Retinal arterial occlusion and patent foramen ovale: A case study-based review.

PURPOSE: To identify all reported cases of retinal artery occlusion (RAO) associated with patent foramen ovale (PFO) in the literature and present a similar case of CRAO from our clinic. METHODS: PubMed database was searched for studies reporting RAO in individuals with PFO. Relevant data were tabulated and reviewed. We estimated each case's Risk of Paradoxical Embolism (RoPE) score. RESULTS: 23 cases of CRAO (n=10; including ours), BRAO (n=10), and CILRAO (n=3) were reviewed. Most cases were under 50 years of age (78.3%). The reported predisposing factors were: hypertension (26.1%), migraine (17.3%), smoking (13.0%), recent immobilization (13.0%), strenuous exertion (8.7%), pregnancy (8.7%), and diabetes (4.3%). A high RoPE score (≥7; suggestive of paradoxical embolism via PFO) was estimated for 71.4% of patients. In most cases, the neurological and cardiovascular examinations, laboratory studies, and imaging were unremarkable, except for the PFO±atrial septal aneurysm (present in 21.7%). In only 28.6% of cases, transthoracic echocardiography (TTE) (± saline contrast) could visualize the PFO; transesophageal echocardiography (TEE) was necessary to detect the PFO in 71.4%. Approximately one-half of the patients underwent percutaneous closure of the PFO; no complications or subsequent acute ischemic events ensued. The visual prognosis was poorer for CRAO than for BRAO or CILRAO. CONCLUSION: Timely diagnosis, acute management, and ensuring urgent initiation of stroke workup in cases with RAO or transient monocular vision loss are crucial. Clues to a possible paradoxical embolism as the cause include the absence of known cardiovascular risk factors, young age, migraine, recent immobility, vigorous exercise, and pregnancy.

Intravitreal fasudil monotherapy for treatment of refractory diabetic macular edema: A prospective interventional case series.

BACKGROUND: Suboptimal response to conventional treatments in refractory diabetic macular edema (rDME) encourages efforts to identify new therapeutic options. PURPOSE: To evaluate the effect of three monthly intravitreal injections of a Rho-associated protein kinase (ROCK) inhibitor (Fasudil, Asahi Kasei Pharma Corporation, Tokyo, Japan) in eyes with rDME. METHODS: Ten eyes of 10 patients with DME unresponsive to at least six previous intravitreal bevacizumab (IVB) injections were recruited and underwent 3 consecutive monthly intravitreal injection of 0.025mg/0.05mL Fasudil. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were evaluated as functional and anatomical response indicators, respectively. RESULTS: The mean age was 60.1±5.1 years (range, 53-68). Five cases responded to treatment, two with both anatomical and functional responses (reduction of CMT from 521 to 395 and from 390 to 301 microns and improvement of BCVA from 0.3 to 0.1 LogMAR and 0.6 to 0.4 LogMAR, respectively) and three with only functional improvement (0.7 to 0.4; 0.7 to 0.4; and 0.3 to 0.1 LogMAR). Of note, cases with no significant change in CMT showed morphologic improvement of the retinal microstructure to some extent. No adverse event was observed during the study period. CONCLUSION: Monotherapy with intravitreal injection of ROCK inhibitors appears to have moderate visual benefits in eyes with DME refractory to IVB. Such effects may be functionally significant without obvious anatomical improvement.

The additive effect of intravitreal dexamethasone combined with bevacizumab in refractory diabetic macular edema.

PURPOSE: To evaluate the short-term structural and visual outcomes and side effects associated with intravitreal dexamethasone (IVD) combined with bevacizumab (IVB) in treating patients with diabetic macular edema (DME) and an inadequate response to anti-vascular endothelial growth factor (anti-VEGF) agents. METHODS: In this prospective interventional case series, a total of 81 eyes of 81 patients with type 2 diabetes mellitus (T2DM) and refractory DME were included and assigned to one of two groups: I) those receiving three monthly intravitreal injections of combined bevacizumab and dexamethasone (IVB+IVD) and II) those receiving three monthly intravitreal injections of bevacizumab alone (IVB). The primary outcome was the inter-group difference in central macular thickness (CMT); secondary outcomes included best-corrected visual acuity (BCVA), baseline optical coherence tomography (OCT) biomarkers, and intraocular pressure (IOP) one month after the last injection. RESULTS: Reduction in CMT and improvement in BCVA were significantly greater in the IVB+IVD group than the IVB group (109.88±156.25 vs. 43±113.67, respectively, P=0.03; and -0.13±0.23 vs. -0.01±0.17, respectively, P=0.008). Presence of neurosensory retinal detachment (NSD) (P<0.001) and complete inner segment/outer segment junction (IS-OS) disruption (P=0.049) on baseline OCT scans were associated with further CMT reductions in response to IVD. Conversely, identifiable epiretinal membrane (ERM) (P=0.002) and multiple hyperreflective foci (>20) (P=0.049) were associated with smaller reductions in CMT. Vitreomacular traction correlated with worse visual outcomes in the IVB+IVD group (P=0.003). The intergroup IOP difference was not clinically significant. CONCLUSION: In patients with refractory DME, addition of IVD to the standard IVB regimen can improve visual and structural outcomes without increasing the risk of endophthalmitis, IOP rise, or intraocular inflammation. Patients with NSD are more likely to respond well to IVD. The presence of ERM may predict poor treatment response.

Endogenous Fungal Endophthalmitis following COVID-19 Hospitalization: Evidence from a Year-Long Observational Study.

PURPOSE: To describe cases of endogenous fungal endophthalmitis (EFE) post-recovery from or hospitalization for coronavirus disease 2019 (COVID-19). METHODS: This prospective audit involved patients with suspected endophthalmitis referred to a tertiary eye care center over a one-year period. Comprehensive ocular examinations, laboratory studies, and imaging were performed. Confirmed cases of EFE with a recent history of COVID-19 hospitalization±intensive care unit admission were identified, documented, managed, followed up, and described. RESULTS: Seven eyes of six patients were reported; 5/6 were male, and the mean age was 55. The mean duration of hospitalization for COVID-19 was approximately 28 days (14-45); the mean time from discharge to onset of visual symptoms was 22 days (0-35). All patients had underlying conditions (5/6 hypertension; 3/6 diabetes mellitus; 2/6 asthma) and had received dexamethasone and remdesivir during their COVID-related hospitalization. All presented with decreased vision, and 4/6 complained of floaters. Baseline visual acuity ranged from light perception (LP) to counting fingers (CF). The fundus was not visible in 3 out of 7 eyes; the other 4 had "creamy-white fluffy lesions" at the posterior pole as well as significant vitritis. Vitreous taps were positive for Candida species in six and Aspergillus species in one eye. Anti-fungal treatment included intravenous amphotericin B followed by oral voriconazole and intravitreal amphotericin B. Three eyes underwent vitrectomy; the systemic health of two patients precluded surgery. One patient (with aspergillosis) died; the others were followed for 7-10 months - the final visual outcome improved from CF to 20/200-20/50 in 4 eyes and worsened (hand motion to LP) or did not change (LP), in two others. CONCLUSION: Ophthalmologists should maintain a high index of clinical suspicion for EFE in cases with visual symptoms and a history of recent COVID-19 hospitalization and/or systemic corticosteroid use - even without other well-known risk factors.

Acetazolamide and bevacizumab combination therapy versus bevacizumab monotherapy in macular edema secondary to retinal vein occlusion.

PURPOSE: To determine and compare the efficacy of intravitreal bevacizumab (IVB) and oral acetazolamide (OA) combination therapy versus IVB monotherapy in patients with macular edema secondary to retinal vein occlusion (RVO). METHODS: This randomized clinical trial included 54 eyes of 52 patients with RVO central macular thickness (CMT) of more than 300µm, and best corrected visual acuity (BCVA) between 20/400 and 20/40. Eligible patients were randomly assigned to two groups: (I) IVB and OA (250mg twice daily) combination therapy or (II) IVB monotherapy. Ocular injections were repeated monthly for up to three months; BCVA and CMT were measured monthly. RESULTS: Both regimens resulted in significant reduction in CMT (534±150µm to 352±90µm in the IVB+OA group, P<0.001; and 580±175µm to 362±90µm in the IVB group, P<0.001); neither showed superiority in this regard. Likewise, BCVA showed significant improvement in both groups (0.87±0.56 to 0.53±0.28 LogMAR in the IVB+OA group, P=0.001; and 0.85±0.62 to 0.46±0.4 LogMAR in the IVB group, P<0.001), with no intergroup difference. CONCLUSION: Addition of oral acetazolamide to IVB in eyes with macular edema secondary to RVO may not result in additional short-term benefits regarding functional and anatomical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05290948, registered on March 22, 2022. https://clinicaltrials.gov/ct2/show/NCT05290948.

Non-infectious meningitis and CNS demyelinating diseases: A conceptual review.

Many cases of aseptic meningitis or meningoencephalitis, unresponsive to antimicrobial treatments, have been reported recently in patients with established/new-onset central nervous system (CNS) inflammatory demyelinating diseases (CNSIDDs). Given the higher probability of infectious etiologies, CNSIDDs are rarely considered among the differentials in meningitis or meningoencephalitis cases. We gathered and tabulated cases of non-infectious, steroid-responsive meningitis or meningoencephalitis associated with neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-associated disease (MOGAD). This conceptual review highlights the need to bolster routine infectious workups with immunological workups in cases of meningoencephalitis or meningitis where potential autoimmune etiologies can be suspected. Although differentiating CNSIDDs with meningeal involvement from infectious meningitis may not substantially affect acute treatment strategies, long-term management and follow-up of the two are entirely different. We also discuss future research directions and hypotheses on how CNSIDDs may be associated with meningitis-like presentations, e.g. overlapping glial fibrillary acidic protein astrocytopathy or autoimmune encephalitis, alterations in regulatory T-helper cells function, and undetected viral agents.

Acute macular neuroretinopathy and COVID-19 vaccination: Case report and literature review.

OBJECTIVE: To review cases of acute macular neuroretinopathy (AMN) after COVID-19 vaccination and add a similar case to the literature. METHODS: A thorough PubMed search was conducted, and data from studies describing AMN after COVID-19 vaccination were extracted, tabulated, pooled, and reviewed. RESULTS: We present a case of AMN in a young woman 5 days after immunization with the BBIBP-CorV (Sinopharm) COVID-19 vaccine. Data from 21 cases were pooled and reviewed. The most frequent vaccines among the cases were recombinant ones (13/21), followed by mRNA-based (6/21) and inactivated vaccines (2/21). Only one patient (5%) was male. Seventeen over twenty-one (81%) were young women, ages 18-33. Most cases (14/21; 67%) reported recent/concurrent use of contraceptive medication. In 90% of cases (19/21), symptoms appeared within 8 days of vaccination. A confined wedge-/oval-shaped lesion morphology was more frequent than a diffuse, semilunar one. Resolution of symptoms took 4 to over 15 weeks. CONCLUSION: Attention should be paid to the history of vaccination and contraceptive use in patients with sudden-onset visual symptoms. Optical coherence tomography is integral to the detection of AMN-related abnormalities.

Risk factors of severe COVID-19 in people with multiple sclerosis : A systematic review and meta-analysis.

OBJECTIVES: To gather, synthesize, and meta-analyze data regarding the risk factors associated with a severe course of COVID-19 among patients with multiple sclerosis (pwMS). METHODS: MEDLINE, Embase, Scopus, and WoS were searched in May 2021. Briefly, the eligibility criteria included: 1) studies assessing COVID-19 severity among adult pwMS; 2) definitive diagnoses or high clinical suspicion of COVID-19; 3) a categorization of COVID-19 severity into at least two categories; 4) quantitative effect size and precision measurements; and 5) English language; and 6) clear effect size/precision measures. internal validity of studies was assessed using the NIH Quality Assessment Tools. A list of possible risk factors was created based on the search results and was later used in extraction, synthesis, and meta-analysis of the data. RESULTS: Thirteen studies were included in the syntheses. Outcome measures were either extracted from the papers, obtained from the primary researchers or calculated manually. The meta-analyses showed a significantly (P<0.05) increased odds of a severe COVID-19 in pwMS with all of the assessed risk factors, except smoking and most DMTs. CONCLUSION: This study facilitates evidence-based risk/benefit assessments in practice. Older men with progressive MS on anti-CD20 therapies are more at risk of an unfortunate COVID-19 outcome.

TRIzol-based RNA extraction for detection protocol for SARS-CoV-2 of coronavirus disease 2019.

Diagnostic testing is important for managing the 2019 novel coronavirus (SARS-CoV-2). We developed an optimized protocol for SARS-CoV-2 RNA extraction from the surface of the respiratory mucosa with nasopharyngeal swabs and compared the sensitivity of RNA extraction methods. RNA extraction was performed using three different procedures (TRIzol, QIAamp, VMT-TRIzol) from nine positive SARS-CoV-2 samples. SARS-CoV-2 was detected by real-time reverse transcriptase PCR (RT-PCR) using a detection kit for SARS-CoV-2 (Sun Yat-sen University). Compared to RT-PCR results, there were no discernible differences in detection rates when comparing the three different extraction procedures. On the basis of these results, the use of TRIzol as a transport medium and RNA extraction method for SARS-CoV-2 detection may be a helpful alternative for laboratories facing shortages of commercial testing kits.

Seizure incidence among neuromyelitis optica spectrum disorder patients.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSDs) are a group of neuroinflammatory diseases, which mainly affect the optic nerve and spinal cord. NMOSD is an astrocytic channelopathy involving the aquaporin-4 (AQP4) water channels in the central nervous system. Patients can present with seizure attacks as a first manifestation or relapse. However, compared with multiple sclerosis (MS) or myelin oligodendrocyte glycoprotein encephalomyelitis (MOG-EM), seizure attacks are less frequent in NMOSD. METHODS: In this study, we aimed to find out the incidence of seizure attacks during the disease course of 137 NMOSD patients who were registered in our centre from January 2011 till January 2020. Furthermore, we reviewed the literature for NMOSD cases with seizure attacks during their follow-up, in order to investigate the reason for this low incidence of seizures. RESULTS: Only one of our patients (0.72%) experienced an episode of generalised tonic-clonic seizure during his follow-up. CONCLUSION: Reviewing the literature revealed that although seizures are rare in NMOSD, AQP4 disruption possibly increases the risk of seizure attacks. We therefore concluded that the role of AQP4 in seizures is controversial and needs more investigation.

WITHDRAWN: Incidence and mortality of COVID-19 in Iranian multiple sclerosis patients treated with disease-modifying therapies.

This article has been withdrawn at the request of the authors and editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.

l-asparaginase production and enhancement by Sarocladium strictum: In vitro evaluation of anti-cancerous properties.

AIMS: Utilization of l-asparaginase has been one of the effective strategies for the treatment of lymphoblastic leukaemia. Since the currently used bacterial l-asparaginase causes side effects, searching for new enzyme sources has been an active field of research. This study focuses on the characterization of an l-asparaginase-producing fungal strain. METHODS AND RESULTS: Sarocladium strictum was identified as a potent enzyme-producing strain. For the enhancement of enzyme production, we used two-level factorial design and response surface methodology. The optimization of significant factors showed a 1·84-fold increase in enzyme production. The Km and Vmax values of the enzyme were 9·74 mmol l-1 and 8·19 µmol min-1 . The toxicity of the produced l-asparaginase was measured on K562 and HL60 cancer cell lines and L6 as normal cells. The IC50 values were calculated as 0·4 and 0·5 IU ml-1 for K562 and HL60 respectively and no significant effect was observed in L6. BrdU proliferation and caspase-3 activity assay in l-asparaginase treated HL60 and K562 cells indicated that cell proliferation rates and apoptotic cell death were reduced. CONCLUSIONS: The cytotoxic properties of the produced fungal enzyme indicated significant growth inhibition in cancer cells while having a little toxic effect on normal cells. The possibility of mass production alongside having suitable cytotoxic and kinetic properties suggest the probable use of the produced l-asparaginase for further researches as a potential chemotherapeutic agent. SIGNIFICANCE AND IMPACT OF THE STUDY: The lack of significant l-glutaminase activity and promising toxicity properties in S. strictum and the closer evolutionary relativeness of fungi enzymes to human enzymes compared to bacterial enzymes suggest a new source with lower toxicity and anti-cancerous properties, causing less side effect problems.

Water scarcity alleviation through water footprint reduction in agriculture: The effect of soil mulching and drip irrigation.

Water scarcity has received global attention in the last decade as it challenges food security in arid and semi-arid regions, particularly in the Middle East and North Africa. This research assesses the possible alleviation of water scarcity by reducing the water footprint in crop production through the application of soil mulching and drip irrigation. The study is the first to do so at catchment scale, taking into account various crops, multi-cropping, cropping patterns, and spatial differences in climate, soil, and field management factors, using field survey and local data. The AquaCrop-OS model and the global water footprint assessment (WFA) standard were used to assess the green and blue water footprint (WF) of ten major crops in the Upper Litani Basin (ULB) in Lebanon. The blue water saving and blue water scarcity reduction under these two alternative practices were compared to the current situation. The results show that the WF of crop production is more sensitive to climate than soil type. The annual blue WF of summer crops was largest when water availability was lowest. Mulching reduced the blue WF by 3.6% and mulching combined with drip irrigation reduced it by 4.7%. The blue water saving from mulching was estimated about 6.3 million m3/y and from mulching combined with drip irrigation about 8.3 million m3/y. This is substantial but by far not sufficient to reduce the overall blue WF in summer to a sustainable level at catchment scale.

Characterization of pyrene degradation and metabolite identification by Basidioascus persicus and mineralization enhancement with bacterial-yeast co-culture.

In this paper, we introduce pyrene degrader halotolerant yeast, Basidioascus persicus EBL-C16 and characterize its growth in different salt concentrations. Investigation of the removal of different concentrations of pyrene showed that B. persicus EBL-C16 was able to eliminate 50-90% of pyrene in the presence of 2.5% salt and also mineralize phenanthrene and anthracene. Growth and depletion kinetics of 500 mg L-1 of pyrene removal revealed 79% degradation and the growth rate reached 1.4 g L-1 of dry weight, decomposition constant rate was obtained as 0.074 day-1 and the half-life was 9.33 days. When minimal medium was replaced with Persian Gulf water, 48% increase in pyrene removal was detected by yeast strain. The mass spectrometry of the treated samples specified the phthalic acid pathway as the metabolic pathway of pyrene degradation by B. persicus. Study of the synergistic effect of using rhamnolipid and co-culture of yeast with Pseudomonas putida ATCC 12633 revealed that the combination of both of them with B. persicus increased 21% pyrene elimination. The findings of this study can be used to comprehend the mechanisms of oil hydrocarbon degradation by yeasts. Furthermore, the results demonstrated the promising potential of yeast-bacteria co-culture for cleaning of oil spills in marine and saline soil contaminated areas.

Motility and oxidative-antioxidant capacity of Huso huso semen, stored at -80°C.

In this study, motility and oxidative-antioxidant capacity (thiobarbituric acid-reactive substance level [TBARS], superoxide dismutase [SOD], catalase [CAT] and glutathione reductase [GR]) of beluga sturgeon (Huso huso) sperm, stored for 6 days at -80°C, were evaluated. After 2 days of storage, sperm motility was significantly decreased (no motile sperm were observed after 6 days of storage; p < .05), while TBARS and SOD values were significantly increased (p < .05). CAT and GR activities did not show significant changes among storage times (p > .05). Furthermore, all investigated parameters showed a significant difference between semen stored at 4°C (control) and -80°C during in vitro storage (p < .05). Data from this work can potentially be useful in sturgeon sperm cryobanking.

Evaluation of CD4+ CD25+ FoxP3+ regulatory T cells during treatment of patients with brucellosis.

Cell-mediated immunity (CMI) plays a critical role in the control of brucellosis. Regulatory T cells (Tregs) have a functional character in modulating the balance between host immune response and tolerance, which can eventually lead to chronic infection or relapse. The aim of this study was to assess the alteration of Tregs in cases of brucellosis before and after treatment. Thirty cases of acute brucellosis with the mean age of 41.03±15.15 years (case group) and 30 healthy persons with the mean age of 40.63±13.95 years (control group) were selected and assessed. Peripheral blood mononuclear cells (PBMCs) were isolated from peripheral blood of all individuals. We analyzed the alteration of Treg cell count using flow cytometry for CD4, CD25, and FoxP3 markers. The level of CD4+ CD25+ FoxP3+ Treg cells was increased in active patients compared with controls (2.5±0.99% vs 1.6±0.84%, p= 0.0004), but it had declined in the treated cases (1.83±0.73%, p=0.02). The level of Tregs was elevated in three relapsed cases. The frequency of Tregs and Treg/Teff (effector T cell) ratio was correlated with inverse serum agglutination test (SAT) and, 2-mercaptoethanol (2-ME) titers as markers of treatment in brucellosis. Based on our findings, we suggest that regulatory cells, such as CD4+ CD25+ FoxP3+ Treg cells, may contribute to the development of infection processes involving immune responses in brucellosis, and evaluation of regulatory T-cell levels may be a potential diagnostic strategy for the treatment outcome in chronic and relapsed cases of brucellosis.