Ophthalmic and Neuroimaging Associations In Optic Nerve Hypoplasia/Septo-Optic-Pituitary Dysplasia.

BACKGROUND: Optic nerve hypoplasia (ONH) and septo-optic-pituitary dysplasia (SOD) are neurodevelopmental disorders associated with congenital visual impairment. Our aim was to investigate associations between several ophthalmic and neuroimaging features in patients with ONH/SOD. METHODS: A retrospective chart and neuroimaging review was performed in patients with ONH/SOD. Ophthalmic signs (e.g., monocular best-corrected visual acuity [BCVA], nystagmus, and strabismus) and neuroimaging data were extracted and their associations were investigated. RESULTS: There were 128 patients (70 males) with ONH/SOD who had neuroimaging. Their mean age at the end of the study was 13.2 (SD: 7.5) years. Ophthalmic data were available on 102 patients (58 males). BCVA varied from normal to no light perception. There were statistically significant associations between: (A) Reduced optic nerve or chiasm size on neuroimaging and more severely impaired BCVA and (B) laterality of the reduced optic nerve or chiasm size on neuroimaging and laterality of: (1) The eye with reduced BCVA, (2) small optic disc size, and (3) RAPD, if present (p ≤ 0.0002 each). The presence of symmetrically small optic nerves on MRI was significantly more common in patients with nystagmus than when nystagmus was absent (N = 96, 75% vs. 38.6%, p < 0.0001). The presence of neuronal migration disorders, their type and laterality were not associated with BCVA and laterality of the reduced BCVA. CONCLUSION: The functional and structural associations in ONH are consistent with the impaired visual function that results from the hypoplastic anterior visual pathways. However, these associations were not perfectly concordant making prediction of adult BCVA challenging in these patients.

Visual Acuity Outcomes in Children With Optic Nerve Hypoplasia and Septo-Optic-Pituitary Dysplasia.

BACKGROUND: To investigate best-corrected visual acuity (BCVA) outcomes in patients with optic nerve hypoplasia (ONH)/septo-optic-pituitary dysplasia (SOD). Our primary hypothesis was that BCVA in patients with ONH/SOD does not change significantly over time. METHODS: A chart review was undertaken in patients with a confirmed diagnosis of ONH/SOD. Demographic and clinical ophthalmologic data were extracted. Quantitative BCVA data were investigated across clinic visits after converting acuities to the logarithm of the minimum angle of resolution (logMAR). RESULTS: There were 102 patients (56 males). Median age at the end of the study was 12.7 years. Median duration of follow-up was 4.5 years. BCVA significantly worsened slightly in the most affected eyes (0.056 average increase in logMAR/year, 95% confidence interval [CI]: 0.037 to 0.075) and significantly improved mildly in the lesser or equally affected eyes (0.014 average decrease in logMAR/year, 95% CI: 0.009 to 0.019) (P < 0.0001). CONCLUSIONS: Although the overall BCVA data showed a statistically significant change with time, the actual changes were small and are of doubtful meaningful clinical significance (less than one line change on a Snellen chart). Our data suggest that ONH/SOD are nonprogressive neurodevelopmental disorders. The mild worsening of BCVA in the most affected eyes may be caused by amblyopia, whereas the small improvement in the lesser or equally affected eyes may be caused by developmental maturation. In addition, the changes in BCVA may also be due to increasing reliability of visual assessments with increasing age.

Selected Ophthalmological Features in Children with Septo-Optic Dysplasia and Optic Nerve Hypoplasia.

Septo-optic dysplasia (SOD) and optic nerve hypoplasia (ONH) cause congenital visual impairment. Their aetiology is mostly unknown. Our aim was to investigate the prevalence of selected ophthalmological features in patients with these disorders. A chart review was performed on patients with SOD/ONH. Ophthalmological data were extracted. There were 102 patients (56 males). The median age at the end of the study was 12.7 years. Best-corrected visual acuity ranged from normal to no light perception. Bilateral ONH was more common than unilateral ONH. Strabismus (85%) and to a lesser extent nystagmus (52%) were both very common in our cohort. Patients with esotropia had worse visual acuity than those who had exotropia. The presence of nystagmus was more likely in cases with bilateral ONH. Therefore, patients with SOD/ONH may have normal visual acuity. Many have strabismus, which may cause amblyopia thereby further decreasing visual acuity. Nystagmus occurs commonly and its presence typically indicates bilateral ONH.

Choosing Wisely in Pre-clinical Medical Education: a Direct Comparison of Active Learning Methods for Teaching Metabolic Liver Disease.

BACKGROUND: With the movement away from lectures and towards active learning sessions, medical school faculty must choose a format that fits the learning objectives and is achievable with available resources. Small groups bring organizational challenges including additional faculty and classrooms. Large groups are an opportunity to conduct case-based active learning exercises with fewer faculty. Our study compares the learning effectiveness of an active learning session on metabolic liver disease conducted in both the small group and large group formats. METHODS: All MS1 students at University of Vermont Larner College of Medicine (LCOM) (n = 120) were randomized to participate in either the small or large group session. The same pre-learning videos and computer-based active learning module were used for all students in both session types. A post-session questionnaire was administered, and student exam performance was analyzed to evaluate each session type on the following criteria: (1) student preparedness for the session, (2) student perceptions of the session's learning effectiveness, (3) learner knowledge upon completion of the session, and (4) knowledge retention at 10 days. RESULTS: No statistically significant differences were found between the large and small group cohorts on student perceptions of learning effectiveness or knowledge assessment, both immediate and delayed. Students assigned to the large group did choose their collaborators differently than those in the small group, tending more often to work with their friends. CONCLUSION: When organized well, a large group active learning format may be used in place of a small group without diminishing the learning effectiveness of the activity.

How much and where: assessment of knowledge level of the application of cricoid pressure.

INTRODUCTION: Application of cricoid pressure is a frequently used technique in both rapid sequence intubation in multiple settings and in a more controlled setting in the operating room. In a survey of emergency department personnel performed at the University of Michigan, it was found that there is a knowledge deficit in the recommended force and the anatomic localization of cricoid pressure. Participants in the original study, which included emergency nurses, medical residents, and attending physicians, rated their training in cricoid pressure as poor or nonexistent. A review of the literature shows that, although cricoid pressure is used during endotracheal intubation to protect against regurgitation of gastric contents, many people applying cricoid pressure do not have a good knowledge of where to apply the pressure or how much pressure to apply to be effective. Because cricoid pressure is applicable in areas other than the emergency department, our study surveys personnel in emergency medical services/flight crew; emergency, intensive care unit, and operating room nurses; and respiratory therapists. Even though the use of cricoid pressure is no longer recommended, it is still routinely used. Although applying cricoid pressure is a simple procedure, persons using it must be thoroughly trained and retrained to prevent complications. METHODS: When we replicated the University of Michigan study at a 254-bed tertiary care facility, a potential of 325 staff members were given access to an online survey using the questions in the original survey. Staff were assigned to a HealthStream module and sent an invitation through their employee e-mail account. The module included a link to the questionnaire, and demographic data were gathered. The module was optional and results confidential. RESULTS: Operating room nurses were most likely to receive supervised instruction on anesthetized patients. These operating room nurses also showed the highest overall knowledge level about the application technique of cricoid pressure. DISCUSSION: There continues to be a lack of knowledge about the application of cricoid pressure during intubation. There is an opportunity for collaboration between staff and academic educators to allow for additional theoretical as well as hands-on practice.

Novel acyl phosphate mimics that target PlsY, an essential acyltransferase in gram-positive bacteria.

PlsY is a recently discovered acyltransferase that executes an essential step in membrane phospholipid biosynthesis in Gram- positive bacteria. By using a bioisosteric replacement approach to generate substrate-based inhibitors of PlsY as potential novel antibacterial agents, a series of stabilized acyl phosphate mimetics, including acyl phosphonates, acyl alpha,alpha-difluoromethyl phosphonates, acyl phosphoramides, reverse amide phosphonates, acyl sulfamates, and acyl sulfamides were designed and synthesized. Several acyl phosphonates, phosphoramides, and sulfamates were identified as inhibitors of PlsY from Streptococcus pneumoniae and Bacillus anthracis. As anticipated, these inhibitors were competitive inhibitors with respect to the acyl phosphate substrate. Antimicrobial testing showed the inhibitors to have generally weak activity against Gram-positive bacteria with the exception of some acyl phosphonates, reverse amide phosphonates, and acyl sulfamates, which had potent activity against multiple strains of B. anthracis.

A microbiological assessment of novel nitrofuranylamides as anti-tuberculosis agents.

OBJECTIVES: Nitrofuranylamides (NFAs) are nitroaromatic compounds that have recently been discovered and have potent anti-tuberculosis (TB) activity. A foundational study was performed to evaluate whether this class of agents possesses microbiological properties suitable for future antimycobacterial therapy. METHODS: Five representative compounds of the NFA series were evaluated by standard microbiological assays to determine MICs, MBCs, activity against anaerobic non-replicating persistent Mycobacterium tuberculosis, post-antibiotic effects (PAEs), antibiotic synergy and the basis for resistance. RESULTS: The antimicrobial activity of these compounds was restricted to bacteria of the M. tuberculosis complex, and all compounds were highly active against drug-susceptible and -resistant strains of M. tuberculosis, with MICs 0.0004-0.05 mg/L. Moreover, no antagonism was observed with front-line anti-TB drugs. Activity was also retained against dormant bacilli in two in vitro low-oxygen models for M. tuberculosis persistence. A long PAE was observed, which was comparable to that of rifampicin, but superior to isoniazid and ethambutol. Spontaneous NFA-resistant mutants arose at a frequency of 10(-5)-10(-7), comparable to that for isoniazid (10(-5)-10(-6)). Some of these mutants exhibited cross-resistance to one or both of the nitroimidazoles PA-824 and OPC-67683. Cross-resistance was associated with inactivation of the reduced F(420)-deazaflavin cofactor pathway and not with inactivation of the Rv3547, the nitroreductase for PA-824 and OPC-67683. CONCLUSIONS: Based on these studies, NFAs have many useful antimycobacterial properties applicable to TB chemotherapy and probably possess a unique mode of action that results in good activity against active and dormant M. tuberculosis. Therefore, the further development of lead compounds in this series is warranted.

N-substituted 3-acetyltetramic acid derivatives as antibacterial agents.

In order to expand the structure-activity relationship of tetramic acid molecules with structural similarity to the antibiotic reutericyclin, 22 compounds were synthesized and tested against a panel of clinically relevant bacteria. Key structural changes on the tetramic acid core affected antibacterial activity. Various compounds in the N-alkyl 3-acetyltetramic acid series exhibited good activity against Gram-positive bacterial pathogens including Bacillus anthracis, Propionibacterium acnes, Enterococcus faecalis, and both Methicillin-sensitive and -resistant Staphylococcus aureus.

Solid-phase synthesis and biological evaluation of a uridinyl branched peptide urea library.

A 1000-member uridinyl branched peptide library was synthesized on PS-DES support using IRORI technology. High-throughput screening of this library for anti-tuberculosis activity identified several members with a MIC(90) value of 12.5 microg/mL.

Clinical comparison of automatic, noninvasive measurements of blood pressure in the forearm and upper arm with the patient supine or with the head of the bed raised 45 degrees: a follow-up study.

BACKGROUND: Noninvasive measurement of blood pressure in the forearm is used when the upper arm is inaccessible and/or when available blood pressure cuffs do not fit a patient's arm. Evidence supporting this practice is limited. OBJECTIVE: To compare noninvasive measurements of blood pressure in the forearm and upper arm of medical-surgical inpatients positioned supine and with the head of the bed raised 45 degrees . METHODS: Cuff size was selected on the basis of forearm and upper arm circumference and manufacturers' recommendations. With a Welch Allyn Vital Signs 420 Series monitor, blood pressures were measured in the forearm and then in the upper arm of 221 supine patients with their arms resting at their sides. Patients were repositioned with the head of the bed elevated 45 degrees and after 2 minutes, blood pressures were measured in the upper arm and then the forearm. Starting position was alternated on subsequent subjects. RESULTS: Paired t tests revealed significant differences between systolic and diastolic blood pressures measured in the upper arm and forearm with patients supine and with the head of the bed elevated 45 degrees . The Bland-Altman procedure revealed that the distances between the mean values and the limits of agreement were from 15 to 33 mm Hg for individual subjects. CONCLUSIONS: Noninvasive measurements of blood pressure in the forearm and upper arm cannot be interchanged in medical-surgical patients who are supine or in patients with the head of the bed elevated 45 degrees .

Clinical comparison of automatic, noninvasive measurements of blood pressure in the forearm and upper arm.

BACKGROUND: When the upper arm (area from shoulder to elbow) is inaccessible and/or a standard-sized blood pressure cuff does not fit, some healthcare workers use the forearm to measure blood pressure. OBJECTIVE: To compare automatic noninvasive measurements of blood pressure in the upper arm and forearm. METHODS: A descriptive, correlational comparison study was conducted in the emergency department of a 1071-bed teaching hospital. Subjects were 204 English-speaking patients 6 to 91 years old in medically stable condition who had entered the department on foot or by wheelchair and who had no exclusions to using their left upper extremity. A Welch Allyn Vital Signs 420 series monitor was used to measure blood pressure in the left upper arm and forearm with the subject seated and the upper arm or forearm at heart level. RESULTS: Pearson r correlation coefficients between measurements in the upper arm and forearm were 0.88 for systolic blood pressure and 0.76 for diastolic blood pressure (P < .001 for both). Mean systolic pressures, but not mean diastolic pressures, in the upper arm and forearm differed significantly (t = 2.07, P = .04). A Bland-Altman analysis indicated that the distances between the mean values and the limits of agreement for the 2 sites ranged from 15 mm Hg (mean arterial pressure) to 18.4 mm Hg (systolic pressure). CONCLUSIONS: Despite strict attention to correct cuff size and placement of the upper arm or forearm at heart level, measurements of blood pressure obtained noninvasively in the arm and forearm of seated patients in stable condition are not interchangeable.

Do performance appraisals of registered nurses reflect a relationship between hospital size and caring?

PROBLEM: Patients and family members expect nurses to demonstrate caring during their contact with patients. If caring is so important, it should be measured on the performance appraisals of registered nurses. METHODS: Watson's carative factors. A review of performance appraisals, for evidence of Watson's carative factors, for medical-surgical nurse positions from 87 hospitals in one Midwestern state. FINDINGS: Facility size did not seem to be associated with the appearance of Watson's carative factors. Size of facility was only significant between small hospitals and Watson's carative factor two, sustaining faith and hope. CONCLUSIONS: Although caring is important to the profession of nursing, it is not measured as a part of nursing performance appraisals.

Vibrational coherence from the dipyridine complex of bacteriochlorophyll a: intramolecular modes in the 10-220-cm(-1) regime, intermolecular solvent modes, and relevance to photosynthesis.

We present the first observations of vibrational coherence in the 10-220-cm-1 region from bacteriochlorophyll a (BChl) in solution. A distinction can be made for the first time between BChl's intramolecular normal modes and intermolecular modes between BChl and solvent. The results show that the low-frequency vibrations that accompany the initial electron-transfer reaction from the paired BChl primary electron donor, P, in photosynthetic reaction centers arise predominantly from intramolecular modes of histidine-ligated BChl macrocycles. The results also suggest that polar-solvent interactions can significantly perturb the electronic properties of BChl in a manner that might have important functional consequences.