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Heterogeneous polyaminoamido diphosphonated dendrimers built on the surface of silica, when complexed to rhodium via (Rh(CO)2Cl)2, are excellent catalysts for the hydroformylation reactions. The excellent selectivities observed especially favored the branched aldehydes derived from aryl olefins and vinyl esters. It was also found that the heterogeneous Rh(I) catalyst is recyclable and reusable, without compromising its selectivity or activity.

The importance of the length of the spacer chain on the activity and recyclability of the dendrimer rhodium complex is demonstrated.

PURPOSE: To evaluate subjective outcomes and use of continuous positive airway pressure (CPAP) after maxillomandibular advancement surgery for treatment of obstructive sleep apnea syndrome (OSAS). PATIENTS AND METHODS: A self-administered questionnaire was completed pre- and postoperatively by 116 patients who underwent maxillomandibular advancement surgery for treatment of OSAS from February 2000 through September 2010. The questionnaire included the Epworth Sleepiness Scale (ESS) for assessment of daytime somnolence and questions regarding snoring, witnessed apneas, CPAP use, and overall satisfaction. RESULTS: Preoperatively, 40% of patients were very sleepy (ESS >=16), 32% were sleepy (ESS 10 to 16), and 28% were not sleepy (ESS <=10). Postoperatively, only 1 patient (<1%) was very sleepy, 9% were sleepy, and 90% were not sleepy (McNemar test, P < .001). The mean ESS score for the very sleepy, sleepy, and not-sleepy groups decreased from 18.3 to 5.9, 12.9 to 4.4, and 7.3 to 4.5, respectively (P < .001). Surgery decreased snoring by 83%, witnessed apneas by 94%, and CPAP use by 96% (P < .001). The surgery was judged to be worthwhile by 89% of patients, and 95% of patients said they would recommend the treatment to other patients with OSAS. CONCLUSIONS: Maxillomandibular advancement surgery for treatment of OSAS is very effective at improving excessive daytime sleepiness, snoring, and witnessed apneas. Most patients in this study were able to discontinue the use of CPAP after surgery. Overall, patients reported the treatment to be worthwhile and would recommend it to others. [ABSTRACT FROM AUTHOR]

Dorsal root ganglion (DRG) toxicity has been consistently reported as a potential safety concern after delivery of adeno-associated viruses (AAVs) containing gene-replacement vectors but has yet to be reported for RNAi-based vectors. Here, we report DRG toxicity after AAV intra-CSF delivery of an RNAi expression construct-artificial microRNA targeting superoxide dismutase 1 (SOD1)-in non-human primates (NHPs) and provide evidence that this can be recapitulated within mice. Histopathology evaluation showed that NHPs and mice develop DRG toxicity after AAV delivery, including DRG neuron degeneration and necrosis and nerve-fiber degeneration that were associated with increases in cerebrospinal fluid (CSF) and serum phosphorylated neurofilament heavy chain (pNF-H). RNA-sequencing analysis of DRGs showed that dysregulated pathways were preserved between NHPs and mice, including increases in innate/adaptive immune responses and decreases in mitochondrial- and neuronal-related genes, following AAV treatment. Finally, endogenous miR-21-5p was upregulated in DRGs of AAV-treated NHPs and mice. Increases in miR-21-5p were also identified within the CSF of NHPs, which significantly correlated with pNF-H, implicating miR-21-5p as a potential biomarker of DRG toxicity in conjunction with other molecular analytes. This work highlights the importance of assessing safety concerns related to DRG toxicity when developing RNAi-based AAV vectors for therapeutic purposes., Competing Interests: Declaration of interests M.L.H. is a paid advisor from Charter Preclinical Services. All other authors are or were paid employees at Biogen., (Copyright © 2024 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Age and comorbidity are key factors in assessing patient prognosis and informing stopping rules for cancer screening eligibility, but their impact has not been rigorously evaluated in patients with hepatocellular carcinoma (HCC)., Methods: We conducted a retrospective cohort study of patients diagnosed with HCC at 2 health systems between January 2010 and February 2023. We used multivariable logistic regression and Cox proportional hazards models to evaluate the associations between older age (≥65 years) and comorbidity burden (Charlson Comorbidity Index) with early-stage presentation, curative treatment receipt, and overall survival. We performed subgroup analyses in patients with early-stage HCC., Results: We identified 2002 patients with HCC (median age, 61 years; 76% male; 21% early-stage), with a median survival of 15.7 months. In adjusted analyses, curative treatment receipt was associated with higher comorbidity but not older age. Conversely, overall survival was significantly associated with older age (hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.06-1.47) but not high comorbidity (HR, 0.92; 95% CI, 0.77-1.09). Older age continued to be associated with worse survival among patients with early-stage HCC (HR, 1.99; 95% CI, 1.45-2.73) and those who underwent curative treatment (HR, 1.52; 95% CI, 1.10-2.10). Median survival for younger versus older individuals was 20 versus 14 months overall, 65 versus 49 months for patients with early-stage HCC, and 113 versus 60 months for those with curative treatment., Conclusions: Older age but not comorbidity burden is associated with worse survival, including among patients with early-stage HCC. Further studies are needed to define the role of comorbidity in HCC prognostication., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Racial and ethnic disparities have been reported for HCC prognosis, although few studies fully account for clinically important factors and social determinants of health, including neighborhood socioeconomic status., Methods: We conducted a retrospective multicenter cohort study of patients newly diagnosed with HCC from January 2010 through August 2018 at 4 large health systems in the United States. We used multivariable logistic regression and cause-specific Cox proportional hazard models to identify factors associated with early-stage HCC presentation and overall survival., Results: Of 2263 patients with HCC (37.6% non-Hispanic White, 23.5% non-Hispanic Black, 32.6% Hispanic, and 6.4% Asian/other), 42.0% of patients presented at an early stage (Barcelona Clinic Liver Cancer stage 0/A). In fully adjusted models, there were persistent Black-White disparities in early-stage presentation (OR: 0.63, 95% CI: 0.45-0.89) but not Hispanic-White disparities (OR: 0.93, 95% CI: 0.70-1.24). Median survival was 16.2 (IQR: 5.8-36.8) months for White patients compared to 15.7 (IQR: 4.6-34.4) months for Hispanic, 10.0 (IQR: 2.9-29.0) months for Black, and 9.5 (IQR: 3.4-31.9) months for Asian/other patients. Black-White disparities in survival persisted after adjusting for individual demographics and clinical factors (HR: 1.30, 95% CI: 1.09-1.53) but were no longer observed after adding HCC stage and treatment (HR: 1.05, 95% CI: 0.88-1.24), or in fully adjusted models (HR: 0.97, 95% CI: 0.79-1.18). In fully adjusted models, Hispanic-White (HR: 0.87, 95% CI: 0.73-1.03) and Asian/other-White (HR: 0.85, 95% CI: 0.63-1.15) differences in survival were not statistically significant, although patients in high-SES neighborhoods had lower mortality (HR: 0.69, 95% CI: 0.48-0.99)., Conclusions: In a multicenter cohort of patients with HCC, racial and ethnic differences in HCC prognosis were explained in part by differences in tumor stage at diagnosis and neighborhood SES. These data inform targets to intervene and reduce disparities., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Circulating tumour DNA (ctDNA) detection via liquid biopsy is an emerging alternative to tissue biopsy, but its potential in treatment response monitoring and prognosis in triple negative breast cancer (TNBC) is not yet well understood. Here we determined the prevalence of actionable mutations detectable in ctDNA using a clinically validated cancer gene panel assay in patients with TNBC, without recurrence at the time of study entry. Sequencing of plasma DNA and validation of variants from 130 TNBC patients collected within 7 months of primary treatment completion revealed that 7.7% had detectable residual disease with a hotspot panel. Among neoadjuvant treated patients, we observed a trend where patients with incomplete pathologic response and positive ctDNA within 7 months of treatment completion were at much higher risk of reduced progression free survival. We propose that a high risk subset of early TNBC patients treated in neoadjuvant therapy protocols may be identifiable by combining tissue response and sensitive ctDNA detection., (© 2024. The Author(s).)

Indigenous communities in the United States experience some of the highest rates of food insecurity and diet-related diseases despite an abundance of food assistance programs and other public health interventions. New approaches that center Indigenous perspectives and solutions are emerging and urgently needed to better understand and address these challenges. This Practice Note shares lessons learned from ongoing collaboration between the Karuk Tribe and University of California, Berkeley researchers and other partners to assess and enhance food sovereignty among Tribes and Tribal communities in the Klamath River Basin. Through two participatory research and extension projects, we demonstrate the importance of centering Indigenous knowledge to strengthen research findings and identify more culturally appropriate solutions to community identified food access, health, and ecosystem challenges. Key findings suggest that approaches to food sovereignty and community health must emanate from the community, be approached holistically, reflect community values and priorities, and center Indigenous land stewardship.

Mitochondrial dysfunction is a major cause and/or contributor to the development and progression of vision defects in many ophthalmologic and mitochondrial diseases. Despite their mechanistic commonality, these diseases exhibit an impressive variety in sex- and tissue-specific penetrance, incidence, and severity. Currently, there is no functional explanation for these differences. We measured the function, relative capacities, and patterns of control of various oxidative phosphorylation pathways in the retina, the eyecup, the extraocular muscles, the optic nerve, and the sciatic nerve of adult male and female rats. We show that the control of mitochondrial respiratory pathways in the visual system is sex- and tissue-specific and that this may be an important factor in determining susceptibility to mitochondrial dysfunction between these groups. The optic nerve showed a low relative capacity of the NADH pathway, depending on complex I, compared to other tissues relying mainly on mitochondria for energy production. Furthermore, NADH pathway capacity is higher in females compared to males, and this sexual dimorphism occurs only in the optic nerve. Our results propose an explanation for Leber's hereditary optic neuropathy, a mitochondrial disease more prevalent in males where the principal tissue affected is the optic nerve. To our knowledge, this is the first study to identify and provide functional explanations for differences in the occurrence and severity of visual defects between tissues and between sexes. Our results highlight the importance of considering sex- and tissue-specific mitochondrial function in elucidating pathophysiological mechanisms of visual defects., (Copyright © 2020 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)

Objective: To determine associations between home oxygen use and 1-year readmissions for preterm infants with bronchopulmonary dysplasia (BPD) discharged from regional neonatal intensive care units., Study Design: We performed a secondary analysis of the Children's Hospitals Neonatal Database, with readmission data via the Pediatric Hospital Information System and demographics using ZIP-code-linked census data. We included infants born <32 weeks of gestation with BPD, excluding those with anomalies and tracheostomies. Our primary outcome was readmission by 1 year corrected age; secondary outcomes included readmission duration, mortality, and readmission diagnosis-related group codes. A staged multivariable logistic regression was adjusted for center, clinical, and social risk factors; at each stage we included variables associated at P < .1 in bivariable analysis with home oxygen use or readmission., Results: Home oxygen was used in 1906 of 3574 infants (53%) in 22 neonatal intensive care units. Readmission occurred in 34%. Earlier gestational age, male sex, gastrostomy tube, surgical necrotizing enterocolitis, lower median income, nonprivate insurance, and shorter hospital-to-home distance were associated with readmission. Home oxygen was not associated with odds of readmission (OR, 1.2; 95% CI, 0.98-1.56), readmission duration, or mortality. Readmissions for infants with home oxygen were more often coded as BPD (16% vs 4%); readmissions for infants on room air were more often gastrointestinal (29% vs 22%; P < .001). Clinical risk factors explained 72% of center variance in readmission., Conclusions: Home oxygen use is not associated with readmission for infants with BPD in regional neonatal intensive care units. Center variation in home oxygen use does not impact readmission risk. Nonrespiratory problems are important contributors to readmission risk for infants with BPD., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Equilibrative nucleoside transporter 4 (ENT4), encoded by SLC29A4, mediates the flux of both 5-hydroxytryptamine (5-HT) and adenosine across cell membranes. We hypothesized that loss of ENT4 function in mice would modify the effects of these established regulators of vascular function. Male and female wild-type (WT) and slc29a4-null (ENT4-KO) mice were compared with respect to their hemodynamics and mesenteric vascular function. Male ENT4-KO mice had a complete loss of myogenic tone in their mesenteric resistance arteries. This was accompanied by a decrease in blood flow in the superior mesenteric artery in the male ENT4-KO mice, and a reduced responsiveness to 5-HT. In contrast, endothelium-dependent relaxations of mesenteric arteries from female ENT4-KO mice were more sensitive to Ca 2+ -activated K + (K Ca ) channel blockade than WT mice. Female ENT4-KO mice also demonstrated an enhanced vasodilatory response to adenosine in vivo that was not seen in males. Ketanserin (5-HT 2A inhibitor) and GR55562 (5-HT 1B/1D inhibitor) decreased 5-HT-induced tone, but only ketanserin inhibited the relaxant effect of 5-HT in mesenteric arteries. 5-HT-evoked increases in tone were elevated in arteries from ENT4-KO mice upon block of endothelial relaxant pathways, with arteries from female ENT4-KO mice showing the greatest increase. Adenosine A 2b receptor expression was decreased, while other adenosine transporter subtypes, as well as adenosine deaminase and adenosine kinase were increased in mesenteric arteries from male, but not female, ENT4-KO mice. These findings indicate that deletion of slc29a4 leads to sex-specific changes in vascular function with significant consequences for regulation of blood flow and pressure by adenosine and 5-HT., (© 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)