Sex-based dyad differences on informant reports of participants' daily functioning.

Functional assessment in neurocognitive evaluation is often provided via informant reports. These subjective reports can vary based on the characteristics of informants and their relationships with participants, such as informant sex. However, whether informant sex intersects with participant sex to impact subjective ratings of participants' daily functioning, and whether such effects mirror observed patterns in neuropsychological performance, has not been adequately examined with ethnoracially diverse samples. We examined differences among participant-informant sex-based dyads on subjective informant reports of participants' daily functioning (assessed via the Functional Activities Questionnaire [FAQ]), and whether any observed differences on reported functioning corresponded to differences in objective participant performance on neuropsychological performance, among middle-aged and older Hispanic/Latino (n = 543), non-Hispanic Black (NHB; n = 1030), and non-Hispanic White (NHW; n = 5356) adults in the National Alzheimer's Coordinating Center cohort (n = 6929). Analysis of covariance (ANCOVA) tests revealed significant dyad differences on FAQ scores in the NHB (p<.001) and NHW subsamples (p<.05), but not in the Hispanic/Latino subsample (p>.05). For the Hispanic/Latino and NHB subsamples, ANCOVA tests revealed no significant effects of dyad on neuropsychological performance (ps>.01), whereas for the NHW subsample, ANCOVA tests revealed significant dyad differences on performance in multiple cognitive domains (ps<.01). Nevertheless, the pattern of dyad differences on neuropsychological performance did not mirror the pattern of observed differences on FAQ scores in the NHW subsample. Findings and their implications, including potential contributions of other informant characteristics on observed dyad differences on reported functioning, are discussed.

Furosemide to lower antenatal severe hypertension: a randomized placebo-controlled trial.

BACKGROUND: Hypertensive disorders of pregnancy are a leading cause of perinatal morbidity, and timely treatment of severely elevated blood pressure is recommended to prevent serious sequelae. In acute hypertension marked by increased blood volume, it is unknown whether diuretics used as an adjunct to antihypertensive medications lead to more effective blood pressure control. OBJECTIVE: This study aimed to evaluate whether the addition of intravenous furosemide to first-line antihypertensive agents reduces systolic blood pressure in acute-onset, severe antenatal hypertension with wide (≥60 mm Hg) pulse pressure. STUDY DESIGN: In this double-blinded randomized trial, participants received 40 mg of intravenous furosemide or placebo in addition to a first-line antihypertensive agent. The primary outcome was mean systolic blood pressure during the first hour after intervention. Secondary outcomes included corresponding diastolic blood pressure; systolic blood pressure, diastolic blood pressure, and pulse pressure at 2 hours after intervention; total reduction from qualifying blood pressure; duration of blood pressure control; need for additional antihypertensive doses within 1 hour; and electrolytes and urine output. A sample size of 35 participants per group was planned to detect a 15-mm Hg difference in blood pressure. RESULTS: Between January 2021 and March 2022, 65 individuals were randomized: 33 to furosemide and 32 to placebo. Baseline characteristics were similar between the groups. There was no difference in the primary outcome of mean 1-hour systolic blood pressure (147 [14.8] vs 152 [13.8] mm Hg; P=.200). We found a reduction in 2-hour systolic blood pressure (139 [18.5] vs 154 [18.4] mm Hg; P=.007) and a decrease in 2-hour pulse pressure (55 [12.5] vs 67 [15.1]; P=.003) in the furosemide group. Subgroup analysis according to hypertension type showed a significant reduction in 2-hour systolic blood pressure and 2-hour pulse pressure among patients with new-onset hypertension, but not among those with preexisting hypertension. Urine output was greater in the furosemide group, with no difference in electrolytes and creatinine before and after intervention. CONCLUSION: Intravenous furosemide in conjunction with a first-line antihypertensive agent did not significantly reduce systolic blood pressure in the first hour after administration. However, both systolic blood pressure and pulse pressure at 2 hours were decreased in the furosemide group. These findings suggest that a 1-time dose of intravenous furosemide is a reasonable adjunct to achieve blood pressure control, particularly in patients in whom increased volume is suspected.

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Transcutaneous Electrical Nerve Stimulation for Post-Cesarean Birth Pain Control: A Randomized Controlled Trial.

OBJECTIVE: To evaluate whether transcutaneous electrical nerve stimulation (TENS) reduces opioid use after cesarean birth. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of TENS after cesarean birth, with the primary outcome of opioid use during the first 60 hours postoperatively. Secondary outcomes included pain scores and satisfaction with pain control on each postoperative day, duration of postoperative hospitalization, and adverse effects of TENS. We estimated 60 patients in each arm for 80% power to detect a 25% decrease in opioid use, assuming 10% attrition. To assess for a placebo effect, an additional 60 patients were randomized to no TENS during recruitment for secondary analyses comparing opioid use, pain scores, and pain control satisfaction between no TENS and placebo TENS. Analysis was by intention-to-treat. RESULTS: From January 2020 through March 2021, we enrolled 180 participants-60 per group. Baseline characteristics were similar across groups. Median (interquartile range) opioid consumption in the first 60 hours postoperatively, in morphine milligram equivalents, was 7.5 (0-30) with active TENS and 0 (0-22.5) with placebo TENS (P=.31). There were no significant differences in pain scores, satisfaction with pain control, or postoperative length of stay. In the no TENS group, median (interquartile range) opioid consumption in the first 60 hours postoperatively was 7.5 (0-21.9), similar to that in the placebo group (P=.57). There were also no significant differences in pain scores or pain control satisfaction between participants allocated to no TENS and those allocated to placebo TENS. CONCLUSION: Use of TENS after cesarean birth did not change hospital opioid consumption, pain scores, or length of postoperative stay. There was no evidence for a placebo effect of TENS on opioid use or pain scores. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT04399707. FUNDING SOURCE: Cardinal Health.

Calorimetric Analysis of the Interplay between Synthetic Tn Antigen-Presenting MUC1 Glycopeptides and Human Macrophage Galactose-Type Lectin.

Human macrophage galactose-type lectin (hMGL, HML, CD301, CLEC10A), a C-type lectin expressed by dendritic cells and macrophages, is a receptor for N-acetylgalactosamine α-linked to serine/threonine residues (Tn antigen, CD175) and its α2,6-sialylated derivative (sTn, CD175s). Because these two epitopes are among malignant cell glycan displays, particularly when presented by mucin-1 (MUC1), assessing the influence of the site and frequency of glycosylation on lectin recognition will identify determinants governing this interplay. Thus, chemical synthesis of the tandem-repeat O-glycan acceptor region of MUC1 and site-specific threonine glycosylation in all permutations were carried out. Isothermal titration calorimetry (ITC) analysis of the binding of hMGL to this library of MUC1 glycopeptides revealed an enthalpy-driven process and an affinity enhancement of an order of magnitude with an increasing glycan count from 6-8 µM for monoglycosylated peptides to 0.6 µM for triglycosylated peptide. ITC measurements performed in D2O permitted further exploration of the solvation dynamics during binding. A shift in enthalpy-entropy compensation and contact position-specific effects with the likely involvement of the peptide surroundings were detected. KinITC analysis revealed a prolonged lifetime of the lectin-glycan complex with increasing glycan valency and with a change in the solvent to D2O.

Kidney-Targeted Redox Scavenger Therapy Prevents Cisplatin-Induced Acute Kidney Injury.

Cisplatin-induced acute kidney injury (CI-AKI) is a significant co-morbidity of chemotherapeutic regimens. While this condition is associated with substantially lower survival and increased economic burden, there is no pharmacological agent to effectively treat CI-AKI. The disease is hallmarked by acute tubular necrosis of the proximal tubular epithelial cells primarily due to increased oxidative stress. We investigated a drug delivery strategy to improve the pharmacokinetics of an approved therapy that does not normally demonstrate appreciable efficacy in CI-AKI, as a preventive intervention. In prior work, we developed a kidney-selective mesoscale nanoparticle (MNP) that targets the renal proximal tubular epithelium. Here, we found that the nanoparticles target the kidneys in a mouse model of CI-AKI with significant damage. We evaluated MNPs loaded with the reactive oxygen species scavenger edaravone, currently used to treat stroke and ALS. We found a marked and significant therapeutic benefit with edaravone-loaded MNPs, including improved renal function, which we demonstrated was likely due to a decrease in tubular epithelial cell damage and death imparted by the specific delivery of edaravone. The results suggest that renal-selective edaravone delivery holds potential for the prevention of acute kidney injury among patients undergoing cisplatin-based chemotherapy.

A pragmatic regional interdependence approach to primary frozen shoulder: a retrospective case series.

OBJECTIVES: Although the shoulder is known to move together with the scapula and other upper quarter joints, the current frozen shoulder clinical practice guidelines describe only physical therapy study treatments directed to the shoulder. None received a strong recommendation, highlighting the need for alternate interventions. This retrospective case series describes a pragmatic regional interdependence approach to frozen shoulder with impairment and functional outcomes, noting whether final ROM approached normal. METHODS: Five consecutive patients referred with frozen shoulder diagnoses attended 11-21 sessions over 5-10 weeks with one physical therapist. Treatment addressed inter-related regions (shoulder, shoulder girdle, scapulothoracic/humerothoracic, and spine) following a pragmatic approach using impairment-based interventions (joint/soft tissue mobilization, muscle stretching/strengthening) as well as patient education, modalities and warm up that addressed individual presentations. RESULTS: All patients improved on all outcomes. Mean shoulder ROM at discharge, the impairment outcome, demonstrated large effect size increases: flexion (117 ± 10-179 ± 12, d = 5.9), abduction (74 ± 8-175 ± 9, d = 9.3), external rotation (23 ± 7-89 ± 2, d = 12.0). The Disability of Arm Shoulder Hand functional outcome score upon follow up demonstrated a large effect size improvement (d = 1.5) from 40.0 ± 19.4-6.2 ± 3.7. Final ROM approached normal. DISCUSSION: This case series utilized a regional interdependence approach to frozen shoulder that included manual therapy interventions directed to consistent upper quarter body segments. Shoulder ROM was returned to near normal with functional improvements evident months after discharge. A pragmatic regional interdependence approach addressing multiple joints related to shoulder function may benefit other people with frozen shoulder. LEVEL OF EVIDENCE: 4.

Control of Carbon Nanotube Solvatochromic Response to Chemotherapeutic Agents.

Alkylating agents such as cisplatin play an essential role in chemotherapy regimens, but initial and acquired resistance in many cancer types often dampen therapeutic response. The poor understanding of the mechanisms of resistance highlight the need for quantitative measurements of alkylating agent distribution at both the tissue and subcellular levels. Sensors for use in live animals and cells would allow for more effective study of drug action and resistance. Toward this end, single-walled carbon nanotubes suspended with single-stranded DNA have suitable optical properties for in vivo sensors, such as near-infrared emission and sensitivity to the local environment via solvatochromic responses. Currently, solvatochromic changes of such sensors have been limited by the chemical nature of the analyte, making it impossible to control the direction of energy emission changes. Here, we describe a new approach to control the direction and magnitude of solvatochromic responses of carbon nanotubes. We found that the alkylation of DNA on the nanotube surface can result in small changes in DNA conformation that allow the adsorption of amphiphiles to produce large differences (>14 nm) in response to different drugs. The technique surprisingly revealed differences among drugs upon alkylation. The ability to control carbon nanotube solvatochromism as desired may potentially expand the application of nanotube-based optical sensors for new classes of analytes.

Laparotomy attenuates lipopolysaccharide-induced gastric bleeding in the rat.

Lipopolysaccharide (LPS) increases systemic inflammation and causes duodenogastric reflux of bile and gastric bleeding. Laparotomy prevents gastric injury from the luminal irritant bile, but its effects on LPS-induced gastric injury are unknown. We hypothesized that laparotomy would diminish inflammation and attenuate gastric bleeding caused by LPS. In the rat, laparotomy, done either before or after administration of LPS, attenuated LPS-induced bile reflux, gastric bleeding, and cyclooxygenase-2, but not inducible nitric oxide synthase, expression when compared to controls given LPS. Laparotomy also blunted LPS-induced changes in serum cytokine production. These data suggest that laparotomy has gastroprotective effects by preventing LPS-induced bile reflux and gastric bleeding and by a mechanism mediated, at least in part by cyclooxygenase-2.