Vitreous Humor Positive for DNA of Human Herpesvirus 7 in Eye With Ocular Toxoplasmosis.

The aim of this article was to report our findings in a case of infectious uveitis in which the DNAs of both Toxoplasma gondii and human herpesvirus 7 (HHV-7) were detected in the vitreous fluid. A 31-year-old Brazilian man was examined in our hospital with a one-month history of blurred vision (20/40) in the right eye. He had been diagnosed with ocular toxoplasmosis of the right eye at nine years of age and has had repeated relapses. Because of the persistent vitreous opacities and refractoriness to acetylspiramycin and betamethasone, pars plana vitrectomy was performed. Multiplex PCR of the vitreous sample demonstrated the DNAs for both T. gondii and HHV-7. Trimethoprim/sulfamethoxazole with prednisone was prescribed. Six months after the beginning of the therapy, a resolution of the retinochoroiditis was found and the vision recovered to 20/25. Two months later, we performed a pars plana vitrectomy for an epiretinal membrane. The DNAs of both T. gondii and HHV-7 were not detected in the vitreous fluid and the epiretinal membrane. After continued treatment, the best-corrected visual acuity (BCVA) in the right eye improved to 20/16 and the metamorphopsia was reduced. It is inferred from this work that HHV-7 reactivation can activate refractory infectious uveitis in patients with chronic ocular toxoplasmosis.

The impact of geriatric nutritional risk index on one-year outcomes in hospitalized elderly patients with heart failure.

Background: Strategies that accurately predict outcomes in elderly heart failure (HF) patients have not been sufficiently established. In previous reports, nutritional status, ability to perform activities of daily living (ADL), and lower limb muscle strength are known prognostic factors associated with cardiac rehabilitation (CR). In the present study, we investigated which CR factors can accurately predict one-year outcomes in elderly patients with HF among the above factors. Methods: Hospitalized patients with HF over 65 years of age from January 2016 to January 2022 were retrospectively enrolled in the Yamaguchi Prefectural Grand Medical (YPGM) Center. They were consequently recruited to this single-center retrospective cohort study. Nutritional status, ADL, and lower limb muscle strength were assessed by geriatric nutritional risk index (GNRI), Barthel index (BI), and short physical performance battery (SPPB) at discharge, respectively. One year after discharge, the primary and secondary outcomes were evaluated by all-cause death or HF readmission and major adverse cardiac and cerebrovascular events (MACCE), respectively. Results: Overall, 1,078 HF patients were admitted to YPGM Center. Of those, 839 (median age 84.0, 52% female) met the study criteria. During the follow-up of 228.0 days, 72 patients reached all-cause death (8%), 215 experienced HF readmission (23%), and 267 reached MACCE (30%: 25 HF death, six cardiac death, and 13 strokes). A multivariate Cox proportional hazard regression analysis revealed that the GNRI predicted the primary outcome (Hazard ratio [HR]: 0.957; 95% confidence interval [CI]: 0.934-0.980; p < 0.001) and the secondary outcome (HR: 0.963; 95%CI: 0.940-0.986; p = 0.002). Furthermore, a multiple logistic regression model using the GNRI most accurately predicted the primary and secondary outcomes compared to those with the SPPB or BI models. Conclusion: A nutrition status model using GNRI provided a better predictive value than ADL ability or lower limb muscle strength. It should be recognized that HF patients with a low GNRI at discharge may have a poor prognosis at one year.

Four cases of cytokine storm after COVID-19 vaccination: Case report.

The global coronavirus disease 2019 (COVID-19) pandemic has led to the rapid development of vaccines against this disease. Despite the success of the international vaccination program, adverse events following vaccination, and the mechanisms behind them, remain poorly understood. Here we present four cases of death following receipt of a second dose of COVID-19 vaccine, with no obvious cause identified at autopsy. Using RNA sequencing, we identified genes that were differentially expressed between our post-vaccination cases and a control group that died of blood loss and strangulation. Three hundred and ninety genes were found to be upregulated and 115 genes were downregulated in post-vaccination cases compared with controls. Importantly, genes involved in neutrophil degranulation and cytokine signaling were upregulated. Our results suggest that immune dysregulation occurred following vaccination. Careful observation and care may be necessary if an abnormally high fever exceeding 40°C occurs after vaccination, even with antipyretic drugs.

A method for determining valproic acid in human whole blood and urine via gas chromatography-mass spectrometry and small-scale inter-laboratory trial.

A simple and cost-effective method for analyzing valproic acid (VPA) in biological samples was developed. VPA was extracted in methyl tertiary-butyl ether (MTBE) and derivatized using trimethylsilyldiazomethane. The MTBE extract was analyzed by gas chromatography-mass spectrometry (GC-MS). The extraction recovery in human whole blood and urine was over 90 %, with good linearity in the range of 1.0 to 250 µg/mL of VPA. The RSD for 2.0, 20, and 200 µg/mL VPA in whole blood ranged from 0.9 to 4.7 % for intra-day and 1.5 to 5.9 % for inter-day. The RSD for 2.0, 20, and 200 µg/mL VPA in urine ranged from 1.9 to 2.6 % for intra-day and 1.2 to 2.9 % for inter-day. As a preliminary cross-validation study, a cross-check was conducted using blinded concentration samples. The results demonstrated that the assay data of the two laboratories were comparable.

Factors associated with recurrence of bleb-related infections.

PURPOSE: To identify the risk factors for a recurrence of a bleb-related infection (BRI). STUDY DESIGN: Retrospective cohort study. METHODS: The medical records of all patients diagnosed with BRI at Gifu University Hospital between January 1989 and December 2020 were reviewed. The time when conjunctival hyperemia could not be detected and when the anterior chamber was quiet were defined as the resolution time of the BRI. The primary endpoint was a recurrence of a BRI. Kaplan-Meier estimation and the Cox proportional hazards model were used to determine the risk of a recurrence from the initial onset data of each eye. Bacteriological studies were performed to determine the pathogen causing the BRI. RESULTS: There were 108 eyes of 103 patients followed for at least 3 months after the initial BRI. A recurrent bleb infection developed in 21 (19.4%) eyes of 21 patients (13 men, 8 women). Log-rank test at the 10-year follow-up examination revealed that hypotony at the onset of the BRI (P=0.004), the prophylactic use of topical antibiotics at the onset of the BRI (P=0.046), and bleb leakage after the resolution of the BRI (P=0.021) were significantly associated with a BRI recurrence. Cox proportional hazards model showed that ocular hypotony at the onset of the BRI (unadjusted, P=0.007; adjusted for bleb leakage, P=0.015) and bleb leakage after the resolution of the BRI (unadjusted, P=0.027; adjusted for hypotony, P=0.024) were significantly associated with a BRI recurrence. Other factors were not significantly associated with the recurrence of a BRI. CONCLUSION: We recommend close observations when a bleb leakage is detected after the BRI has resolved.

Corrigendum: Malnutrition and Frailty Are Critical Determinants of 6-Month Outcome in Hospitalized Elderly Patients With Heart Failure Harboring Surgically Untreated Functional Mitral Regurgitation.

[This corrects the article DOI: 10.3389/fcvm.2021.764528.].

Malnutrition and Frailty Are Critical Determinants of 6-Month Outcome in Hospitalized Elderly Patients With Heart Failure Harboring Surgically Untreated Functional Mitral Regurgitation.

Background: Hospitalized patients with acute decompensated heart failure (ADHF) frequently exhibit aggravating mitral regurgitation (MR). Those patients do not always undergo surgical mitral valve repair, but particularly in the elderly, they are often treated by conservative medical therapy. This study was aimed to investigate factors affecting 6-month outcomes in hospitalized patients with heart failure (HF) harboring surgically untreated MR. Methods: We screened the presence of MR in hospitalized patients with HF between September 2017 and May 2020 in the Yamaguchi Prefectural Grand Medical (YPGM) center. At the time of discharge of these patients, individuals with surgically unoperated MR, including primary and secondary origin, were consequently recruited to this single-center prospective cohort study. The patients with severe MR who undergo surgical mitral valve treatment were not included in this study. The primary endpoint was all-cause readmission or all-cause death and the secondary endpoint was HF-related endpoint at 6 months after discharge. The Cox proportional hazard regression analyses were employed to assess the predictors for the composite endpoint. Results: Overall, 489 patients with ADHF were admitted to the YPGM center. Of those, 146 patients (30% of total patients with HF) (median age 83.5 years, 69 men) were identified as harboring grade II MR or greater. Consequently, all the recruited patients were diagnosed as functional MR. During a median follow-up of 186.0 days, a total of 55 patients (38%) reached the primary or secondary endpoints (HF death and readmission in 31 patients, other in 24 patients). As a result of multivariate analysis, geriatric nutritional risk index [hazard ratio (HR) = 0.932; 95% CI = 0.887-0.979, p = 0.005], age (HR = 1.058; 95% CI = 1.006-1.112, p = 0.027), and left ventricular ejection fraction (HR = 0.971; 95% CI = 0.945-0.997, p = 0.030) were independent predictors of all-cause death or all-cause admission. Body mass index (HR = 0.793; 95% CI = 0.614-0.890, p = 0.001) and ischemic heart disease etiology (HR = 2.732; 95% CI = 1.056-7.067, p = 0.038) were also independent predictors of the HF-related endpoints. Conclusion: Malnutrition and underweight were substantial predictors of adverse outcomes in elderly patients with HF harboring surgically untreated moderate-to-severe functional MR.

BIMP affects tubulin structure and causes abnormalities in cell division.

Although organophosphorus agents are used worldwide as pesticides, there have been many reports of pesticide poisoning. Nerve agents are organophosphorus agents that interfere with neurotransmission and have been used as chemical weapons in wars. These agents mainly irreversibly inhibit the action of acetylcholinesterase, an enzyme that breaks down acetylcholine, a neurotransmitter, and are believed to cause acute symptoms of poisoning. However, in recent years, the presence of subacute, delayed toxicity independent of acetylcholinesterase inhibition has been reported for some organophosphorus agents. We analyzed the subacute and delayed toxicity of bis(isopropylmethyl)phosphonate (BIMP), which has the same phosphonate group as sarin. BIMP rounded out the morphology of the cells and reduced the proportion of cells in the G1 phase of the cell cycle over time. No DNA damage was observed, suggesting that BIMP may affect cell division.

Intraocular penetration of liposomal amphotericin B after intravenous injection in inflamed human eyes.

PURPOSE: To determine the intraocular penetration of amphotericin B (AMPH-B) after an intravenously injection of liposomal amphotericin B (L-AMB) in inflamed human eyes. METHODS: Seven eyes of 5 patients with fungal eye diseases (endophthalmitis in 6 eyes and keratitis in 1 eye) were treated with intravenous injections of 100-250 mg/day of L-AMB. Samples of blood, corneal button, aqueous humor, and vitreous humor were collected and assessed for AMPH-B. RESULTS: The AMPH-B level in the cornea (604.0 µg/g) of the case with fungal keratitis exceeded the minimum inhibitory concentration. However, the levels in the aqueous and vitreous humors of the cases with fungal endophthalmitis were lower, e.g., 0.02 ± 0.01 µg/ml (0.09% of serum level) in the aqueous humor and 0.05 ± 0.08 µg/ml (0.17% of serum level) in the vitreous humor. CONCLUSIONS: The AMPH-B levels administered intravenously were very low in the aqueous and vitreous humors. Our findings indicate that intravenous L-AMB can be considered only for patients with mild endogenous fungal endophthalmitis, e.g., isolated chorioretinitis without vitreous extensions.

Neural dysfunctions following experimental permanent occlusions of bilateral common carotid arteries cause an increase of rat voluntary alcohol drinking behavior.

We have previously reported that ischemic animal models treated with a respiratory inhibitor, rotenon, show an increased voluntary alcohol intake. Although it is clear that ischemic brain, as a result of reduced-blood flow, shows pathological events and/or neuro-degenerations apparently, little is known of causal relationship between the mechanism of neural dysfunction and voluntary alcohol consumption. Authors have investigated effects of permanent two-vessel occlusion (p2VO) on rat voluntary alcohol drinking behavior. In first experiment the p2VO-treated rats showed an increase of voluntary alcohol drinking behavior, as compared with sham controls. Using brain microdialysis technique, increases of only nucleus accumbens (ACC) dopamine (DA) releases were suppressed in the p2VO-treated rats significantly, following the high K+ (40 mM) perfusion through the microdialysis probe membrane. Alcohol (200 mM) perfusion-induced DA and serotonin (5-HT) releases in the ACC of the p2VO-treated rats were suppressed significantly in the second experiment, as compared with the sham-treated rats. In third experiment p2VO-treated rats showed significant decreases of the contents of DA, not 5-HT, in the ACC, caudate-putamen (C/P), ventral tegmental area-substantia nigra (VT/SN) and lateral hypothalamus (LH). Dopaminergic neurons in the ACC showed more functional vulnerability against the p2VO treatments, as compared with the serotonergic neurons. An increase of alcohol intake in the p2VO-treated rats means the compensation for the neural degeneration of the dopaminergic system in the ACC consisted brain rewarding system. It was likely suggested that neural disturbance of higher functions involved with incomplete global brain ischemia leads the risk of an abnormal alcohol drinking in human.

Brachybacterium paraconglomeratum Endophthalmitis Postcataract Operation.

PURPOSE: To present our findings in a case of delayed-onset postoperative endophthalmitis caused by Brachybacterium paraconglomeratum, a rare organism. Observations. A 57-year-old man presented with epiphora and photophobia 17 weeks after a routine cataract extraction with phacoemulsification and intraocular lens implantation. Because endophthalmitis was suspected to be caused by a low-grade pathogen or fungus, an anterior chamber tap was performed. However, both multiplex PCR and culturing were negative. The patient was treated with topical cefmenoxime, oral minocycline, and subconjunctival injection of vancomycin and ceftazidime, but the intraocular inflammation increased. Then, the anterior chamber was tapped again, and the second PCR amplification and direct sequencing which targeted Actinomycetes detected Brachybacterium paraconglomeratum, a rare organism. CONCLUSION: This is the first reported case of an ocular disorder caused by B. paraconglomeratum. We recommend that B. paraconglomeratum be considered in cases of delayed-onset postcataract endophthalmitis.B. paraconglomeratum. We recommend that B. paraconglomeratum be considered in cases of delayed-onset postcataract endophthalmitis.

The characteristics of Posner-Schlossman syndrome: A comparison in the surgical outcome between cytomegalovirus-positive and cytomegalovirus-negative patients.

This retrospective observational study aims to report the clinical characteristics and surgical results in eyes with Posner-Schlossman syndrome (PSS), and compare these outcomes between cytomegalovirus (CMV)-positive and -negative eyes.We reviewed the medical records of 21 consecutive immunocompetent patients clinically diagnosed with PSS between the years 2010 and 2018. Aqueous humor was collected from all the affected eyes to detect if CMV was present, and polymerase chain reaction (PCR) was performed using the herpesvirus family primers.The average period between the initial PSS attack and aqueous humor sampling at our institute was 9.3 years. Out of the 21 patients, 62% were CMV-positive. Regardless of CMV status, the mean intraocular pressure (IOP), mean deviation (MD), and central corneal endothelium cell (CEC) density, at the initial examination at our institute were already significantly worse in the affected eyes than in the unaffected eyes (all P values < .05). The average visual acuity (VA) was only significantly worse in the CMV-positive group (P = .02). Out of all the patients, those that were CMV-positive had undergone more glaucoma surgeries (P = .056). Fourteen patients underwent either a trabeculectomy (TRAB) or a trabeculotomy (LOT), and their IOP significantly reduced following surgery (P < .001). In 85.7% of those that had surgery, their IOP was successfully lowered to less than 20 mm Hg.Long-lasting PSS causes a decrease in VA, MD, and the CEC density. A prompt diagnosis is required, and an appropriate treatment plan should be formulated. In those patients with PSS that develop uncontrolled glaucoma, both TRAB and LOT may be effective in controlling IOP.

Moraxella species: infectious microbes identified by use of time-of-flight mass spectrometry.

PURPOSE: To report the clinical manifestations, identification, antimicrobial susceptibilities, and treatment outcomes of ocular infections caused by Moraxella species. STUDY DESIGN: Retrospective study. PATIENTS AND METHODS: The medical records of all patients treated at the Departments of Ophthalmology of the Ogaki Municipal Hospital and the Gifu University Graduate School of Medicine for ocular infections caused by Moraxella species between January 2011 and June 2017 were examined. The stored Moraxella species isolated from ocular samples were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), molecular identification, and the biochemical properties. RESULTS: Sixteen eyes of 16 patients were treated for Moraxella ocular infections. The patients' median age was 72 years. A predisposing systemic or ocular condition was identified in 15 of the patients. Nine of the patients developed keratitis; four, conjunctivitis; and three, blebitis. M lacunata (6 eyes), M catarrhalis (6), M nonliquefaciens (3), and M osloensis (1) were identified by MALDI-TOF MS. All isolates were sensitive to levofloxacin, tobramycin, ceftazidime, ceftriaxone, and cefazolin. Twelve patients with keratitis or blebitis were treated with various topical antimicrobial combinations, and systemic antibiotics were used in 10 of the 12 patients. The mean time for the complete closure of the epithelial defects with keratitis was 24 days. The visual outcomes after treatment were favorable except in 1 keratitis patient who underwent enucleation. CONCLUSIONS: The use of duo-therapy with a combination of fluoroquinolone and cefmenoxime should be considered in cases nonresponsive to monotherapy, such as keratitis and bleb-associated infections. MALDI-TOF MS is useful for the identification of Moraxella to the species level.

Case of cryptococcal choroiditis in adult with T-cell leukemia/lymphoma.

A rare case of 70-year-old woman with adult T-cell leukemia/lymphoma who developed multifocal choroiditis from a dissemination of Cryptococcus neoformans is reported. Ophthalmologic examination revealed multiple yellowish choroidal lesions in the posterior pole of both eyes. Sequential optical coherence tomographic images disclosed the involvement of the choroid and the consecutive changes in its architecture during the course of treatment. The recognition of these ocular manifestations may be important for the rapid diagnosis of C. nerformans-disseminated diseases. Rapid diagnosis and prompt therapy with intravitreal injection as well as systemic fosfluconazole and liposomal amphotericin B led to clinical improvement of intraocular cryptococcosis.

Publisher Correction to: Effect of glaucoma implant surgery on intraocular pressure reduction, flare count, anterior chamber depth, and corneal endothelium in primary open-angle glaucoma.

The publisher regrets that the original version.

Optimization and application of octadecyl-modified monolithic silica for solid-phase extraction of drugs in whole blood samples.

Monolithic silica in MonoSpin for solid-phase extraction of drugs from whole blood samples was developed to facilitate high-throughput analysis. Monolithic silica of various pore sizes and octadecyl contents were synthesized, and their effects on recovery rates were evaluated. The silica monolith M18-200 (20µm through-pore size, 10.4nm mesopore size, and 17.3% carbon content) achieved the best recovery of the target analytes in whole blood samples. The extraction proceeded with centrifugal force at 1000rpm for 2min, and the eluate was directly injected into the liquid chromatography-mass spectrometry system without any tedious steps such as evaporation of extraction solvents. Under the optimized condition, low detection limits of 0.5-2.0ngmL-1 and calibration ranges up to 1000ngmL-1 were obtained. The recoveries of the target drugs in the whole blood were 76-108% with relative standard deviation of less than 14.3%. These results indicate that the developed method based on monolithic silica is convenient, highly efficient, and applicable for detecting drugs in whole blood samples.

Roussoella solani causing keratomycosis, with an observed both sexual and asexual morphs.

We describe an 82-year-old male farmer who had diabetes mellitus with no history of ocular trauma by soil or plants and who developed a corneal infection due to a fungus. The organism was identified as Roussoella solani based on both the morphological characteristics and phylogenetic analysis using LSU and ITS nrDNA sequences. The sexual stage of R. solani is described and illustrated for the first time. The patient was treated successfully with a combination of topical and systemic voriconazole and micafungin. This case is the first report of keratomycosis caused by R. solani.

Effect of glaucoma implant surgery on intraocular pressure reduction, flare count, anterior chamber depth, and corneal endothelium in primary open-angle glaucoma.

PURPOSE: To evaluate the effect of filtering surgery using the EX-PRESS device on intraocular pressure (IOP), flare count, anterior chamber (AC) depth, and the corneal endothelium in primary open-angle glaucoma (POAG), including normal-tension glaucoma (NTG). PATIENTS AND METHODS: The study comprised 63 consecutive patients with POAG or NTG. They underwent complete ophthalmologic examinations, including measurement of visual acuity (VA), IOP, flare count, AC depth, and cell density of the corneal endothelium (CE). Two outcomes were used for surgical success: outcome 1 was defined as a ≥20% reduction in the IOP from the preoperative value, with an IOP ≥ 5 mmHg but ≤18 mmHg, and outcome 2 was defined as a ≥20% reduction in the IOP, with an IOP ≥ 5 mmHg but ≤15 mmHg. RESULTS: The IOP significantly decreased from 17.7 preoperatively to 12.4 mmHg postoperatively (P < 0.0001). The success rates for outcome 1 at 24 months were 81.3 and 46.7% for POAG and NTG, respectively (P = 0.0065); the corresponding success rates for outcome 2 were 79.4 and 46.7% (P = 0.0120). The flare count significantly increased on postoperative day 1 (P = 0.0002) but recovered to insignificant levels by day 3 (P = 0.0686). A transient decrease in AC depth was observed by 4 weeks after surgery (P = 0.0017). The CE changed from 2529 preoperatively to 2428/mm2 at 24 months (P = 0.0089). CONCLUSION: The advantage of filtering surgery using the EX-PRESS device includes reduced inflammation, and the disadvantages include loss of the CE and reduced effectiveness of NTG.

The sarin-like organophosphorus agent bis(isopropyl methyl)phosphonate induces ER stress in human astrocytoma cells.

Organophosphorus (OP) compounds such as sarin are toxic agents that irreversibly inhibit the enzyme acetylcholinesterase. A recent study showed that OP compounds also have multiple toxicity mechanisms, and another suggested that endoplasmic reticulum (ER) dysfunction contributes to OP toxicity. However, the signaling pathway and mechanisms involved are poorly understood. We examined whether the sarin-like OP agent bis(isopropyl methyl)phosphonate (BIMP), which exhibits toxicity similar to that of sarin, induced ER stress in human astrocytoma CCF-STTG1 cells. Our results demonstrate that BIMP exposure reduced cell viability. Moreover, it induced changes in mitochondrial membrane potential and increased cleavage of caspase 3. Treatment with BIMP increased the mRNA levels of the ER stress marker genes binding immunoglobulin protein (BiP) and the transcription factor C/EBP homologous protein (CHOP). Furthermore, BIMP increased the protein expressions and phosphorylation of BiP, CHOP, and protein kinase RNA-like ER kinase and the phosphorylation of eukaryotic translation initiation factor 2. Compared to BIMP treatment alone, pretreatment with the CHOP siRNA, siCHOP, decreased BIMP-dependent CHOP expression and improved CCF-STTG1 cell viability. Our findings suggest that BIMP induced mitochondrial dysfunction and apoptotic cell death event mediated by ER stress in CCF-STTG1 cells and that treatment targeted at managing ER stress has the potential to attenuate the toxicity of OP nerve agents.

Essential role of autoactivation circuitry on Aurora B-mediated H2AX-pS121 in mitosis.

Proper deposition and activation of Aurora B at the centromere is critical for faithful chromosome segregation in mammals. However, the mechanistic basis for abrupt Aurora B kinase activation at the centromere has not yet been fully understood. We demonstrate here that Aurora B-mediated phosphorylation of histone H2AX at serine 121 (H2AX-pS121) promotes Aurora B autophosphorylation and is essential for proper chromosome segregation. Aurora B-mediated H2AX-pS121 is specifically detected at the centromere during mitosis. H2AX depletion results in a severe defect in activation and deposition of Aurora B at this locus. A phosphomimic mutant of H2AX at S121 interacts with activated Aurora B more efficiently than wild-type in vitro. Taken together, these results propose a model in which Aurora B-mediated H2AX-pS121 probably provide a platform for Aurora B autoactivation circuitry at centromeres and thus play a pivotal role in proper chromosome segregation.