Psychometrics of the scale of attitudes toward physician-pharmacist collaboration: a study with medical students.

BACKGROUND: Despite the emphasis placed on interdisciplinary education and interprofessional collaboration between physicians and pharmacologists, no psychometrically sound instrument is available to measure attitudes toward collaborative relationships. AIM: This study was designed to examine psychometrics of an instrument for measuring attitudes toward physician-pharmacist collaborative relationships for administration to students in medical and pharmacy schools and to physicians and pharmacists. METHODS: The Scale of Attitudes Toward Physician-Pharmacist Collaboration was completed by 210 students at Jefferson Medical College. Factor analysis and correlational methods were used to examine psychometrics of the instrument. RESULTS: Consistent with the conceptual framework of interprofessional collaboration, three underlying constructs, namely responsibility and accountability; shared authority; and interdisciplinary education emerged from the factor analysis of the instrument providing support for its construct validity. The reliability coefficient alpha for the instrument was 0.90. The instrument\u27s criterion-related validity coefficient with scores of a validated instrument (Jefferson Scale of Attitudes Toward Physician-Nurse Collaboration) was 0.70. CONCLUSIONS: Findings provide support for the validity and reliability of the instrument for medical students. The instrument has the potential to be used for the evaluation of interdisciplinary education in medical and pharmacy schools, and for the evaluation of patient outcomes resulting from collaborative physician-pharmacist relationships

Xeroderma pigmentosum: overview of pharmacology and novel therapeutic strategies for neurological symptoms

Xeroderma Pigmentosum (XP) encompasses a group of rare diseases characterised in most cases by nucleotide excision repair (NER) malfunction, resulting in an increased sensitivity to ultraviolet radiation in affected individuals. Approximately 25-30% of XP patients present with neurological symptoms, such as sensorineural deafness, mental deterioration, and ataxia. Although it is known that dysfunctional DNA repair is the primary pathogenesis in XP, growing evidence suggests that mitochondrial pathophysiology may also occur. This appears to be secondary to dysfunctional NER but may contribute to the neurodegenerative process in these patients. The available pharmacological treatments in XP mostly target the dermal manifestations of the disease. In the present review, we outline how current understanding of the pathophysiology of XP could be used to develop novel therapies to counteract the neurological symptoms. Moreover, the coexistence of cancer and neurodegeneration present in XP, lead us to focus on possible new avenues targeting mitochondrial pathophysiology

Direct contribution of the sensory cortex to the judgment of stimulus duration

Decision making frequently depends on monitoring the duration of sensory events. To determine whether, and how, the perception of elapsed time derives from the neuronal representation of the stimulus itself, we recorded and optogenetically modulated vibrissal somatosensory cortical activity as male rats judged vibration duration. Perceived duration was dilated by optogenetic excitation. A second set of rats judged vibration intensity; here, optogenetic excitation amplified the intensity percept, demonstrating sensory cortex to be the common gateway both to time and to stimulus feature processing. A model beginning with the membrane currents evoked by vibrissal and optogenetic drive and culminating in the representation of perceived time successfully replicated rats' choices. Time perception is thus as deeply intermeshed within the sensory processing pathway as is the sense of touch itself, suggesting that the experience of time may be further investigated with the toolbox of sensory coding

Transformation of Perception from Sensory to Motor Cortex

To better understand how a stream of sensory data is transformed into a percept, we examined neuronal activity in vibrissal sensory cortex, vS1, together with vibrissal motor cortex, vM1 (a frontal cortex target of vS1), while rats compared the intensity of two vibrations separated by an interstimulus delay. Vibrations were “noisy,” constructed by stringing together over time a sequence of velocity values sampled from a normal distribution; each vibration’s mean speed was proportional to the width of the normal distribution. Durations of both stimulus 1 and stimulus 2 could vary from 100 to 600 ms. Psychometric curves reveal that rats overestimated the longer-duration stimulus—thus, perceived intensity of a vibration grew over the course of hundreds of milliseconds even while the sensory input remained, on average, stationary. Human subjects demonstrated the identical perceptual phenomenon, indicating that the underlying mechanisms of temporal integration generalize across species. The time dependence of the percept allowed us to ask to what extent neurons encoded the ongoing stimulus stream versus the animal’s percept. We demonstrate that vS1 firing correlated with the local features of the vibration, whereas vM1 firing correlated with the percept: the final vM1 population state varied, as did the rat’s behavior, according to both stimulus speed and stimulus duration. Moreover, vM1 populations appeared to participate in the trace of the percept of stimulus 1 as the rat awaited stimulus 2. In conclusion, the transformation of sensory data into the percept appears to involve the integration and storage of vS1 signals by vM1

Transcription restores DNA repair to heterochromatin, determining regional mutation rates in cancer genomes

SummarySomatic mutations in cancer are more frequent in heterochromatic and late-replicating regions of the genome. We report that regional disparities in mutation density are virtually abolished within transcriptionally silent genomic regions of cutaneous squamous cell carcinomas (cSCCs) arising in an XPC−/− background. XPC−/− cells lack global genome nucleotide excision repair (GG-NER), thus establishing differential access of DNA repair machinery within chromatin-rich regions of the genome as the primary cause for the regional disparity. Strikingly, we find that increasing levels of transcription reduce mutation prevalence on both strands of gene bodies embedded within H3K9me3-dense regions, and only to those levels observed in H3K9me3-sparse regions, also in an XPC-dependent manner. Therefore, transcription appears to reduce mutation prevalence specifically by relieving the constraints imposed by chromatin structure on DNA repair. We model this relationship among transcription, chromatin state, and DNA repair, revealing a new, personalized determinant of cancer risk

Evaluation of sesamum gum as an excipient in matrix tablets

In developing countries modern medicines are often beyond the affordability of the majority of the population. This is due to the reliance on expensive imported raw materials despite the abundance of natural resources which could provide an equivalent or even an improved function. The aim of this study was to investigate the potential of sesamum gum (SG) extracted from the leaves of Sesamum radiatum (readily cultivated in sub-Saharan Africa) as a matrix former. Directly compressed matrix tablets were prepared from the extract and compared with similar matrices of HPMC (K4M) using theophylline as a model water soluble drug. The compaction, swelling, erosion and drug release from the matrices were studied in deionized water, 0.1 N HCl (pH 1.2) and phosphate buffer (pH 6.8) using USP apparatus II. The data from the swelling, erosion and drug release studies were also fitted into the respective mathematical models. Results showed that the matrices underwent a combination of swelling and erosion, with the swelling action being controlled by the rate of hydration in the medium. SG also controlled the release of theophylline similar to the HPMC and therefore may have use as an alternative excipient in regions where Sesamum radiatum can be easily cultivated

100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care — Preliminary Report

BACKGROUND: The U.K. 100,000 Genomes Project is in the process of investigating the role of genome sequencing in patients with undiagnosed rare diseases after usual care and the alignment of this research with health care implementation in the U.K. National Health Service. Other parts of this project focus on patients with cancer and infection. METHODS: We conducted a pilot study involving 4660 participants from 2183 families, among whom 161 disorders covering a broad spectrum of rare diseases were present. We collected data on clinical features with the use of Human Phenotype Ontology terms, undertook genome sequencing, applied automated variant prioritization on the basis of applied virtual gene panels and phenotypes, and identified novel pathogenic variants through research analysis. RESULTS: Diagnostic yields varied among family structures and were highest in family trios (both parents and a proband) and families with larger pedigrees. Diagnostic yields were much higher for disorders likely to have a monogenic cause (35%) than for disorders likely to have a complex cause (11%). Diagnostic yields for intellectual disability, hearing disorders, and vision disorders ranged from 40 to 55%. We made genetic diagnoses in 25% of the probands. A total of 14% of the diagnoses were made by means of the combination of research and automated approaches, which was critical for cases in which we found etiologic noncoding, structural, and mitochondrial genome variants and coding variants poorly covered by exome sequencing. Cohortwide burden testing across 57,000 genomes enabled the discovery of three new disease genes and 19 new associations. Of the genetic diagnoses that we made, 25% had immediate ramifications for clinical decision making for the patients or their relatives. CONCLUSIONS: Our pilot study of genome sequencing in a national health care system showed an increase in diagnostic yield across a range of rare diseases. (Funded by the National Institute for Health Research and others.)

Germline selection shapes human mitochondrial DNA diversity.

Approximately 2.4% of the human mitochondrial DNA (mtDNA) genome exhibits common homoplasmic genetic variation. We analyzed 12,975 whole-genome sequences to show that 45.1% of individuals from 1526 mother-offspring pairs harbor a mixed population of mtDNA (heteroplasmy), but the propensity for maternal transmission differs across the mitochondrial genome. Over one generation, we observed selection both for and against variants in specific genomic regions; known variants were more likely to be transmitted than previously unknown variants. However, new heteroplasmies were more likely to match the nuclear genetic ancestry as opposed to the ancestry of the mitochondrial genome on which the mutations occurred, validating our findings in 40,325 individuals. Thus, human mtDNA at the population level is shaped by selective forces within the female germ line under nuclear genetic control, which ensures consistency between the two independent genetic lineages.NIHR, Wellcome Trust, MRC, Genomics Englan