Post-meal exercise under ecological conditions improves post-prandial glucose levels but not 24-hour glucose control.

We investigated whether post-meal walking (PMW) improved post-prandial glucose and 24h glucose control under free-living conditions among physically inactive young women. METHODS: Young women (Age: 20±1years; percent body fat: 28.2 ± 12%; BMI: 23.8 ± 4.2kg·m-1) completed a randomised crossover study to assess if PMW confers benefit. On the PMW day, women completed three bouts of brisk walks, and on the Control day they were instructed to follow normal habitual activities. Continuous glucose monitors captured post-prandial and 24h glucose, and physical activity monitors tracked physical activity throughout the study. RESULTS: PMW walking increased total daily step count (Control = 9,159 ± 2,962 steps vs. PMW = 14,611±3,891 steps, p<0.001) and activity scores (Control=33.87±1.16 METs·h vs. PMW = 36.11±1.58 METs·h, p < 0.001). PMW led to lower 3h average post-prandial glucose (main effect of condition, p=0.011) and 3h post-prandial area under curve glucose responses (main effect of condition, p = 0.027) compared to the control condition. Post hoc analysis revealed the largest decline occurred after dinner (3h average glucose Control = 7.55±1.21 mmol/L vs. PMW = 6.71 ± 0.80mmol/L, p = 0.039), when insulin sensitivity is typically diminished. Despite improvements in post-prandial glucose control, this did not translate to improvements in 24h glucose control (p > 0.05). CONCLUSION: Physically inactive and metabolically healthy young women, PMW improves post-prandial glucose but not 24h glucose control.

Quasi-One-Dimensional Transition-Metal Chalcogenide Semiconductor (Nb4Se15I2)I2.

The discovery of new low-dimensional transition-metal chalcogenides is contributing to the already prosperous family of these materials. In this study, needle-shaped single crystals of a quasi-one-dimensional (1D) material, (Nb4Se15I2)I2, were grown by chemical vapor transport, and the structure was solved by single-crystal X-ray diffraction (XRD). The structure has 1D (Nb4Se15I2)n chains along the [101] direction, with two I- ions per formula unit directly bonded to Nb5+. The other two I- ions are loosely coordinated and intercalated between the chains. Individual chains are chiral and stack along the b axis in opposing directions, giving space group P21/c. The phase purity and crystal structure were verified by powder XRD. Density functional theory calculations show (Nb4Se15I2)I2 to be a semiconductor with a direct band gap of around 0.6 eV. Resistivity measurements of bulk crystals and micropatterned devices demonstrate that (Nb4Se15I2)I2 has an activation energy of around 0.1 eV, and no anomaly or transition was seen upon cooling. Low-temperature XRD shows that (Nb4Se15I2)I2 does not undergo a structural phase transformation from room temperature to 8.2 K, unlike related compounds (NbSe4)nI (n = 2, 3, or 3.33), which all exhibit charge-density waves. This compound represents a well-characterized and valence-precise member of a diverse family of anisotropic transition-metal chalcogenides.

Outpatient pain clinic and intranasal fentanyl to improve sickle cell disease outcomes.

BACKGROUND: Acute pain events are a leading complication for sickle cell patients. In an attempt to improve pain outcomes, we developed an outpatient pain clinic, and included intranasal fentanyl in the opioid emergency department (ED) pain order set. We evaluated admission rates and opioid administration for patients that attended both the outpatient pain clinic and ED within a 3-month period. METHODS: We recorded the admission rate, IV morphine equivalents, and time from triage for each opioid order and administration from both an outpatient pain clinic and ED visit within a 3-month period for an individual pediatric patient with sickle cell disease. RESULTS: Thirty patients received acute pain management in both settings. We identified a significant reduction in hospital admission when patients received care in the pain clinic as compared to the ED (17% vs 43%, P = .02). Additionally, outpatient pain clinic patients received significantly less IV morphine equivalents than patients received in the ED (5.6 vs 10.6 IV morphine equivalents, P < .0001). In the ED, intranasal fentanyl was administered in a significantly shorter time than patients ordered intravenous opioid (43 vs 75 min, P = .02). The mean time to receiving an opioid in the outpatient pain clinic was 57 min. CONCLUSION: The use of an outpatient pain clinic can reduce admission rates as compared to the ED. The use of intranasal fentanyl reduced the time to first opioid administration in the ED. Patient-centered research or quality improvement projects should continue to focus on novel approaches to acute pain event management.

Impact of early analgesia on hospitalization outcomes for sickle cell pain crisis.

BACKGROUND: Painful events are the leading cause of hospitalizations for patients with sickle cell disease. Individualized pain plans targeting patient-specific maximum opioid dosing may shorten hospitalization length and are recommended by national guidelines. Prior to implementing individualized sickle cell pain plans, we tested the hypothesis that a shorter time to achieve a maximum opioid dose would improve hospitalization outcomes. PROCEDURE: Two-year IRB-approved, retrospective study of pediatric patients admitted for vaso-occlusive crisis (VOC). We recorded the emergency department admission time, order entry time for the maximum opioid dose during the hospitalization, and time of discharge orders.  We categorized patients as infrequent if they required <3 admissions for VOC over two years and patients as frequent if they required ≥3 admissions for VOC over two years. To account for multiple admissions, generalized linear modeling was performed. RESULTS: We identified 236 admissions for acute pain observed in 108 patients. Achieving an earlier maximum opioid dose was significantly associated with shorter length of hospitalization for frequent and infrequent pain patients (both P ≤ 0.0001). As total hospitalization length can be impacted by the time a maximum opioid order was placed, we also analyzed hospitalization length after the maximum opioid order was placed. Frequent pain patients who achieved earlier analgesia had a significantly shorter hospitalization from the time the maximum opioid order was placed (P = 0.03) while no association was found for infrequent pain patients (P = 0.84). CONCLUSIONS: Early achievement of maximum analgesia improved hospitalization outcomes and warrant further investigation in prospective studies of individualized pain plans.

Red blood cell transfusion therapy for sickle cell patients with frequent painful events.

BACKGROUND: Recurrent pain events or chronic pain are among the most common complications of sickle cell disease. Despite attempts to maximize adherence to and dosing of hydroxyurea, some patients continue to suffer from pain. Our institution developed a program to initiate chronic red blood cell transfusions for one year in patients clinically deemed to have high healthcare utilization from sickle cell pain, despite being prescribed hydroxyurea. PROCEDURE: An institutional review board approved retrospective study to evaluate the health outcomes associated with a one-year red blood cell transfusion protocol in sickle cell patients experiencing recurrent pain events as compared with the health outcomes for these patients in the one year prior to receiving transfusion therapy. We performed a matched-pair analysis using a Wilcoxon signed rank to determine the impact of transfusion therapy on clinic visits, emergency department visits, hospital admissions, hospitalization days, and opioid prescriptions filled. RESULTS: One year of transfusion therapy significantly reduced the number of total emergency department visits for pain (6 vs 2.5 pain visits/year, P = 0.005), mean hospitalizations for pain (3.4 vs 0.9 pain admissions/year), and mean hospital days per year for pain crisis (23.5 vs 4.5, P = 0.0001), as compared with the one year prior to transfusion therapy. We identified no significant difference in opioid prescriptions filled during the year of transfusion therapy. CONCLUSION: Patients with frequent pain episodes may benefit from one year of transfusion therapy.

Excess adiposity contributes to higher ambulatory central blood pressure and arterial stiffness in physically inactive young adults.

BACKGROUND: It remains unknown if physical inactivity and excess adiposity increases 24-h central blood pressure and arterial stiffness in young adults. This study examined 24-h central blood pressure and indirect measures of arterial stiffness (e.g., central pulse pressure) in physically inactive young adults with and without excess adiposity. METHODS: Body fat and ambulatory 24-h blood pressure were measured in 31 young adults (men: 22±4 years, N.=15; women: 22±5 years, N=16). Multi-frequency bioelectrical impedance measured body fat. Normal adiposity was defined as <20% body fat in men and <32% body fat in women, whereas excess adiposity was defined as ≥20% and ≥32% in men and women, respectively. Ambulatory 24-h central blood pressure was calculated based on brachial blood pressure and volumetric displacement waveforms. RESULTS: By design, the normal adiposity group had a lower body fat percentage (men: 15.5±4.6%; women: 20.8±2.5%) compared to the physically inactive excess adiposity group (men: 29.8±5.4%; women: 34.3±7.5%). Men and women with excess adiposity group had elevated central blood pressure (central systolic, P<0.05 vs. normal adiposity groups). Central pulse pressure was elevated in the excess adiposity group (men: 45±5 mmHg; women: 41±9 mmHg) compared to normal adiposity groups (men: 36±4 mmHg; women: 32±3 mmHg, P<0.05 for both), while other arterial stiffness (augmentation index and ambulatory arterial stiffness index) measures trended toward significance only in men with excess adiposity. CONCLUSIONS: Physically inactive men and women with excess adiposity have increased 24h central blood pressure and pulse pressure compared to physically inactive young adults with normal adiposity.

Image registration of low signal-to-noise cryo-STEM data.

Combining multiple fast image acquisitions to mitigate scan noise and drift artifacts has proven essential for picometer precision, quantitative analysis of atomic resolution scanning transmission electron microscopy (STEM) data. For very low signal-to-noise ratio (SNR) image stacks - frequently required for undistorted imaging at liquid nitrogen temperatures - image registration is particularly delicate, and standard approaches may either fail, or produce subtly specious reconstructed lattice images. We present an approach which effectively registers and averages image stacks which are challenging due to their low-SNR and propensity for unit cell misalignments. Registering all possible image pairs in a multi-image stack leads to significant information surplus. In combination with a simple physical picture of stage drift, this enables identification of incorrect image registrations, and determination of the optimal image shifts from the complete set of relative shifts. We demonstrate the effectiveness of our approach on experimental, cryogenic STEM datasets, highlighting subtle artifacts endemic to low-SNR lattice images and how they can be avoided. High-SNR average images with information transfer out to 0.72 Å are achieved at 300 kV and with the sample cooled to near liquid nitrogen temperature.

T-cell prolymphocytic leukemia in an adolescent with ataxia-telangiectasia: novel approach with a JAK3 inhibitor (tofacitinib).

A 19-year-old ataxia-telangiectasia patient with T-cell prolymphocytic leukemia harbored 2 JAK3-activating hotspot mutations.The patient suffered toxicities with chemotherapy, but demonstrated a clinical response to novel use of a JAK3 inhibitor (tofacitinib).