Methazolamide is a new hepatic insulin sensitizer that lowers blood glucose in vivo

We previously used Gene Expression Signature technology to identify methazolamide (MTZ) and related compounds with insulin sensitizing activity in vitro. The effects of these compounds were investigated in diabetic db/db mice, insulin-resistant diet-induced obese (DIO) mice, and rats with streptozotocin (STZ)-induced diabetes. MTZ reduced fasting blood glucose and HbA(1c) levels in db/db mice, improved glucose tolerance in DIO mice, and enhanced the glucose-lowering effects of exogenous insulin administration in rats with STZ-induced diabetes. Hyperinsulinemic-euglycemic clamps in DIO mice revealed that MTZ increased glucose infusion rate and suppressed endogenous glucose production. Whole-body or cellular oxygen consumption rate was not altered, suggesting MTZ may inhibit glucose production by different mechanism(s) to metformin. In support of this, MTZ enhanced the glucose-lowering effects of metformin in db/db mice. MTZ is known to be a carbonic anhydrase inhibitor (CAI); however, CAIs acetazolamide, ethoxyzolamide, dichlorphenamide, chlorthalidone, and furosemide were not effective in vivo. Our results demonstrate that MTZ acts as an insulin sensitizer that suppresses hepatic glucose production in vivo. The antidiabetic effect of MTZ does not appear to be a function of its known activity as a CAI. The additive glucose-lowering effect of MTZ together with metformin highlights the potential utility for the management of type 2 diabetes.     

Pediatric hearing assessment by auditory brainstem response in the operating room

Objectives

To investigate the factors contributing to the discrepancies between auditory brainstem response (ABR) thresholds obtained in the operating room (OR) and hearing outcomes obtained in the follow-up period and to explore the benefits and limitations of performing ABR in the OR.

Methods

A retrospective review study was conducted in a pediatric tertiary care facility. A total of 116 patients were identified with complete records, including OR-ABR results, medical examination and surgical procedure notes, and follow-up medical/audiological evaluation. Patients were divided into three groups: (1) 58 patients with middle ear effusion underwent myringotomy and tube placement, (2) 12 patients underwent myringotomy without tube placement, (3) 46 patients underwent ear examination only without effusion found. OR-ABR results were compared to audiological follow-up evaluations and analyzed for each group.

Results

In patients with middle ear effusion and tube placement, the average threshold difference between OR-ABR and follow-up audiological evaluation was 9.7 dB (±12.7), with highest discrepancy of 45 dB. On the other hand, in patients with dry ears and/or no tube placement, the average threshold difference was only 3.8 dB (±8.6). Moreover, the discrepancy was more prominent in patients with mucoid effusion and larger at lower frequency, i.e., 1000 Hz.

Conclusions

The hearing thresholds estimated by ABR testing in the OR can be elevated and follow-up hearing evaluation after tube placement is needed. While ABR testing is valuable in the assessment of pediatric patients, especially for children who are difficult-to-test or have complicated medical conditions, caution should be taken when interpreting OR-ABR results.     

Thromboangiitis obliterans (Buerger's disease): searching for a therapeutic strategy

Treatment of thromboangiitis obliterans (Buerger's disease) includes both surgical and nonsurgical approaches, or a combination of both. A definite therapeutic approach has not yet been set. This article reviews the proposed therapeutic strategies and considers the advantages and disadvantages of each treatment. Cessation of smoking seems to be the only globally accepted therapeutic measure to prevent disease progression. A number of promising novel therapeutic strategies may prove useful for the treatment of this physically and socially mutilating disease.     

Maternal and perinatal risk factors associated with congenital syphilis

Objective

Mother-to-child transmission of syphilis remains an important global public health problem. Untreated intrauterine infection may result in adverse events for the fetus or newborn (NB). Maternal risk factors, such as prenatal care, early diagnosis, and appropriate treatment, significantly impact the likelihood of vertical transmission of syphilis. The purpose of this review is to evaluate maternal risk factors for congenital syphilis and the characteristics of exposed NB.

Methods

A total of 14 studies were evaluated, including 8 cohort studies, 4 cross-sectional and 2 control cases. A total of 12,230 women were included, with confirmed or highly probable congenital syphilis outcome, and 2285 NB. The studies evaluated risk factors for congenital syphilis, which were maternal, demographic, obstetric factors and characteristics of the exposed NB.

Results

Included in the risk factors studied, inadequate prenatal care and late onset, as well as inadequate or late treatment of maternal syphilis were significant risk factors for the outcome of congenital syphilis. When the time set of maternal diagnosis was correlated with neonatal infection, there was a tendency to worsen prognosis (more infected NB) in women diagnosed later in pregnancy, as well as in women who underwent few prenatal consultations and inadequate treatment. Women with recent syphilis with high VDRL titres had a higher rate of vertical transmission. The prior history of syphilis with adequate treatment was identified as a protective factor, resulting in lower rates of congenital syphilis. Among the epidemiological and demographic aspects surveyed, it was observed that young age, lower schooling, unemployment, low family income and no fixed residence were associated with higher risk of congenital syphilis.

Conclusions

The association of syphilis with adverse socio-economic conditions and inadequate prenatal care suggests that the improvement of the population's living conditions and equitable access to quality health services may have an impact on the reduction of congenital syphilis.     

Impact of Procalcitonin Guidance with an Educational Program on Management of Adults Hospitalized with Pneumonia

Background

Community-acquired pneumonia and healthcare-associated pneumonia are often treated with prolonged antibiotic therapy. Procalcitonin (PCT) has effectively and safely reduced antibiotic use for pneumonia in controlled studies. However, limited data exist regarding PCT guidance in real-world settings for management of pneumonia.

Structure of peptide sex pheromone receptor PrgX and PrgX/pheromone complexes and regulation of conjugation in Enterococcus faecalis

Many bacterial activities, including expression of virulence factors, horizontal genetic transfer, and production of antibiotics, are controlled by intercellular signaling using small molecules. To date, understanding of the molecular mechanisms of peptide-mediated cell-cell signaling has been limited by a dearth of published information about the molecular structures of the signaling components. Here, we present the molecular structure of PrgX, a DNA- and peptide-binding protein that regulates expression of the conjugative transfer genes of the Enterococcus faecalis plasmid pCF10 in response to an intercellular peptide pheromone signal. Comparison of the structures of PrgX and the PrgX/pheromone complex suggests that pheromone binding destabilizes PrgX tetramers, opening a 70-bp pCF10 DNA loop required for conjugation repression.     

Rehabilitation Utilization for Falls Among Community-Dwelling Older Adults in the United States in the National Health and Aging Trends Study

Objective

To determine the characteristics of community-dwelling older adults receiving fall-related rehabilitation.

Clinical impact of calcified nodules in patients with heavily calcified lesions requiring rotational atherectomy

• Coronary atherectomy has been around for many years, and the body of evidence for its use in complex calcified lesions has grown.
• Calcific coronary disease presents a particularly challenging clinical scenario in PCI, having poorer outcomes than noncalcified lesions.
• This study is the first to identify calcified nodules as an independent predictor of worse outcomes after atherectomy and PCI. Continued study of lesion characteristics will improve our understanding of PCI outcomes and help manage patients in the long-term after PCI and stenting.