Enduring effects of prenatal cocaine exposure on selective attention and reactivity to errors: evidence from an animal model

Adult Long-Evans rats, exposed prenatally to 1 of 4 doses of cocaine (0.0,0.5,1.0, or 3.0 mg/kg iv), were tested on a 3-choice visual attention task with an olfactory distractor presented unpredictably on one third of the trials. The performance of all 3 cocaine-exposed groups was significantly more disrupted than that of controls by the presentation of distractors. Results demonstrate that prenatal cocaine exposure increases susceptibility to distractors, using a task specifically designed to measure this function. In addition, the present study revealed that individuals exposed to cocaine in utero exhibit greater performance disruption after an error than controls, in certain types of tasks. Both areas of dysfunction, impaired selective attention and impaired arousal regulation, have important functional consequences in humans, possibly affecting the school performance and social development of cocaine-exposed children.     

Streptococcus pyogenes infection in mouse skin leads to a time-dependent up-regulation of protein H expression

Streptococcus pyogenes protein H (sph) is an immunoglobulin-binding protein present in the Mga regulon of certain M1 serotype isolates. Although sph is present in many strains, it is frequently not expressed. In this paper we show that protein H was highly expressed after bacteria were injected into the skin of mice and were recovered from the blood, kidney, or spleen at various times postinfection. The percentage of protein H-positive colonies increased with time, reaching 100% in the spleen and kidney within 24 to 72 h postinfection. The up-regulation of sph expression was also observed in a mga mutant.     

<Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis> Ats1p interacts with Nap1p,a cytoplasmic protein that controls bud morphogenesis

Saccharomyces cerevisiae ATS1 (-tubulin suppressor 1) was originally identified as a high-copy suppressor of class two -tubulin mutations and was proposed to have a regulatory role in coordinating the microtubule state with the cell cycle. Here, we show that Ats1p interacts with Nap1p, a cytoplasmic protein that regulates the activity of the Cdc28p/Clb2p complex. Loss of Nap1p results in a delayed switch from polar to isotropic bud growth. The delayed switch results in elongated buds. Nap1p and Ats1p interact in two-hybrid and co-immunoprecipitation assays. Both nap1 and ats1 cells have a Clb2p-dependent elongated bud morphology. Deletion of ATS1 partially suppresses the elongated bud morphology and benomyl resistance of nap1 mutants. Our results suggest Ats1p might regulate coordination of the microtubule state with the cell cycle through an interaction with Nap1p.Communicated by S. Hohmann     

A phase 3, randomized,double-blind,parallel-group study to evaluate tezacaftor/ivacaftor in people with cystic fibrosis heterozygous for F508del-CFTR and a gating mutation

BackgroundTezacaftor (TEZ)/ivacaftor (IVA) is an approved CFTR modulator shown to be efficacious and generally safe and well tolerated in people ≥12 years of age with cystic fibrosis (CF) homozygous for the F508del-CFTR mutation or heterozygous for the F508del-CFTR mutation and a residual function mutation. Although previous studies with IVA alone showed clinical benefits in people with CFTR gating mutations, TEZ/IVA has not yet been evaluated in a Phase 3 study of participants heterozygous for F508del-CFTR and a gating mutation (F/gating genotypes). Here, we present results from a randomized, double-blind, IVA-controlled, parallel-group, Phase 3 study assessing the efficacy, safety, and pharmacokinetics (PK) of TEZ/IVA in participants ≥12 years of age with F/gating genotypes.MethodsEnrolled participants entered a 4-week IVA run-in period to create a stable IVA baseline. Participants were then randomized to receive IVA or TEZ/IVA for 8 weeks in an active comparator treatment period (ACTP). The primary endpoint was absolute change in percent predicted forced expiratory volume in 1 second (ppFEV₁). Key secondary endpoints were relative change in ppFEV₁ and absolute change in CF Questionnaire–Revised respiratory domain score. Secondary endpoints included absolute change in sweat chloride (SwCl) concentration, PK parameters, and safety. All endpoints except PK parameters and safety were assessed from baseline through Week 8.ResultsSixty-nine participants (92.0%) in the IVA group and 75 participants (98.7%) in the TEZ/IVA group completed treatment. No improvements were seen in efficacy endpoints from baseline at the end of the IVA run-in period through the end of the ACTP in the IVA group. No significant differences in ppFEV₁ or any key secondary endpoint were observed between the IVA and TEZ/IVA groups. SwCl concentrations decreased more in the TEZ/IVA versus IVA group during the ACTP. The safety profile and PK parameters of TEZ/IVA were consistent with those of previous studies in participants ≥12 years of age with CF.ConclusionsThis Phase 3 study showed that the dual-combination regimen of TEZ/IVA demonstrated clinical efficacy but did not have significantly greater clinical efficacy than IVA alone in participants ≥12 years of age with F/gating genotypes. However, as reported in other studies, TEZ/IVA was generally safe and well tolerated (NCT02412111).     

Diphenylhydantoin-induced pure red cell aplasia after neurological surgery: report of two cases

Pure red cell aplasia (PRCA) is characterized by severe anemia, reticulocytopenia, marked selective hypoplasia of the erythroid precursor cells in the bone marrow and normal peripheral leukocyte and platelet counts. We reported two cases of diphenylhydantoin (DPH)-induced PRCA after neurological surgery. They recovered completely with discontinuance of DPH therapy. Neurosurgeons should be aware of this side effect because most reported cases of PRCA have occurred about a few months after neurological surgery under general anaesthesia and DPH therapy.     

Effectiveness and safety of loop electrosurgical excision procedure in a low-resource setting

Objective

To evaluate the effectiveness and safety of the loop electrosurgical excision procedure (LEEP) to treat cervical intraepithelial neoplasia (CIN) in a low-resource setting.

Methods

Women participating in a cervical screening study in India with histologically confirmed CIN unsuitable for cryotherapy were advised to undergo LEEP. One year after treatment the cervix was visually inspected with acetic acid, followed by colposcopy and biopsy taken from abnormal areas. Cure was defined as no clinical or histologic evidence of CIN. Factors influencing cure rates were evaluated by ^χ2 tests.

Results

Of the 311 women who underwent LEEP, 283 reported for 1-year follow-up and 248 (87.6%) were disease free. Cure rates were 93.0% for CIN 1, 85.5% for CIN 2, and 72.7% for CIN 3. Minor adverse effects were observed in 34 women and complications were seen in 5 women.

Conclusion

LEEP was associated with minimal complications and acceptable cure rates in a low-resource setting, although women with larger lesions had lower cure rates.