We demonstrate one-dimensional sub-Doppler laser cooling of a beam of YbF molecules to 100 μK. This is a key step towards a measurement of the electron's electric dipole moment using ultracold ...molecules. We compare the effectiveness of magnetically assisted and polarization-gradient sub-Doppler cooling mechanisms. We model the experiment and find good agreement with our data.
The ubiquitin-proteasome system is an important regulator of cell growth and apoptosis. The potential of specific proteasome inhibitors to act as novel anti-cancer agents is currently under intensive ...investigation. Several proteasome inhibitors exert anti-tumour activity in vivo and potently induce apoptosis in tumour cells in vitro, including those resistant to conventional chemotherapeutic agents. By inhibiting NF-kappaB transcriptional activity, proteasome inhibitors may also prevent angiogenesis and metastasis in vivo and further increase the sensitivity of cancer cells to apoptosis. Proteasome inhibitors also exhibit some level of selective cytotoxicity to cancer cells by preferentially inducing apoptosis in proliferating or transformed cells or by overcoming deficiencies in growth-inhibitory or pro-apoptotic molecules. High expression of oncogene products like c-Myc also makes cancer cells more susceptible to proteasome inhibitor-induced apoptosis. The induction of apoptosis by proteasome inhibitors varies between cell types but often occurs following an initial accumulation of short-lived proteins such as p53, p27, pro-apoptotic Bcl-2 family members or activation of the stress kinase JNK. These initial events often result in a perturbation of mitochondria with concomitant release of cytochrome c and activation of the Apaf-1 containing apoptosome complex. This results in activation of the apical caspase-9 followed by activation of effector caspases-3 and -7, which are responsible for the biochemical and morphological changes associated with apoptosis.
To report a case that substantiates the presence of hypoglycemia at the time of death of a young man with type 1 diabetes, who was found unresponsive in his undisturbed bed in the morning.
We ...describe a 23-year-old man with a history of type 1 diabetes treated with an insulin pump, who had recurrent severe hypoglycemia. In an effort to understand these episodes better and attempt to eliminate them, a retrospective (non-real-time) continuous subcutaneous glucose monitoring system (CGMS) was attached to the patient. He was found dead in his undisturbed bed 20 hours later. The insulin pump and CGMS were both downloaded for postmortem study.
Postmortem download of the data in the CGMS demonstrated glucose levels below 30 mg/dL around the time of his death, with only a minimal counter-regulatory response. This finding corresponded to a postmortem vitreous humor glucose of 25 mg/dL. An autopsy showed no major anatomic abnormalities that could have contributed to his death.
To our knowledge, this is the first documentation of hypoglycemia at the time of death in a patient with the "dead-in-bed" syndrome. This report should raise the awareness of physicians to the potentially lethal effects of hypoglycemia and provide justification for efforts directed at avoiding nocturnal hypoglycemia.
Sportfishing and hatchery practices routinely subject fish to acute temperature changes through placement of fish in live wells and normal handling and transportation procedures. Acute temperature ...changes alter metabolic rate in ectotherms; however, the rapidity of the response to reach a new homeostatic state is not well known. Therefore, the response duration in metabolic rate after acute temperature change was measured in two centrarchid species, the Largemouth Bass Micropterus salmoides and Redear Sunfish Lepomis microlophus, which are representative of two different body shapes and are both commonly pursued in recreational fishing and reared in hatcheries. Largemouth Bass were acclimated to either 20°C or 30°C, and Redear Sunfish were acclimated to 24°C. Aerobic metabolic rate was measured immediately after acute temperature change (−4, +0, or +4°C) and was measured repeatedly in cycles of 5.5 or 10.0 min, respectively, until the metabolic rate stabilized. In Largemouth Bass, the metabolic rate stabilized similarly or more slowly following a moderate high‐temperature shock (+4°C; 44 min) compared to transfer to conditions with no temperature change (+0°C) or a moderate low‐temperature shock (−4°C; 16–48 min). In contrast, the metabolic rate in Redear Sunfish stabilized faster after transfer to +4°C (15 min) than after transfer to −4°C or +0°C (both 31 min), possibly because the elevated metabolic rate after transfer was sustained. Notably, for both species, metabolic rates stabilized at a generally lower level after transfer to −4°C than after transfer to +0°C or +4°C. Therefore, the duration until stabilization of metabolic rate after acute temperature change may depend upon species and acclimation temperature, although for both species examined, the energy savings in reduced metabolic rates after moderate cold shock may be beneficial for recovery from sportfishing or hatchery practices.
The results from this and other studies suggest that the vast majority of patients undergoing Roux-en-y gastric bypass (RYGB) will be spared from experiencing post-RYGB hypoglycemia. However, for ...those unfortunate individuals who have to deal with hypoglycemia, it can be an extremely frustrating and difficult experience for both the patient and provider.
Inpatient hyperglycemia, hypoglycemia, and glucose variability are associated with increased mortality. The use of an electronic glucose management system (eGMS) to guide intravenous (IV) insulin ...infusion has been found to significantly improve blood glucose (BG) control. This retrospective observational study evaluated the 7-year (January 2009-December 2015) impact of the EndoTool
eGMS in intensive and intermediate units at Vidant Medical Center, a 900-bed tertiary teaching hospital.
Patients assigned to eGMS had indications for IV insulin infusion, including uncontrolled diabetes, stress hyperglycemia, and/or postoperative BG levels >140 mg/dL. This study evaluated time required to achieve BG control (<180 mg/dL; <140 mg/dL for cardiovascular surgery patients); hypoglycemia incidence (<70 and <40 mg/dL); glucose variability (assessed by SD and coefficient of variation percentage CV%); excursions (BG levels >180 mg/dL after control attained); and the impact of eGMS on hospital-acquired condition (HAC)-8 rates.
Data were available for all treated patients (492,078 BG readings from 16,850 patients). With eGMS, BG levels were brought to target within 1.5 to 2.3 hours (4.5 to 4.8 hours for cardiovascular patients). Minimal hypoglycemia was observed (BG values <70 mg/dL, 0.93%; <40 mg/dL, 0.03%), and analysis of variance of BG values <70 mg/dL showed significant reductions over time in hypoglycemia frequency, from 1.04% in 2009 to 0.46% in 2015 (P<.0001). The CV% per patient visit was 26.5 (±12.9)%, and 4% of patients experienced glucose excursions (defined as BG levels >180 mg/dL once control was attained). HAC-8 rates were reduced from 0.083 per 1,000 patients (2008) to 0.032 per 1,000 patients (2011).
The use of eGMS resulted in rapid, effective control of inpatient BG levels, including significantly reduced hypoglycemia rates.
BG = blood glucose CMS = Centers for Medicare and Medicaid Services CV = coefficient of variation CV% = coefficient of variation percentage eGMS = electronic glucose management system GV = glycemic variability HAC = Hospital-Acquired Condition ICU = intensive care unit IU = intermediate unit IV = intravenous LOS = length of stay VMC = Vidant Medical Center.
Background
Oral meal consumption increases glucagon-like peptide 1 (GLP-1) release which maintains euglycemia by increasing insulin secretion. This effect is exaggerated during short-term follow-up ...of Roux-en-y gastric bypass (RYGB). We examined the durability of this effect in patient with type 2 diabetes (T2DM) >10 years after RYGB.
Methods
GLP-1 response to a mixed meal in the 10-year post-RYGB group (
n
= 5) was compared to lean (
n
= 9), obese (
n
= 6), and type 2 diabetic (
n
= 10) controls using a cross-sectional study design. Analysis of variance (ANOVA) was used to evaluate GLP-1 response to mixed meal consumption from 0 to 300 min, 0–20 min, 20–60 min, and 60–300 min, respectively. Weight, insulin resistance, and T2DM were also assessed.
Results
GLP-1 response 0–300 min in the 10-year post-RYGB showed a statistically significant overall difference (
p
= 0.01) compared to controls. Furthermore, GLP-1 response 0–20 min in the 10-year post-RYGB group showed a very rapid statistically significant rise (
p
= 0.035) to a peak of 40 pM. GLP-1 response between 20 and 60 min showed a rapid statistically significant (
p
= 0.041) decline in GLP-1 response from ~40 pM to 10 pM. GLP-1 response in the 10-year post-RYGB group from 60 to 300 min showed no statistically significant difference from controls. BMI, HOMA, and fasting serum glucose before and >10 years after RYGB changed from 59.9 → 40.4, 8.7 → 0.88, and 155.2 → 87.6 mg/dl, respectively, and were statistically significant (
p
< 0.05).
Conclusions
An exaggerated GLP-1 response was noted 10 years after RYGB, strongly suggesting a durability of this effect. This phenomenon may play a key role in maintaining type 2 diabetes remission and weight loss after RYGB.
Coatings are used extensively in concentrating solar systems to improve the performance of both reflectors and absorbers in terms of costs, efficiency, durability and maintenance. Different coatings ...are needed for different applications, operating conditions and material combinations as there are no universally perfect materials. There is also often wide variation in reported performance between nominally the same materials. The purpose of this review is to look at the underlying chemistry and stability of some of the main coatings that are in use or currently under investigation in order to identify reasons for the variations, gaps in knowledge and scope for performance improvement. It is evident that much better data on the intrinsic physical and chemical properties of the coatings and their performance are needed and would help avoid failures that may not be discovered for many years.
Worker policing (mutual repression of reproduction) in the eusocial Hymenoptera represents a leading example of how coercion can facilitate cooperation. The occurrence of worker policing in ..."primitively" eusocial species with low mating frequencies, which lack relatedness differences conducive to policing, suggests that separate factors may underlie the origin and maintenance of worker policing. We tested this hypothesis by investigating conflict over male parentage in the primitively eusocial, monandrous bumblebee, Bombus terrestris. Using observations, experiments, and microsatellite genotyping, we found that: (a) worker- but not queen-laid male eggs are nearly all eaten (by queens, reproductive, and nonreproductive workers) soon after being laid, so accounting for low observed frequencies of larval and adult worker-produced males; (b) queen- and worker-laid male eggs have equal viabilities; (c) workers discriminate between queen- and worker-laid eggs using cues on eggs and egg cells that almost certainly originate from queens. The cooccurrence in B. terrestris of these three key elements of "classical" worker policing as found in the highly eusocial, polyandrous honeybees provides novel support for the hypothesis that worker policing can originate in the absence of relatedness differences maintaining it. Worker policing in B. terrestris almost certainly arose via reproductive competition among workers, that is, as "selfish" policing.
Human native milk lactoferrin (LF) and recombinant forms of lactoferrin (rLF) are available with identical aa sequences, but different glycosylation patterns. Native lactoferrin (NLF) possesses the ...intrinsic ability to stimulate vigorous IgG and IgE antibody responses in BALB/c mice, whereas recombinant forms (Aspergillus or rice) are 40‐fold less immunogenic and 200‐fold less allergenic. Such differences are independent of endotoxin or iron content and the glycans do not contribute to epitope formation. A complex glycoprofile is observed for NLF, including sialic acid, fucose, mannose, and Lewis (Le)x structures, whereas both rLF species display a simpler glycoprofile rich in mannose. Although Lex type sugars play a Th2‐type adjuvant role, endogenous expression of Lex on NLF did not completely account for the more vigorous IgE responses it provoked. Furthermore, coadminstration of rLF downregulated IgE and upregulated IgG2a antibody responses provoked by NLF, but was without effect on responses to unrelated peanut and chicken egg allergens. These results suggest glycans on rLF impact the induction phase to selectively inhibit IgE responses and that differential glycosylation patterns may impact on antigen uptake, processing and/or presentation, and the balance between Th1 and Th2 responses.
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