growing as sphere suspensions in serum-free medium. CONCLUSIONS: The results of our study indicate that ALDH enzyme expression and activity may be associated with specific cell types in ovarian tumor tissues and vary according to cell states. Elucidating the function of the ALDH isozymes in lineage differentiation and pathogenesis may have significant implications for ovarian cancer pathophysiology

A simple and robust method for connecting small-molecule drugs using gene-expression signatures

Interaction of a drug or chemical with a biological system can result in a gene-expression profile or signature characteristic of the event. Using a suitably robust algorithm these signatures can potentially be used to connect molecules with similar pharmacological or toxicological properties. The Connectivity Map was a novel concept and innovative tool first introduced by Lamb et al to connect small molecules, genes, and diseases using genomic signatures [Lamb et al (2006), Science 313, 1929-1935]. However, the Connectivity Map had some limitations, particularly there was no effective safeguard against false connections if the observed connections were considered on an individual-by-individual basis. Further when several connections to the same small-molecule compound were viewed as a set, the implicit null hypothesis tested was not the most relevant one for the discovery of real connections. Here we propose a simple and robust method for constructing the reference gene-expression profiles and a new connection scoring scheme, which importantly allows the valuation of statistical significance of all the connections observed. We tested the new method with the two example gene-signatures (HDAC inhibitors and Estrogens) used by Lamb et al and also a new gene signature of immunosuppressive drugs. Our testing with this new method shows that it achieves a higher level of specificity and sensitivity than the original method. For example, our method successfully identified raloxifene and tamoxifen as having significant anti-estrogen effects, while Lamb et al's Connectivity Map failed to identify these. With these properties our new method has potential use in drug development for the recognition of pharmacological and toxicological properties in new drug candidates.Comment: 8 pages, 2 figures, and 2 tables; supplementary data supplied as a ZIP fil

The effects of low frequency electrical stimulation on satellite cell activity in rat skeletal muscle during hindlimb suspension

<p>Abstract</p> <p>Background</p> <p>The ability of skeletal muscle to grow and regenerate is dependent on resident stem cells called satellite cells. It has been shown that chronic hindlimb unloading downregulates the satellite cell activity. This study investigated the role of low-frequency electrical stimulation on satellite cell activity during a 28 d hindlimb suspension in rats.</p> <p>Results</p> <p>Mechanical unloading resulted in a 44% reduction in the myofiber cross-sectional area as well as a 29% and 34% reduction in the number of myonuclei and myonuclear domains, respectively, in the soleus muscles (<it>P </it>< 0.001 <it>vs </it>the weight-bearing control). The number of quiescent (M-cadherin⁺), proliferating (BrdU⁺and myoD⁺), and differentiated (myogenin⁺) satellite cells was also reduced by 48-57% compared to the weight-bearing animals (<it>P </it>< 0.01 for all). Daily application of electrical stimulation (2 × 3 h at a 20 Hz frequency) partially attenuated the reduction of the fiber cross-sectional area, satellite cell activity, and myonuclear domain (<it>P </it>< 0.05 for all). Extensor digitorum longus muscles were not significantly altered by hindlimb unloading.</p> <p>Conclusion</p> <p>This study shows that electrical stimulation partially attenuated the decrease in muscle size and satellite cells during hindlimb unloading. The causal relationship between satellite cell activation and electrical stimulation remain to be established.</p

Clinical Characteristics and Outcomes of Fungal Keratitis in the United Kingdom 2011–2020: A 10-Year Study

Fungal keratitis (FK) is a serious ocular infection that often poses significant diagnostic and therapeutic dilemmas. This study aimed to examine the causes, clinical characteristics, outcomes, and prognostic factors of FK in the UK. All culture-positive and culture-negative presumed FK (with complete data) that presented to Queen’s Medical Centre, Nottingham, and the Queen Victoria Hospital, East Grinstead, between 2011 and 2020 were included. We included 117 patients (n = 117 eyes) with FK in this study. The mean age was 59.0 ± 19.6 years (range, 4–92 years) and 51.3% of patients were female. Fifty-three fungal isolates were identified from 52 (44.4%) culture-positive cases, with Candida spp. (33, 62.3%), Fusarium spp. (9, 17.0%), and Aspergillus spp. (5, 9.4%) being the most common organisms. Ocular surface disease (60, 51.3%), prior corneal surgery (44, 37.6%), and systemic immunosuppression (42, 35.9%) were the three most common risk factors. Hospitalisation for intensive treatment was required for 95 (81.2%) patients, with a duration of 18.9 ± 16.3 days. Sixty-six (56.4%) patients required additional surgical interventions for eradicating the infection. Emergency therapeutic/tectonic keratoplasty was performed in 29 (24.8%) cases, though 13 (44.8%) of them failed at final follow-up. The final corrected-distance-visual-acuity (CDVA) was 1.67 ± 1.08 logMAR. Multivariable logistic regression analyses demonstrated increased age, large infiltrate size (>3 mm), and poor presenting CDVA (60 days of healing time or occurrence of corneal perforation requiring emergency keratoplasty; all p < 0.05). In conclusion, FK represents a difficult-to-treat ocular infection that often results in poor visual outcomes, with a high need for surgical interventions. Innovative treatment strategies are urgently required to tackle this unmet need

12-year analysis of incidence, microbiological profiles and in vitro antimicrobial susceptibility of infectious keratitis: the Nottingham Infectious Keratitis Study

Background/aims: To examine the incidence, causative microorganisms and in vitro antimicrobial susceptibility and resistance profiles of infectious keratitis (IK) in Nottingham, UK.Methods: A retrospective study of all patients who were diagnosed with IK and underwent corneal scraping between July 2007 and October 2019 (a 12-year period) at a UK tertiary referral centre. Relevant data, including demographic factors, microbiological profiles and in vitro antibiotic susceptibility of IK, were analysed.Results: The estimated incidence of IK was 34.7 per 100 000 people/year. Of the 1333 corneal scrapes, 502 (37.7%) were culture-positive and 572 causative microorganisms were identified. Sixty (4.5%) cases were of polymicrobial origin (caused by ≥2 different microorganisms). Gram-positive bacteria (308, 53.8%) were most commonly isolated, followed by Gram-negative bacteria (223, 39.0%), acanthamoeba (24, 4.2%) and fungi (17, 3.0%). Pseudomonas aeruginosa (135, 23.6%) was the single most common organism isolated. There was a significant increase in Moraxella spp (