Sensing the structural and conformational properties of single-stranded nucleic acids using electrometry and molecular simulations.

Inferring the 3D structure and conformation of disordered biomolecules, e.g., single stranded nucleic acids (ssNAs), remains challenging due to their conformational heterogeneity in solution. Here, we use escape-time electrometry (ETe) to measure with sub elementary-charge precision the effective electrical charge in solution of short to medium chain length ssNAs in the range of 5-60 bases. We compare measurements of molecular effective charge with theoretically calculated values for simulated molecular conformations obtained from Molecular Dynamics simulations using a variety of forcefield descriptions. We demonstrate that the measured effective charge captures subtle differences in molecular structure in various nucleic acid homopolymers of identical length, and also that the experimental measurements can find agreement with computed values derived from coarse-grained molecular structure descriptions such as oxDNA, as well next generation ssNA force fields. We further show that comparing the measured effective charge with calculations for a rigid, charged rod-the simplest model of a nucleic acid-yields estimates of molecular structural dimensions such as linear charge spacings that capture molecular structural trends observed using high resolution structural analysis methods such as X-ray scattering. By sensitively probing the effective charge of a molecule, electrometry provides a powerful dimension supporting inferences of molecular structural and conformational properties, as well as the validation of biomolecular structural models. The overall approach holds promise for a high throughput, microscopy-based biomolecular analytical approach offering rapid screening and inference of molecular 3D conformation, and operating at the single molecule level in solution.

Affordances for throwing: An uncontrolled manifold analysis.

Movement systems are massively redundant, and there are always multiple movement solutions to any task demand; motor abundance. Movement consequently exhibits 'repetition without repetition', where movement outcomes are preserved but the kinematic details of the movement vary across repetitions. The uncontrolled manifold (UCM) concept is one of several methods that analyses movement variability with respect to task goals, to quantify repetition without repetition and test hypotheses about the control architecture producing a given abundant response to a task demand. However, like all these methods, UCM is under-constrained in how it decomposes a task and performance. In this paper, we propose and test a theoretical framework for constraining UCM analysis, specifically the perception of task-dynamical affordances. Participants threw tennis balls to hit a target set at 5m, 10m or 15m, and we performed UCM analysis on the shoulder-elbow-wrist joint angles with respect to variables derived from an affordance analysis of this task as well as more typical biomechanical variables. The affordance-based UCM analysis performed well, although data also showed thrower dynamics (effectivities) need to be accounted for as well. We discuss how the theoretical framework of affordances and affordance-based control can be connected to motor abundance methods in the future.

Defining Electronic Health Record Standards for Child Health: A State-of-the-Art Review.

BACKGROUND: Improving child health using health information technology (IT) requires a unique set of functionalities that are built into the electronic health record (EHR) and are used to support patient care. In this article, we review and discuss the milestones preceding the development of a new child health EHR standard and describe the salient features of this contemporary standard. METHODS AND RESULTS: The Health Level Seven Pediatric Care Health IT Functional Profile (HL7 PCHIT FP) is an informative standard that encompasses the EHR functions required to care for patients less than 21 years of age in any clinical setting, developed to address the pediatric-specific functionality gaps in the EHR. It includes criteria that support communication between providers and all caregivers, inclusion of pediatric-specific vital signs and diagnosis, support for transition to adult care, and support for reporting and documentation of child abuse or neglect including communication with involved authorities. EHR functionalities for documentation and reporting of newborn screening tests with follow-up for abnormal results and functionality for children with special health care needs with support for identifying patients who may benefit from care coordination are also incorporated, in addition to school-based linkages enabling communication between the health care system and their school environment. CONCLUSION: The HL7 PCHIT FP is envisioned to be another vital step towards improving pediatric health by enhancing EHRs to address the unique health IT needs of children and their health providers. While the HL7 PCHIT FP is the most recently published standard on pediatric EHR systems, standards development is an iterative process, and recommendations for continuous refinement and additional functionalities for the next standards release are encouraged.

Far-Field Electrostatic Signatures of Macromolecular 3D Conformation.

In solution as in vacuum, the electrostatic field distribution in the vicinity of a charged object carries information on its three-dimensional geometry. We report on an experimental study exploring the effect of molecular shape on long-range electrostatic interactions in solution. Working with DNA nanostructures carrying approximately equal amounts of total charge but each in a different three-dimensional conformation, we demonstrate that the geometry of the distribution of charge in a molecule has substantial impact on its electrical interactions. For instance, a tetrahedral structure, which is the most compact distribution of charge we tested, can create a far-field effect that is effectively identical to that of a rod-shaped molecule carrying half the amount of total structural charge. Our experiments demonstrate that escape-time electrometry (ETe) furnishes a rapid and facile method to screen and identify 3D conformations of charged biomolecules or molecular complexes in solution.

Fundamentals of Fluorescein Angiography.

In order to provide safe patient care during fluorescein angiography, it is critical that ophthalmic team members understand the use of fluorescein for diagnosing eye-related diseases and conditions, including appropriate doses for adult and pediatric patients. Awareness of side effects, adverse reactions, and complications of the contrast agent allow the ophthalmic health-care team to anticipate, respond quickly, and support the patient during and following the angiographic procedure using fluorescein.

A case of diprosopus: perinatal counseling and management.

Diprosopus is a rare congenital malformation associated with high mortality. Here, we describe a patient with diprosopus, multiple life-threatening anomalies, and genetic mutations. Prenatal diagnosis and counseling made a beneficial impact on the family and medical providers in the care of this case.

Perniosis in a long-distance cyclist crossing Mongolia.

We report a case of severe perniosis in a long-distance cyclist. This case demonstrates the importance of identifying those at risk of cold-related injuries who are about to embark on extensive travel in cold environments.

Effect of ophthalmic examination procedures on the quality of spectral domain OCT images.

The authors compare the image quality of spectral domain optical coherence tomography (OCT) images in eyes before and after routine ophthalmic screening procedures. The study population in this prospective case series included 24 patients (45 eyes). No significant difference in OCT scan quality factor was found in the study population pre-screening and post-screening (P > .05 for the horizontal, vertical, and raster pattern scans performed in each OCT scan series). Routine ophthalmic screening procedures do not affect the quality of spectral domain OCT images.

Ophthalmic imaging today: an ophthalmic photographer's viewpoint - a review.

Ophthalmic imaging has changed dramatically since the 1960s with increasingly complex technologies now available. Arguably, the greatest changes have been the development of the digital camera and the speed, processing power and storage of electronic data. Already, ophthalmic practices in many major institutions overseas have paperless medium storage and electronically generated reporting from all equipment that use a computer interface. It is hard to remember the widespread use of photographic film with its attendant costs, or even to remember the days before optical coherence tomography (OCT). These latest technical improvements in ophthalmic imaging are now standard in large Australian institutions and becoming more widespread in smaller private practices. The technicians that operate and maintain this ever-increasing plethora of gadgetry have seen their work practices change from the darkroom to the complexities of data-based imaging and storage. It is a fitting time to examine the contemporary state of ophthalmic imaging and what lies on the horizon as we move towards 2020.

Incidence of significant adhesions at repeat cesarean section and the relationship to method of prior peritoneal closure.

OBJECTIVE: To examine the effect of peritoneal closure at prior cesarean section on the occurrence of abdomino-pelvic adhesions at subsequent cesarean section. STUDY DESIGN: An observational chart review study was performed involving 191 cases of repeat cesarean section occurring from January 2001 through July 30, 2002. An adhesion score was created according to the following: a grade 1 score was assigned when no adhesions were present, a grade 2 when adhesions were present but no surgery required, a grade 3 when adhesiolysis was required and there was inability to exteriorize the uterus, and a grade 4 when adhesiolysis was required prior to delivery. Scores were assigned and tabulated as a result of the review of the operative records of 191 cases. When available, the operative record of prior cesarean section was examined to determine if visceral and parietal peritoneal closure had been performed at the prior operation. RESULTS: During the year and a half for which data were examined, significant abdominopelvic adhesions (grades 3 and 4) were encountered 21% of the time (40 of 191) at repeat cesarean section. Prior peritoneal closure resulted in significant adhesions in 1 of 18 patients compared to 17 of 40 patients when no prior peritoneal closure was recorded (Fisher's exact probability = 0.003). CONCLUSION: While preliminary, in the absence of any substantive benefit or published data regarding adhesionformation in cesarean section that contradict this finding, the practice of nonclosure of visceral and parietal peritoneum at cesarean section should be questioned.

Fibrolamellar hepatocellular carcinoma arising in a background of focal nodular hyperplasia: a report of 2 cases.

BACKGROUND: Fibrolamellar carcinoma, a rare variant of hepatocellular carcinoma, and focal nodular hyperplasia, a benign lesion, are rare hepatic lesions that are known to occur in young women with noncirrhotic livers. Some have suggested that fibrolamellar carcinoma might be the malignant counterpart of focal nodular hyperplasia. The coexistence of the 2 lesions is very rare. CASES: Two cases of fibrolamellar hepatocellular carcinoma arising in a background of focal nodular hyperplasia followed long-term oral contraception, and 1 of the 2 occurred during pregnancy. CONCLUSION: Distinguishing fibrolamellar carcinoma from focal nodular hyperplasia has important implications for treatment and prognosis. One should be aware of such conditions, especially in patients with a long history of oral contraception.

Transient corneal microcysts associated with interferon therapy.

PURPOSE: To report transient corneal epithelial microcysts associated with interferon therapy. METHODS: Case report. RESULTS: Transient corneal epithelial microcysts appeared bilaterally with the onset of therapy with pegylated interferon and ribavirin for the treatment of hepatitis C. These microcysts resolved completely after discontinuation of the pegylated interferon with ribavirin therapy. CONCLUSIONS: Pegylated interferon therapy was associated with transient corneal epithelial microcysts in our patient.

The effect of leukaemia inhibitory factor on SOD1 G93A murine amyotrophic lateral sclerosis.

Before potential therapeutic strategies for the treatment of amyotrophic lateral sclerosis (ALS) can be advanced to human clinical trials, there is a need to assess them in an animal model that best resembles the disease process. SOD1 G93A mice have close resemblance to familial ALS (fALS) and have been used in this study to evaluate the therapeutic potential of leukaemia inhibitory factor (LIF). LIF action was investigated by assessing three delivery methods: (1) daily subcutaneous injection; (2) through LIF rods placed adjacent to hind limb skeletal muscle and (3) continuous intrathecal infusion. The effect on disease progression was assessed by semi-quantitative and quantitative functional measurements, and histologically on the survival of motor neurons and number of reactive astrocytes. The results show that LIF had no beneficial effects when administered using the three methods of drug delivery. These results suggest that further evaluation of LIF in this transgenic model is required to fully characterize its' therapeutic potential.

Immediate and delayed nerve repair: improved muscle mass and function with leukemia inhibitory factor.

In this study we examined the effect of leukemia inhibitory factor (LIF) on delayed repair of injured nerves. In a standard entubulation gap repair model of sciatic nerve in the rat, repair was performed immediately and after delays of 1 day, 1 week, and 4 weeks. Repaired nerves were treated with either LIF (10 ng) or saline, and assessment was by muscle mass and force contraction at 12 weeks after repair. After immediate nerve repair LIF administration resulted in 2.5- to 3-fold improvements compared with saline. In the 1-day delayed group, both saline and LIF treatment groups were comparable with that achieved with immediate repair combined with LIF. This result is consistent with the concept of preconditioning. In the 1-week delayed repair groups with LIF, muscle mass recovery and maximum force contraction were improved by 32% and 55%, respectively, compared with saline, whereas repairs delayed for 4 weeks showed increases of 50% and 36%. All delayed repairs treated with LIF were more effective than immediate repair with saline, but not as effective as primary repair with LIF. Our findings support the view that factors such as LIF may be efficacious for improving recovery of function in cases of delayed peripheral nerve repair.

Plasma endorphin-like immunoreactivity in pelvic and abdominal pain.

This study was undertaken to determine the association, if any, of plasma endorphins with pelvic pain in a defined population. The study group was comprised of 37 patients who presented to the emergency room at Wishard Memorial Hospital for evaluation of gynecologic complaints. These subjects were divided into 3 groups depending on the degree of pelvic pain assessed both by the subject and the examining physician. Group I (control) consisted of those subjects who were pain-free (9 subjects). Group II contained those whose pelvic pain was not felt to require hospital admission (18 subjects). Group III subjects represented those with pelvic pain whose diagnosis warranted hospitalization (10 subjects). Plasma endorphin levels were determined on each subject before and after pelvic examination using standard radioimmunoassay techniques. Data analysis was accomplished by analysis of variance methods. The timing of the pelvic examination made no difference on the plasma endorphin levels. Levels between groups were statistically similar, though differences between both group I and group II, and that of group III levels approached significance.