Extract from Aronia melanocarpa, Lonicera caerulea, and Vaccinium myrtillus Improves near Visual Acuity in People with Presbyopia.

Presbyopia is a global problem with an estimated 1.3 billion patients worldwide. In the area of functional food applications, dietary supplements or herbs, there are very few reports describing the positive effects of their use. In the available literature, there is a lack of studies in humans as well as on an animal model of extracts containing, simultaneously, compounds from the polyphenol group (in particular, anthocyanins) and iridoids, so we undertook a study of the effects of a preparation composed of these compounds on a condition of the organ of vision. Our previous experience on a rabbit model proved the positive effect of taking an oral extract of Cornus mas in stabilizing the intraocular pressure of the eye. The purpose of this study was to evaluate the effect of an orally administered ternary compound preparation on the status of physiological parameters of the ocular organ. The preparation contained an extract of the chokeberry Aronia melanocarpa, the honeysuckle berry Lonicera caerulea L., and the bilberry Vaccinium myrtillus (hereafter AKB) standardized for anthocyanins and iridoids, as bioactive compounds known from the literature. A randomized, double-blind, cross-over study lasting with a "wash-out" period of 17 weeks evaluated a group of 23 people over the age of 50, who were subjects with presbyopia and burdened by prolonged work in front of screen monitors. The group of volunteers was recruited from people who perform white-collar jobs on a daily basis. The effects of the test substances contained in the preparation on visual acuity for distance and near, sense of contrast for distance and near, intraocular pressure, and conjunctival lubrication, tested by Schirmer test, LIPCOF index and TBUT test, and visual field test were evaluated. Anthocyanins (including cyanidin 3-O-galactoside, delphinidin 3-O-arabinoside, cyanidin 3-O-glucoside, cyanidin 3-O-rutinoside, cyanidin 3-O-arabinoside) and iridoids (including loganin, sweroside, loganic acid) were identified as substances present in the extract obtained by HPLC-MS. The preliminary results showed that the composition of AKB applied orally does not change visual acuity in the first 6 weeks of administration. Only in the next cycle of the study was an improvement in near visual acuity observed in 92.3% of the patients. This may indicate potential to correct near vision in presbyopic patients. On the other hand, an improvement in conjunctival wetting was observed in the Schirmer test at the beginning of week 6 of administration in 80% of patients. This effect was weakened in subsequent weeks of conducting the experiment to 61.5%. The improvement in conjunctival hydration in the Schirmer test shows the potential beneficial effect of the AKB formulation in a group of patients with dry eye syndrome. This is the first study of a preparation based on natural, standardized extracts of chokeberry, honeysuckle berry, and bilberry. Preliminary studies show an improvement in near visual acuity and conjunctival hydration on the Schirmer test, but this needs to be confirmed in further studies.

Glycoprotein Matrix Zinc Exhibits Improved Absorption: A Randomized Crossover Trial.

Biotransformation of minerals via glycosylation by microorganisms such as yeast and/or probiotics yields nutrients bound to a food matrix, resulting in increased bioavailability. The purpose of this study was to compare the effects of glycoprotein matrix-bound zinc (GPM) on absorption compared to inorganic zinc oxide. Sixteen participants ingested 11 mg of zinc as either GPM™ Soy-Free Zinc (GPM, Ashland, Kearny, NJ, USA) or zinc oxide (USP). Blood samples were taken at 0 (i.e., baseline), 30, 60, 90, 120, 180, 240, 300, 360, 420, and 480 min post-ingestion. GPM zinc concentrations were significantly higher at 120 min (p = 0.02; 12.4 ± 5.1 mcg/dL), 180 min (p = 0.002; 16.8 ± 5.1 mcg/dL), and 240 min (p = 0.007; 14.6 ± 5.1 mcg/dL) in comparison to USP zinc oxide. In addition, GPM zinc significantly increased iAUC by 40% (5840 ± 2684 vs. 4183 ± 1132 mcg/dL * 480 min, p = 0.02), and Cmax values were 10% higher in GPM compared to USP (148 ± 21 mcg/dL vs. 135 ± 17.5 mcg/dL, p = 0.08). Tmax was 12% slower in GPM compared to USP (112.5 ± 38.7 min vs. 127.5 ± 43.1 min); however, differences in Tmax failed to reach statistical significance (p = 0.28). Zinc bound to a glycoprotein matrix significantly increased absorption compared to zinc oxide.

The effect of ascending- descending ultrafiltration and sodium profiles on blood pressure in hemodialysis patients: a randomized cross-over study.

BACKGROUND: Considering no previous research into the utilization of ascending/descending ultrafiltration and linear sodium profiles in improving blood pressure among hemodialysis patients, the present study aimed to explore the effect of the A/D-UF along with linear sodium profiles on HD patients with hypotension. METHODS: Applying a crossover design, this clinical trial was fulfilled between December 2022 and June 2023 on 20 patients undergoing HD, randomized into two groups, each one receiving two intervention protocols, viz., (a) an intervention protocol in which the liquid sodium in the dialysis solution was linear and the UF profiling was A/D, and (b) a routine protocol or HD, wherein both liquid sodium and UF in the dialysis solution remained constant. The HD patients' BP was then checked and recorded at six intervals, namely, before HD, one, two, three, and four hours after it, and following its completion, within each session. The data were further statistically analyzed using the IBM SPSS Statistics 20 and the related tests. RESULTS: In total, 20 patients, including 12 men (60%) and 8 women (40%), with the mean age of 58.00 ± 14.54 on HD for an average of 54 months, were recruited in this study. No statistically significant difference was observed in the mean systolic and diastolic BP levels in the group receiving the A/D-UF profile all through the desired hours (p > 0.05), indicating that the patients did not face many changes in these two numbers during HD. Our cross-over clinical trial demonstrated a statistically significant reduction in symptomatic IDH episodes from 55 to 15% with the application of the A/D-UF profile (p < 0.05). CONCLUSION: The study demonstrated that the A/D-UF profile could contribute to the stability of blood pressure levels among HD patients, with no significant fluctuations observed during treatment sessions. TRIAL REGISTRATION: This study was registered in the Iranian Registry of Clinical Trials (no. IRCT20180429039463N5) on 07/01/2023.

Enantiomer-Specific Cardiovascular Effects of the Ketone Body 3-Hydroxybutyrate.

BACKGROUND: The ketone body 3-hydroxybutyrate (3-OHB) increases cardiac output (CO) by 35% to 40% in healthy people and people with heart failure. The mechanisms underlying the effects of 3-OHB on myocardial contractility and loading conditions as well as the cardiovascular effects of its enantiomeric forms, D-3-OHB and L-3-OHB, remain undetermined. METHODS AND RESULTS: Three groups of 8 pigs each underwent a randomized, crossover study. The groups received 3-hour infusions of either D/L-3-OHB (racemic mixture), 100% L-3-OHB, 100% D-3-OHB, versus an isovolumic control. The animals were monitored with pulmonary artery catheter, left ventricle pressure-volume catheter, and arterial and coronary sinus blood samples. Myocardial biopsies were evaluated with high-resolution respirometry, coronary arteries with isometric myography, and myocardial kinetics with D-[11C]3-OHB and L-[11C]3-OHB positron emission tomography. All three 3-OHB infusions increased 3-OHB levels (P<0.001). D/L-3-OHB and L-3-OHB increased CO by 2.7 L/min (P<0.003). D-3-OHB increased CO nonsignificantly (P=0.2). Circulating 3-OHB levels correlated with CO for both enantiomers (P<0.001). The CO increase was mediated through arterial elastance (afterload) reduction, whereas contractility and preload were unchanged. Ex vivo, D- and L-3-OHB dilated coronary arteries equally. The mitochondrial respiratory capacity remained unaffected. The myocardial 3-OHB extraction increased only during the D- and D/L-3-OHB infusions. D-[11C]3-OHB showed rapid cardiac uptake and metabolism, whereas L-[11C]3-OHB demonstrated much slower pharmacokinetics. CONCLUSIONS: 3-OHB increased CO by reducing afterload. L-3-OHB exerted a stronger hemodynamic response than D-3-OHB due to higher circulating 3-OHB levels. There was a dissocitation between the myocardial metabolism and hemodynamic effects of the enantiomers, highlighting L-3-OHB as a potent cardiovascular agent with strong hemodynamic effects.

Functional Limitations and Exercise Intolerance in Patients With Post-COVID Condition: A Randomized Crossover Clinical Trial.

Importance: Many patients with post-COVID condition (PCC) experience persistent fatigue, muscle pain, and cognitive problems that worsen after exertion (referred to as postexertional malaise). Recommendations currently advise against exercise in this population to prevent symptom worsening; however, prolonged inactivity is associated with risk of long-term health deterioration. Objective: To assess postexertional symptoms in patients with PCC after exercise compared with control participants and to comprehensively investigate the physiologic mechanisms underlying PCC. Design, Setting, and Participants: In this randomized crossover clinical trial, nonhospitalized patients without concomitant diseases and with persistent (≥3 months) symptoms, including postexertional malaise, after SARS-CoV-2 infection were recruited in Sweden from September 2022 to July 2023. Age- and sex-matched control participants were also recruited. Interventions: After comprehensive physiologic characterization, participants completed 3 exercise trials (high-intensity interval training [HIIT], moderate-intensity continuous training [MICT], and strength training [ST]) in a randomized order. Symptoms were reported at baseline, immediately after exercise, and 48 hours after exercise. Main Outcomes and Measures: The primary outcome was between-group differences in changes in fatigue symptoms from baseline to 48 hours after exercise, assessed via the visual analog scale (VAS). Questionnaires, cardiopulmonary exercise testing, inflammatory markers, and physiologic characterization provided information on the physiologic function of patients with PCC. Results: Thirty-one patients with PCC (mean [SD] age, 46.6 [10.0] years; 24 [77%] women) and 31 healthy control participants (mean [SD] age, 47.3 [8.9] years; 23 [74%] women) were included. Patients with PCC reported more symptoms than controls at all time points. However, there was no difference between the groups in the worsening of fatigue in response to the different exercises (mean [SD] VAS ranks for HIIT: PCC, 29.3 [19.5]; controls, 28.7 [11.4]; P = .08; MICT: PCC, 31.2 [17.0]; controls, 24.6 [11.7]; P = .09; ST: PCC, 31.0 [19.7]; controls, 28.1 [12.2]; P = .49). Patients with PCC had greater exacerbation of muscle pain after HIIT (mean [SD] VAS ranks, 33.4 [17.7] vs 25.0 [11.3]; P = .04) and reported more concentration difficulties after MICT (mean [SD] VAS ranks, 33.0 [17.1] vs 23.3 [10.6]; P = .03) compared with controls. At baseline, patients with PCC showed preserved lung and heart function but had a 21% lower peak volume of oxygen consumption (mean difference: -6.8 mL/kg/min; 95% CI, -10.7 to -2.9 mL/kg/min; P < .001) and less isometric knee extension muscle strength (mean difference: -37 Nm; 95% CI, -67 to -7 Nm; P = .02) compared with controls. Patients with PCC spent 43% less time on moderate to vigorous physical activity (mean difference, -26.5 minutes/d; 95% CI, -42.0 to -11.1 minutes/d; P = .001). Of note, 4 patients with PCC (13%) had postural orthostatic tachycardia, and 18 of 29 (62%) showed signs of myopathy as determined by neurophysiologic testing. Conclusions and Relevance: In this study, nonhospitalized patients with PCC generally tolerated exercise with preserved cardiovascular function but showed lower aerobic capacity and less muscle strength than the control group. They also showed signs of postural orthostatic tachycardia and myopathy. The findings suggest cautious exercise adoption could be recommended to prevent further skeletal muscle deconditioning and health impairment in patients with PCC. Trial Registration: ClinicalTrials.gov Identifier: NCT05445830.

Gastric emptying of a glucose drink is predictive of the glycaemic response to oral glucose and mixed meals, but unrelated to antecedent glycaemic control, in type 2 diabetes.

BACKGROUND: Gastric emptying (GE), with wide inter-individual but lesser intra-individual variations, is a major determinant of postprandial glycaemia in health and type 2 diabetes (T2D). However, it is uncertain whether GE of a carbohydrate-containing liquid meal is predictive of the glycaemic response to physiological meals, and whether antecedent hyperglycaemia influences GE in T2D. We evaluated the relationships of (i) the glycaemic response to both a glucose drink and mixed meals with GE of a 75 g glucose drink, and (ii) GE of a glucose drink with antecedent glycaemic control, in T2D. METHODS: Fifty-five treatment-naive Chinese adults with newly diagnosed T2D consumed standardised meals at breakfast, lunch and dinner with continuous interstitial glucose monitoring. On the subsequent day, a 75 g glucose drink containing 150 mg 13C-acetate was ingested to assess GE (breath test) and plasma glucose response. Serum fructosamine and HbA1c were also measured. RESULTS: Plasma glucose incremental area under the curve (iAUC) within 2 hours after oral glucose was related inversely to the gastric half-emptying time (T50) (r = -0.34, P = 0.012). The iAUCs for interstitial glucose within 2 hours after breakfast (r = -0.34, P = 0.012) and dinner (r = -0.28, P = 0.040) were also related inversely to the T50 of oral glucose. The latter, however, was unrelated to antecedent fasting plasma glucose, 24-hour mean interstitial glucose, serum fructosamine, or HbA1c. CONCLUSIONS: In newly diagnosed, treatment-naive, Chinese with T2D, GE of a 75 g glucose drink predicts the glycaemic response to both a glucose drink and mixed meals, but is not influenced by spontaneous short-, medium- or longer-term elevation in glycaemia.

Metabolite profiling of foslevodopa/foscarbidopa in plasma of healthy human participants by LC-HRMS indicates no major differences compared to administration of levodopa/carbidopa intestinal gel.

Analysis was conducted to compare levodopa/carbidopa pharmacokinetics and drug-related material in plasma of healthy participants after receiving a continuous infusion of Levodopa/Carbidopa Intestinal Gel (LCIG) to a continuous subcutaneous infusion of foslevodopa/foscarbidopa. Study samples were from a randomized, open-label, 2-period crossover study in 20 healthy participants. Participants received either 24-h foslevodopa/foscarbidopa SC infusion to the abdomen or LCIG delivered for 24 h to the jejunum through a nasogastric tube with jejunal extension. Serial blood samples were collected for PK. Comparability of the LD PK parameters between the two treatment regimens was determined. Selected plasma samples were pooled per treatment group and per time point for metabolite profiling. LC-MSn was performed using high-resolution mass spectrometry to identify drug-related material across the dosing regimens and time points. The LD PK parameter central values and 90% confidence intervals following the foslevodopa/foscarbidopa subcutaneous infusion were between 0.8 and 1.25 relative to the LCIG infusion. With LCIG administration, LD, CD, 3-OMD, DHPA, DOPAC, and vanillacetic acid were identified in plasma at early and late time points (0.75 and 24 h); the metabolic profile after administration of foslevodopa/foscarbidopa demonstrated the same drug-related compounds with the exception of the administered foslevodopa. 3-OMD and vanillacetic acid levels increased over time in both treatment regimens. Relative quantification of LC-MS peak areas showed no major differences in the metabolite profiles. These results indicate that neither the addition of monophosphate prodrug moieties nor SC administration affects the circulating metabolite profile of foslevodopa/foscarbidopa compared to LCIG.

Comparing Equil patch versus traditional catheter insulin pump in type 2 diabetes using continuous glucose monitoring metrics and profiles.

AIMS: It is not clear whether there are differences in glycemic control between the Equil patch and the MMT-712 insulin pump. Our objective was to compare two types of insulin pumps in the treatment of type 2 diabetes mellitus (T2DM), using continuous glucose monitoring (CGM) metrics and profiles. METHODS: This was a randomized case-crossover clinical trial. Participants were hospitalized and randomly allocated to two groups and underwent two types of insulin pump treatments (group A: Equil patch-Medtronic MMT-712 insulin pump; group B: Medtronic MMT-712-Equil patch insulin pump) separated by a 1-day washout period. Glycemic control was achieved after 7-8 days of insulin pump therapy. Each patient received CGM for 5 consecutive days (from day 1 to day 5). On day 3 of CGM performance, the Equil patch insulin pump treatment was switched to Medtronic MMT-712 insulin pump treatment at the same basal and bolus insulin doses or vice versa. CGM metrics and profiles including glycemic variability (GV), time in range (TIR, 3.9-10.0 mmol/L), time below range (TBR, <3.9 mmol/L), time above range (TAR, >10.0 mmol/L), and postprandial glucose excursions, as well as incidence of hypoglycemia. RESULTS: Forty-six T2DM patients completed the study. There was no significant difference in parameters of daily GV and postprandial glucose excursions between the Equil patch insulin pump treatment and the Medtronic insulin pump treatment. Similarly, there was no between-treatment difference in TIR, TBR, and TAR, as well as the incidence of hypoglycemia. CONCLUSION: The Equil patch insulin pump was similar to the traditional MMT-712 insulin pump in terms of glycemic control. Equil patch insulin pump is a reliable tool for glycemic management of diabetes mellitus.

Oral Delta-9-Tetrahydrocannabinol (THC) Increases Parasympathetic Activity and Supraspinal Conditioned Pain Modulation in Chronic Neuropathic Pain Male Patients: A Crossover, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Disordered autonomic nervous system regulation and supraspinal pain inhibition have been repeatedly described in chronic pain. We aimed to explore the effects of δ-9-tetrahydrocannabinol (THC), an emerging treatment option, on autonomic nervous system and central pain modulation measures in patients with chronic pain. METHODS: Twelve male patients with chronic radicular neuropathic pain participated in a randomized, double-blind, crossover, placebo-controlled, single-administration trial. Low/high frequency (LF/HF) heart rate variability (HRV) ratio and conditioned pain modulation (CPM) response were measured and resting-state functional magnetic resonance imaging (MRI) was performed at baseline and after sublingual administration of either 0.2 mg/kg oral THC or placebo. RESULTS: THC significantly reduced the LF/HF ratio compared with placebo (interaction effect F(1,11) = 20.5; p < 0.005) and significantly improved CPM responses (interaction effect F(1,9) = 5.2; p = 0.048). The THC-induced reduction in LF/HF ratio correlated with increased functional connectivity between the rostral ventrolateral medulla and the dorsolateral prefrontal cortex [T(10) = 6.4, cluster p-FDR < 0.005]. CONCLUSIONS: THC shifts the autonomic balance towards increased parasympathetic tone and improves inhibitory pain mechanisms in chronic pain. The increase in vagal tone correlates with connectivity changes in higher-order regulatory brain regions, suggesting THC exerts top-down effects. These changes may reflect a normalizing effect of THC on multiple domains of supraspinal pain dysregulation. CLINICAL TRIAL REGISTRY NUMBER: NCT02560545.

Enhanced muscle activity during interrupted sitting improves glycemic control in overweight and obese men.

The efficacy of interrupting prolonged sitting may be influenced by muscle activity patterns. This study examined the effects of interrupting prolonged sitting time with different muscle activity patterns on continuously monitored postprandial glycemic response. Eighteen overweight and obese men (21.0 ± 1.2 years; 28.8 ± 2.2 kg/m2) participated in this randomized four-arm crossover study, including uninterrupted sitting for 8.5 h (SIT) and interruptions in sitting with matched energy expenditure and duration but varying muscle activity: 30-min walking at 4 km/h (ONE), sitting with 3-min walking at 4 km/h (WALK) or squatting (SQUAT) every 45 min for 10 times. Net incremental area under the curve (netiAUC) for glucose was compared between conditions. Quadriceps, hamstring, and gluteal muscles electromyogram (EMG) patterns including averaged muscle EMG amplitude (aEMG) and EMG activity duration were used to predict the effects on glucose netiAUC. Compared with SIT (10.2 mmol/L/h [95%CI 6.3 to 11.7]), glucose netiAUC was lower during sitting interrupted with any countermeasure (ONE 9.2 mmol/L/h [8.0 to 10.4], WALK 7.9 mmol/L/h [6.4 to 9.3], and SQUAT 7.9 mmol/L/h [6.4 to 9.3], all p < 0.05). Furthermore, WALK and SQUAT resulted in a lower glucose netiAUC compared with ONE (both p < 0.05). Only increased aEMG in quadriceps (-0.383 mmol/L/h [-0.581 to -0.184], p < 0.001) and gluteal muscles (-0.322 mmol/L/h [-0.593 to -0.051], p = 0.022) was associated with a reduction in postprandial glycemic response. Collectively, short, frequent walking or squatting breaks effectively enhance glycemic control in overweight and obese men compared to a single bout of walking within prolonged sitting. These superior benefits seem to be associated with increased muscle activity intensity in the targeted muscle groups during frequent transitions from sitting to activity.

Moral decision-making at night and the impact of night work with blue-enriched white light or warm white light: a counterbalanced crossover study.

BACKGROUND: Cognitive function, including moral decision-making abilities, can be impaired by sleep loss. Blue-enriched light interventions have been shown to ameliorate cognitive impairment during night work. This study investigated whether the quality of moral decision-making during simulated night work differed for night work in blue-enriched white light, compared to warm white light. METHODS: Using a counterbalanced crossover design, three consecutive night shifts were performed in blue-enriched white light (7000 K) and warm white light (2500 K) provided by ceiling-mounted LED luminaires (photopic illuminance: ∼200 lx). At 03:30 h on the second shift (i.e. twice) and at daytime (rested), the Defining Issues Test-2, assessing the activation of cognitive schemas depicting different levels of cognitive moral development, was administered. Data from 30 (10 males, average age 23.3 ± 2.9 years) participants were analysed using linear mixed-effects models. RESULTS: Activation of the post-conventional schema (P-score), that is, the most mature moral level, was significantly lower for night work in warm white light (EMM; estimated marginal mean = 44.3, 95% CI = 38.9-49.6; pholm=.007), but not blue-enriched white light (EMM = 47.5, 95% CI = 42.2-52.8), compared to daytime (EMM = 51.2, 95% CI = 45.9-56.5). Also, the P-score was reduced for night work overall (EMM = 45.9, 95% CI = 41.1-50.8; p=.008), that is, irrespective of light condition, compared to daytime. Neither activation of the maintaining norms schema (MN-score), that is, moderately developed moral level, nor activation of the personal interest schema (i.e. the lowest moral level) differed significantly between light conditions. The MN-score was however increased for night work overall (EMM = 26.8, 95% CI = 23.1-30.5; p=.033) compared to daytime (EMM = 23.1, 95% CI = 18.9-27.2). CONCLUSION: The results indicate that moral decisions during simulated night work in warm white light, but not blue-enriched white light, become less mature and principle-oriented, and more rule-based compared to daytime, hence blue-enriched white light may function as a moderator. Further studies are needed, and the findings should be tentatively considered.Trial registration: ClinicalTrials.gov (ID: NCT03203538) Registered: 26/06/2017; https://clinicaltrials.gov/study/NCT03203538.

The quality of moral decision-making, seen as the activation of cognitive schemas depicting different levels of moral development, was reduced during simulated night work in warm white light, but not blue-enriched light, compared to daytime.The quality of moral decision-making sems to be reduced during simulated night work, compared to daytime.More studies assessing the impact of night work and light interventions on the quality of moral decision-making are needed to validate these tentative findings.

Load carriage exercise increases calcium absorption and retention in healthy young women.

Aerobic exercise reduces circulating ionized Ca (iCa) and increases parathyroid hormone (PTH), but the cause and consequences on Ca handling are unknown. The objective of this study was to determine the effects of strenuous exercise on Ca kinetics using dual stable Ca isotopes. Twenty-one healthy women (26.4 ± 6.7 yr) completed a randomized, crossover study entailing two 6-d iterations consisting of either 60 min of treadmill walking at 65% VO2max wearing a vest weighing 30% body weight on study days 1, 3, and 5 (exercise [EX]), or a rest iteration (rest [REST]). On day 1, participants received intravenous 42Ca and oral 44Ca. Isotope ratios were determined by thermal ionization mass spectrometry. Kinetic modeling determined fractional Ca absorption (FCA), Ca deposition (Vo+), resorption (Vo-) from bone, and balance (Vbal). Circulating PTH and iCa were measured before, during, and after each exercise/rest session. Data were analyzed by paired t-test or linear mixed models using SPSS. iCa decreased and PTH increased (P < .001) during each EX session and were unchanged during REST. On day 1, urinary Ca was lower in the EX pool (25 ± 11 mg) compared to REST (38 ± 16 mg, P = .001), but did not differ over the full 24-h collection (P > .05). FCA was greater during EX (26.6 ± 8.1%) compared to REST (23.9 ± 8.3%, P < .05). Vbal was less negative during EX (-61.3 ± 111 mg) vs REST (-108 ± 23.5 mg, P < .05), but VO+ (574 ± 241 vs 583 ± 260 mg) and VO- (-636 ± 243 vs -692 ± 252 mg) were not different (P > .05). The rapid reduction in circulating iCa may be due to a change in the miscible Ca pool, resulting in increased PTH and changes in intestinal absorption and renal Ca handling that support a more positive Ca balance.

The clinical effect of an electric massage chair on chemotherapy-induced nausea and vomiting in cancer patients: randomized phase II cross-over trial.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) is a common adverse events in cancer patients and can negatively affect their quality of life (QoL). This study aimed to evaluate the clinical efficacy of an electric massage chair (EMC) for the treatment of CINV. METHODS: A randomized phase II cross-over trial was conducted on solid cancer patients who received moderate (MEC) to high emetogenic chemotherapy (HEC). The participants were randomly assigned to receive their first chemotherapy either on a standard bed (Group A) or in an EMC (Group B) during the infusion. The patients were then crossed over to the next cycle. CINV and QoL questionnaires were collected from the participants. RESULTS: A total of 59 patients completed the trial protocol and were included in the analysis, with 29 and 30 patients in Groups A and B, respectively. The mean INVR (Index of Nausea, Vomiting, and Retching) score in the 2nd day of the first cycle was higher in Group B (3.63 ± 5.35) than Group A (2.76 ± 4.78), but the difference was not statistically significant (p = 0.5367). The complete response rate showed little difference between the groups. Among the high-emetic risk subgroups, patients who received HEC (p = 0.04595), younger patients (p = 0.0108), and non-colorectal cancer patients (p = 0.0495) presented significantly lower CINV scores when EMC was applied. CONCLUSION: Overall, there was no significant difference in INVR scores between standard care and EMC. Applying EMC at the first chemotherapy infusion may help preserve QoL and reduce CINV in high-risk patients. TRIAL REGISTRATION: KCT0008200, 17/02/2023, Retrospectively registered.

Evaluation of open-face maxillary complete denture for patients with prominent premaxilla: a crossover study.

BACKGROUND: The establishment of good facial esthetics is one of the main objectives of complete denture construction. Unfortunately, it may be the caused issue for patients having a prominent premaxilla due to excessive lip support by the labial flange of the maxillary denture. Open-face dentures (OFD) may suggest suitable prosthetic management for these patients. However, clinical evidence regarding the efficiency of OFD is scarce. METHODS: A total of 38 completely edentulous participants having prominent premaxilla and skeletal class I Angle's classification were enrolled in this study. Each participant received a mandibular complete denture and 2 opposing maxillary dentures; conventional (CD) and open-face (OFD). On the day of denture insertion, the participants were divided into 2 groups; CD-OFD and OFD-CD where CD-OFD group was instructed to use the mandibular denture and the maxillary CD for 3 months and then to use the maxillary OFD for another 3 months after a wash-out period of 2 weeks. While group OFD-CD was instructed to use the mandibular denture and the maxillary OFD for 3 months then to use the maxillary CD for another 3 months after a wash-out period of 2 weeks. The dislodging force of the maxillary dentures was evaluated using the universal testing machine and the patient perception of retention, esthetics, and comfort was evaluated using the Visual Analogue Scale (VAS). Evaluation was carried out 1 day, 1 month, and 3 months after denture insertion. The Student t-test was used to compare the 2 maxillary dentures and the intervals for each denture were compared by using the ANOVA test with repeated measures followed by a Post Hoc test (adjusted Bonferroni) for pairwise comparison. RESULTS: The significance of the obtained results was judged at the 5% level (P value). The dislodging force and patient perception of retention did not show significant differences between the 2 dentures, while the perception of esthetics showed significant differences throughout the follow-up period. Perception of comfort showed an insignificant difference only at the 3-month interval. CONCLUSIONS: Open-face maxillary dentures can be a suitable alternative for patients with prominent premaxilla to achieve satisfactory retention, aesthetics, and comfort.

Some plasma biomarkers of residual feed intake in beef cattle remain consistent regardless of intake level.

This study investigated whether plasma biomarkers of residual feed intake (RFI), identified under ad libitum feeding conditions in beef cattle, remained consistent during feed restriction. Sixty Charolais crossbred young bulls were divided into two groups for a crossover study. Group A was initially fed ad libitum (first test) and then restricted (second test) on the same diet, while Group B experienced the opposite sequence. Blood samples were collected from the 12 most divergent RFI animals in each group at the end of the first test and again after the second test. 12 plasma variables consistently increased, while three consistently decreased during feed restriction (FDR < 0.05). Only two metabolites, α-aminoadipic acid for Group A and 5-aminovaleric acid for Group B, were associated with RFI independent of feed intake level (FDR < 0.05), demonstrating moderate-to-high repeatability across feeding levels (intraclass correlation coefficient ≥ 0.59). Notably, both metabolites belong to the same metabolic pathway: lysine degradation. These metabolites consistently correlated with RFI, irrespective of fluctuations in feed intake, indicating a connection to individual metabolic processes influencing feed efficiency. These findings suggest that a portion of RFI phenotypic variance is inherent to an individual's metabolic efficiency beyond variations in feed intake.

Effects of ankle-foot orthoses on gait parameters in post-stroke patients with different Brunnstrom stages of the lower limb: a single-center crossover trial.

BACKGROUND: Ankle-foot orthoses (AFO) can improve gait posture and walking ability in post-stroke patients. However, the effect of AFO on gait parameters in post-stroke patients according to the Brunnstrom stage of stroke recovery of the lower limbs remains unclear. The study aimed to investigate whether stroke patients with different Brunnstrom stages benefit from wearing AFO. METHODS: Twenty-five post-stroke participants included 18 men (50 ± 13 years) and 7 women (60 ± 15 years). The patients were divided based on Brunnstrom stage III or IV of the lower limbs. All patients underwent the gait and timed up and go (TUG) test using a gait analysis system while walking barefoot or with an AFO. The spatiotemporal and asymmetric parameters were analyzed. RESULTS: All 25 patients completed the study. Significant differences were observed between barefoot and AFO use in TUG time (P < 0.001) but not walking velocity (P > 0.05). The main effect of the swing time ratio was significant in both groups (P < 0.05); however, the main effects of stride length, stance time, and gait asymmetry ratio were nonsignificant (P > 0.05). For barefoot versus AFO, the main effects of stride length (P < 0.05) and swing time (P < 0.01) ratios were significant, whereas those of stance time and gait asymmetry ratio were nonsignificant (P > 0.05). CONCLUSIONS: Post-stroke patients with lower Brunnstrom stages benefitted more from AFO, particularly in gait asymmetry.

Effects of PDE-3 inhibition in persistent post-traumatic headache: evidence of cAMP-dependent signaling.

BACKGROUND: Phosphodiesterase 3 (PDE-3) inhibition have been implicated in the neurobiologic underpinnings of migraine. Considering the clinical similarities between migraine and persistent post-traumatic headache (PPTH), we aimed to ascertain whether PDE-3 inhibition can elicit migraine-like headache in persons with PPTH. METHODS: We tested cilostazol, which inhibits PDE-3, in a randomized, double-blind, placebo-controlled, two-way crossover study involving persons with PPTH attributed to mild traumatic brain injury. The randomized participants were allocated to receive oral administration of either 200-mg cilostazol or placebo (calcium tablet) on two separate experiment days. The primary end point was the incidence of migraine-like headache during a 12-hour observation window post-ingestion. The secondary endpoint was the area under the curve (AUC) for reported headache intensity scores during the same observation window. RESULTS: Twenty-one persons underwent randomization and completed both experiment days. The mean participants' age was 41.4 years, and most (n = 17) were females. During the 12-hour observation window, 14 (67%) of 21 participants developed migraine-like headache post-cilostazol, in contrast to three (14%) participants after placebo (P =.003). The headache intensity scores were higher post-cilostazol than after placebo (P <.001). CONCLUSIONS: Our results provide novel evidence showing that PDE-3 inhibition can elicit migraine-like headache in persons with PPTH. Given that PDE-3 inhibition increases intracellular cAMP levels, our findings allude to the potential therapeutic value of targeting cAMP-dependent signaling pathways in the management of PPTH. Further investigations are imperative to substantiate these insights and delineate the importance of cAMP-dependent signaling pathways in the neurobiologic mechanisms underlying PPTH. GOV IDENTIFIER: NCT05595993.

Heat and hospital admission via the emergency department for people with intellectual disability, autism, and mental disorders in South Korea: a nationwide, time-stratified, case-crossover study.

BACKGROUND: Given the anticipated increase in ambient temperature due to climate change, the hazardous effects of heat on health have been extensively studied; however, its impact on people with intellectual disability, autism, and mental illness is largely unknown. We aimed to estimate the association between heat and hospitalisation through the emergency department (ED) among people with these mental disorders. METHODS: In this nationwide study, we used data from the National Health Insurance Database (NHID) of the National Health Insurance Service, the single universal insurer in South Korea, the claims data for which is based on the ICD-10. We included individuals with identified intellectual disability, autism, and mental disorders (including schizophrenia, bipolar disorder, recurrent depressive disorder, schizoaffective disorder and persistent obsessive-compulsive disorder, Tourette's disorder, and narcolepsy) and we established two control groups of people without these disorders: one including 1 million systematically sampled individuals, and one matched to the cohort based on sex, age, and income group. Data on hospital admission via the ED were obtained from the NHID, including the primary cause of admission and corresponding medical costs, for the warm season (June-September) of the period 2006-2021. We used the Google Earth Engine with the ERA5-Land dataset to collect data on the daily mean temperature. We applied a time-stratified case-crossover design using a distributed lag non-linear model and performed a conditional logistic regression. The risk ratio was estimated as the odds ratio (OR) with calculated odds at the 99th percentile temperature compared with that at the local 75th percentile temperature. We did not include people with lived experience of mental illness in this study. FINDINGS: Of the 456 946 people with intellectual disability, autism, or mental disorder in the NHID records, 99 845 were admitted to the ED, including 59 821 (59·9%) males and 40 024 (40·1%) females, and including 29 192 people with intellectual disability, 1428 people with autism, and 69 225 people with mental disorders. We were not able to collect data on ethnicity. The mean age at ED admission was 42·1 years (SD 17·9, range 0-102) for people with intellectual disability, 18·6 years (SD 10·4, range 1-72) for people with autism, and 50·8 years (SD 11·9, range 2-94) for people with mental disorders. The heat OR (odds at the 99th percentile vs 75th percentile of temperature) of ED admission was 1·23 (95% CI 1·11-1·36) for intellectual disability, 1·06 (0·68-1·63) for autism, and 1·20 (1·12-1·29) for mental disorders. People with intellectual disability, female individuals, people living in rural areas, or those with a low-income status were at increased risk of ED admission due to heat. The risk of ED admission due to genitourinary diseases was higher than that from other causes. Annual increase in medical costs attributable to heat among people with intellectual disability, autism, and mental disorders was US$ 224 970 per 100 000 person-years (95% empirical CI 139 784-305 770). INTERPRETATION: People with intellectual disability, autism, and mental disorders should be included in groups considered at a high-risk for heat exposure, and heat adaptation policies should be implemented with consideration of these groups and their needs. FUNDING: The National Research Foundation of Korea, Korean Ministry of Environment, and Korean Ministry of Education. TRANSLATION: For the Korean translation of the abstract see Supplementary Materials section.

Group-by-Treatment Interaction Effects in Comparative Bioavailability Studies.

Comparative bioavailability studies often involve multiple groups of subjects for a variety of reasons, such as clinical capacity limitations. This raises questions about the validity of pooling data from these groups in the statistical analysis and whether a group-by-treatment interaction should be evaluated. We investigated the presence or absence of group-by-treatment interactions through both simulation techniques and a meta-study of well-controlled trials. Our findings reveal that the test falsely detects an interaction when no true group-by-treatment interaction exists. Conversely, when a true group-by-treatment interaction does exist, it often goes undetected. In our meta-study, the detected group-by-treatment interactions were observed at approximately the level of the test and, thus, can be considered false positives. Testing for a group-by-treatment interaction is both misleading and uninformative. It often falsely identifies an interaction when none exists and fails to detect a real one. This occurs because the test is performed between subjects in crossover designs, and studies are powered to compare treatments within subjects. This work demonstrates a lack of utility for including a group-by-treatment interaction in the model when assessing single-site comparative bioavailability studies, and the clinical trial study structure is divided into groups.

The effect of a visuospatial interference intervention on posttraumatic intrusions: a cross-over randomized controlled trial.

Background: Intrusive memories form a core symptom of Posttraumatic Stress Disorder (PTSD). Based on concepts of visuospatial interference and memory-updating accounts, technological innovations aim to attenuate such intrusions using visuospatial interventions.Objective: This study aims to test the effect of a visuospatial Tetris-based intervention versus a verbal condition (Wiki) and a never-targeted control (no intervention) on intrusion frequency.Method: A randomized crossover trial was conducted including N = 38 PTSD patients who had at least 3 distinct intrusive memories of trauma. After both 2 weeks (intervention 1) and 4 weeks (intervention 2), one of the three memories was randomly selected and either the visuospatial intervention (memory reminder of a traumatic memory + Tetris) or verbal condition (reading a Wikipedia article + answering questions) was performed on their first memory in randomized order. In the week 4 session, the patient conducted the other intervention condition on their second memory (crossover). The third memory was never targeted (no intervention). Daily occurrence of intrusions over 8 weeks was collected using a diary and analysed using mixed Poisson regression models.Results: Overall, there was no significant reduction in intrusion frequency from either intervention compared to each other, and to no intervention control (relative risk Tetris/Wiki: 0.947; p = .31; relative risk no intervention/Tetris: 1.060; p = .15; relative risk no intervention/Wiki: 1.004; p = .92).Conclusions: There was no effect of either intervention on intrusions when administered in a crossover design where participants received both interventions. Design shortcomings and consequences for future studies are discussed.

Visuospatial interventions, including the computer game Tetris, have been studied as a potential means to decrease intrusive memories, a core feature of Posttraumatic Stress Disorder.In this study, two interventions are tested in a crossover design with patients with intrusive memories after traumatic experiences.There was no effect of either the visuospatial intervention or the verbal condition in this design.