SGLT2 inhibition attenuates arterial dysfunction and decreases vascular F-actin content and expression of proteins associated with oxidative stress in aged mice

GeroScience - Aging of the vasculature is characterized by endothelial dysfunction and arterial stiffening, two key events in the pathogenesis of cardiovascular disease (CVD). Treatment with sodium...     

J波与J波综合征

J波是指心电图上QRS波与ST段之间的圆顶状或驼峰状电位变化。新近临床研究表明，在早期复极综合征、Brugada综合征和特发性心室颤动等心电图中，均存在J波形态、时限和幅度的显著改变，上述与J波密切相关的一系列临床综合征统称为J波综合征。本文详尽阐述了J波的细胞电生理和离子流机制，分析了早期复极综合征、Brugada综合征、心电图下壁导联高大J波相关的心脏性猝死的临床特点及内在机制。     

Plasma membrane phospholipid content in non-insulin-dependent streptozotocin-diabetic rats — effect of insulin

Summary The activity of (Ca²⁺ + Mg²⁺)-ATPase is impaired in kidney basolateral membranes from non-insulin-dependent streptozotocin-diabetic rats. To study the possible role of changes in membrane phospholipid content in the malfunction of this enzyme in kidney membranes of the diabetic animals, phospholipid (phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, and sphingomyelin) content was measured in kidney and liver membranes obtained from non-insulin-dependent diabetic rats. Total phospholipid content was similar in liver and kidney membranes of diabetic and control rats (595±47 versus 624±29 in liver and 469±22 versus 458±17 nmol Pi/mg protein in kidney respectively). Phosphatidylethanolamine content in kidney and liver membranes of diabetic rats was lower than in control rats (87.7±1.8 versus 96.4±2.2 nmol Pi/mg protein, p<0.01 and 87.1±3.7 versus 101.8±3.5, p<0.02 respectively). Phosphatidylinositol content was higher in kidney (28.0±0.6 versus 23.9±2.1, p<0.02) but not liver membranes from diabetic rats.The in vitro direct effect of insulin on the phospholipid content in kidney membranes was also measured. Physiologic concentrations of insulin (718 pmol/l for 30 min) increased the phosphatidic acid content in membranes from control but not from diabetic rats by 34.2% (p<0.02). This rise was readily measurable after 3 min of exposure to insulin. Insulin did not induce a significant change in the content of any other phospholipid in membranes from control or diabetic rats.These differences in phospholipid content demonstrated in isolated membranes obtained from non-insulin-dependent diabetic and control rats, before and after exposure to insulin, may explain, in part, the impaired function of the (Ca²⁺+Mg²⁺)-ATPase observed previously in kidney membranes of the diabetic rats.     

On generalized fixed sequence procedures for controlling the FWER

Testing a sequence of pre‐ordered hypotheses to decide which of these can be rejected or accepted while controlling the familywise error rate (FWER) is of importance in many scientific studies such as clinical trials. In this paper, we first introduce a generalized fixed sequence procedure whose critical values are defined by using a function of the numbers of rejections and acceptances, and which allows follow‐up hypotheses to be tested even if some earlier hypotheses are not rejected. We then construct the least favorable configuration for this generalized fixed sequence procedure and present a sufficient condition for the FWER control under arbitrary dependence. Based on the condition, we develop three new generalized fixed sequence procedures controlling the FWER under arbitrary dependence. We also prove that each generalized fixed sequence procedure can be described as a specific closed testing procedure. Through simulation studies and a clinical trial example, we compare the power performance of these proposed procedures with those of the existing FWER controlling procedures. Finally, when the pairwise joint distributions of the true null p‐values are known, we further improve these procedures by incorporating pairwise correlation information while maintaining the control of the FWER. Copyright © 2015 John Wiley & Sons, Ltd.     

Vital Signs: Trends in Use of Long-Acting Reversible Contraception Among Teens Aged 15–19 Years Seeking Contraceptive Services — United States, 2005–2013

Background

Nationally, the use of long-acting reversible contraception (LARC), specifically intrauterine devices (IUDs) and implants, by teens remains low, despite their effectiveness, safety, and ease of use.

Methods

To examine patterns in use of LARC among females aged 15–19 years seeking contraceptive services, CDC and the U.S. Department of Health and Human Services’ Office of Population Affairs analyzed 2005–2013 data from the Title X National Family Planning Program. Title X serves approximately 1 million teens each year and provides family planning and related preventive health services for low-income persons.

Results

Use of LARC among teens^* seeking contraceptive services at Title X service sites increased from 0.4% in 2005 to 7.1% in 2013 (p-value for trend <0.001). Of the 616,148 female teens seeking contraceptive services in 2013, 17,349 (2.8%) used IUDs, and 26,347 (4.3%) used implants. Use of LARC was higher among teens aged 18–19 years (7.6%) versus 15–17 years (6.5%) (p<0.001). The percentage of teens aged 15–19 years who used LARC varied widely by state, from 0.7% (Mississippi) to 25.8% (Colorado).

Conclusions

Although use of LARC by teens remains low nationwide, efforts to improve access to LARC among teens seeking contraception at Title X service sites have increased use of these methods.Implications for public health practice: Health centers that provide quality contraceptive services can facilitate use of LARC among teens seeking contraception. Strategies to address provider barriers to offering LARC include: 1) educating providers that LARC is safe for teens; 2) training providers on LARC insertion and a client-centered counseling approach that includes discussing the most effective contraceptive methods first; and 3) providing contraception at reduced or no cost to the client.     

Altered Pharmacokinetics in Prolonged Infusions of Sedatives and Analgesics Among Adult Critically Ill Patients: A Systematic Review

Purpose

The pharmacokinetic (PK) parameters of many drugs are altered as a consequence of the pathophysiological changes associated with critical illness. The critically ill population presents challenges when titrating infusions of sedatives and analgesics to maintain optimal sedation and pain levels. This systematic review examined the PK data in critically ill adult patients with prolonged infusions (>24 hours) of commonly used sedatives and analgesics to highlight possible altered PK parameters compared with noncritically ill patients.

Total and free insulin-like growth factor I, insulin-like growth factor binding protein 3 and acid-labile subunit reflect clinical activity in acromegaly

The aim was to evaluate, markers of disease activity in acromegaly in relation to perceived disease activity. Thirty-seven consecutively treated, acromegalic patients, classified by clinical symptoms as inactive (n=16), slightly active (n=10) and active (n=11), entered the study. When evaluating the inactive and the active groups, we found that positive and negative predictive values (PV(pos), PV(neg)) for clinical disease activity of total and free insulin-like growth factor-I (IGF-I) were 0.59, 0.90 and 1.00, 0.82 respectively. Acid-labile subunit (ALS) showed diagnostic merit similar to insulin-like growth factor binding protein-3 (IGFBP-3) with PV(pos) of 0.69 and 0.71 and PV(neg) of 0.91 and 0.92 respectively. We conclude that free IGF-I is more closely related than total IGF-I to perceived disease activity and is as such useful when evaluating previously treated acromegaly for disease activity. Total IGF-I, IGFBP-3 and ALS possess a higher PV(neg) for the clinical disease activity. None of the parameters can at present be claimed to be superior to the others and thus all the measured parameters are recommended to be part of the evaluation of acromegalic patients.     

Utility of Web-based assessment of patient satisfaction with endoscopy

OBJECTIVES: The dramatic growth of the World Wide Web (Web) holds potential for use in survey distribution and submission. Its use has not previously been studied in the context of patient satisfaction with endoscopy procedures. In this study we compared standard mail, telephone, and Web-based modes of endoscopy satisfaction survey administration with respect to response rate and response content. METHODS: An endoscopy satisfaction questionnaire consisting of seven core items from the modified Group Health Association of America (GHAA-9) was distributed to patients after routine outpatient endoscopy. Patients were randomized to receive the questionnaire by standard mail, telephone, or Web (if applicable). Response rates and satisfaction scores in the groups were compared. The nonresponders to the standard mail and Web surveys were subsequently contacted by telephone to determine their level of satisfaction. RESULTS: Response rates to the telephone survey (81% among those designated as non-Web users and 78% among Web users) and standard mail (75% non-Web users, 67% Web users) were higher than response rate to the Web-based survey (34%) (p < or = 0.0005). There was no significant difference in satisfaction scores among the groups or between satisfaction of nonresponders and responders. CONCLUSIONS: The potential of our Web-based survey was limited by poor response rates. This arose from privacy protection precautions that complicated access to the Web site. Future Web-based strategies for surveying patients will need to be more user-friendly while maintaining the intent of the recent Health Insurance Portability and Accountability Act regulations.