The prescribing of prisms in clinical practice

The use of prisms in cases of decompensated heterophoria is an established treatment modality. The clinical literature lacks consensus upon the appropriate use of prisms, and fails to provide the necessary evidence base. While the experimental literature can guide the practitioner, the lack of double-blind, placebo-controlled clinical studies needs to be addressed

Mu Insertions Are Repaired by the Double-Strand Break Repair Pathway of Escherichia coli

Mu is both a transposable element and a temperate bacteriophage. During lytic growth, it amplifies its genome by replicative transposition. During infection, it integrates into the Escherichia coli chromosome through a mechanism not requiring extensive DNA replication. In the latter pathway, the transposition intermediate is repaired by transposase-mediated resecting of the 5′ flaps attached to the ends of the incoming Mu genome, followed by filling the remaining 5 bp gaps at each end of the Mu insertion. It is widely assumed that the gaps are repaired by a gap-filling host polymerase. Using the E. coli Keio Collection to screen for mutants defective in recovery of stable Mu insertions, we show in this study that the gaps are repaired by the machinery responsible for the repair of double-strand breaks in E. coli—the replication restart proteins PriA-DnaT and homologous recombination proteins RecABC. We discuss alternate models for recombinational repair of the Mu gaps

Expression of V1A and GRP receptors leads to cellular transformation and increased sensitivity to substance-P analogue-induced growth inhibition.

Small-cell lung cancer (SCLC) is a particularly aggressive cancer, which metastasises early. Despite initial sensitivity to radio- and chemo-therapy, it invariably relapses, so that the 2-year survival remains less than 5%. Neuropeptides particularly arginine vasopressin (AVP) and gastrin-releasing peptide (GRP) act as autocrine and paracrine growth factors and the expression of these and their receptors are a hallmark of the disease. Substance-P analogues including [D-Arg1,D-Phe5,D-Trp7,9,Leu11]-substance-P (SP-D) and [Arg6,D-Trp7,9,NmePhe8]-substance-P (6-11) (SP-G) inhibit the growth of SCLC cells by modulating neuropeptide signalling. We show that GRP and V1A receptors expression leads to the development of a transformed phenotype. Addition of neuropeptide provides some protection from etoposide-induced cytotoxicity. Receptor expression also leads to an increased sensitivity to substance-P analogue-induced growth inhibition. We show that SP-D and SP-G act as biased agonists at GRP and V1A receptors causing blockade of Gq-mediated Ca2+ release while directing signalling to activate ERK via a pertussis toxin-sensitive pathway. This is the first description of biased agonism at V1A receptors. This unique pharmacology governs the antiproliferative properties of these agents and highlights their potential therapeutic potential for the treatment of SCLC and particularly in tumours, which have developed resistance to chemotherapy

Prognostic Factors of Long Term Disability Due to Mental Disorders: A Systematic Review

Introduction In the past few decades, mental health problems have increasingly contributed to sickness absence and long-term disability. However, little is known about prognostic factors of return to work (RTW) and disability of persons already on sick leave due to mental health problems. Understanding these factors may help to develop effective prevention and intervention strategies to shorten the duration of disability and facilitate RTW. Method We reviewed systematically current scientific evidence about prognostic factors for mental health related long term disability, RTW and symptom recovery. Searching PubMed, PsycINFO, Embase, Cinahl and Business Source Premier, we selected articles with a publication date from January 1990 to March 2009, describing longitudinal cohort studies with a follow-up period of at least 1 year. Participants were persons on sick leave or receiving disability benefit at baseline. We assessed the methodological quality of included studies using an established criteria list. Consistent findings in at least two high quality studies were defined as strong evidence and positive findings in one high quality study were defined as limited evidence. Results Out of 796 studies, we included seven articles, all of high methodological quality describing a range of prognostic factors, according to the ICF-model categorized as health-related, personal and external factors. We found strong evidence that older age (>50 years) is associated with continuing disability and longer time to RTW. There is limited evidence for the association of other personal factors (gender, education, history of previous sickness absence, negative recovery expectation, socio-economic status), health related (stress-related and shoulder/back pain, depression/anxiety disorder) and external i.e., job-related factors (unemployment, quality and continuity of occupational care, supervisor behavior) with disability and RTW. We found limited evidence for the association of personal/external factors (education, sole breadwinner, partial/full RTW, changing work tasks) with symptom recovery. Conclusion This systematic review identifies a number of prognostic factors, some more or less consistent with findings in related literature (mental health factors, age, history of previous sickness absence, negative recovery expectation, socio-economic status, unemployment, quality and continuity of occupational care), while other prognostic factors (gender, level of education, sole breadwinner, supervisor support) conflict with existing evidence. There is still great need for research on modifiable prognostic factors of continuing disability and RTW among benefit claimants with mental health problems. Recommendations are made as to directions and methodological quality of further research, i.e., prognostic cohort studies

The effect of electroporation pulses on functioning of the heart

Electrochemotherapy is an effective antitumor treatment currently applied to cutaneous and subcutaneous tumors. Electrochemotherapy of tumors located close to the heart could lead to adverse effects, especially if electroporation pulses were delivered within the vulnerable period of the heart or if they coincided with arrhythmias of some types. We examined the influence of electroporation pulses on functioning of the heart of human patients by analyzing the electrocardiogram. We found no pathological morphological changes in the electrocardiogram; however, we demonstrated a transient RR interval decrease after application of electroporation pulses. Although no adverse effects due to electroporation have been reported so far, the probability for complications could increase in treatment of internal tumors, in tumor ablation by irreversible electroporation, and when using pulses of longer durations. We evaluated the performance of our algorithm for synchronization of electroporation pulse delivery with electrocardiogram. The application of this algorithm in clinical electroporation would increase the level of safety for the patient and suitability of electroporation for use in anatomical locations presently not accessible to existing electroporation devices and electrodes