Determinants and impact of calcium oxalate crystal deposition on renal outcomes in acute kidney injury patients.

OBJECTIVES: Calcium oxalate (CaOx) crystal deposition in acute kidney injury (AKI) patients is under recognized but impacts renal outcomes. This study investigates its determinants and effects. METHODS: We studied 814 AKI patients with native kidney biopsies from 2011 to 2020, identifying CaOx crystal deposition severity (mild: <5, moderate: 5-10, severe: >10 crystals per section). We assessed factors like urinary oxalate, citrate, urate, electrolytes, pH, tubular calcification index, and SLC26A6 expression, comparing them with creatinine-matched AKI controls without oxalosis. We analyzed how these factors relate to CaOx severity and their impact on renal recovery (eGFR < 15 mL/min/1.73 m2 at 3-month follow-up). RESULTS: CaOx crystal deposition was found in 3.9% of the AKI cohort (32 cases), with 72% due to nephrotoxic medication-induced tubulointerstitial nephritis. Diuretic use, higher urinary oxalate-to-citrate ratio induced by hypocitraturia, and tubular calcification index were significant contributors to moderate and/or severe CaOx deposition. Poor baseline renal function, low urinary chloride, high uric acid and urea nitrogen, tubular SLC26A6 overexpression, and glomerular sclerosis were also associated with moderate-to-severe CaOx deposition. Kidney recovery was delayed, with 43.8%, 31.2%, and 18.8% of patients having eGFR < 15 mL/min/1.73 m2 at 4, 12, and 24-week post-injury. Poor outcomes were linked to high urinary α1-microglobulin-to-creatinine (α1-MG/C) ratios and active tubular injury scores. Univariate analysis showed a strong link between this ratio and poor renal outcomes, independent of oxalosis severity. CONCLUSIONS: In AKI, CaOx deposition is common despite declining GFR. Factors worsening tubular injury, not just oxalate-to-citrate ratios, are key to understanding impaired renal recovery.

Chronic Opioid Treatment Arrests Neurodevelopment and Alters Synaptic Activity in Human Midbrain Organoids.

Understanding the impact of long-term opioid exposure on the embryonic brain is critical due to the surging number of pregnant mothers with opioid dependency. However, this has been limited by human brain inaccessibility and cross-species differences in animal models. Here, a human midbrain model is established that uses hiPSC-derived midbrain organoids to assess cell-type-specific responses to acute and chronic fentanyl treatment and fentanyl withdrawal. Single-cell mRNA sequencing of 25,510 cells from organoids in different treatment groups reveals that chronic fentanyl treatment arrests neuronal subtype specification during early midbrain development and alters synaptic activity and neuron projection. In contrast, acute fentanyl treatment increases dopamine release but does not significantly alter gene expression related to cell lineage development. These results provide the first examination of the effects of opioid exposure on human midbrain development at the single-cell level.

Therapeutic strategies and predictive models for Xp11.2 translocation/TFE3 gene fusion renal cell carcinoma in adults based on data of two Chinese medical centers.

OBJECTIVE: This study aims to establish an effective predictive model for predicting Xp11.2 translocation/TFE3 gene fusion renal cell carcinoma (TFE3-RCC) and develop optimal therapeutic strategies. METHODS: Data from 4961 patients diagnosed with renal cell carcinoma at two medical centers in China were retrospectively analyzed. A cohort of 1571 patients from Zhejiang Provincial People's Hospital (Ra cohort) was selected to construct the model. Another cohort of 1124 patients from the Second Affiliated Hospital of Zhejiang Chinese Medical University was used for external validation (the Ha cohort). All patients with TFE3-RCC in both cohorts were included in the Ta cohort for the prognostic analysis. Univariate and multivariate binary logistic regression analyses were performed to identify independent predictors of the predictive nomogram. The apparent performance of the model was validated. Decision curve analysis was also performed to assess the clinical utility of the developed model. Factors associated with progression and prognosis in the Ta cohort were analyzed using the log-rank method, and Cox regression analysis and Kaplan-Meier survival curves were used to describe the effects of factors on prognosis and progression. RESULTS: Univariate and multivariate logistic regression analyses demonstrated that age, sex, BMI, smoking, eosinophils, and LDL were independent predictors of TFE3-RCC. Therefore, a predictive nomogram for TFE3-RCC, which had good discriminatory power (AUC = 0.796), was constructed. External validation (AUC = 0.806) also revealed good predictive ability. The calibration curves displayed good consistency between the predicted and observed incidences of TFE3-RCC. Invasion of regional lymph nodes, tyrosine kinase inhibitors, and surgical methods were independent factors associated with progression. Tyrosine kinase inhibitors are independent prognostic factors. CONCLUSION: This study not only proposed a high-precision clinical prediction model composed of various variables for the early diagnosis of Xp11.2 translocation/TFE3 gene fusion renal cell carcinoma but also optimized therapeutic strategies through prognostic analysis.

Patient Satisfaction with the Hybrid Telemedicine Model for Ophthalmology.

Background: The purpose of this research was to compare patient satisfaction between hybrid ophthalmology telemedicine and standard-of-care in-person visits. A retrospective, cross-sectional, case-control analysis of patient satisfaction based on survey data was used. Methods: Responses to the National Research Council Health Patient Survey were retrieved for randomly sampled hybrid ophthalmology telemedicine and in-person visits between March 11, 2020 and December 31, 2021 at a hospital-based eye clinic in Boston, Massachusetts. The primary outcome was based on the question "How likely would you be to recommend this provider to your family and friends?" (0-10 scale) with a score of 9 or 10 coded as satisfied. Two-sample t-tests, Pearson's chi-square tests, and bivariate logistic regressions were used to compare patient satisfaction scores between the hybrid and in-person cohorts. Demographic data, including age, sex, language, and self-reported race and ethnicity, were used as potential predictors of patient satisfaction in a multivariable logistic regression model. Results: There were 49 surveys from hybrid visits and 3,390 surveys from in-person visits. Hybrid visit patients reported high satisfaction scores without significant differences compared to in-person visit patients (hybrid 79% satisfied, in-person 82% satisfied, p = 0.728). Age was significantly associated with satisfaction in the hybrid cohort with the 65+ age group reporting lower satisfaction (below 65 years 100% satisfied, 65+ years 60% satisfied, p = 0.003). No association with age was observed in the in-person cohort. Conclusions: The hybrid ophthalmology telemedicine model can provide effective care without sacrificing patient satisfaction. Older patients may benefit from targeted interventions in future telemedicine models.

Effect of race and ethnicity on surgical outcomes for rhegmatogenous retinal detachments.

OBJECTIVE: To evaluate the effect of socioeconomic and demographic factors on outcomes in rhegmatogenous retinal detachments (RRDs). DESIGN: Retrospective cohort study. METHODS: A total of 71 white and 124 black and/or Hispanic patients who had surgical repair of RRDs between October 2013 and September 2021 at a single-centre safety net hospital. Main outcomes were single surgery success rates (SSSR) and postoperative visual acuity at 6-month and final follow-up. RESULTS: Black and (or) Hispanic patients were significantly younger (black and [or] Hispanic, 50.7 years vs white, 57.6 years; p = 0.003), had lower mean household incomes (black and [or] Hispanic, $80,932 vs white, $92,911; p = 0.007), were more likely to have more than 1 retinal break (black and [or] Hispanic, 65% vs white, 49%; p = 0.04), and had higher rates of proliferative vitreoretinopathy (PVR) at presentation (black and [or] Hispanic, 35% vs white, 18%; p = 0.02). SSSR was similar (black and [or] Hispanic, 73.4% vs white, 73.2%; p = 0.98), but black and (or) Hispanic patients had worse visual acuity postoperatively (black and [or] Hispanic, 20/63 vs white, 20/40 at final follow-up; p = 0.03). While race was linked to visual outcome in univariate testing; multivariate analysis revealed only macula status (p = 0.007 at 6 months; p = 0.01 at final follow-up), presence of PVR (p < 0.001 at both time points), and SSSR (p = 0.003 at final follow-up) as predictors of worse visual outcomes. CONCLUSIONS: Preoperative factors such as higher rates of PVR may contribute to worse vision outcomes in black and (or) Hispanic patients undergoing surgical repair for RRD.

Performance of SHOX2 and RASSF1A methylation assay in supernatants and matched cell pellets for the diagnosis of malignant pleural effusion.

BACKGROUND: It is difficult to distinguish between malignant pleural effusion (MPE) and benign pleural effusion (BPE). The purpose of this study was to determine the best specimen type by evaluating the DNA methylation status of SHOX2 and RASSF1A in 3 matched PE components. METHODS: In total, 94 patients were enrolled, including 45 MPE, 35 BPE, and 14 undefined PE (UPE) with malignancies. PE samples were processed into supernatants, fresh-cell pellets, and formalin-fixed and paraffin-embedded (FFPE) cell blocks, respectively. A quantitative real-time PCR was used to detect the methylation status of SHOX2 and RASSF1A. RESULTS: SHOX2 and RASSF1A methylation levels were significantly higher in the 3 MPE sample types than those of BPE (P < 0.05). The area under the curve using cell-free DNA (cf-DNA) was the highest. The detection sensitivity of SHOX2 and RASSF1A in fresh-cell DNA, cf-DNA and FFPE cell-block were 71.1% (32/45), 97.8% (44/45) and 66.7% (28/42), respectively, with specificities of 97.1% (34/35), 94.3% (33/35), and 96.9% (31/32). Notably, a combination of the cytological analysis and cf-DNA methylation assay showed an increase in positivity rate from 75.6% to 100%. CONCLUSIONS: The SHOX2 and RASSF1A methylation assay using cf-DNA, the primary recommended specimen type, can excellently increase the diagnostic sensitivity of MPE. A combination of methylation assay with cytological analysis can be used for auxiliary diagnosis of PE.

Demographic and socioeconomic disparities in the hybrid ophthalmology telemedicine model.

IMPORTANCE: As telemedicine use expands, it is important to evaluate demographic and socioeconomic disparities among patients receiving ophthalmic care through new hybrid telemedicine models. OBJECTIVE: To evaluate whether there are demographic and socioeconomic disparities in the delivery of the hybrid telemedicine model. DESIGN: Retrospective, cross-sectional, case-control analysis of patient encounters from April to December 2020. SETTING: A single, academic, hospital-based eye clinic in Boston, Massachusetts. METHODS: Electronic medical records of all patient encounters from April to December 2020 were reviewed and categorized into hybrid, virtual-only, and standard in-person visits. Patient-level data for all visits were extracted including age, sex, race/ethnicity, primary language, Area Deprivation Index (ADI), insurance type, and marital status. Visit-level data for all hybrid visits were also extracted from the medical record including the visit dates and patient adherence. Demographics for the cohort of patients with at least one no-show visit were compared with demographics for the cohort of patients who only had completed visits. The primary study outcomes were the differences in demographic characteristics between the hybrid visit show and no-show groups. The secondary outcomes included demographic characteristics of patients who did not complete their hybrid visit versus a time-matched cohort of patients who did not complete their standard in-person visit. Continuous variables for patient characteristics were compared with independent samples t-tests and categorical variables were compared using Pearson chi-square tests. Multivariate logistic regression was used to examine the differences between the cohorts. Variables with missing values other than suppressed ADI values were imputed using multiple imputations by chained equations. RESULTS: Of a total of 1025 patients who were scheduled for a hybrid visit, 145 (14.1%) patients failed to complete their visit. Primary language and insurance were found to be statistically different between patients who completed and did not complete their hybrid visits. More English speakers and fewer Haitian Creole speakers completed their hybrid visits (p = 0.007) while more patients with private insurance and fewer patients with Medicaid completed their hybrid telemedicine visits (p = 0.026). No associations were found between hybrid telemedicine visit adherence and age, sex, race/ethnicity, marital status, or ADI. When the 145 patients who failed to complete their hybrid visits were compared to a time-matched cohort of patients who failed to complete their standard in-person visit, we found that patients who missed hybrid visits were similar to those who missed standard in-person visits except for patients insured by Medicare. These patients were more likely to miss a hybrid visit than a standard in-person visit (Odds Ratio 2.199, 95% confidence interval 1.136-4.259, p = 0.019). No associations were found between patient nonadherence with hybrid telemedicine versus with standard in-person visits based on age, sex, primary language, race/ethnicity, marital status, or ADI. CONCLUSION: The hybrid telemedicine model was associated with insurance and language-based disparities. Patients with non-English primary language and Medicaid recipients were more likely to miss a hybrid visit than their counterparts. Our findings support developing deliberate interventions to ensure hybrid telemedicine care is delivered equitably to all patients.

Comprehensive Analysis of Gut Microbiota Alteration in the Patients and Animal Models with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a common disease of endocrine-metabolic disorder, and its etiology remains largely unknown. The gut microbiota is possibly involved in PCOS, while the association remains unclear. The comprehensive analysis combining gut microbiota with PCOS typical symptoms was performed to analyze the role of gut microbiota in PCOS in this study. The clinical patients and letrozole-induced animal models were determined on PCOS indexes and gut microbiota, and fecal microbiota transplantation (FMT) was conducted. Results indicated that the animal models displayed typical PCOS symptoms, including disordered estrous cycles, elevated testosterone levels, and ovarian morphological change; meanwhile, the symptoms were improved after FMT. Furthermore, the microbial diversity exhibited disordered, and the abundance of the genus Ruminococcus and Lactobacillus showed a consistent trend in PCOS rats and patients. The microbiota diversity and several key genera were restored subjected to FMT, and correlation analysis also supported relevant conclusions. Moreover, LEfSe analysis showed that Gemmiger, Flexispira, and Eubacterium were overrepresented in PCOS groups. Overall, the results indicate the involvement of gut microbiota in PCOS and its possible alleviation of endocrinal and reproductive dysfunctions through several special bacteria taxa, which can function as the biomarker or potential target for diagnosis and treatment. These results can provide the new insights for treatment and prevention strategies of PCOS.

Unrelenting Vision Loss: The Virulence of Klebsiella pneumoniae.

A 37-year-old Hispanic male with a recent history of COVID-19 infection and type 2 diabetes mellitus was admitted to the hospital with shortness of breath, chest pain, and hyperglycemia. Eye exam and imaging findings indicated endogenous endophthalmitis confirmed by blood cultures that speciated to Klebsiella pneuomoniae. The patient's eye condition progressed, ultimately resulting in no light perception less than a month after the initial evaluation. Due to the rapidly progressive nature of Klebsiella endogenous endophthalmitis, we recommend that primary teams consult ophthalmology for close monitoring of patients with a high index of suspicion.

Socioeconomic Disparities in Patients Receiving Intravitreal Injections for Age-Related Macular Degeneration Amid the COVID-19 Pandemic.

Purpose: To determine the effects of socioeconomic factors on visit adherence and the resultant visual outcomes for patients receiving intravitreal injections for neovascular age-related macular degeneration during the COVID-19 pandemic. Methods: In this retrospective case-control study, medical records were reviewed to collect appointment attendance, age, sex, self-reported race/ethnicity, primary language, marital status, insurance, distance from clinic, and Area Deprivation Index (ADI), a measure of socioeconomic disadvantage. Multivariate regression models were created to determine differences in socioeconomic factors between individuals who attended (show group) and those who did not attend (no-show group) appointments. Results: The study enrolled 126 patients in the show group and 115 in the no-show group. On univariate analysis, nonadherence was significantly higher in non-White patients than in White patients (P = .04), urban sites than in suburban sites (P = 1.7 × 10-4), and non-English-speaking patients than in English-speaking patients (P = 4.0 × 10-3). The associations remained significant in multivariate analysis for non-English-speaking patients (P = .03) and urban-site patients (P = .01) after adjusting for age, sex, self-reported race/ethnicity, primary language, marital status, insurance, distance from clinic, site of visit, and ADI. At 6 months and 1 year, a 1-, 2-, and 3-line vision loss was significantly higher in the no-show group than in the show group on univariate and multivariate analysis after adjusting for age, sex, race, lens status, and presence of glaucoma and diabetic retinopathy. Conclusions: Non-English-speaking patients and urban-based patients were less likely to present for intravitreal injection appointments during the initial peak of the COVID-19 pandemic. This disparity translated to worse vision outcomes at 6 months and 1 year.

Simultaneous diagnosis of tuberculous pleurisy and malignant pleural effusion using metagenomic next-generation sequencing (mNGS).

BACKGROUND: Metagenomic next-generation sequencing (mNGS) has become a powerful tool for pathogen detection, but the value of human sequencing reads generated from it is underestimated. METHODS: A total of 138 patients with pleural effusion (PE) were diagnosed with tuberculous pleurisy (TBP, N = 82), malignant pleural effusion (MPE, N = 35), or non-TB infection (N = 21), whose PE samples all underwent mNGS analysis. Clinical TB tests including culture, Acid-Fast Bacillus (AFB) test, Xpert, and T-SPOT, were performed. To utilize mNGS for MPE identification, 25 non-MPE samples (20 TBP and 5 non-TB infection) were randomly selected to set human chromosome copy number baseline and generalized linear modeling was performed using copy number variant (CNV) features of the rest 113 samples (35 MPE and 78 non-MPE). RESULTS: The performance of TB detection was compared among five methods. T-SPOT demonstrated the highest sensitivity (61% vs. culture 32%, AFB 12%, Xpert 35%, and mNGS 49%) but with the highest false-positive rate (10%) as well. In contrast, mNGS was able to detect TB-genome in nearly half (40/82) of the PE samples from TBP subgroup, with 100% specificity. To evaluate the performance of using CNV features of the human genome for MPE prediction, we performed the leave-one-out cross-validation (LOOCV) in the subcohort excluding the 25 non-MPE samples for setting copy number standards, which demonstrated 54.1% sensitivity, 80.8% specificity, 71.7% accuracy, and an AUC of 0.851. CONCLUSION: In summary, we exploited the value of human and non-human sequencing reads generated from mNGS, which showed promising ability in simultaneously detecting TBP and MPE.

Genomic and Transcriptomic Survey Provides Insights into Molecular Basis of Pathogenicity of the Sunflower Pathogen Phoma macdonaldii.

Phoma macdonaldii (teleomorph Leptosphaeria lindquistii) is the causal agent of sunflower (Helianthus annuus L.) black stem. In order to investigate the molecular basis for the pathogenicity of P. ormacdonaldii, genomic and transcriptomic analyses were performed. The genome size was 38.24 Mb and assembled into 27 contigs with 11,094 putative predicted genes. These include 1133 genes for CAZymes specific for plant polysaccharide degradation, 2356 for the interaction between the pathogen and host, 2167 for virulence factors, and 37 secondary metabolites gene clusters. RNA-seq analysis was conducted at the early and late stages of the fungal spot formation in infected sunflower tissues. A total of 2506, 3035, and 2660 differentially expressed genes (DEGs) between CT and each treatment group (LEAF-2d, LEAF-6d, and STEM) were retrieved, respectively. The most significant pathways of DEGs from these diseased sunflower tissues were the metabolic pathways and biosynthesis of secondary metabolites. Overall, 371 up-regulated DEGs were shared among LEAF-2d, LEAF-6d, and STEM, including 82 mapped to DFVF, 63 mapped to PHI-base, 69 annotated as CAZymes, 33 annotated as transporters, 91 annotated as secretory proteins, and a carbon skeleton biosynthetic gene. The most important DEGs were further confirmed by RT-qPCR. This is the first report on the genome-scale assembly and annotation for P. macdonaldii. Our data provide a framework for further revealing the underlying mechanism of the pathogenesis of P. macdonaldii, and also suggest the potential targets for the diseases caused by this fungal pathogen.

Aß Induces Neuroinflammation and Microglial M1 Polarization via cGAS-STING-IFITM3 Signaling Pathway in BV-2 Cells.

Microglia, innate immune cells of the brain, constantly monitor the dynamic changes of the brain microenvironment under physiological conditions and respond in time. Growing evidence suggests that microglia-mediated neuroinflammation plays an important role in the pathogenesis of Alzheimer's disease. In this study, we investigated that the expression of IFITM3 was significantly upregulated in microglia under the Aß treatment, and knockdown of IFITM3 in vitro suppressed the M1-like polarization of microglia. Moreover, IFITM3 was regulated by cGAS-STING signaling in activated microglia, and inhibition of cGAS-STING signaling reduces IFITM3 expression. Taken together, our findings suggested that the cGAS-STING-IFITM3 axis may be involved in Aß-induced neuroinflammation in microglia.

Effect of Lens Status on Diabetic Vitreous Hemorrhage Resolution.

Purpose: To determine the effect of lens status (pseudophakic vs phakic) on diabetic vitreous hemorrhage (VH) resolution time. Methods: Medical records were reviewed retrospectively for each case of diabetic VH until resolution, pars plana vitrectomy (PPV), or loss to follow-up. Univariate and multivariate Cox regression models were used to determine predictors of diabetic VH resolution time through estimated hazard ratios (HRs). Kaplan-Meier survival analysis compared differences in the resolution rate by lens status and other significant factors. Results: Overall, 243 eyes were included. Pseudophakia (HR, 1.76; 95% CI, 1.07-2.90; P = .03) and prior PPV (HR, 3.28; 95% CI, 1.77-6.07; P < .001) were significant factors for faster resolution. Pseudophakic eyes resolved in 5.5 months (median, 25.1 weeks; 95% CI, 19.3-31.0) and phakic eyes in 10 months (median, 43.0 weeks; 95% CI, 36.0-50.0) (P = .001). More pseudophakic eyes than phakic eyes resolved without PPV (44.2% vs 24.8%) (P = .001). Eyes without prior PPV resolved in 9.5 months (median, 41.0 weeks; 95% CI, 35.7-46.3) compared with 5 months (median, 22.3 weeks; 95% CI, 9.8-34.8) in vitrectomized eyes (P < .001). Age, treatment with antivascular endothelial growth factor injections or panretinal photocoagulation, intraocular pressure medications, and glaucoma history were not significant predictors. Conclusions: Diabetic VH resolved almost twice as fast in pseudophakic eyes than in phakic eyes. Eyes with a history of PPV resolved 3 times quicker than those without PPV. A better understanding of VH resolution can help personalize the decision on when to proceed with PPV.

Clinical and genetic analysis of Christianson syndrome caused by variant of SLC9A6: case report and literature review.

Background: Intellectual disability, X-linked, syndromic, Christianson type (MRXSCH, OMIM: 300243)-known as Christianson syndrome (CS)-is characterized by microcephaly, epilepsy, ataxia, and absence of verbal language ability. CS is attributed to mutations in the solute carrier family 9 member A6 gene (SLC9A6). Materials and methods: This study reports the case of a boy 1 year and 3 months of age who was diagnosed with CS in our department. Genetic etiology was determined by whole-exome sequencing, and a minigene splicing assay was used to verify whether the mutation affected splicing. A literature review of CS cases was conducted and the clinical and genetic features were summarized. Results: The main clinical manifestations of CS include seizures, developmental regression, and exceptional facial features. Whole-exome sequencing revealed a de novo splice variant in intron 11 (c.1366 + 1G > C) of SLC9A6. The mutation produced two abnormal mRNA products (verified by a minigene splicing assay), resulting in the formation of truncated protein. A total of 95 CS cases were identified in the literature, with various symptoms, such as delayed intellectual development (95/95, 100.00%), epilepsy (87/88, 98.86%), and absent verbal language (75/83, 90.36%). At least 50 pathogenic variants of SLC9A6 have been identified, with the highest frequency observed in exon 12. Conclusion: Our patient is the first case with the c.1366 + 1G > C variant of SLC9A6 in CS. The summary of known cases can serve as a reference for analyzing the mutation spectrum and pathogenesis of CS.

Genetic, clinical, and pathological study of patients with severe hypertension-associated renal microangiopathy.

BACKGROUND: Severe hypertension may be a prominent manifestation of complement-mediated thrombotic microangiopathy. Furthermore, patients with severe hypertension-associated thrombotic microangiopathy may present with concurrent hematologic abnormalities that mimic complement-mediated thrombotic microangiopathy. Whether or not severe hypertension-associated thrombotic microangiopathy is associated with genetic susceptibility in complement- and/or coagulation-pathway genes remains unclear, and there is thus a need to identify clinicopathological clues to distinguish between these entities. METHODS: Forty-five patients with concomitant severe hypertension and thrombotic microangiopathy on kidney biopsy were identified retrospectively. Whole-exome sequencing was performed to identify rare variants in 29 complement- and coagulation-cascade genes. Clinicopathological features were compared between patients with severe hypertension-associated thrombotic microangiopathy and complement-mediated thrombotic microangiopathy with severe hypertension. RESULTS: Three patients with pathogenic variants diagnostic of complement-mediated thrombotic microangiopathy and two with anti-factor H antibody positivity were diagnosed with complement-mediated thrombotic microangiopathy with severe hypertension. Among the 40 patients with severe hypertension-associated thrombotic microangiopathy, 53 rare variants of uncertain significance were found in the analyzed genes in 34 (34/40, 85%) patients, of whom 12 patients harbored two or more variants. Compared with complement-mediated thrombotic microangiopathy patients with severe hypertension, patients with severe hypertension-associated thrombotic microangiopathy were more likely to have left ventricular wall thickening (p < 0.001), less-severe acute glomerular thrombotic microangiopathy lesions including mesangiolysis and subendothelial space widening (both p < 0.001), and less arteriolar thrombosis formation (p < 0.001). CONCLUSIONS: Rare genetic variants involving complement and coagulation pathways can be found in patients with severe hypertension-associated thrombotic microangiopathy; their role needs further investigation. Cardiac remodeling and acute glomerular TMA lesions may help to differentiate between severe hypertension-associated thrombotic microangiopathy and complement-mediated thrombotic microangiopathy with severe hypertension.

Self-Healing Binder for High-Voltage Batteries.

Lithium-ion batteries are core components of flexible electronic devices. However, deformation types, such as impinging, bending, stretching, folding, and twisting, can cause internal cracks and, eventually, damage these batteries. The cracks separate the active particles from the conductive particles and the binder, as well as the electrode from the collector. Self-healing binders can alleviate this mechanical damage and improve the stress response of active material particles during high rates of charging and discharging of these batteries and the operation at a high voltage, thereby enhancing their cycle performance. In the present study, a thermoplastic intrinsic self-healing polymer (TISP) binder is proposed. The TISP is obtained by polymerization of butanediol (2,3-BDO), propylene glycol (1,3-PDO), succinic acid (SuA), sebacic acid (SeA), and iconic acid (IA). The hydroxyl and ester groups in its structure can form diverse bonds including the hydrogen and ion-dipole with active particles and the current collector, thereby producing elevated adhesion. Its properties, including a low glass transition temperature (-60 °C), amorphous structure, and low cross-link density, improve the mobility of polymer chains at 40 °C, and this facilitates structural recovery and the maintenance of strong adhesions. Owing to its higher occupied molecular orbital (HOMO) level than the electrolyte solvent, the TISP is likely oxidized before the main component of the electrolyte during charging. This decomposition produces a chemical passivation interphase on the cathode which reduces side reactions of LiCoO2 and the electrolyte under high-voltage conditions. Tests reveal that a LiCoO2 electrode battery using the TISP as a binder retains 162.4 mAh g-1 after 349 cycles at 4.5 V, and this represents an 86.5% capacity retention. In addition, heating (40 °C, 1 h) of a scratch-damaged electrode can recover a specific capacity of 156.6 mAh g-1 after 349 cycles at 4.5 V. Relative to a battery without any mechanical scratch, this capacity recovery represents approximately 96%, and this demonstrates the importance of the TISP to the high-voltage damaged electrode.

Detection of antigen Ag85B expression is useful for the diagnosis of tuberculosis, especially for those with an antituberculosis treatment history.

OBJECTIVES: The present study used immunohistochemistry (IHC) to detect antigen Ag85B in tissue sections and aimed to evaluate its validity in histopathologic diagnosis of tuberculosis (TB). METHODS: In total, 204 patients with confirmed TB and 40 other diseases were included in the present study. Ziehl-Neelsen (Z-N) stains, IHC (anti-Ag85B), and quantitative fluorescence polymerase chain reaction were used to detect acid-fast bacilli, Mycobacterium tuberculosis (MTB) antigen, and MTB DNA. RESULTS: Immunohistochemistry was significantly more sensitive than Z-N stains (93.1% vs 67.2%; P < .001). The sensitivity of Z-N stains significantly correlated with anti-TB treatment history. The sensitivity of Z-N stains was lower in rifampicin (RIF)-resistant TB compared with RIF-sensitive TB (52.8% vs 69.0%; P = .091) and those without treatment history (52.8% vs 84.0%; P = .015). However, IHC was not significantly affected by treatment history (P = .410). Moreover, expression patterns of Ag85B were dependent on treatment history and commonly showed weak scattered spots in RIF-susceptible TB. Conversely, strong brown rods were often found in those with RIF-resistant TB. CONCLUSIONS: Immunohistochemistry is a simple, sensitive technique for the diagnosis of TB, especially for those patients with treatment history. The expression pattern of Ag85B is a potential marker for evaluating anti-TB treatment response.

Incidence and Risk Factors for Delayed Retinal Tears after an Acute, Symptomatic Posterior Vitreous Detachment.

PURPOSE: To determine the long-term incidence of and risk factors for delayed retinal tears after acute, symptomatic posterior vitreous detachment (PVD) without concurrent retinal tears. DESIGN: Retrospective, observational case series. SUBJECTS: Patients diagnosed with an acute, symptomatic PVD without concurrent retinal tears at a tertiary eye center between 2013 and 2018. METHODS: This is a retrospective, consecutive, and observational case series. Acute and symptomatic PVD was defined as experiencing flashes or floaters for 1 month or less at the time of diagnosis. Patients with a retinal tear or detachment at or before the time of diagnosis were not included. The occurrence and timing of subsequent retinal tears after initial PVD diagnosis were recorded. The age, sex, race, refractive error, lens status, lattice degeneration status, and type of physician (retina specialist vs. nonretina specialist) who saw the patient were also recorded. MAIN OUTCOME MEASURES: Time to the development of a delayed retinal tear. RESULTS: A total of 389 eyes from 389 patients had acute and symptomatic PVDs without concurrent retinal tears or detachments at diagnosis. Kaplan-Meier analysis showed that 7.39% of eyes developed delayed retinal tears by 6.24 years after initial PVD diagnosis. Of these tears, 50% occurred within 4.63 months of PVD diagnosis, and 63.46% occurred within 1 year of PVD diagnosis. Cox-Mantel log-rank analysis showed that those who were younger (age < 60 years), myopic, or had lattice degeneration were more likely to develop tears. A multivariate Cox proportional-hazards models controlling for other significant risk factors supported lattice degeneration as a likely risk factor for delayed retinal tear. CONCLUSIONS: This study demonstrates that 7.39% of patients with acute, symptomatic PVD without concurrent retinal tears develop delayed retinal tears by 6.24 years after PVD diagnosis, with many developing tears well after a typical 6-week follow-up time for PVD. Lattice degeneration is a significant risk factor for delayed tears. These findings can guide clinicians in establishing optimal follow-up protocols for patients with acute, symptomatic PVD. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Comparison of brain microstructure alterations on diffusion kurtosis imaging among Alzheimer's disease, mild cognitive impairment, and cognitively normal individuals.

Objective: Our study aimed to explore the differences in brain microstructure in patients with Alzheimer's disease (AD) and with mild cognitive impairment (MCI) and in individuals with normal cognition using diffusion kurtosis imaging (DKI) to identify a potential non-invasive biomarker of AD. Materials and methods: A total of 61 subjects were included in our study, including 20 subjects diagnosed with AD, 21 patients diagnosed with amnestic MCI, and 20 cognitively normal individuals. We acquired magnetic resonance imaging (MRI) scans, and DKI images were processed. Twelve regions of interest were drawn, and various parameters were measured and analyzed using SPSS version 11.0 software. Results: Comparative analysis showed that differences in brain regions in terms of mean diffusion (MD) and mean kurtosis (MK) between groups were the most marked. Precuneus MD, temporal MK, precuneus MK, and hippocampal MK were significantly correlated with neuropsychological test scores. Hippocampal MK showed the strongest correlation with the medial temporal lobe atrophy score (r = -0.510), and precuneus MD had the strongest correlation with the Koedam score (r = 0.463). The receiver operating curve analysis revealed that hippocampal MK exhibited better diagnostic efficacy than precuneus MD for comparisons between any group pair. Conclusion: DKI is capable of detecting differences in brain microstructure between patients with AD, patients with MCI, and cognitively normal individuals. Moreover, it compensates for the deficiencies of conventional MRI in detecting pathological changes in microstructure before the appearance of macroscopic atrophy. Hippocampus MK was the most sensitive single parameter map for differentiating patients with AD, patients with MCI, and cognitively normal individuals.