Mutations in mtDNA: Are We Scraping the Bottom of the Barrel?

The small, maternally inherited mtDNA has turned out to be a Pandora's box of pathogenic mutations: 12 years into the era of "mitochondrial medicine," about 100 pathogenic point mutations and innumerable rearrangements have been associated with a bewildering variety of multisystemic as well as tissue-specific human diseases. After reviewing the principles of mitochondrial genetics, we compare and contrast the clinical and pathological features of disorders due to mutations in genes affecting mitochondrial protein synthesis with those of mutations in protein-coding genes. In contrast to the striking progress in our understanding of etiology, pathogenesis is only partially explained by the rules of mitochondrial genetics and remains largely terra incognita. We review recent progress in prenatal diagnosis and epidemiology. Therapy is still woefully inadequate, but a number of promising approaches are being developed.     

The Genetic Basis of Emotional Behavior: Has the Time Come for a Drosophila Model?

Abstract: The aim of this review was to summarize the studies potentially relevant to whether Drosophila can be used as a genetically tractable model to study the genetic and molecular basis of emotional behavior. Can these studies contribute to a better understanding of neural substrates of abnormal emotional states and specific neuropsychiatric illnesses, such as depression and anxiety?     

Global Eradication of Measles: Are We Poised?

Measles, a highly infectious viral disease is the next target for eradication following poliovirus. Decades of experience with highly effective vaccination has invigorated us to take on this virus. The task is not only Titanic but is laced with intricate issues. Recently, an outbreak of fever with rash occurred on a tertiary care teaching hospital campus and was confirmed serologically as measles outbreak by IgMELISA. Therefore, we searched the literature related to outbreaks, transmission of the measles virus, age groups involved, vaccination strategies, vaccination failure and epidemiological features of the disease and reviewed the possible reasons for such outbreaks and problems in the global eradication of the virus.     

Outbreak of Colistin-Resistant,Carbapenemase-Producing Klebsiella pneumoniae: Are We at the End of the Road?

Carbapenem-resistant Klebsiella pneumoniae strains that produce K. pneumoniae carbapenemase (KPC) have spread globally in the last decade. Colistin is a key agent in treating infections caused by this pathogen. In this issue of the Journal of Clinical Microbiology, Giani et al. (T. Giani, F. Arena, G. Vaggelli, V. Conte, A Chiarell, L. H. De Angelis, R. Fornaini, M. Grazzini, F. Niccolini, P. Pecile, and G. M. Rossolini, J Clin Microbiol 53:3341–3344, 2015, http://dx.doi.org/10.1128/JCM.01017-15) describe a sustained outbreak of colistin-resistant KPC-producing K. pneumoniae.     

Genetic basis of Sjögren's syndrome. How strong is the evidence?

Sj?gren's syndrome (SS) is a late-onset chronic autoimmune disease (AID) affecting the exocrine glands, mainly the salivary and lachrymal. Genetic studies on twins with primary SS have not been performed, and only a few case reports describing twins have been published. The prevalence of primary SS in siblings has been estimated to be 0.09% while the reported general prevalence of the disease is approximately 0.1%. The observed aggregation of AIDs in families of patients with primary SS is nevertheless supportive for a genetic component in its etiology. In the absence of chromosomal regions identified by linkage studies, research has focused on candidate gene approaches (by biological plausibility) rather than on positional approaches. Ancestral haplotype 8.1 as well as TNF, IL10 and SSA1 loci have been consistently associated with the disease although they are not specific for SS. In this review, the genetic component of SS is discussed on the basis of three known observations: (a) age at onset and sex-dependent presentation, (b) familial clustering of the disease, and (c) dissection of the genetic component. Since there is no strong evidence for a specific genetic component in SS, a large international and collaborative study would be suitable to assess the genetics of this disorder.     

Genetic Covariation Between the Author Recognition Test and Reading and Verbal Abilities: What Can We Learn from the Analysis of High Performance?

The Author Recognition Test (ART) measures print exposure and is a unique predictor of phonological and orthographic processes in reading. In a sample of adolescent and young adult twins and siblings (216 MZ/430 DZ pairs, 307 singletons; aged 11–29 years) ART scores were moderately heritable (67%) and correlated with reading and verbal abilities, with genes largely accounting for the covariance. We also examine whether high (and low) (i.e. 1SD above the mean) represents a quantitative extreme of the normal distribution. Heritability for high ART was of similar magnitude to the full sample, but, a specific genetic factor, independent from both low ART performance and high reading ability, accounted for 53–58% of the variance. This suggests a distinct genetic etiology for high ART ability and we speculate that the specific genetic influence is on orthographical processing, a critical factor in developing word recognition skills. Edited by Robert Plomin.     

Understanding the viridians group streptococci: Are we there yet?

The viridans group streptococci are a heterogeneous group of organisms which exist as commensals in the oropharynx and the gut. They cause serious infections when they gain entry into sterile sites particularly in patients with predisposing conditions. Classification and species differentiation of these organisms has always been a challenge because of phenotypic differences between strains of the same species. Facklam’s typing scheme based on six metabolic properties has been the most widely used and many commercial identification systems are based on it. Due to the ambiguity in species differentiation based on phenotypic tests, nucleic acid-based methods have been developed to improve the identification of these organisms. Results using genotypic methods such as 16S rRNA and sodA gene sequencing have been promising. Multilocus sequence analysis of seven house-keeping genes map, pfl, pyk, ppaC, rpoB, soda and tuf amplified by polymerase chain reaction was found to be an accurate alternative to other methods and could be useful in the characterisation of larger collections of isolates.     

Are We Doing Our Homework?

[Clin Psychol Sci Prac 17: 162–165, 2010] Kazantzis, Whittington, and Dattilio (2010 ) provide convincing evidence for the role of homework in effective psychotherapy. Homework is a common element of many empirically supported treatments for a variety of clinical problems, but we cannot assume that homework is used commonly in routine, community‐based psychotherapy. This commentary reviews emerging data on the use of homework in routine care for childhood behavioral disorders, and identifies potential barriers of use as well as research priorities to address these barriers.     

Chimeric Antigen Receptor Therapy: How Are We Driving in Solid Tumors?

Immune effector cell (IEC) therapy is emerging as a promising approach in the field of cancer immunotherapy. Clinical IEC trials, predominantly using chimeric antigen receptor (CAR) T cells, have shown excellent responses in CD19⁺ B cell malignancies and multiple myeloma. In solid tumors, preclinical data are encouraging, but clinical data are in their infancy, and there are challenges in using CAR T therapy in this setting, including (1) on-target off-tumor toxicity, (2) optimal target identification, (3) effective trafficking into bulky tumor tissue, and (4) resistance to tumor immune evasion mechanisms.Novel techniques and modifications are being explored in both the preclinical and clinical settings, aiming to improve treatment efficacy and address the aforementioned obstacles to successful CAR T therapy in solid tumors. Here we review these challenges in a clinically oriented approach and summarize published clinical trials using CAR T therapy in a variety of solid tumors.     

“Far from the heart far from the eye”: Evidence from the Capgras delusion

Introduction. Capgras syndrome is characterised by the belief that a significant other has been replaced by an identical-looking impostor. These patients have no difficulties with visual recognition but fail to show a skin conductance response (SCR) to the objects of the delusion. A case of Capgras delusion (YY), specifically characterised by the absence of brain lesions, constituted a good opportunity to test the relationship between SCR hyporesponsiveness and eye movement patterns to familiar and unfamiliar faces.

Methods. Visual scan path and SCR were recorded for YY and 8 controls during the presentation of family members’ photographs matched with unfamiliar faces of the same sex, age, and physical likeness. Eye movement patterns were explored by selecting three specific areas of interest (AOI) involving the eyes, the mouth, and the face regions.

Results. In contrast with controls, YY showed a reduction in number and sum of fixation durations to the eyes (p<.01) and no differential SCRs (p>.05) to familiar vs. nonfamiliar faces. SCR and fixation duration to family members’ eyes were significantly correlated (r=.77) in both YY and controls.

Conclusions. Eye region exploration seems to be related to the autonomic reactivity elicited by the affective valence of familiar faces.     

Radiology Reporting in the Era of Patient-Centered Care: How Can We Improve Readability?

Radiology reports are consumed not only by referring physicians and healthcare providers, but also by patients. We assessed report readability in our enterprise and implemented a two-part quality improvement intervention with the goal of improving report accessibility. A total of 491,813 radiology reports from ten hospitals within the enterprise from May to October, 2018 were collected. We excluded echocardiograms, rehabilitation reports, administrator reports, and reports with negative scores leaving 461,219 reports and report impressions for analysis. A grade level (GL) was calculated for each report and impression by averaging four readability metrics. Next, we conducted a readability workshop and distributed weekly emails with readability GLs over a period of 6 months to each attending radiologist at our primary institution. Following this intervention, we utilized the same exclusion criteria and analyzed 473,612 reports from May to October, 2019. The mean GL for all reports and report impressions was above 13 at every hospital in the enterprise. Following our intervention, a statistically significant drop in GL for reports and impressions was demonstrated at all locations, but a larger and significant improvement was observed in impressions at our primary site. Radiology reports across the enterprise are written at an advanced reading level making them difficult for patients and their families to understand. We observed a significantly larger drop in GL for impressions at our primary site than at all other sites following our intervention. Radiologists at our home institution improved their report readability after becoming more aware of their writing practices.