The Expression of Toll-like Receptors (TLR7 and TLR9) in Class III and Class IV of Recently Diagnosed Lupus Nephritis with 12-Month Follow-Up.

Renal involvement is an important cause of morbidity and mortality in systemic lupus erythematosus (SLE). The present study included patients with recently diagnosed Class III and Class IV lupus nephritis (LN) treated by Rheumatology who, upon the detection of alterations in their kidney function, were referred to Nephrology for the joint management of both medical specialties. The purpose of this study was to compare the plasma expression of Toll-Like Receptor 7 (TLR7) and TLR9 in healthy control (HC) subjects and newly diagnosed Class III and Class IV LN patients with 12-month follow-ups. The plasma expression of TLR7 and TLR9 proteins was determined by the ELISA method. A significant increase in the expression of TLR7 protein was found in Class III LN in the basal determination compared to the expression in the HC (p = 0.002) and at 12 months of follow-up (p = 0.03) vs. HC. The expression of TLR9 showed a behavior opposite to that of TLR7. TLR9 showed decreased protein expression in LN Class III patients' baseline and final measurements. The result was similar in the basal and final determinations of LN Class IV compared to the expression in HC. A significant decrease in SLEDAI -2K was observed at 12 months of follow-up in patients in Class III (p = 0.01) and Class IV (p = 0.0001) of LN. Complement C3 levels improved significantly at 12-month follow-up in Class IV patients (p = 0.0001). Complement C4 levels decreased significantly at 12-month follow-up in LN Class III compared to baseline (p = 0.01). Anti-DNA antibodies decreased significantly at 12 months of follow-up in Class IV LN (p = 0.01). A significant increase in proteinuria was found at 12 months of follow-up in Class III LN, compared to the baseline determination (p = 0.02). In LN Class IV, proteinuria decreased at 12 months of follow-up compared to baseline (p = 0.0001). Albuminuria decreased at 12 months of follow-up in LN Class IV (p = 0.006). Class IV LN, albuminuria also decreased at 12 months of follow-up (p = 0.009). Hematuria persisted in all patients and the glomerular filtration rate did not change. Three Class IV patients died before 12 months of follow-up from various causes. In conclusion, although the rheumatologic data appeared to improve, the renal function data remained inconsistent. Decreased expression of TLR9 and increased expression of TLR7 could be useful in the early diagnosis of Class III and Class IV LN is correct.

Thrombotic microangiopathy associated with calcineurin inhibitor induction doses in patients with a kidney transplant.

We present a case of a 23-year-old male who developed thrombotic microangiopathy associated with the induction dose of tacrolimus. Get an early diagnosis and give timely treatment of thrombotic microangiopathy is essential to improve the prognosis of the kidney transplant.

First Report of White Mold Caused by Sclerotinia sclerotiorum on Hymenocallis glauca in Mexico.

In Mexico, there are 29 native species of the genus Hymenocallis, where H. glauca is one of the most cultivated bulbous plants. It holds economic importance as it is commercialized as a potted plant and cut flower (Leszczyñska and Borys, 2001). In October 2023, field sampling was conducted in the Research Center in Horticulture and Native Plants (18°55'55" N, 98°24'02.8"W) of UPAEP University. H. glauca diseased plants were found in an area of 0.4 ha, with an incidence of 35% and an estimated severity of 45% on infected plants in vegetative stage. The symptoms included chlorosis of foliage, necrosis at the base of the stem, and soft rot with abundant white to gray mycelium and abundant production of black, irregular sclerotia of approximately 3.5 mm diameter. Finally, the plants wilted and died. The fungus was isolated from 40 symptomatic plants. Sclerotia were collected, disinfested with 3% NaOCl for one minute, rinsed with sterile distilled water (SDW), and plated on Petri dishes containing potato dextrose agar (PDA) with sterile forceps. Subsequently, a sterile dissecting needle was used to place fragments of mycelium directly on Petri dishes with PDA. Plates were incubated at 23 °C in dark for 7 days. One isolate was obtained from each diseased plant by the hyphal-tip method (20 isolates from sclerotia and 20 from mycelium). After 7 days, colonies had fast-growing, dense, and cottony-white aerial mycelium forming irregular sclerotia of 3.57 ± 0.59 mm (mean ± standard deviation, n=100). In each Petri dish there were produced 21.5 ± 7.9 sclerotia (mean ± standard deviation, n=40), after 11 days; these were initially white and gradually turned black. The isolates were tentatively identified as Sclerotinia sclerotiorum based on morphological characteristics (Saharan and Mehta 2008). Two representative isolates were chosen for molecular identification and genomic DNA was extracted by the CTAB protocol. The ITS region and the glyceraldehyde 3-phosphate dehydrogenase (G3PDH) gene were amplified and sequenced (Staats et al. 2005; White et al. 1990). The sequences of a representative isolate (SsHg3) were deposited in GenBank (ITS- PP094578; G3PDH- PP101843). BLAST analysis of the partial sequences ITS (519 bp), and G3PDH (950 bp) showed 100% similarity to S. sclerotiorum isolates (GenBank: MG249967, MW082601). Pathogenicity was confirmed by inoculating 30 H. glauca plants in vegetative stage grown in pots with sterile soil. Ten sclerotia were deposited at the base of the stem, 10 mm below the soil surface. As control treatment, SDW was applied to 10 plants. The plants were placed in a greenhouse at 23 °C and 90% relative humidity. After 17 days, all inoculated plants displayed symptoms similar to those observed in the field, while no symptoms were observed on the controls. The fungus was re-isolated from the inoculated plants as described above, fulfilling Koch's postulates. The pathogenicity tests were repeated three times. S. sclerotiorum has been reported causing white mold on other bulbous plants, like fennel (Foeniculum vulgare) in Korea (Choi et al. 2015). To our knowledge, this is the first report of S. sclerotiorum causing white mold on H. glauca in Mexico. Information about diseases affecting this plant is very limited, so this research is essential for developing integrated management strategies and preventing spread to other production areas.

Are alternative variables in a set differently associated with a target variable? Statistical tests and practical advice for dealing with dependent correlations.

The analysis of multiple bivariate correlations is often carried out by conducting simple tests to check whether each of them is significantly different from zero. In addition, pairwise differences are often judged by eye or by comparing the p-values of the individual tests of significance despite the existence of statistical tests for differences between correlations. This paper uses simulation methods to assess the accuracy (empirical Type I error rate), power, and robustness of 10 tests designed to check the significance of the difference between two dependent correlations with overlapping variables (i.e., the correlation between X1 and Y and the correlation between X2 and Y). Five of the tests turned out to be inadvisable because their empirical Type I error rates under normality differ greatly from the nominal alpha level of .05 either across the board or within certain sub-ranges of the parameter space. The remaining five tests were acceptable and their merits were similar in terms of all comparison criteria, although none of them was robust across all forms of non-normality explored in the study. Practical recommendations are given for the choice of a statistical test to compare dependent correlations with overlapping variables.

Liver Transplantation for Hepatocarcinoma: Results over Two Decades of a Transplantation Programme and Analysis of Factors Associated with Recurrence.

BACKGROUND: In recent years, many studies have attempted to develop models to predict the recurrence of hepatocarcinoma after liver transplantation. METHOD: A single-centre, retrospective cohort study analysed patients receiving transplants due to hepatocarcinoma during the 20 years of the transplant programme. We analysed patient survival, hepatocarcinoma recurrence and the influence of the different factors described in the literature as related to hepatocarcinoma recurrence. We compared the results of previous items between the first and second decades of the transplantation programme (1995-2010 and 2010-2020). RESULTS: Of 265 patients, the patient survival rate was 68% at 5 years, 58% at 10 years, 45% at 15 years and 34% at 20 years. The overall recurrence rate of hepatocarcinoma was 14.5%, without differences between periods. Of these, 54% of recurrences occurred early, in the first two years after transplantation. Of the parameters analysed, an alpha-fetoprotein level of >16 ng/mL, the type of immunosuppression used and the characteristics of the pathological anatomy of the explant were significant. A trend towards statistical significance was identified for the number of nodules and the size of the largest nodule. Logistic regression analysis was used to develop a model with a sensitivity of 85.7% and a specificity of 35.7% to predict recurrences in our cohort. Regarding the comparison between periods, the survival and recurrence rates of hepatocarcinoma were similar. The impact of the factors analysed in both decades was similar. CONCLUSIONS: Most recurrences occur during the first two years post-transplantation, so closer follow-ups should be performed during this period, especially in those patients where the model predicts a high risk of recurrence. The detection of patients at higher risk of recurrence allows for closer follow-up and may, in the future, make them candidates for adjuvant or neoadjuvant systemic therapies to transplantation.

Phenotypes of Mineral Bone Disorder in Chronic Kidney Disease in a Dialysis Population.

BACKGROUND: Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is associated with clinical outcomes. It is necessary to identify the phenotype to make clinical decisions that optimize resources and follow-up. OBJECTIVE: To determine the frequency of the CKD-MBD phenotype in dialysis patients and the associated factors. METHODS: Cross-sectional study in 440 patients, evaluated for CKD-MBD. Phenotypes show frequency of high, low or on target levels of PTH, vitamin D and phosphorus. The most common phenotype was used for comparisons. RESULTS: Age was 37.5 ± 15.8 years, 53% male, 28% were diabetic, 60% on peritoneal dialysis (PD), dialysis vintage was 12.0 months (IQR 3.0-34.3). High PTH was 58%, low vitamin D 82%, high phosphorus 39%, low calcium 50%, and vascular calcification 55%. The combination of high PTH and low vitamin D and high on-target phosphorus was 39%. Those with high PTH and low vitamin D were more likely to use PD (71 vs 51%; p <0.0001), had higher lipids: total cholesterol (159 vs. 152; p = 0.002) and triglycerides (137 vs. 123; p = 0.02), higher potassium (4.7 ± 0.7 vs. 4.9 ± 0.9 mg/dL; p = 0.04), and higher serum creatinine (11.9 ± 4.4 vs. 10.6 ± 3.7 mg/dL; p = 0.01). Predictors of the most common phenotypes were PD use, total cholesterol, and serum creatinine. CONCLUSIONS: More than one third (38%) of our sample of patients had high PTH and low vitamin D with either high or normal phosphorus. Patients with these phenotypes more frequently used PD, had higher lipids and low potassium. PD use, total cholesterol and serum creatinine were significantly associated with these phenotypes.

Rotenone Induces a Neuropathological Phenotype in Cholinergic-like Neurons Resembling Parkinson's Disease Dementia (PDD).

Parkinson's disease with dementia (PDD) is a neurological disorder that clinically and neuropathologically overlaps with Parkinson's disease (PD) and Alzheimer's disease (AD). Although it is assumed that alpha-synuclein ( α -Syn), amyloid beta (A ß ), and the protein Tau might synergistically induce cholinergic neuronal degeneration, presently the pathological mechanism of PDD remains unclear. Therefore, it is essential to delve into the cellular and molecular aspects of this neurological entity to identify potential targets for prevention and treatment strategies. Cholinergic-like neurons (ChLNs) were exposed to rotenone (ROT, 10 µ M) for 24 h. ROT provokes loss of Δ Ψ m , generation of reactive oxygen species (ROS), phosphorylation of leucine-rich repeated kinase 2 (LRRK2 at Ser935) concomitantly with phosphorylation of α -synuclein ( α -Syn, Ser129), induces accumulation of intracellular A ß (iA ß ), oxidized DJ-1 (Cys106), as well as phosphorylation of TAU (Ser202/Thr205), increases the phosphorylation of c-JUN (Ser63/Ser73), and increases expression of proapoptotic proteins TP53, PUMA, and cleaved caspase 3 (CC3) in ChLNs. These neuropathological features resemble those reproduced in presenilin 1 (PSEN1) E280A ChLNs. Interestingly, anti-oxidant and anti-amyloid cannabidiol (CBD), JNK inhibitor SP600125 (SP), TP53 inhibitor pifithrin- α (PFT), and LRRK2 kinase inhibitor PF-06447475 (PF475) significantly diminish ROT-induced oxidative stress (OS), proteinaceous, and cell death markers in ChLNs compared to naïve ChLNs. In conclusion, ROT induces p- α -Syn, iA ß , p-Tau, and cell death in ChLNs, recapitulating the neuropathology findings in PDD. Our report provides an excellent in vitro model to test for potential therapeutic strategies against PDD. Our data suggest that ROT induces a neuropathologic phenotype in ChLNs similar to that caused by the mutation PSEN1 E280A.

Decisional Conflict Regarding Disease-Modifying Treatment Choices Among Patients with Mid-Stage Relapsing-Remitting Multiple Sclerosis.

Purpose: Shared decision-making is critical in multiple sclerosis (MS) due to the uncertainty of the disease trajectory over time and the large number of treatment options with differing efficacy, safety and administration characteristics. The aim of this study was to assess patients' decisional conflict regarding the choice of a disease-modifying therapy and its associated factors in patients with mid-stage relapsing-remitting multiple sclerosis (RRMS). Methods: A multicenter, non-interventional study was conducted. Adult patients with a diagnosis of RRMS (2017 revised McDonald criteria) and disease duration of 3 to 8 years were included. The level of uncertainty experienced by a patient when faced with making a treatment choice was assessed using the 4-item Decisional Conflict Scale. A battery of patient-reported and clinician-rated measures was administered to obtain information on symptom severity, illness perception, illness-related uncertainty, regret, MS knowledge, risk taking behavior, preferred role in the decision-making process, cognition, and self-management. Patients were recruited during routine follow-up visits and completed all questionnaires online using electronic tablets at the hospital. A multivariate logistic regression analysis was conducted. Results: A total of 201 patients were studied. Mean age (Standard deviation) was 38.7 (8.4) years and 74.1% were female. Median disease duration (Interquartile range) was 6.0 (4.0-7.0) years. Median EDSS score was 1.0 (0-2.0). Sixty-seven (33.3%) patients reported a decisional conflict. These patients had lower MS knowledge and more illness uncertainty, anxiety, depressive symptoms, fatigue, subjective symptom severity, a threatening illness perception, and poorer quality of life than their counterparts. Lack of decisional conflict was associated with MS knowledge (Odds ratio [OR]=1.195, 95% CI 1.045, 1.383, p=0.013), self-management (OR=1.049, 95% CI 1.013, 1.093, p=0.018), and regret after a healthcare decision (OR=0.860, 95% CI 0.756, 0.973, p=0.018) in the multivariate analysis. Conclusion: Decisional conflict regarding the selection of a disease-modifying therapy was a common phenomenon in patients with mid-stage RRMS. Identifying factors associated with decisional conflict may be useful to implement preventive strategies that help patients better understand their condition and strengthen their self-management resources.

Older urban rats are infected with the zoonotic nematode Angiostrongylus cantonensis.

Rats, being synanthropic, are hosts to agents of zoonotic diseases that pose a threat to human and domestic animal health. The nematode parasite Angiostrongylus cantonensis, commonly known as the rat lungworm, is no exception; it can cause potentially fatal neural disease in humans, dogs and other species. The distribution of A. cantonensis (haplotypes SYD.1 and Ac13) and its close relative, Angiostrongylus mackerrasae is not well understood in Australia. We investigated the prevalence of Angiostrongylus in rats in Sydney, Australia, primarily via faecal qPCR, and identified the species and haplotypes using partial cox1 sequencing. We found a moderate prevalence of infection (29%; 95% CI: 16.1-46.6%) in black (Rattus rattus) and brown (Rattus norvegicus) rats around public parks and residential areas. This study demonstrates that Sydney's urban rat population is a reservoir for A. cantonensis. Modelling infection status as a function of rat species, sex, tibia length (as a proxy for age), and health index (a measure of weight by size) revealed that older rats are statistically more likely to be infected (χ 2 1 = 5.331, P = 0.021). We observed a dominant presence of the A. cantonensis SYD.1 haplotype, for which the implications are not yet known. No A. mackerassae was detected, leading us to suspect it may have a more restricted host- and geographical range. Overall, this study illustrates the presence and potential risk of A. cantonensis infection in Sydney. Public education regarding transmission routes and preventative measures is crucial to safeguard human and animal health.

Postoperative Complications in Emergency Surgeries at a Referral Hospital in Eastern Venezuela.

Background Postoperative complications (POC) are undesirable consequences of surgery and are a major area of concern adversely affecting the quality of surgical care and patient safety. Emergency surgery has been observed to have a higher incidence of different POC. The analysis of POC is of great importance due to their impact on the quality of life of patients and because they have become an indicator to measure the quality of hospital services. Objective This study aimed to describe the POC of emergency surgeries in patients from the general surgery department of a referral hospital in eastern Venezuela. Methodology A cross-sectional retrospective study was conducted, including patients undergoing emergency surgery at "Dr. Luis Razetti" University Hospital, Barcelona, Venezuela, between November 2022 and May 2023. Results Medical records of 178 patients were analyzed. Most were male (53.7%), with an average age of 34.98 and a standard deviation of 18.2 years. POC was registered in 28 (15.7%) patients, with surgical site infection being the most common in 21 (39.62%) patients. Those over 65 years old (21.4% vs. 6.4%, p=0.013), patients with a history of hypertension (25% vs. 6.3%, p=0.002), hypoalbuminemia (100% vs. 43.8%, p=0.027), diagnosed with peritonitis due to hollow viscus perforation (21.4% vs. 6%, p=0.007), trauma (25% vs. 9.3%, p=0.018), and those with a midline incision (75% vs. 31.3%, p<0.001) had a higher frequency of POC. There was a mortality rate of 2.8% with no significant difference based on the development of POC. Conclusion POC represents a significant cause of morbidity and mortality in patients undergoing emergency surgeries. The studied sample showed a similar frequency of POC compared to previous reports but with lower mortality. Complications were associated with higher frequencies of hypertension, midline approach, hypoalbuminemia, and emergency surgery for peritonitis due to hollow viscus perforation and trauma.

Physical activity to reduce the burden of frailty after menopause: effectiveness and adherence rate of a resource saving exercise plan.

OBJECTIVE: Frailty may be increased by menopause. Physical activity has been proposed to reduce frailty, but poor adherence and cost limit effectiveness. We aimed to investigate both the effectiveness against the frailty burden and the adherence rate of a multicomponent physical activity scheme partially managed by the participating women themselves. METHODS: Prospective controlled study consisting of a twice-weekly group physical activity scheme divided into two consecutive periods, one supervised by a health professional (12 wk) and the other supervised by the women themselves (36 wk). Group cohesion and mutual support during the patient-only period were aided by social networking via smartphones. Community-dwelling postmenopausal women were divided into a physical activity group (PAG = 126) and a usual activity control group (UAG = 126), both assessed at baseline and at the end of the study. Participants self-assigned to one of the two study arms. RESULTS: Overall, women in the PAG were more likely to improve their frailty status (60.2% vs 42.6%, P < 0.05). The frailty reversal rate from prefrail to robust was significantly higher in the PAG than in the UAG (34.04 vs 8.00%, P < 0.05). Logistic regression confirmed that women in the PAG were more likely to improve their frailty phenotype (odds ratio [OR], 9.12; 95% confidence interval [CI], 3.45-31.52; P < 0.001). Adherence, defined by participants attending 75% of sessions, was attained by 56.35% of women at 48 wk. CONCLUSION: A physical activity scheme implemented to improve frailty proved effective and attained acceptable adherence. Conditions in the peer-supervised 36-wk phase may increase sustainability.

Ultrasonographic features of nonvascular complications of hyaluronic acid fillers: a retrospective study at a reference center for dermatologic ultrasonography.

Hyaluronic acid filler injections have been associated with early, temporary, and delayed-onset complications. High-resolution ultrasound with Doppler analysis has been increasingly used to detect and identify such complications. We comprehensively describe the most common ultrasonographic findings of nonvascular complications associated with hyaluronic acid filler injections. This retrospective, cross-sectional, observational study was conducted at a reference center for dermatologic ultrasound in Bogotá, Colombia. Ultrasound reports documented the ultrasonographic findings of nonvascular complications of hyaluronic acid filler injections. Fifty-two complications were documented in a cohort of 50 patients (women, 88%). The infraorbital region was the most common site affected (23%), followed by the nasolabial region (22%). The Tyndall effect was the most common complication (25% of all), followed by changes in rheology (21%) and pseudosarcoidal (foreign body granuloma) reaction (15%). The Tyndall effect stood out for its distinctive ultrasonographic characteristics. We discuss the ultrasonographic findings and pathogenesis of other complications, including filler migration, early hypersensitivity, aseptic abscess, overcorrection, and filler material interaction. The clinical presentation of hyaluronic acid filler complications can be confusing, delaying timely diagnosis and treatment. High-resolution ultrasound with Doppler analysis is a valuable tool for avoiding unnecessary treatments and ensuring timely diagnosis and treatment.

An open-label feasibility trial of transdermal cannabidiol for hand osteoarthritis.

Hand osteoarthritis (OA) is an irreversible degenerative condition causing chronic pain and impaired functionality. Existing treatment options are often inadequate. Cannabidiol (CBD) has demonstrated analgesic and anti-inflammatory effects in preclinical models of arthritis. In this open-label feasibility trial, participants with symptomatically active hand OA applied a novel transdermal CBD gel (4% w/w) three times a day for four weeks to their most painful hand. Changes in daily self-reported pain scores were measured on a 0-10 Numeric Pain Rating Scale (NPRS). Hand functionality was determined via daily grip strength measures using a Bluetooth equipped squeeze ball and self-report questionnaire. Quality of life (QoL) ratings around sleep, anxiety, stiffness and fatigue were also measured. All self-report measures and grip strength data were gathered via smartphone application. Urinalysis was conducted at trial end to determine systemic absorption of CBD. Eighteen participants were consented and 15 completed the trial. Pain ratings were significantly reduced over time from pre-treatment baseline including current pain (- 1.91 ± 0.35, p < 0.0001), average pain (- 1.92 ± 0.35, p < 0.0001) and maximum pain (- 1.97 ± 0.34, p < 0.0001) (data represent mean reduction on a 0-10 NPRS scale ± standard error of the mean (SEM)). A significant increase in grip strength in the treated hand (p < 0.0001) was observed although self-reported functionality did not improve. There were significant (p < 0.005) improvements in three QoL measures: fatigue, stiffness and anxiety. CBD and its metabolites were detected at low concentrations in all urine samples. Measured reductions in pain and increases in grip strength seen during treatment reverted back towards baseline during the washout phase. In summary, pain, grip strength and QoL measures, using smartphone technology, was shown to improve over time following transdermal CBD application suggesting feasibility of this intervention in relieving osteoarthritic hand pain. Proof of efficacy, however, requires further confirmation in a placebo-controlled randomised trial.Trial registration: ANZCTR public trials registry (ACTRN12621001512819, 05/11/2021).

Exacerbated atherosclerosis in progeria is prevented by progerin elimination in vascular smooth muscle cells but not endothelial cells.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare disease caused by the expression of progerin, a mutant protein that accelerates aging and precipitates death. Given that atherosclerosis complications are the main cause of death in progeria, here, we investigated whether progerin-induced atherosclerosis is prevented in HGPSrev-Cdh5-CreERT2 and HGPSrev-SM22α-Cre mice with progerin suppression in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), respectively. HGPSrev-Cdh5-CreERT2 mice were undistinguishable from HGPSrev mice with ubiquitous progerin expression, in contrast with the ameliorated progeroid phenotype of HGPSrev-SM22α-Cre mice. To study atherosclerosis, we generated atheroprone mouse models by overexpressing a PCSK9 gain-of-function mutant. While HGPSrev-Cdh5-CreERT2 and HGPSrev mice developed a similar level of excessive atherosclerosis, plaque development in HGPSrev-SM22α-Cre mice was reduced to wild-type levels. Our studies demonstrate that progerin suppression in VSMCs, but not in ECs, prevents exacerbated atherosclerosis in progeroid mice.

Trends in volumes and survival after hematopoietic cell transplantation in racial/ethnic minorities.

ABSTRACT: There has been an increase in volume as well as an improvement in overall survival (OS) after hematopoietic cell transplantation (HCT) for hematologic disorders. It is unknown if these changes have affected racial/ethnic minorities equally. In this observational study from the Center for International Blood and Marrow Transplant Research of 79 904 autologous (auto) and 65 662 allogeneic (allo) HCTs, we examined the volume and rates of change of autoHCT and alloHCT over time and trends in OS in 4 racial/ethnic groups: non-Hispanic Whites (NHWs), non-Hispanic African Americans (NHAAs), and Hispanics across 5 2-year cohorts from 2009 to 2018. Rates of change were compared using Poisson model. Adjusted and unadjusted Cox proportional hazards models examined trends in mortality in the 4 racial/ethnic groups over 5 study time periods. The rates of increase in volume were significantly higher for Hispanics and NHAAs vs NHW for both autoHCT and alloHCT. Adjusted overall mortality after autoHCT was comparable across all racial/ethnic groups. NHAA adults (hazard ratio [HR] 1.13; 95% confidence interval [CI] 1.04-1.22; P = .004) and pediatric patients (HR 1.62; 95% CI 1.3-2.03; P < .001) had a higher risk of mortality after alloHCT than NHWs. Improvement in OS over time was seen in all 4 groups after both autoHCT and alloHCT. Our study shows the rate of change for the use of autoHCT and alloHCT is higher in NHAAs and Hispanics than in NHWs. Survival after autoHCT and alloHCT improved over time; however, NHAAs have worse OS after alloHCT, which has persisted. Continued efforts are needed to mitigate disparities for patients requiring alloHCT.

APOE3 Christchurch modulates ß-catenin/Wnt signaling in iPS cell-derived cerebral organoids from Alzheimer's cases.

A patient with the PSEN1 E280A mutation and homozygous for APOE3 Christchurch (APOE3Ch) displayed extreme resistance to Alzheimer's disease (AD) cognitive decline and tauopathy, despite having a high amyloid burden. To further investigate the differences in biological processes attributed to APOE3Ch, we generated induced pluripotent stem (iPS) cell-derived cerebral organoids from this resistant case and a non-protected control, using CRISPR/Cas9 gene editing to modulate APOE3Ch expression. In the APOE3Ch cerebral organoids, we observed a protective pattern from early tau phosphorylation. ScRNA sequencing revealed regulation of Cadherin and Wnt signaling pathways by APOE3Ch, with immunostaining indicating elevated ß-catenin protein levels. Further in vitro reporter assays unexpectedly demonstrated that ApoE3Ch functions as a Wnt3a signaling enhancer. This work uncovered a neomorphic molecular mechanism of protection of ApoE3 Christchurch, which may serve as the foundation for the future development of protected case-inspired therapeutics targeting AD and tauopathies.

Assessing illness-related uncertainty in relapsing-remitting multiple sclerosis: A psychometric analysis of the Mishel Uncertainty of Illness Scale.

A multicenter study involving 204 adults with relapsing-remitting multiple sclerosis (RRMS) assessed the dimensionality and item characteristics of the Mishel-Uncertainty of Illness Scale (MUIS), a generic self-assessment tool. Mokken analysis identified two dimensions in the MUIS with an appropriate item and overall scale scalability after excluding nonclassifiable items. A refined 12-item MUIS, employing a grade response model, effectively discriminated uncertainty levels among RRMS patients (likelihood ratio test p-value = .03). These findings suggest the potential value of the 12-item MUIS as a reliable measure for assessing uncertainty associated with the course of illness in RRMS.