Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by mutations in the transcriptional regulator MeCP2. Much of our understanding of MeCP2 function is derived from transcriptomic ...studies with the general assumption that alterations in the transcriptome correlate with proteomic changes. Advances in mass spectrometry-based proteomics have facilitated recent interest in the examination of global protein expression to better understand the biology between transcriptional and translational regulation.
We therefore performed the first comprehensive transcriptome-proteome comparison in a RTT mouse model to elucidate RTT pathophysiology, identify potential therapeutic targets, and further our understanding of MeCP2 function. The whole cortex of wild-type and symptomatic RTT male littermates (
= 4 per genotype) were analyzed using RNA-sequencing and data-independent acquisition liquid chromatography tandem mass spectrometry. Ingenuity® Pathway Analysis was used to identify significantly affected pathways in the transcriptomic and proteomic data sets.
Our results indicate these two "omics" data sets supplement one another. In addition to confirming previous works regarding mRNA expression in
-deficient animals, the current study identified hundreds of novel protein targets. Several selected protein targets were validated by Western blot analysis. These data indicate RNA metabolism, proteostasis, monoamine metabolism, and cholesterol synthesis are disrupted in the RTT proteome. Hits common to both data sets indicate disrupted cellular metabolism, calcium signaling, protein stability, DNA binding, and cytoskeletal cell structure. Finally, in addition to confirming disrupted pathways and identifying novel hits in neuronal structure and synaptic transmission, our data indicate aberrant myelination, inflammation, and vascular disruption. Intriguingly, there is no evidence of reactive gliosis, but instead, gene, protein, and pathway analysis suggest astrocytic maturation and morphological deficits.
This comparative omics analysis supports previous works indicating widespread CNS dysfunction and may serve as a valuable resource for those interested in cellular dysfunction in RTT.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The chin is recognized as an essential element in overall facial balance and contributes to the perception of youthfulness. Age-related chin retrusion and resorption can alter the shape and ...projection of the chin, disrupting facial harmony. Hyaluronic acid-based dermal fillers offer a temporary, non-surgical option to correct mild to moderate chin retrusion and resorption. In this case series of three patients, we sought to describe a modified injection technique of the chin with hyaluronic acid-based filler using a tapered lateral to medial approach aimed at correcting mild to moderate chin retrusion and resorption. The aesthetic improvement in appearance, compared to pretreatment, was measured by the investigators using the Global Aesthetic Improvement Scale. Each patient received either a score of 4 or 5 indicating improvement from baseline or achievement of optimal corrective results, respectively. An advantage of using this approach is that starting from a lateral to medial approach with a needle allows the injector to rebuild the chin compartment using precise volumes of filler, requiring minimal total filler volume to achieve optimal corrective results. While this report demonstrates promising results in aesthetic outcomes, further research is required to demonstrate reproducible results and long-term efficacy.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
To estimate the association between discussion of all options (adoption, abortion, and parenting) in pregnancy options counseling and patient-reported experience with counseling.
Patients (n = 316) ...who received a positive pregnancy test Oct 2018-June 2019 at one of 14 randomly selected clinics in a southern US publicly funded family planning system participated in an anonymous digital survey about their experience with counseling. The survey assessed which options (parenting, adoption, abortion) they discussed with their provider and how they rated their counseling experience using a 20-item scale based on validated measures of patient reproductive health counseling experience. We used Poisson regression to estimate the prevalence ratio for discussing all pregnancy options and rating their provider with a perfect score.
Approximately 10% of patients reported their provider discussed all options. After adjustment for patient, provider, and clinic characteristics, patients were approximately 80% more likely to rate their counseling as “excellent” on all analyzed scale items when their provider discussed all options compared to when they did not (adjusted prevalence ratio aPR = 1.80, 95% CI: 1.43, 2.28). Discussion of all pregnancy options was associated with a more positive patient-reported experience among patients who planned to continue their pregnancy (aPR = 1.82, 95% CI: 1.37, 2.42) and among those who did not (aPR = 1.62, 95% CI: 1.08, 2.44). Patients whose provider had received options counseling training were more likely to report all options were discussed.
Discussion of all options during pregnancy counseling is associated with a more positive patient experience. These findings indicate patient preference for supportive, nondirective counseling on all pregnancy options.
Our study's findings support nondirective discussion of all pregnancy options (including parenting, abortion and adoption) as a best practice, and stand in contrast to regulations that restrict discussion of all options.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Although unfamiliar accents can pose word identification challenges for children and adults, few studies have directly compared perception of multiple nonnative and regional accents or quantified how ...the extent of deviation from the ambient accent impacts word identification accuracy across development. To address these gaps, 5- to 7-year-old children's and adults' word identification accuracy with native (Midland American, British, Scottish), nonnative (German-, Mandarin-, Japanese-accented English) and bilingual (Hindi-English) varieties (one talker per accent) was tested in quiet and noise. Talkers' pronunciation distance from the ambient dialect was quantified at the phoneme level using a Levenshtein algorithm adaptation. Whereas performance was worse on all non-ambient dialects than the ambient one, there were only interactions between talker and age (child vs adult or across age for the children) for a subset of talkers, which did not fall along the native/nonnative divide. Levenshtein distances significantly predicted word recognition accuracy for adults and children in both listening environments with similar impacts in quiet. In noise, children had more difficulty overcoming pronunciations that substantially deviated from ambient dialect norms than adults. Future work should continue investigating how pronunciation distance impacts word recognition accuracy by incorporating distance metrics at other levels of analysis (e.g., phonetic, suprasegmental).
Abstract Black race has been associated with a higher rate of complications following total joint arthroplasty, such as infection, deep vein thrombosis, pulmonary embolism, and death. We hypothesized ...that there would be no significant association between black race and adverse outcome when medical conditions were adjusted for. Data on 585,269 patients from the Nationwide Inpatient Samples were assessed by multivariable logistic regression analysis. Black race was significantly associated with postoperative complication and death. Comorbidities do not account for racial differences in adverse events. Black race was an independent predictive factor for increased complications and death following hip and knee arthroplasty.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Water scarcity in the United States needs to be addressed with demand- and supply-side initiatives. Yet, water is often provided for a low cost to households in residential areas that have the ...potential to reduce water consumption. The theory of planned behavior (TpB) is a social science theory used to understand why volitional conservation behaviors, including water conservation, are performed by consumers. Additional predictors are included in TpB in water literature, and motivations for behavioral actions may help further explain residential water conservation behavior. This study sought to determine whether TpB and motivation predicted residential water conservation behavior. Data were collected with an online survey (n = 907) in September 2022 from residents of Florida, Georgia, and Alabama using non-probability opt-in quota sampling. The data were analyzed in R using the lavaan package. The results indicate that there was a significant direct effect of attitude and subjective norms on intention. There was a significant direct effect of intention on behavior. There was a significant negative direct effect of extrinsic motivation on behavior. Mediation was present in the model with intrinsic motivation. Perhaps the respondents had not thought about rewards or punishments in the context of water conservation because of the availability of water at a low cost and therefore were not extrinsically motivated to conserve water.
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Background: The Phase 3 VISION and TheraP trials excluded men with Hgb≤ 9 g/dL or blood transfusion within 30 days of Lu-177. Patients (pts) with mCRPC who are eligible for Lu-177 are often ...pancytopenic due to marrow infiltration and previous cytotoxic therapy. Clinicians are often faced with the dilemma of packed red blood cell (RBC) transfusion (Tx) to meet “eligibility requirements" of Lu-177. The impact of low Hgb levels on treatment (trt) outcomes is unclear. Methods: We retrospectively identified pts with mCRPC who received at least one cycle of Lu-177 between July 2022 and January 2023 at a single institution. Demographic, disease, laboratory and trt characteristics were recorded. Pts with Hgb level ≤10 g/dL or who received RBC Tx up to 14 days prior to the first Lu-177 dose were compared to pts with a pre-trt Hgb level ≥10 g/dL and no prior PRBC Tx. Data were summarized using descriptive statistics. Time to trt discontinuation was defined as the time from the first Lu-177 cycle until progressive disease per treating physician (clinical, radiographic, PSA progression) or adverse effect necessitating cessation and compared using the Kaplan Meier method. Cox proportional hazard regression analysis were utilized to assess the association of Hgb ≤ or ≥ 10 g/dL on the risk of trt discontinuation. Results: 51 pts were included, median follow up was 5.75 months, median age 70 years, 90% Caucasian. 49% (n = 25) had Gleason 9 /10 disease. Median number of prior trt was 4. 94% (n = 48), received prior docetaxel and 39% (n = 20) received prior cabazitaxel. 27% (n = 14) of pts had either Hgb≤10 or received a RBC Tx prior to trt. Of these, 50% of pts (n = 7) had stopped Lu-177 prior to completion of 6 cycles. Median number of cycles was 3. Reasons for trt cessation included clinical decline (n = 4), PSA or radiographic disease progression (n = 2), cytopenia (n = 1). Of pts who had Hgb ≥10 (n = 37), most (86%) are in ongoing trt, 11% (n = 4) have stopped trt due to progressive disease, 1 pt died. Pts with Hgb≤10 had a shorter time to trt discontinuation, 4.5 months (95% CI: 4.43- NA) vs not reached for those with Hgb≥10, p = 0.004 and an increased risk of trt discontinuation HR = 1.65 (95% CI: 1.53-18.09, p = 0.009). Conclusions: Pre-trt Hgb≤10 g/dL may be associated with worse outcomes in pts with mCRPC undergoing trt with Lu-177 and caution should be exercised. A larger data set and longer follow up is needed to further investigate outcomes in this pt population. Multivariable analysis is planned. Table: see text
Abstract Violence among youth is a pervasive public health problem. In order to make progress in reducing the burden of injury and mortality that result from youth violence, it is imperative to ...identify evidence-based programs and strategies that have a significant impact on violence. There have been many rigorous evaluations of youth violence prevention programs. However, the literature is large, and it is difficult to draw conclusions about what works across evaluations from different disciplines, contexts, and types of programs. The current study reviews the meta-analyses and systematic reviews published prior to 2009 that synthesize evaluations of youth violence prevention programs. This meta-review reports the findings from 37 meta-analyses and 15 systematic reviews; the included reviews were coded on measures of the social ecology, prevention approach, program type, and study design. A majority of the meta-analyses and systematic reviews were found to demonstrate moderate program effects. Meta-analyses yielded marginally smaller effect sizes compared to systematic reviews, and those that included programs targeting family factors showed marginally larger effects than those that did not. In addition, there are a wide range of individual/family, program, and study moderators of program effect sizes. Implications of these findings and suggestions for future research are discussed.
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