Discovery of a pathway for terminal-alkyne amino acid biosynthesis.

Living systems can generate an enormous range of cellular functions, from mechanical infrastructure and signalling networks to enzymatic catalysis and information storage, using a notably limited set of chemical functional groups. This observation is especially notable when compared to the breadth of functional groups used as the basis for similar functions in synthetically derived small molecules and materials. The relatively small cross-section between biological and synthetic reactivity space forms the foundation for the development of bioorthogonal chemistry, in which the absence of a pair of reactive functional groups within the cell allows for a selective in situ reaction1-4. However, biologically 'rare' functional groups, such as the fluoro5, chloro6,7, bromo7,8, phosphonate9, enediyne10,11, cyano12, diazo13, alkene14 and alkyne15-17 groups, continue to be discovered in natural products made by plants, fungi and microorganisms, which offers a potential route to genetically encode the endogenous biosynthesis of bioorthogonal reagents within living organisms. In particular, the terminal alkyne has found broad utility via the Cu(I)-catalysed azide-alkyne cycloaddition 'click' reaction18. Here we report the discovery and characterization of a unique pathway to produce a terminal alkyne-containing amino acid in the bacterium Streptomyces cattleya. We found that L-lysine undergoes an unexpected reaction sequence that includes halogenation, oxidative C-C bond cleavage and triple bond formation through a putative allene intermediate. This pathway offers the potential for de novo cellular production of halo-, alkene- and alkyne-labelled proteins and natural products from glucose for a variety of downstream applications.

[Results of measuring neutron dose inside the Russian segment of the International Space Station using bubble detectors in experiment Matreshka-R].

Distribution of neutron equivalent dose both inside and outside the spherical phantom (experiment Matryeshka-R) was determined with the help of dedicated research equipment "Bubble-dosimeter". Equipment is built up from an automatic bubbles counter and 8 bubble detectors of neutrons with energy ranging from approximately 200 keV to 15 MeV. Measurements inside the ISS were made in several 7-day sessions in the period from April 2006 till October 2007 (ISS increments 13-15). According to the bubble detectors on the outside of the phantom, ambient neutron dose H*(10) was equal to 0.1 mSv/d or approximately 20% of the dose from charged particles inside the ISS. In the tissue-equivalent phantom, neutron dose was 1.2 +/- 0.2 times less as compared with the phantom surface which characterized the degree of dose attenuation in cosmonaut's body.

Potential acuity meter to predict postoperative visual acuity.

Thirty-three eyes were examined with the potential acuity meter (PAM) to determine preoperatively the expected visual acuity for patients undergoing cataract surgery. The preoperative visual acuity was compared to the best postoperative visual acuity. Although several patients had moderate macular degeneration as well as cataracts, there was an overall accuracy to within two lines of the best visual acuity in 96% of patients. There was a tendency to underestimate rather than overestimate postoperative visual acuity when these readings were in error. The instrument was only used if the cataract examined had some clarity. Older patients who were unsteady had difficulty performing the test.

Diagnosing oral diseases that affect the eyes.

Dentists can often help diagnose diseases that affect the eyes. This article discusses the diseases and iatrogenic dental conditions where ophthalmic and oral findings play a key role in diagnosis and treatment.

Early surgical alignment for congenital esotropia.

To provide sufficient numbers of patients varying in age of initial adequate surgical alignment for congenital esotropia, 154 patients managed by seven ophthalmologists in three countries were personally examined by the author and the results compiled for a clinical study. Examiner bias was minimized by having the examination performed without prior knowledge of the clinical history and the tests were standardized in both method of examination and test devices. From this population group 106 patients were chosen who had reliable answers, satisfactory alignment and an ophthalmologist's exam of the congenital nature of the problem by at least one year of age. The results of sensory testing showed that those adequately aligned by the age of 6 months versus 12 months versus 24 months were not statistically different, but those patients aligned after 24 months of age demonstrated a significantly lower percentage with evidence for binocularity (p less than .001).

The timing of surgical alignment for congenital (infantile) esotropia.

At this time, the beneficial effect of accurate alignment by age 2 in congenital esotropia has been well established by clinical and laboratory studies. There is, however, only scanty clinical evidence that alignment before age 1, much less before 6 months of age, may yield a better quality of binocularity (i.e., refined stereoacuity) than alignment by age 2. Pitfalls of very early alignment are present. In addition, the ophthalmologist must be vigilant in following the initially aligned patient and be ready to treat vertical motor defects, amblyopia, and acquired refractive errors. The need for additional horizontal surgery after initial alignment is also common. The optimum result in the surgical treatment of congenital esotropia generally shows binocularity that is within the confines of a monofixation syndrome, and refined stereoacuity remains an elusive target and a rare outcome, no matter at what age the alignment is achieved.

Botulinum alignment for congenital esotropia.

This is the first report of a group of patients with congenital esotropia examined for motor and sensory evidence of binocularity a minimum of 3 years after alignment by botulinum. Evidence for binocularity was clearly present in approximately one half of the patients. Lag time to satisfactory alignment was at least 1 month (average, 5 months) following the initial botulinum injection. The results must be considered preliminary. However, when these results are compared with those of patients with congenital esotropia aligned by incisional surgery by age 2 years and examined with the same testing devices by this same investigator, botulinum alignment appears to be less effective than surgical alignment in establishing evidence for binocularity (P < 0.005).

Progressive increase in the angle of deviation in congenital esotropia.

The majority of patients with congenital esotropia in this consecutive series of 41 patients showed an increase in the angle of deviation when followed over an average of 3 months. The ages at the initial measurement and surgery, the cycloplegic refraction, and the clinical response to patching could not be used to identify those patients with a progressive increase in the quantity of the deviation. It was found, however, that if the preliminary surgical plan was adjusted (as it was in the majority of the patients in this series) to reflect the latest measurements obtained the day before surgery, a relatively high percentage of patients (90%) could be found to have achieved satisfactory alignment by the 6-week postoperative visit.

Surgical alignment prior to six months of age for congenital esotropia.

PURPOSE: To complete the first independent and largest multicenter outcome investigation to analyze the motor and functional results of a series of patients surgically aligned prior to age 6 months and followed for a minimum of 4 years. METHODS: Sixteen patients, surgically aligned at an average age of 4.2 months, were examined at an average of 7.1 years to assess their motor and functional outcomes. RESULTS: Motor and sensory tests showed 11 patients to have a small or negligible motor misalignment at near point with both binocular fusion and gross stereopsis ability. A single patient aligned by 3 months of age demonstrated reproducible refined stereoacuity on sensory testing. However, the patients who achieved alignment by 4 or 5 months did not demonstrate any better quality of binocularity than that found in a previously studied group of patients aligned at 6 months. CONCLUSION: Binocularity that includes refined stereoacuity remains an elusive target and a rare outcome for an ophthalmologist treating congenital esotropia, despite very early surgical alignment.

Outcome study of bilateral lateral rectus recession for intermittent exotropia in children.

PURPOSE: This paper reports an outcome study of 52 consecutive children treated by bilateral lateral rectus recession for intermittent exotropia over a 9 year period (1981-90) with a minimum follow up of 6 months. METHODS: Successful alignment was defined as the absence of any postoperative intermittent or constant tropia in any position of gaze. The study examined the variables that might be predictive of successful alignment. The charts were abstracted for age at initial surgery, quantity of initial deviation, initial refraction, motor alignment at 1 week and 6 months, final alignment, secondary surgery results and the incidence of a monofixation syndrome result. RESULTS: Motor tests demonstrated that 32 (62%) of the patients were successfully aligned by the initial procedure performed for a mean of 25 prism diopters of preoperative deviation while viewing distant targets at a mean age of 4 years 8 months, followed for a mean of 4 years, 4 months. The incidence of undercorrections and overcorrections were approximately equal in quantity suggesting that the current surgical dosage was adequate, but the age at initial surgery, initial deviation, initial refraction and 1 week postoperative alignment results were not predictive of success. Alignment at 6 months, however, was highly correlated with successful alignment by the end of the study (p = 0.002). Secondary surgery was performed for 11 patients and 5 patients were found to have a monofixation syndrome result. CONCLUSION: Successful alignment was achieved in the majority of children treated for intermittent exotropia by an initial bilateral lateral rectus recession. However, 20% of the patients received secondary surgery for a residual deviation, and the study confirmed a previously reported 10% incidence of monofixation syndrome result in children surgically treated for this type of strabismus.

Progressive increase in the quantity of deviation in congenital esotropia.

BACKGROUND AND OBJECTIVE: It was the author's clinical impression that many individuals with congenital esotropia demonstrated an increase in the quantity of deviation measured over time. The present study statistically examines the prevalence and quantity of increase in the amount of deviation measured for a consecutive series of patients with congenital esotropia prior to surgical alignment. PATIENTS AND METHODS: A retrospective chart review was conducted for patients treated during a 5-year period. Data were recorded for the initial and final measurements of the strabismus and the initial and final surgical plans prior to surgery. Also recorded were the age at surgery, length of observation before surgery, refraction, use of patching, and initial motor alignment outcome. RESULTS: Approximately 50% of 41 patients showed an average increase of 20 prism diopters (PD) in the quantity of the deviation when they were observed for an average of 3 months. The age at initial measurement, age at surgery, length of observation prior to surgery, refraction, or use of patching could not be used to identify patients with the increase in the amount of strabismus. However, in cases where the final surgical plan was based on the measurements made the day before surgery, 90% of the patients showed an initial surgical alignment to within 10 PD or orthotropia by 6 weeks postoperatively. CONCLUSIONS: These data indicate that a significant increase in the amount of preoperative deviation is very prevalent in patients being observed for congenital esotropia. This finding suggests that the timing of preoperative measurements is very important, and that the data collected close to the date of surgery are the most important with which to plan surgery.

Outcome study of bilateral lateral rectus recession for intermittent exotropia in children.

BACKGROUND AND OBJECTIVE: The purpose of this paper is to report a statistical analysis of the surgical results in a consecutive series of 52 children treated by bilateral lateral rectus recession for intermittent exotropia when the operating surgeon was confronted by an increase in manifestation of the strabismus. PATIENTS AND METHODS: The charts were abstracted for age at initial surgery, quantity of initial deviation, initial refraction, motor alignment at one week, six months, and at the end of the study. The incidence and result of secondary surgery and the incidence of the monofixation syndrome result was also determined. RESULTS: Thirty-two (62%) of the patients were successfully aligned at six months by the initial surgery performed for a mean of 25 prism diopters (PD) of preoperative deviation at a mean age of 4 years 8 months. Eleven patients (21%) were undercorrected and 9 patients (17%) were overcorrected at the six month exam. The patients were followed for a mean of 4 years, 4 months. Alignment at 6 months postoperatively was predictive of success by the end of the study, but the age at initial surgery, the size of the deviation, esotropia at 1 week, and initial refraction were not predictive of success. Secondary surgery was performed in 11 patients and the monofixation syndrome result was found in 5 patients. CONCLUSION: Successful alignment was achieved in the majority of children treated by an initial bilateral lateral rectus recession utilizing a currently popular surgical dosage table. Long term alignment success was not predicted by esotropia during the first postoperative week or the age at initial surgery but was correlated with the 6-month data. Secondary surgery was performed in 20% and the incidence of the monofixation syndrome was approximately 10% at the end of the study.

Anxiety and unrealistic optimism.

Substantial evidence suggest that people tend to be unrealistically optimistic that positive events will happen to them and that negative events will not. However, recent research indicates that under certain conditions they may be unrealistically pessimistic. Variations in the levels of optimism and pessimism experienced towards events are generally given cognitive explanations. A relation between optimism and pessimism and anxiety, a variable related to emotion as well as cognition, was investigated in the present study. An inverse correlation was found between how anxious female students in England felt about certain negative events and how unrealistically optimistic they were about the occurrence of those events. It was concluded that the degree of anxiety experienced toward a negative event may affect the level of unrealistic optimism or pessimism toward it.

Retinopathy of prematurity: incidence and severity in Hawaii.

Because survival of low birth-weight infants requiring intensive care has improved recently, particularly since the advent of exogenous surfactant therapy, we reviewed our experience at Kapiolani Medical Center for Women and Children (KMCWC) from 1989 to 1991 to determine if the incidence of retinopathy of prematurity (ROP), a serious long-term complication, had also increased. During this 3-year period, threshold disease, the ROP stage in which cryosurgery is recommended, occurred only in infants < or = 1000 grams. Seventy-four infants < or = 1000 grams were diagnosed with ROP of any stage. Sixteen eyes (9 infants) reached threshold; 14 were treated with cryosurgery. Six of these eyes have useful vision on follow up; 8 do not. Exogenous surfactant therapy had no significant effect on ROP incidence or severity in our series. Although ROP incidence did not increase during this review period, it remains a serious problem in high-risk premature infants in our Newborn Intensive Care Unit.

Telepathology for intraoperative consultations and expert opinions: the experience of the Eastern Québec Telepathology Network.

CONTEXT: The Eastern Québec Telepathology Network was created to provide uniform diagnostic telepathology services in a huge territory with a low population density. OBJECTIVES: To evaluate the diagnostic concordance and turnaround times of intraoperative consultations (IOCs) and the turnaround time of expert opinions by telepathology. DESIGN: For the IOC part of the study, the first 104 IOC diagnoses from a single hospital were compared with those in the final pathology report. The turnaround time of the IOC was calculated from the arrival of the specimen at the pathology laboratory until the time of the call to the surgeon. For the expert opinion part of this study, the first 94 expert opinions from 5 hospitals were reviewed by comparing the time of the initial request until the time of the final report. RESULTS: Of the 104 cases in the IOC study, 8 diagnoses (7.7%) were slightly discrepant because of differences in terminology but remained in the same category of interpretation. Two cases (1.9%) were significantly discordant. Therefore, 102 cases (98.1%) were either concordant or had no clinically significant discrepancies. The average turnaround time for IOCs was 20 minutes (range, 8-43). For the expert opinion part of the study, reports were signed out within 24 hours in 64 cases (68%) and within 72 hours in 80 cases (85.1%). CONCLUSIONS: The Eastern Québec Telepathology Network allows a rapid, high-quality IOC service to be maintained for a hospital where no pathologist was available on site. It also provides a fast, expert opinion service to pathologists working alone.

Development of a multiplex microsphere immunoassay for the quantitation of salivary antibody responses to selected waterborne pathogens.

Saliva has an important advantage over serum as a medium for antibody detection due to non-invasive sampling, which is critical for community-based epidemiological surveys. The development of a Luminex multiplex immunoassay for measurement of salivary IgG and IgA responses to potentially waterborne pathogens, Helicobacter pylori, Toxoplasma gondii, Cryptosporidium, and four noroviruses, involved selection of antigens and optimization of antigen coupling to Luminex microspheres. Coupling confirmation was conducted using antigen specific antibody or control sera at serial dilutions. Dose-response curves corresponding to different coupling conditions were compared using statistical tests. Control proteins in the specific antibody assay and a separate duplex assay for total immunoglobulins G and A were employed to assess antibody cross-reactivity and variability in saliva composition. 200 saliva samples prospectively collected from 20 adult volunteers and 10 paired sera from a subset of these volunteers were used to test this method. For chronic infections, H. pylori and T. gondii, individuals who tested IgG seropositive using commercial diagnostic ELISA also had the strongest salivary antibody responses in salivary antibody tests. A steep increase in anti-norovirus salivary antibody response (immunoconversion) was observed after an episode of acute diarrhea and vomiting in a volunteer. The Luminex assay also detected seroconversions to Cryptosporidium using control sera from infected children. Ongoing efforts involve further verification of salivary antibody tests and their application in larger pilot community studies.