Plasma 5'-nucleotidase activities increase in women with hyperemesis gravidarum

OBJECTIVES: To investigate plasma activities of 5'-nucleotidase, a key enzyme in the production of adenosine and evaluate the relationship between changes in 5'-nucleotidase activities and pregnancy-related hormones, estrogen, progesterone and human chorionic gonadotropin (hCG) in women with hyperemesis gravidarum. DESIGN AND METHODS: Plasma 5'-nucleotidase activities and estradiol, progesterone and hCG levels were measured in 21 women with hyperemesis gravidarum and normal pregnancies, matched for age, parity and gestational week. RESULTS: In women with hyperemesis gravidarum, plasma 5'-nucleotidase activities averaged 8.1 +/- 0.6 IU/L, which were significantly increased compared to those in normal pregnant women (5.5 +/- 0.5 IU/L)(p < 0.05). The increases in plasma 5'-nucleotidase activities were accompanied by elevations of plasma estradiol, progesterone and hCG levels. CONCLUSIONS: The increase of plasma 5'-nucleotidase activities may be at least partly attributed to elevations of pregnancy-related hormones, suggesting changes in purine metabolism in women with hyperemesis gravidarum.     

Treating coagulopathy in trauma patients

Coagulopathy in patients with severe trauma is related to platelet and coagulation factor loss, consumption, and dysfunction. It is exacerbated by dilution, acidosis, and hypothermia. Hemorrhage control, warming, and appropriate blood product support are lifesaving. Further improvements in hemorrhage control will save additional lives and resources.     

Design and Development of a Medical Image Databank for Assisting Studies in Radiomics

Journal of Digital Imaging - CompreHensive Digital ArchiVe of Cancer Imaging - Radiation Oncology (CHAVI-RO) is a multi-tier WEB-based medical image databank. It supports archiving de-identified...     

Augmented blood removal after medicinal leech feeding in congested tissue flaps

Reconstructive microsurgery is performed to reattach, transfer, or transplant body tissues. Venous congestion is a complication that threatens the viability of the affected tissue and is often treated with medicinal leeches. Leech therapy has two phases: active bloodletting and passive bleeding from the leech wound after detachment, which can last for several hours. Unfortunately, the small blood volumes removed by medicinal leeches are generally ineffective in decongesting tissue. Our goal was to develop a device to augment blood removal during the passive-bleeding phase of leech therapy with the use of a porcine model of venous congestion. Results indicated that the use of the device resulted in significant increases in blood retrieval relative to reports of passive bleeding alone (141%, 156%, and 155% in 1, 2, and 3 hours, respectively). These results are an encouraging first step toward development of a mechanical device that completely replaces the use of medicinal leeches in modern medicine.     

Attitudes of Dilated Cardiomyopathy Patients and Investigators Toward Genomic Study Enrollment,Consent Process,and Return of Genetic Results

Precision medicine genetics study design requires large, diverse cohorts and thoughtful use of electronic technologies. Involving patients in research design may increase enrollment and engagement, thereby enabling a means to relevant patient outcomes in clinical practice. Few data, however, illustrate attitudes of patients with dilated cardiomyopathy (DCM) and their family members toward genetic study design. This study assessed attitudes of 16 enrolled patients and their family members (P/FM), and 18 investigators or researchers (I/R) of the ongoing DCM Precision Medicine Study during a conjoint patient and investigator meeting using structured, self‐administered surveys examining direct‐to‐participant enrollment and web‐based consent, return of genetic results, and other aspects of genetic study design. Survey respondents were half women and largely identified as white. Web‐based consent was supported by 93% of P/FM and 88% of I/R. Most respondents believed that return of genetic results would motivate study enrollment, but also indicated a desire to opt out. Ideal study design preferences included a 1‐hour visit per year, along with the ability to complete study aspects by telephone or web and possibility of prophylactic medication. This study supports partnership of patients and clinical researchers to inform research priorities and study design to attain the promise of precision medicine for DCM.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

☑ Involving patients in research study designs may enhance study relevance and improve the value of health research. No studies, however, clarify attitudes of patients with dilated cardiomyopathy , family members, and doctors toward genetic study design.

• WHAT QUESTION DID THIS STUDY ADDRESS?

☑ This study aggregated patient and researcher attitudes toward direct‐to‐participant enrollment, receipt of expanded genetic results, and study design elements to facilitate study design with a patient‐centric focus.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

☑ The results suggest that patient feedback may help attract and retain enrollees as well as benefit patient outcomes. Web‐based consent was viewed favorably, which coincides with increased implementation of direct‐to‐consumer technologies in research. Return of complete genetic testing results could be motivating to patient enrollment as long as only actionable results are delivered by an engaged, knowledgeable healthcare team.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

☑ Findings from this study may help researchers and clinicians more fully realize the potential of precision medicine and inform the future design of large genetics research studies.

Enrollment and continued engagement of thousands of participants in genetics studies are ideal for precision medicine research. Large, family‐based cohorts that include racially diverse and potentially environmentally exposed individuals may be necessary to comprehend complex genetic architecture. To ensure study success and ultimately improve the value of health research, there is a need for recruitment and enrollment motivation strategies. ¹ Researchers must then maintain enrollee engagement throughout the study. We designed a qualitative pilot study to understand study participant preferences and inform design of large genetics research studies.We surveyed enrolled patients, their family members, and investigators of the ongoing Dilated Cardiomyopathy (DCM) Precision Medicine Study funded by the National Institutes of Health, a multisite consortium‐based study that is determining whether idiopathic DCM has a genetic basis. ² Capitalizing on the unique opportunity afforded by a conjoint patient and investigator meeting, we anonymously queried participants about genetic study enrollment motivations, attitudes toward direct‐to‐participant consent processes, desirability of return of genetic results, and other aspects of study design. Our goal was to collect this information to facilitate design of future studies with a patient‐centric focus.Due to widespread adoption of direct‐to‐consumer genome sequencing, electronic results, and data platforms, and mobile health applications (“apps”), ³ we aimed to determine desirability of direct‐to‐participant recruitment and consent, which places patients and research participants at the center of decision making and has been shown to facilitate study enrollment and retention. ⁴ Return of electronic, complete genetic testing results were considered another key incentive to maintain study interest. ⁵ , ⁶ However, no studies about patient attitudes toward DCM genetic studies have been performed, especially in the context of direct‐to‐participant enrollment and receipt of expanded genetic results. ⁷ Furthermore, we wanted to understand patient preferences for length, format, and frequency of study visits, as well as acceptability of proactive treatment. We therefore conducted a pilot study to address these issues and to benefit researchers considering design of genetics studies.     

Telavancin, a multifunctional lipoglycopeptide, disrupts both cell wall synthesis and cell membrane integrity in methicillin-resistant Staphylococcus aureus

The emergence and spread of multidrug-resistant gram-positive bacteria represent a serious clinical problem. Telavancin is a novel lipoglycopeptide antibiotic that possesses rapid in vitro bactericidal activity against a broad spectrum of clinically relevant gram-positive pathogens. Here we demonstrate that telavancin's antibacterial activity derives from at least two mechanisms. As observed with vancomycin, telavancin inhibited late-stage peptidoglycan biosynthesis in a substrate-dependent fashion and bound the cell wall, as it did the lipid II surrogate tripeptide N,N'-diacetyl-L-lysinyl-D-alanyl-D-alanine, with high affinity. Telavancin also perturbed bacterial cell membrane potential and permeability. In methicillin-resistant Staphylococcus aureus, telavancin caused rapid, concentration-dependent depolarization of the plasma membrane, increases in permeability, and leakage of cellular ATP and K(+). The timing of these changes correlated with rapid , concentration-dependent loss of bacterial viability, suggesting that the early bactericidal activity of telavancin results from dissipation of cell membrane potential and an increase in membrane permeability. Binding and cell fractionation studies provided direct evidence for an interaction of telavancin with the bacterial cell membrane; stronger binding interactions were observed with the bacterial cell wall and cell membrane relative to vancomycin. We suggest that this multifunctional mechanism of action confers advantageous antibacterial properties.