Search

•Cataract surgery is the most frequently performed surgery in the world, yet few studies have investigated predictors of associated pain.•The significant risk factors for pain during phacoemulsification are IOL power<19 D, chronic analgesic use, white/brown cataract, iris complications, surgery time≥20min, and blood pressure increase.•A larger study may help develop a predictive score for pain that could, for example, be integrated into a biometer.

Abstract The use of a drug to modify a person's behaviour for criminal gain is not a recent phenomenon. However, the recent increase in reports of drug-facilitated crimes (sexual assault, [...]

Abstract Chemical dependency is a disease that can affect all professions. Among the health care professionals, anesthesiologists represent a specific group. Numerous factors have been proposed to explain the high [...]

Abstract A procedure is presented for the screening of 17 benzodiazepines and hypnotics in oral fluid after collection with the Intercept@ device by LC-MS/MS (alprazolam, 7-aminoclonazepam, 7-aminoflunitrazepam, bromazepam, clobazam, diazepare, [...]

Abstract A solid-phase enzyme immunoassay involving microtiter plates was recently proposed by International Diagnostic Systems corporation (IDS) to screen for buprenorphine in human serum. The performance of the kit led [...]

Abstract Since gamma-hydroxybutyrate (GHB) is present in both blood and urine of the general population as an endogenous compound, toxicologists must be able to discriminate between these endogenous levels and [...]

Abstract A LC--MS/MS method for the detection of zolpidem in hair was developed to detect this drug after a single dose in possible drug facilitated sexual assaults. To determine the [...]

The use of a drug to modify a person's behavior for criminal gain is not a recent phenomenon. However, the recent increase in reports of drug-facilitated crimes (sexual assault, robbery) has caused alarm in the general public. Drugs involved can be pharmaceuticals, such as benzodiazepines (flunitrazepam, lorazepam, etc.), hypnotics (zopiclone, zolpidem), sedatives (neuroleptics, some histamine H1-antagonists) or anaesthetics (@c-hydroxybutyrate, ketamine), drugs of abuse, such as cannabis, ecstasy or lysergide, or more often ethanol. Drugs said to be used to facilitate sexual assaults can be difficult to detect (active products at low dosages, chemical instability), possess amnesic properties and can be rapidly cleared from the body (short half-life). We present here a case involving a 23-year old girl that declared a sexual assault 6 days after the event was said to have occurred. To the Police, the victim claimed a total amnesia of the offense associated with intense sedation. Toxicological analyses for unknown sedative drugs achieved by LC-MS/MS revealed the presence of zolpidem (Stilnox), a non-benzodiazepine hypnotic. Concentrations after 6 days were 16 and 32 pg/mL in blood and urine, respectively. The drug tested also positive in the corresponding hair segment at 0.75 pg/mg. The requested extraordinary sensitivity of LC-MS/MS appears as a pre-requisite to document any case involving drug-facilitated sexual assault.

A novel strategy to generate thioester peptides compatible with Fmoc chemistry is presented. Peptide-C^αoxy-(2-mercapto-1-carboxyamide)ethyl ester undergoes an O to S acyl shift during ligation and the newly formed thioester intermediate reacts with an N-terminal cysteine fragment generating a product with native amide bond at the ligation site.

This report describes the use of the concept of inversion of hydropathy patterns to the de novo design of peptides targeted to a predetermined site on a protein. Eight- and 12-residue peptides were constructed with the EF hands or Ca(2+)-coordinating sites of calmodulin as their anticipated points of interaction. These peptides, but not unrelated peptides nor those with the same amino acid composition but a scrambled sequence, interacted with the two carboxyl-terminal Ca(2+)-binding sites of calmodulin as well as the EF hands of troponin C. The interactions resulted in a conformational change whereby the 8-mer peptide-calmodulin complex could activate phosphodiesterase in the absence of Ca(2+). In contrast, the 12-mer peptide-calmodulin complex did not activate phosphodiesterase but rather inhibited activation by Ca(2+). This inhibition could be overcome by high levels of Ca(2+). Thus, it would appear that the aforementioned concept can be used to make peptide agonists and antagonists that are targeted to predetermined sites on proteins such as calmodulin.

Expression of the modABCD operon in Escherichia coli, which codes for a molybdate-specific transporter, is repressed by ModE in vivo in a molybdate-dependent fashion. In vitro DNase I-footprinting experiments identified three distinct regions of protection by ModE-molybdate on the modA operator/promoter DNA, GTTATATT (-15 to -8; region 1), GCCTACAT (-4 to +4; region 2), and GTTACAT (+8 to +14; region 3). Within the three regions of the protected DNA, a pentamer sequence, TAYAT (Y = C or T), can be identified. DNA-electrophoretic mobility experiments showed that the protected regions 1 and 2 are essential for binding of ModE-molybdate to DNA, whereas the protected region 3 increases the affinity of the DNA to the repressor. The stoichiometry of this interaction was found to be two ModE-molybdate per modA operator DNA. ModE-molybdate at 5 nM completely protected the modABCD operator/promoter DNA from DNase I-catalyzed hydrolysis, whereas ModE alone failed to protect the DNA even at 100 nM. The apparent K(d) for the interaction between the modA operator DNA and ModE-molybdate was 0.3 nM, and the K(d) increased to 8 nM in the absence of molybdate. Among the various oxyanions tested, only tungstate replaced molybdate in the repression of modA by ModE, but the affinity of ModE-tungstate for modABCD operator DNA was 6 times lower than with ModE-molybdate. A mutant ModE(T125I) protein, which repressed modA-lac even in the absence of molybdate, protected the same region of modA operator DNA in the absence of molybdate. The apparent K(d) for the interaction between modA operator DNA and ModE(T125I) was 3 nM in the presence of molybdate and 4 nM without molybdate. The binding of molybdate to ModE resulted in a decrease in fluorescence emission, indicating a conformational change of the protein upon molybdate binding. The fluorescence emission spectra of mutant ModE proteins, ModE(T125I) and ModE(Q216*), were unaffected by molybdate. The molybdate-independent mutant ModE proteins apparently mimic in its conformation the native ModE-molybdate complex, which binds to a DNA sequence motif of TATAT-7bp-TAYAT.

Calcium activation of fast striated muscle results from an opening of the regulatory N-terminal domain of fast skeletal troponin C (fsTnC), and a substantial exposure of a hydrophobic patch, essential for Ca(2+)-dependent interaction with fast skeletal troponin I (fsTnI). This interaction is obligatory to relieve the inhibition of strong, force-generating actin-myosin interactions. We have determined intersite distances in the N-terminal domain of cardiac TnC (cTnC) by fluorescence resonance energy transfer measurements and found negligible increases in these distances when the single regulatory site is saturated with Ca(2+). However, in the presence of bound cardiac TnI (cTnI), activator Ca(2+) induces significant increases in the distances and a substantial opening of the N-domain. This open conformation within the cTnC.cTnI complex has properties favorable for the Ca(2+)-induced interaction with an additional segment of cTnI. Thus, the binding of cTnI to cTnC is a prerequisite to achieve a Ca(2+)-induced open N-domain similar to that previously observed in fsTnC with no bound fsTnI. This role of cardiac TnI has not been previously recognized. Our results also indicate that structural information derived from a single protein may not be sufficient for inference of a structure/function relationship.

One of the primary points of regulation of transforming growth factor-beta (TGF-beta) activity is control of its conversion from the latent precursor to the biologically active form. We have identified thrombospondin-1 as a major physiological regulator of latent TGF-beta activation. Activation is dependent on the interaction of a specific sequence in thrombospondin-1 (K412RFK415) with the latent TGF-beta complex. Platelet thrombospon-din-1 has TGF-beta activity and immunoreactive mature TGF-beta associated with it. We now report that the latency-associated peptide (LAP) of the latent TGF-beta complex also interacts with thrombospondin-1 as part of a biologically active complex. Thrombospondin.LAP complex formation involves the activation sequence of thrombospondin-1 (KRFK) and a sequence (LSKL) near the amino terminus of LAP that is conserved in TGF-beta1-5. The interactions of LAP with thrombospondin-1 through the LSKL and KRFK sequences are important for thrombospondin-mediated activation of latent TGF-beta since LSKL peptides can competitively inhibit latent TGF-beta activation by thrombospondin or KRFK-containing peptides. In addition, the association of LAP with thrombospondin-1 may function to prevent the re-formation of an inactive LAP.TGF-beta complex since thrombospondin-bound LAP no longer confers latency on active TGF-beta. The mechanism of TGF-beta activation by thrombospondin-1 appears to be conserved among TGF-beta isoforms as latent TGF-beta2 can also be activated by thrombospondin-1 or KRFK peptides in a manner that is sensitive to inhibition by LSKL peptides.

Summary This work is based on the microscopic study of 30 trochlear nerve trunks (15 heads). In 17 cases, the trunk arose from two nerve bundles, in 8 cases from one bundle, and for the other 5 nerves, three or four bundles. The mean total length of the trochlear nerve was 86 mm. The nerve may be separated into the 3 following parts: infratentorial, intracavernous, intraorbital. In all 30 cases studied, the first part of the nerve was infratentorial, thus leading us to suggest the term “infratentorial part” for this segment of the nerve. In 27 cases, contact was found with the superior cerebellar artery, in the infratentorial part. In the intracavernous part of ten nerves we found two rami tentorii and in eight cases fibers were exchanged with the ophthalmic nerve. In the orbit, 18 trochlear nerves crossed the posterior ethmoidal artery. 23 trochlear nerves ended on the medial face of the superior oblique muscle. The remaining 7 ended at the superior border of the muscle.

Post-stroke depression is a frequent complication of stroke that has detrimental consequences for quality of life and functional outcomes. Daily life routines may increase feelings of security for some individuals confronted with age-related health concerns, but little information is available concerning their role following stroke. The aim of this investigation was to examine the association of depression and other psychological variables at hospitalization for stroke and behavioral routines and mood symptoms three months later using Ecological Momentary Assessment (EMA).

La chirurgie de la cataracte est l’acte chirurgical le plus pratiqué en France et dans les pays occidentaux. Nous rapportons les disparités départementales de la chirurgie de cataracte primaire en 2015–2016 et l’évolution du nombre de séjours et des taux d’incidence entre 2008 et 2016.

A 25-year-old man sustained bilateral ocular trauma from an explosion, which resulted in ocular injuries from the blast, mineral projections, and heat. Before the accident, the patient had eight-incision radial keratotomy in the left eye followed 1 week later by photorefractive keratectomy in the right eye. After the accident, the left cornea had a full-thickness rupture of four incisions; the fellow cornea had a full-thickness laceration from a mineral projection. Five months after the accident, the left eye had an uncorrected visual acuity of 20/25; the right eye did not achieve an acuity of 20/200 until 20 months after the accident.