Hydrothermal duodenal mucosal resurfacing (DMR) is a safe, outpatient endoscopic procedure. REVITA-2, a double-blind, superiority randomised controlled trial, investigates safety and efficacy of DMR ...using the single catheter Revita system (Revita DMR (catheter and system)), on glycaemic control and liver fat content in type 2 diabetes (T2D).
Eligible patients (haemoglobin A1c (HbA1c) 59-86 mmol/mol, body mass index≥24 and ≤40 kg/m
, fasting insulin >48.6 pmol/L, ≥1 oral antidiabetic medication) enrolled in Europe and Brazil. Primary endpoints were safety, change from baseline in HbA1c at 24 weeks, and liver MRI proton-density fat fraction (MRI-PDFF) at 12 weeks.
Overall mITT (DMR n=56; sham n=52), 24 weeks post DMR, median (IQR) HbA1c change was -10.4 (18.6) mmol/mol in DMR group versus -7.1 (16.4) mmol/mol in sham group (p=0.147). In patients with baseline liver MRI-PDFF >5% (DMR n=48; sham n=43), 12-week post-DMR liver-fat change was -5.4 (5.6)% in DMR group versus -2.9 (6.2)% in sham group (p=0.096). Results from prespecified interaction testing and clinical parameter assessment showed heterogeneity between European (DMR n=39; sham n=37) and Brazilian (DMR n=17; sham n=16) populations (p=0.063); therefore, results were stratified by region. In European mITT, 24 weeks post DMR, median (IQR) HbA1c change was -6.6 mmol/mol (17.5 mmol/mol) versus -3.3 mmol/mol (10.9 mmol/mol) post-sham (p=0.033); 12-week post-DMR liver-fat change was -5.4% (6.1%) versus -2.2% (4.3%) post-sham (p=0.035). Brazilian mITT results trended towards DMR benefit in HbA1c, but not liver fat, in context of a large sham effect. In overall PP, patients with high baseline fasting plasma glucose ((FPG)≥10 mmol/L) had significantly greater reductions in HbA1c post-DMR versus sham (p=0.002). Most adverse events were mild and transient.
DMR is safe and exerts beneficial disease-modifying metabolic effects in T2D with or without non-alcoholic liver disease, particularly in patients with high FPG.
NCT02879383.
The duodenum has been shown to play a key role in glucose homeostasis. Duodenal mucosal resurfacing (DMR) is an endoscopic procedure for patients with type 2 diabetes (T2D) in which the duodenal ...mucosa is hydrothermally ablated. DMR improves glycemic control, but the underlying mechanisms remain unclear. Here, we report changes in glucoregulatory hormones and indices of insulin sensitivity and beta cell function after DMR.
We included 28 patients on non-insulin glucose lowering medications who underwent open-label DMR and a mixed meal test (MMT) in Revita-1 or Revita-2. Inclusion criteria were hemoglobin A1c (HbA1c) 7.6-10.4% and BMI 24-40kg/m
. Baseline and 3-months MMT data included plasma glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), and gastric inhibitory polypeptide (GIP) concentrations. Glucoregulatory hormones, insulin sensitivity indices (homeostatic model assessment for insulin resistance HOMA-IR, Matsuda index MI and hepatic insulin resistance HIR), and beta cell function (insulinogenic index IGI, disposition index DI and insulin secretion rate ISR) were assessed.
Fasting insulin, glucagon, and C-peptide decreased significantly. Insulin sensitivity (HOMA-IR, MI, and HIR) and beta cell function (DI and ISR) all improved significantly. Decline in postprandial glucose, mainly driven by a decrease in fasting levels, was observed, as well as a decline in postprandial glucagon whereas GLP-1 and GIP did not change.
Insulin sensitivity and insulin secretion improved 3 months after DMR. It is unlikely that incretin changes are responsible for improved glucose control after DMR. These data add to the growing evidence validating the duodenum as a therapeutic target for patients with T2D.
To describe the demographics, clinical characteristics, and hospital course among persons <21 years of age with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated death.
We ...conducted a retrospective case series of suspected SARS-CoV-2-associated deaths in the United States in persons <21 years of age during February 12 to July 31, 2020. All states and territories were invited to participate. We abstracted demographic and clinical data, including laboratory and treatment details, from medical records.
We included 112 SARS-CoV-2-associated deaths from 25 participating jurisdictions. The median age was 17 years (IQR 8.5-19 years). Most decedents were male (71, 63%), 31 (28%) were Black (non-Hispanic) persons, and 52 (46%) were Hispanic persons. Ninety-six decedents (86%) had at least 1 underlying condition; obesity (42%), asthma (29%), and developmental disorders (22%) were most commonly documented. Among 69 hospitalized decedents, common complications included mechanical ventilation (75%) and acute respiratory failure (82%). The sixteen (14%) decedents who met multisystem inflammatory syndrome in children (MIS-C) criteria were similar in age, sex, and race and/or ethnicity to decedents without MIS-C; 11 of 16 (69%) had at least 1 underlying condition.
SARS-CoV-2-associated deaths among persons <21 years of age occurred predominantly among Black (non-Hispanic) and Hispanic persons, male patients, and older adolescents. The most commonly reported underlying conditions were obesity, asthma, and developmental disorders. Decedents with coronavirus disease 2019 were more likely than those with MIS-C to have underlying medical conditions.
Congenital cutaneous papillomas were identified in five foals. Age at diagnosis ranged from 305 days’ gestation to 2 days of age. Breeds were thoroughbred (2), standard‐bred (1), warmblood (1) and ...paint (1). Two were female, one was male and the gender of two cases was not specified. Masses were pedunculated with a roughened, wart‐like (verrucous) or a smoother, cauliflower‐like surface. Masses occurred as single lesions on the forelimb, lip and face, or as multiple lesions on the trunk. Histological features included relatively uniform epidermal papillary hyperplasia with variable melanin pigment within basal layers and vacuolization of keratinocytes in all layers, but with no evidence of nuclear or cytoplasmic changes (koilocytes) characteristic of viral infection. One case showed epidermal proliferation with proliferation of pilosebaceous units. Results of immunohistochemical studies for the detection of papillomavirus antigens were negative in all cases. These results suggest that equine congenital papilloma may be a hamartomatous lesion (epidermal nevus) and not a viral‐induced growth.
In the pursuit of urgently needed, energy dense solid-state batteries for electric vehicle and portable electronics applications, halide solid electrolytes offer a promising path forward with ...exceptional compatibility against high-voltage oxide electrodes, tunable ionic conductivities, and facile processing. For this family of compounds, synthesis protocols strongly affect cation site disorder and modulate Li+ mobility. In this work, we reveal the presence of a high concentration of stacking faults in the superionic conductor Li3YCl6 and demonstrate a method of controlling its Li+ conductivity by tuning the defect concentration with synthesis and heat treatments at select temperatures. Leveraging complementary insights from variable temperature synchrotron X-ray diffraction, neutron diffraction, cryogenic transmission electron microscopy, solid-state nuclear magnetic resonance, density functional theory, and electrochemical impedance spectroscopy, we identify the nature of planar defects and the role of nonstoichiometry in lowering Li+ migration barriers and increasing Li site connectivity in mechanochemically synthesized Li3YCl6. We harness paramagnetic relaxation enhancement to enable 89Y solid-state NMR and directly contrast the Y cation site disorder resulting from different preparation methods, demonstrating a potent tool for other researchers studying Y-containing compositions. With heat treatments at temperatures as low as 333 K (60 °C), we decrease the concentration of planar defects, demonstrating a simple method for tuning the Li+ conductivity. Findings from this work are expected to be generalizable to other halide solid electrolyte candidates and provide an improved understanding of defect-enabled Li+ conduction in this class of Li-ion conductors.
In the pursuit of urgently needed, energy dense solid-state batteries for electric vehicle and portable electronics applications, halide solid electrolytes offer a promising path forward with ...exceptional compatibility against high-voltage oxide electrodes, tunable ionic conductivities, and facile processing. For this family of compounds, synthesis protocols strongly affect cation site disorder and modulate Li+ mobility. In this work, we reveal the presence of a high concentration of stacking faults in the superionic conductor Li3YCl6 and demonstrate a method of controlling its Li+ conductivity by tuning the defect concentration with synthesis and heat treatments at select temperatures. Leveraging complementary insights from variable temperature synchrotron X-ray diffraction, neutron diffraction, cryogenic transmission electron microscopy, solid-state nuclear magnetic resonance, density functional theory, and electrochemical impedance spectroscopy, we identify the nature of planar defects and the role of nonstoichiometry in lowering Li+ migration barriers and increasing Li site connectivity in mechanochemically synthesized Li3YCl6. We harness paramagnetic relaxation enhancement to enable 89Y solid-state NMR and directly contrast the Y cation site disorder resulting from different preparation methods, demonstrating a potent tool for other researchers studying Y-containing compositions. With heat treatments at temperatures as low as 333 K (60 °C), we decrease the concentration of planar defects, demonstrating a simple method for tuning the Li+ conductivity. Findings from this work are expected to be generalizable to other halide solid electrolyte candidates and provide an improved understanding of defect-enabled Li+ conduction in this class of Li-ion conductors.
ABSTRACT
Background
Ischaemic end-organ damage during haemodialysis (HD) is a significant problem that may be ameliorated by intradialytic cooling. A randomised trial was performed to compare ...standard HD (SHD; dialysate temperature 37°C) and programmed cooling of the dialysate thermocontrolled HD (TCHD) using multiparametric magnetic resonance imaging (MRI) to assess structural, functional and blood flow changes in the heart, brain and kidneys.
Methods
Prevalent HD patients were randomly allocated to receive either SHD or TCHD for 2 weeks before undergoing serial MRI at four time points: pre-, during (30 min and 180 min) and post-dialysis. MRI measures include cardiac index, myocardial strain, longitudinal relaxation time (T1), myocardial perfusion, internal carotid and basilar artery flow, grey matter perfusion and total kidney volume. Participants then crossed to the other modality to repeat the study protocol.
Results
Eleven participants completed the study. Separation in blood temperature between TCHD (−0.1 ± 0.3°C) and SHD (+0.3 ± 0.2°C; P = .022) was observed, although there was no difference in tympanic temperature changes between arms. There were significant intradialytic reductions in cardiac index, cardiac contractility (left ventricular strain), left carotid and basilar artery blood flow velocities, total kidney volume, longitudinal relaxation time (T1) of the renal cortex and transverse relaxation rate (T2*) of the renal cortex and medulla, but no differences between arms. Pre-dialysis T1 of the myocardium and left ventricular wall mass index were lower after 2 weeks of TCHD compared with SHD 1266 ms (interquartile range 1250–1291) versus 1311 ± 58 ms, P = .02; 66 ± 22 g/m2 versus 72 ± 23 g/m2, P = .004.
Conclusions
HD adversely affects cardiac function, reduces carotid and basilar artery blood flow and total kidney volume, but mild dialysate cooling using a biofeedback module did not result in differences in intradialytic MRI measures compared with SHD.
In May 2009, the Marion County Public Health Department in Indiana declared a tuberculosis (TB) outbreak among persons experiencing homelessness in Marion County, began active case finding to detect ...additional cases, and formed a TB outbreak response team to plan and coordinate outbreak activities. Outbreak-associated cases had 1 of 2 outbreak genotypes and either reported experiencing homelessness themselves or had an epidemiologic link to a shelter or a person experiencing homelessness. The last of 53 outbreak-associated cases was detected in 2019 after more than 2 years without a case. The Marion County Public Health Department continues to address TB-related issues and implement prevention measures at homeless shelters and among persons experiencing homelessness in 2019. This example, in addition to other published guidance, can be used by jurisdictions to plan and implement their own TB outbreak prevention and response activities among persons experiencing homelessness.
Mycobacterium tuberculosis transmission through solid organ transplantation has been well described, but transmission through transplanted tissues is rare. We investigated a tuberculosis outbreak in ...the USA linked to a bone graft product containing live cells derived from a single deceased donor.
In this outbreak report, we describe the management and severity of the outbreak and identify opportunities to improve tissue transplant safety in the USA. During early June, 2021, the US Centers for Disease Control and Prevention (CDC) worked with state and local health departments and health-care facilities to locate and sequester unused units from the recalled lot and notify, evaluate, and treat all identified product recipients. Investigators from CDC and the US Food and Drug Administration (FDA) reviewed donor screening and tissue processing. Unused product units from the recalled and other donor lots were tested for the presence of M tuberculosis using real-time PCR (rt PCR) assays and culture. M tuberculosis isolates from unused product and recipients were compared using phylogenetic analysis.
The tissue donor (a man aged 80 years) had unrecognised risk factors, symptoms, and signs consistent with tuberculosis. Bone was procured from the deceased donor and processed into 154 units of bone allograft product containing live cells, which were distributed to 37 hospitals and ambulatory surgical centres in 20 US states between March 1 and April 2, 2021. From March 3 to June 1, 2021, 136 (88%) units were implanted into 113 recipients aged 24–87 years in 18 states (some individuals received multiple units). The remaining 18 units (12%) were located and sequestered. 87 (77%) of 113 identified product recipients had microbiological or imaging evidence of tuberculosis disease. Eight product recipients died 8–99 days after product implantation (three deaths were attributed to tuberculosis after recognition of the outbreak). All 105 living recipients started treatment for tuberculosis disease at a median of 69 days (IQR 56–81) after product implantation. M tuberculosis was detected in all eight sequestered unused units tested from the recalled donor lot, but not in lots from other donors. M tuberculosis isolates from unused product and recipients were more than 99·99% genetically identical.
Donor-derived transmission of M tuberculosis via bone allograft resulted in substantial morbidity and mortality. All prospective tissue and organ donors should be routinely assessed for tuberculosis risk factors and clinical findings. When these are present, laboratory testing for M tuberculosis should be strongly considered.
None.
Diodes are a basic component of electrical circuits to control the flow of charge, and geometric diodes (GDs) are a special class that can operate using ballistic or quasi-ballistic transport in ...conjunction with geometric asymmetry to direct charge carriers preferentially in one direction, enabling an electron ratcheting effect. Nanomaterials present a unique platform for the development of GDs, and silicon nanowire (NW)-based GDscylindrically symmetric but translationally asymmetric three-dimensional nanostructureshave recently been demonstrated functioning at room temperature. These devices can theoretically achieve a near zero-bias turn-on voltage and rectify up to THz frequencies. Here, we synthesize silicon NW GDs and fabricate single-NW devices from which significant changes in diode performance are observed from relatively minor changes in geometry. To elucidate the interplay between geometry and ballistic behavior, we develop a Monte Carlo simulation that describes the quasi-ballistic behavior of electrons within a three-dimensional NW GD. We examine the effects of doping level, temperature, and geometry on charge carrier transport, revealing the relationships between charge carrier mean free path (MFP), specular reflection at surfaces, and geometry on GD performance. As expected, geometry strongly influences performance by directing or blocking charge carrier passage through the nanostructure. Interestingly, we find that the blocking effect is at least as important as the directing effect. Moreover, within certain geometric limits, the diode behavior is less sensitive to the MFP than might be initially expected because of the short relevant length scales and importance of the blocking effect. The results provide guidelines for the future design of NW GDs and enable the prediction and interpretation of trends in experimental results. An improved understanding of quasi-ballistic transport is crucial to guiding future experiments toward realizing THz rectification for applications in high-speed data transfer and long-wavelength energy harvesting.
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