EXPRESS: Influence of Rheological Modifications on Primary Network Chemical and Structural Cure Kinetics for an Interpenetrating Polymer Network Resin.

The development of non-contact in situ techniques for monitoring of cure kinetics has the potential to greatly improve both resin formulation and processing. We have recently shown that low-frequency Raman spectroscopy is a viable method for assessing resin structural cure kinetics and complements the traditional chemical conversion determined from the fingerprint region of the spectrum. In this work we further evaluate the relationship between the structural and chemical conversion by investigating two chemically identical yet rheologically different interpenetrating polymer network resin formulations. Rheological analysis demonstrates a relationship between structural conversion and storage modulus, which is not observed in the chemical conversion data. We show that one can produce master cure kinetics curves with comparable kinetic constants using both the chemical and structural conversion methodologies. Parametric analysis of the structural conversion, chemical conversion, and photorheological conversion was combined with a semi-empirical model for the storage shear modulus as a function of extent of cure.

Experimental characterization of littoral atmospheric acoustics: Concurrent meteorological and acoustic observations.

The aim of this work is to describe a rich set of acoustic transmission loss observations that were completed in a coastal environment. The data library, enumerated in detail and publicly posted, is comprised of pitch-catch acoustic transmission loss measurements along with concurrent high spatial resolution meteorological observations. The meteorological parameters include near-surface temperature profiles, vertical wind speed profiles in the acoustic propagation direction, and significant wave height estimates. The acoustic source is positioned on an anchored vessel such that the first several hundred meters of the acoustic range is over open water with one microphone array positioned at the shore. A second microphone array is placed several hundred meters inland along the same source-to-receiver heading. The path between the two acoustic arrays is uniform salt marsh vegetation. Observations were made during seven sessions, which represent a variety of atmospheric conditions. That variety of conditions allows for some experimental generalizations about transmission loss as a function of meteorological observations. These include (1) the relationship between vertical effective sound speed profile and transmission loss, and (2) the variability of acoustic pressure with turbulence over time and elevation.

Combined Micro-Invasive Glaucoma Surgery (MIGS) with Phacoemulsification in Open Angle Glaucoma: A Systematic Review and Meta-Analysis.

PURPOSE: The purpose of this study is to compare efficacies and safeties of combined phacoemulsification-Micro-Invasive Glaucoma Surgeries (MIGS) to phacoemulsification only in eyes with open angle glaucoma. DESIGN: Systematic Review and Meta-Analysis. METHODS: A multi-database literature search was conducted to caputre MIGS articles published prior to April 19th, 2024. Key exclusion criteria were inadequate follow-up, significant loss to follow-up, standalone MIGS surgery, or primary outcomes unreported. MIGS were grouped according to mechanisms of action: 1) Trabecular Meshwork (TM) bypass which improve aqueous drainage into Schlemm's canal (SC), 2) non-GATT Goniotomies which remove TM with varying devices, and 3) GATT which remove TM with a catheter or suture placed into SC. Efficacy was measured by reductions in IOP and medications while safety was compared using incidence of sight-threatening and other adverse events. RESULTS: A total of 95 studies were included, accounting for 9733 eyes followed up at 1-year. The control group had a baseline IOP of 16.9(95%CI 15.9-17.9) mmHg on 1.43(1.19-1.68) medications and a postoperative IOP of 15.2(14.4-15.9) mmHg on 0.80(0.54-1.00) medications. The TM bypass baseline IOP was 18.2(17.6-18.7) mmHg on 1.89(1.78-2.01) medications which lowered to an IOP of 14.8(14.5-15.1) mmHg on 0.80(0.65-0.95) medications at 1-year-postoperation. The non-GATT goniotomy baseline IOP was 20.0(19.2-20.8) mmHg on 2.30(2.09-2.53) medications, and at 1-year followup the IOP was 14.6(14.3-15.0) mmHg on 1.41(1.22-1.62) medications. Lastly, the GATT baseline IOP of 21.8(19.5-24.1) mmHg on 2.90(2.36-3.44) medications was reduced to an IOP of 12.5(10.0-15.0) mmHg on 0.73(0.37-1.09) medications at 1-year-postoperation. All MIGS groups had equal or lower rates of sight-threatening events and secondary glaucoma surgery when compared to control. GATT had the highest hyphema rate at 27.7(13.5-44.5) % followed by non-GATT goniotomy with 15.5(7.8-25.0) %. These were both significantly higher than TM bypass and control groups, with hyphema rates of 3.5(1.6-5.9) % and 4% (only 1 study reporting hyphema rate), respectively. CONCLUSION: Based on current peer-reviewed articles, there is strong evidence that when compared to phacoemulsification alone, combined phaco-MIGS is beneficial for patients with open angle glaucoma and does not increase the incidence of vision-threatening events. Key limitations of our review stem from heterogeneities in protocol design or outcome reporting, and a limited number of high-quality studies with long-term follow-up.

ω-3 PUFA for Secondary Prevention of White Matter Lesions and Neuronal Integrity Breakdown in Older Adults: A Randomized Clinical Trial.

Importance: Older adults with lower intake and tissue levels of long-chain ω-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA; 20:5) and docosahexaenoic acid (DHA; 22:6) have more brain white matter lesions (WMLs), an association suggesting that small-vessel ischemic disease, a major contributor to the development of dementia, including Alzheimer disease, may be preventable through ω-3 treatment. Objective: To determine whether ω-3 treatment reduces WML accumulation in older adults without dementia harboring WMLs and with suboptimal ω-3 status. Design, Setting, and Participants: This quadruple-blinded, placebo-controlled, randomized clinical trial with treatment stratification by apolipoprotein E ε4 allele (APOE*E4) carrier status used linear mixed-effects models to estimate mean annual change between groups. The study was conducted at Oregon Health & Science University, a major academic medical center in the Pacific Northwest, from May 2014 to final participant visit in September 2019. Data analysis concluded in July 2022. Participants were adults without dementia aged 75 years and older with WMLs greater than or equal to 5 cm3 and plasma ω-3 PUFA less than 5.5 weight percentage of total. Intervention: Three-year treatment with 1.65 g of ω-3 PUFA (975 mg of EPA and 650 mg of DHA) vs a soybean oil placebo matched for taste, smell, and appearance. Main Outcomes and Measures: The primary outcome was annual WML progression measured using magnetic resonance imaging. Secondary outcomes included diffusion tensor imaging of fractional anisotropy (DTI-FA), representing neuronal integrity breakdown. Results: A total of 102 participants (62 women [60.8%]; mean age, 81 years [range, 75-96 years]) were equally randomized, 51 per treatment group. Although the ω-3 group had less annual WML accumulation than the placebo group, the difference was not statistically significant (1.19 cm3 [95% CI, 0.64-1.74 cm3] vs 1.34 cm3 [95% CI, 0.80-1.88 cm3]; P = .30). Similarly, the ω-3 group had less annual DTI-FA decline than the placebo group, but the difference was not statistically significant (-0.0014 mm2/s [95% CI, -0.0027 to 0.0002 mm2/s] vs -0.0027 mm2/s [95% CI, -0.0041 to -0.0014 mm2/s]; P = .07). Among APOE*E4 carriers, the annual DTI-FA decline was significantly lower in the group treated with ω-3 than the placebo group (-0.0016 mm2/s [95% CI, -0.0032 to 0.0020 mm2/s] vs -0.0047 mm2/s [95% CI, -0.0067 to -0.0025 mm2/s]; P = .04). Adverse events were similar between treatment groups. Conclusions and Relevance: In this 3-year randomized clinical trial, ω-3 treatment was safe and well-tolerated but failed to reach significant reductions in WML accumulation or neuronal integrity breakdown among all participants, which may be attributable to sample size limitations. However, neuronal integrity breakdown was reduced by ω-3 treatment in APOE*E4 carriers, suggesting that this treatment may be beneficial for this specific group. Trial Registration: ClinicalTrials.gov Identifier: NCT01953705.

Using exploratory pharmacokinetic and pharmacodynamic analyses to predict the probability of flu-like symptoms in healthy volunteers and patients with chronic hepatitis B treated with the toll-like receptor 7 agonist ruzotolimod.

Ruzotolimod (Toll-like receptor 7 (TLR7) agonist, RG7854) is an oral, small molecule immuno-modulator activating the TLR 7 and is being evaluated in patients with CHB. As with other TLR7 agonists, the study drug-related adverse events of flu-like symptoms have been reported in some participants during phase I studies with ruzotolimod. An exploratory analysis of the relationship between pharmacokinetic (PK)/pharmacodynamic (PD) and flu-like symptoms was performed in participants from two phase I studies including both healthy volunteers and NUC-suppressed CHB patients who received either single or multiple ascending doses of orally administered ruzotolimod. Linear and logistic regression were used to explore potential relationships between dose, flu-like symptoms, PK, and PD. Generalized linear regression was performed to predict the probability of flu-like symptoms of all intensities at different RO7011785 (the active metabolite of the double prodrug ruzotolimod) PK exposure. This analysis showed that single or multiple doses of ruzotolimod at ⩾100 mg, the immune PD (IFN-α, neopterin, IP-10, and the transcriptional expression of ISG15, OAS-1, MX1, and TLR7) responses increase with the RO7011785 PK exposure, which increases linearly with the doses from 3 mg to 170 mg of ruzotolimod. The analysis also showed that the probability of flu-like symptoms occurrence increases with PD responses (IFN-α and IP-10). Dose reduction of ruzotolimod can be an effective way to reduce the magnitude of PD response, thus reducing the probability of study drug-related flu-like symptoms occurrence at all intensity in the participants who are highly sensitive to PD activation and intolerant to flu-like symptoms.

Anteroposterior cervical spine canal diameter: exploring ethnic variation between European and Polynesian populations.

BACKGROUND: Reduced spinal canal anteroposterior (AP) diameter and AP-transverse diameter ratio have been linked to the development of spinal cord injury and myelopathy. Previously unpublished data has suggested Maori and Pacifica individuals may have narrower cervical spine canals than their NZ European counterparts. PURPOSE: We evaluate the existence of potential differences in dimensions of the sub-axial cervical spine canal between New Zealand European, Maori and Polynesian individuals. STUDY DESIGN: A computed tomography (CT) analysis of 645 intact adult sub-axial cervical vertebrae from 129 patients. METHODS: A total of 645 human sub-axial (C3-C7) cervical vertebrae were analysed radiographically, using 1 mm resolution CT scans to measure AP diameter, transverse diameter and AP:transverse ratio. CT data were obtained from normal trauma scans demonstrating no acute pathology. CT data was reformatted in digital software allowing multi-planar reconstruction (MPR) to increase accuracy of measurements. Statistical analysis was performed using analysis of variance (ANOVA). RESULTS: A total of 245 vertebrae were from Maori individuals, 245 from NZ European and 155 from Polynesians. There were 455 male vertebrae and 215 female vertebrae. Statistically significant differences were found in AP canal diameter between all ethnic groups, at all spinal levels. The average cervical spine canal was around 2.5 mm narrower in Polynesians and around 1.5 mm narrower in Maori than NZ Europeans. No differences in Transverse canal diameter were observed, however statistically significant differences were found in the AP:transverse ratio at all spinal levels. CONCLUSIONS: Our study, utilizing a normal patient cohort, confirms differences in canal dimensions between ethnic groups. CLINICAL SIGNIFICANCE: Ethnic variation in cervical canal dimensions as herein described, must be considered when defining and diagnosing congenital stenosis. Neglecting to account for these differences may lead to misdiagnosis of congenital stenosis in normal individuals in certain ethnic groups.

Postoperative radiotherapy in women with early operable breast cancer (Scottish Breast Conservation Trial): 30-year update of a randomised, controlled, phase 3 trial.

BACKGROUND: Breast-conserving surgery, adjuvant systemic therapy, and radiotherapy are the standard of care for most women with early breast cancer. There are few reports of clinical outcomes beyond the first decade of follow-up of randomised trials comparing breast-conserving surgery with or without radiotherapy. We present a 30-year update of the Scottish Breast Conservation Trial. METHODS: In this randomised, controlled, phase 3 trial across 14 hospitals in Scotland, women aged younger than 70 years with early breast cancer (tumours ≤4 cm [T1 or T2 and N0 or N1]) were included. They underwent breast-conserving surgery (1 cm margin) with axillary node sampling or clearance. Oestrogen receptor (ER)-rich patients (≥20 fmol/mg protein) received 20 mg oral tamoxifen daily for 5 years. ER-poor patients (<20 fmol/mg protein) received chemotherapy (cyclophosphamide 600 mg/m2, methotrexate 50 mg/m2, and fluorouracil 600 mg/m2 every 21 days intravenously in eight courses). Stratification was by menstrual status (within or more than 12 months from last menstrual period) and ER status (oestrogen concentration ≥20 fmol/mg protein, <20 fmol/mg protein, or unknown) and patients were randomly assigned (1:1) to high-dose (50 Gy in 20-25 fractions) local or locoregional radiotherapy versus no radiotherapy. No blinding was possible due to the nature of the treatment. We report the primary endpoint of the original trial, ipsilateral breast tumour recurrence, and the co-primary endpoint, overall survival. Clinical outcomes were compared by the log-rank test. Hazard ratios (HRs) are reported, with no radiotherapy as the reference group. Failures of the proportional hazards assumption are reported if significant. All analyses are by intention to treat. FINDINGS: Between April 1, 1985, and Oct 2, 1991, 589 patients were enrolled and randomly assigned to the two treatment groups (293 to radiotherapy and 296 to no radiotherapy). After exclusion of four ineligible patients (two in each group), there were 291 patients in the radiotherapy group and 294 patients in the no radiotherapy group. Median follow-up was 17·5 years (IQR 8·4-27·9). Ipsilateral breast tumour recurrence was significantly lower in the radiotherapy group than in the no radiotherapy group (46 [16%] of 291 vs 107 [36%] of 294; HR 0·39 [95% CI 0·28-0·55], p<0·0001). Although there were differences in the hazard rate for ipsilateral breast tumour recurrence in the first decade after treatment (HR 0·24 [95% CI 0·15-0·38], p<0·0001), subsequent risks of ipsilateral breast tumour recurrence were similar in both groups (0·98 [0·54-1·79], p=0·95). There was no difference in overall survival between the two groups (median 18·7 years [95% CI 16·5-21·5] in the no radiotherapy group vs 19·2 years [16·9-21·3] in the radiotherapy group; HR 1·08 [95% CI 0·89-1 ·30], log-rank p=0·43). INTERPRETATION: Our findings suggest that patients whose biology predicts a late relapse a decade or more after breast-conserving surgery for early breast cancer might gain little from adjuvant radiotherapy. FUNDING: Breast Cancer Institute (part of Edinburgh and Lothian Health Foundation) and PFS Genomics (now part of Exact Sciences).

Relative breeding timing and reproductive success of a resident montane bird species.

Wild populations appear to synchronize their reproductive phenology based on numerous environmental and ecological factors; yet, there is still individual variation in the timing of reproduction within populations and such variation may be associated with fitness consequences. For example, many studies have documented a seasonal decline in reproductive fitness, but breeding timing may have varying consequences across different environments. Using 11 years of data, we investigated the relationship between relative breeding timing and reproductive success in resident mountain chickadees (Poecile gambeli) across two elevational bands in the Sierra Nevada mountains, USA. Chickadees that synchronized breeding with the majority of the population ('peak' of breeding) did not have the highest breeding success. Instead, birds that bred early performed best at high elevation, while at low elevation early and peak nests performed similarly. At both elevations, late nests consistently performed the worst. Overall, breeding success decreased with increasing relative timing at both high and low elevations, but the relationship between breeding success and timing differed among years. Our results suggest that in mountain chickadees, earlier breeding is associated with higher reproductive success, especially at high elevations, while late breeding is consistently associated with lower reproductive success at both elevations.

Perceptions of organizational culture among mental health providers at a Veterans Affairs hospital.

A mixed method approach was utilized to assess the organizational culture of the mental health service line at a large Veterans Affairs (VA) hospital. The goals of the study were to assess the organizational culture, identify how employees differ in perceptions of organizational culture, and identify areas of strength and challenges. Two hundred thirteen participants returned a questionnaire assessing perceptions of organizational culture using the Organizational Culture Assessment Questionnaire (Sashkin & Rosenbach, 2013). Additionally, 22 employees and seven service line leaders participated in five focus groups that assessed for perceptions of culture. Quantitative results suggest that employees had a generally average to high average opinion of the organizational culture of the mental health service line within their VA hospital. Subscale scores suggested that customer orientation was a particular strength of the organization. Relative areas of weakness were that staff felt many decisions were imposed from outside the service line and that hard-working clinical staff were not always sufficiently recognized or rewarded for their actions. In general, demographic variables were not significantly related toward respondent opinion of the organizational culture. Substantial overlap existed between the qualitative and quantitative results. This study suggests that, at this VA's mental health service line, customer service was a strength. However, increased recognition of employees and externally imposed decision-making needed improvement. Although interventions have been implemented in these areas, it would be useful to repeat aspects of this study over time and across different institutions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Excipient-Induced Lattice Disorder in Active Pharmaceutical Ingredient: Implications on Drug Product Continuous Manufacturing.

Our previous work (Mol Pharm, 20 (2023) 3427) showed that crystalline excipients, specifically anhydrous dibasic calcium phosphate (DCPA), facilitated the dehydration of carbamazepine dihydrate (CBZDH) and the formation of an amorphous product phase during the mixing stage of continuous tablet manufacturing. Understanding the mechanism of this excipient-induced effect was the object of this study. Blending with DCPA for 15 min caused pronounced lattice disorder in CBZDH. This was evident from the 190% increase in the apparent lattice strain determined by the Williamson-Hall plot. The rapid dehydration was attributed to the increased reactivity of CBZDH caused by this lattice disorder. Lattice disorder in CBZDH was induced by a second method, cryomilling it with DCPA. The dehydration was accelerated in the milled sample. Annealing the cryomilled sample reversed the effect, thus confirming the effect of lattice disorder on the dehydration kinetics. The hardness of DCPA appeared to be responsible for the disordering effect. DCPA exhibited a similar effect in other hydrates, thereby revealing that the effect was not unique to CBZDH. However, its magnitude varied on a case-by-case basis. The high shear powder mixing was necessary for rapid and efficient powder mixing during continuous drug product manufacturing. The mechanical stress imposed on the CBZDH, and exacerbated by DCPA, caused this unexpected destabilization.

A hop testing alternative for functional performance following anterior cruciate ligament reconstruction.

The purpose of this work was to provide a simple method to determine reactive strength during the 6-meter timed hop test (6mTH) and evaluate its association with isokinetic peak torque in patients following anterior cruciate ligament reconstruction (ACLR). Twenty-nine ACLR patients who were at least four months from surgery were included in this analysis. Participants were brought into the laboratory on one occasion to complete functional testing. Quadriceps and hamstring isokinetic testing was completed bilaterally at 60, 180, and 300 deg∙s-1, using extension peak torque from each speed as the outcome measure. The 6mTH was completed bilaterally using a marker-based motion capture system, and reactive strength ratio (RSR) was calculated from the vertical velocity of the pelvis during the test. An adjustment in RSR was made using the velocity of the 6mTH test to account for different strategies employed across participants. Repeated measures correlations were used to determine associations among isokinetic and hop testing variables. A two-way mixed analysis of variance was used to determine differences in isokinetic and hop testing variables between operated and non-operated legs and across male and female participants. Moderate positive associations were found between RSR (and adjusted RSR) and isokinetic peak torque at all speeds (r = .527 to .577). Mean comparisons showed significant main effects for leg and sex. Patients showed significant deficits in their operated versus non-operated legs in all isokinetic and hop testing variables, yet only isokinetic peak torque and timed hop time showed significant differences across male and female groups. Preliminary results are promising but further development is needed to validate other accessible technologies available to calculate reactive strength during functional testing after ACLR. Pending these developments, the effects of movement strategies, demographics, and levels of participation on RSR can then be explored to translate this simple method to clinical environments.

Prevalence and Impact of Unacceptable Symptom State among Patients with Psoriatic Arthritis: Results from the National Psoriasis Foundation's 2019 Annual Survey.

The National Psoriasis Foundation surveyed a random, stratified sample of individuals with psoriatic disease in the United States to determine the prevalence of an unacceptable psoriatic arthritis (PsA) symptom state and its effect on depression and social participation. Acceptable and unacceptable levels of PsA were defined using established cutoff points (acceptable ≤4 vs unacceptable >4) on the Psoriatic Arthritis Impact of Disease 9. Psoriasis severity was defined by body surface area: mild < 3%, moderate-severe ≥ 3%. Depression was assessed utilizing the Patient Health Questionnaire 2. Social participation was assessed by the Patient Reported Outcome Information Measurement System Ability to Participate in Social Role and Activities-SF4a. The analysis cohort comprised 801 patients with PsA. Unacceptable disease activity level (Psoriatic Arthritis Impact of Disease >4) was reported by 59.6% of participants. After adjusting for age, sex, and psoriasis severity, individuals with likely depression (OR = 0.014, P < .001) and those with limited ability to participate in social roles and activities (OR = 0.05, P < .001) were less likely to experience acceptable levels of PsA activity. Ultimately, the results demonstrated that most United States patients with PsA have unacceptable levels of disease activity, which is associated with increased prevalence of depression and limitations in social participation.

Differences in power and performance during sit-to-stand test and its relationships to functional measures in older adults with and without Parkinson's disease.

AIMS: i) to compare 30-s sit-to-stand (STS) test repetitions and power between older adults with and without Parkinson's disease (PD) and ii) to evaluate the relationship of STS repetitions and power with functional measures in older people with PD. METHODS: STS repetitions and power (Alcazar's equation) during the 30-s STS test were assessed in forty-six age- and sex-matched older adults with and without PD. Functional measures included habitual (HGS) and maximum gait speed (MGS), timed-up-and-go (TUG) test and the Mini-Balance Evaluation System Test (Mini-BEST). PD-specific tests were as follows: the motor subscale of the Unified Parkinson's Disease Rating Scale (UPDRS-III), quality of life [Parkinson's Disease Questionnaire (PDQ-39)], perceived freezing of gait (FOG questionnaire), and fear of falling [Falls Efficacy Scale (FES)]. T scores, repeated measures ANOVA and linear regression analyses were used. RESULTS: T scores for older adults with PD were - 2.7 ± 4.5 for STS repetitions, -5.2 ± 4.2 for absolute STS power, and - 3.1 ± 4.6 for relative STS power compared to older adults without PD. T scores for absolute STS power were lower than T scores for STS repetitions (p < 0.001) and relative STS power (p < 0.001). Both absolute and relative STS power and STS repetitions showed similar correlations with functional measures (r = 0.44 to 0.59; both p < 0.05). Relative STS power (r = -0.55; p < 0.05) and STS repetitions (r = -0.47 to -0.55; p < 0.05) but not absolute STS power were correlated to PD-specific tests. CONCLUSIONS: STS repetitions and power values estimated through the 30-s STS test were lower in older people with PD than without PD. Overall, STS power measures were similarly associated with functional performance as STS repetitions, indicating these power equations can be implemented when assessing lower extremity function in older people with PD.

If the Crown Fits: Sterically Demanding N-Heterocyclic Carbene Promotes the Formation of Au8Pt Nanoclusters.

While N-heterocyclic carbenes (NHCs) have recently been shown to be effective ligands for gold nanoclusters, very few examples of heterometallic clusters incorporating nongroup 11 metals are known. We present herein an Au-Pt NHC cluster featuring a crown-shaped [Au8Pt(NHC)8]2+ core, produced in high yield without the need for chromatographic purification. The method was largely independent of the substitution pattern of the NHC backbone; however, bulky wingtip groups were needed for clean conversion to the Au8Pt cluster. Clusters were characterized using single crystal X-ray diffraction, multinuclear nuclear magnetic resonance, electrospray ionization mass spectroscopy, and ultraviolet-visible spectroscopy, and electrochemical features of the cluster are also presented. A detailed analysis of the in-progress reaction mixture by ESI-MS supports the direct involvement of Au-H species as intermediates in cluster formation. These studies further demonstrate that NHC wingtip sterics play a key part in determining the nature of the initial cluster species, providing critical information for the generation of new NHC-stabilized nanoclusters.

Characterizing primary transcriptional responses to short term heat shock in Down syndrome.

Heat shock stress induces genome-wide changes in transcription regulation, activating a coordinated cellular response to enable survival. We noticed many heat shock genes are up-regulated in blood samples from individuals with trisomy 21. We characterized the immediate transcriptional response to heat shock of two lymphoblastoid cell lines derived from brothers with and without trisomy 21. The trisomy 21 cells displayed a more robust heat shock response after just one hour at 42°C than the matched disomic cells.

Posterior Circulation Ischemic Stroke Is Associated with More Severe Forward Head Posture in Patients with Cervicalgia.

BACKGROUND: Chronic risk factors of posterior circulation ischemic strokes remain unknown. There is, however, evidence that anatomical variations within the vertebrobasilar system could potentially lead to the development of posterior circulation strokes. We investigated the association of forward head posturing (FHP), a chronic anatomical change seen in patients with cervicalgia, with posterior circulation strokes. METHODS: In this case-control study, we identified adult patients diagnosed with cervicalgia and ischemic posterior circulation infarcts from 2007 to 2023. Cases were paired with controls with cervicalgia without posterior circulation stroke and matched for known risk factors. C0-C2 angle, C2-C7 angle, and sagittal vertical axis shift were measured as metrics for FHP severity on lateral cervical spine x-rays. Paired t tests were applied to compare stroke risk factors and FHP between groups. RESULTS: Participants included 206 patients (103 cases and 103 controls) with a mean age of 64.4 years; 51.5% were female. There were no statistically significant differences between risk factors for stroke, including hypertension, hyperlipidemia, diabetes, smoking, hypercoagulable state, and atrial fibrillation. There were statistically significant differences in C0-C2 angle (30.7° vs. 23.2°, P = 0.002) and sagittal vertical axis shift (35.4 mm vs. 25.3 mm, P < 0.001). CONCLUSIONS: This case-control matched-pair study found that in adults with cervicalgia, posterior circulation ischemic stroke was associated with more severe FHP as noted in C0-C2 angle and sagittal vertical axis shift measurements. Further, this association may be due to chronic changes in circulation flow dynamics within the vertebrobasilar system with the postural change.

Metabolic pathway and network analysis integration for discovering the biomarkers in pig feces after a controlled fruit-vegetable dietary intervention.

This study aimed to establish a strategy for identifying dietary intake biomarkers using a non-targeted metabolomic approach, including metabolic pathway and network analysis. The strategy was successfully applied to identify dietary intake biomarkers in fecal samples from pigs fed two doses of a polyphenol-rich fruit and vegetable (FV) diet following the Dietary Guidelines for Americans (DGA) recommendations. Potential biomarkers were identified among dietary treatment groups using liquid chromatography-high resolution mass spectrometry (LC-HRMS) based on a non-targeted metabolomic approach with metabolic pathway and network analysis. Principal component analysis (PCA) results showed significant differences in fecal metabolite profiles between the control and two FV intervention groups, indicating a diet-induced differential fecal metabolite profile after FV intervention. Metabolites from common flavonoids, e.g., (epi)catechin and protocatechuic acid, or unique flavonoids, e.g., 5,3',4'-trihydroxy-3-methoxy-6,7-methylenedioxyflavone and 3,5,3',4'-tetrahydroxy-6,7-methylenedioxyflavone, were identified as highly discriminating factors, confirming their potential as fecal markers for the FV dietary intervention. Microbiota pathway prediction using targeted flavonoids provided valuable and reliable biomarker exploration with high confidence. A correlation network analysis between these discriminatory ion features was applied to find connections to possible dietary biomarkers, further validating these biomarkers with biochemical insights. This study demonstrates that integrating metabolic pathways and network analysis with a non-targeted metabolomic approach is highly effective for rapid and accurate identification and prediction of fecal biomarkers under controlled dietary conditions in animal studies. This approach can also be utilized to study microbial metabolisms in human clinical research.

Treatment of early oligoarticular psoriatic arthritis with apremilast: primary outcomes at week 16 from the FOREMOST randomised controlled trial.

OBJECTIVES: Oligoarticular psoriatic arthritis (PsA) is frequent but rarely studied. The objective was to assess the efficacy of apremilast in early oligoarticular PsA. METHODS: FOREMOST (NCT03747939) was a phase 4 multicentre, randomised, double-blind, placebo-controlled trial. Patients had early (symptom duration ≤5 years) oligoarticular PsA (>1 but ≤4 swollen and >1 but ≤4 tender joints; 2-8 total active joints). Patients were randomised 2:1 to apremilast 30 mg two times per day or placebo for 24 weeks, with an early escape at week 16. The primary endpoint was the proportion of patients at week 16 who achieved minimal disease activity (MDA)-Joints (modification of MDA mandating ≤1 swollen joint and ≤1 tender joint) based on sentinel joints (those affected at baseline) with a combination of non-responder imputation and multiple imputations. Exploratory analysis assessed all joints. RESULTS: Of 308 patients randomised (apremilast: n=203; placebo: n=105), mean (SD) PsA duration was 9.9 (10.2) months, mean (SD) age was 50.9 (12.5) years and 39.9% of patients were using a conventional synthetic disease-modifying antirheumatic drug. MDA-Joints (sentinel joints (primary endpoint) and all joints) were achieved by significantly more patients with apremilast (33.9% and 21.3%) vs placebo (16.0% and 7.9%) at week 16 (p=0.0008 and nominal p=0.0028, respectively). Greater improvements in patient-reported outcomes, clinical disease activity and skin involvement were also seen with apremilast versus placebo. CONCLUSIONS: FOREMOST is the first randomised controlled trial designed for early oligoarticular PsA and showed apremilast improves clinical and patient-reported outcomes. This trial may inform the optimal management of PsA in these patients. TRIAL REGISTRATION NUMBER: NCT03747939.

Expanding Medicare Coverage Of Anti-Obesity Medicines Could Increase Annual Spending By $3.1 Billion To $6.1 Billion.

The introduction of highly effective anti-obesity drugs, such as Wegovy, has prompted debate over Medicare's prohibition on coverage of such products. In this study, we estimated the costs of allowing Medicare coverage of anti-obesity medications. Our analysis incorporated data on drug costs, real-world adherence rates, and potential changes to other health care spending. Using Medicare claims, we also documented beneficiaries' eligibility for nearly identical products approved for different indications. Assuming that anti-obesity drugs were covered in 2025 and that 5 percent or 10 percent of newly eligible patients were prescribed one, annual Part D costs were estimated to increase by $3.1 billion or $6.1 billion, respectively. The marginal costs of this policy could fall by as much as 62.5 percent from baseline estimates if products were approved for additional indications in coming years because these additional conditions are common among people with obesity. This would increase Medicare spending but would occur regardless of a policy change. Longer-term estimates come with significant uncertainty about utilization and price changes, but these results are consistent with this policy change likely increasing Medicare costs by the low to middle tens of billions of dollars over ten years.