Cytomegalovirus Genetic Diversity Following Primary Infection.

BACKGROUND: Infection with multiple cytomegalovirus (CMV) strains (mixed infection) was reported in a variety of hosts. As the virus genetic diversity in primary CMV infection and the changes over time remain incompletely defined, we examined CMV diversity and changes in diversity over time in healthy adolescent females who participated in a phase 2 CMV gB/MF59 vaccine trial. METHODS: CMV genetic diversity was determined by genotyping of 5 genes-gB (UL55), gH (UL75), gN (UL73), US28, and UL144-in urine, saliva, and plasma samples from 15 study subjects. RESULTS: At the time of primary infection, 5 of 12 (42%) urine samples had multiple virus strains, and 50% of vaccine recipients were infected with gB1 genotype (vaccine strain). Mixed infection was documented in all 15 subjects within 3 months after primary infection, and the majority had different CMV genotypes in different compartments. Changes in genotypes over time were observed in all subjects. CONCLUSIONS: Infection with multiple CMV genotypes was common during primary infection and further diversification occurred over time. Infection with gB1 genotype in vaccine recipients suggests a lack of strain-specific protection from the vaccine. As only 5 polymorphic genes were assessed, this study likely underestimated the true genetic diversity in primary CMV infection.

Emergence of categorical face perception after extended early-onset blindness.

It is unknown whether the ability to visually distinguish between faces and nonfaces is subject to a critical period during development. Would a congenitally blind child who gains sight several years after birth be able to acquire this skill? This question has remained unanswered because of the rarity of cases of late sight onset. We had the opportunity to work with five early-blind individuals who gained sight late in childhood after treatment for dense bilateral cataracts. We tested their ability to categorize patterns as faces, using natural images that spanned a spectrum of face semblance. The results show that newly sighted individuals are unable to distinguish between faces and nonfaces immediately after sight onset, but improve markedly in the following months. These results demonstrate preserved plasticity for acquiring face/nonface categorization ability even late in life, and set the stage for investigating the informational and neural basis of this skill acquisition.

BRAF inhibitor and hairy cell leukemia-related transient acantholytic dermatosis.

Grover disease (GD) is an acquired, nonfamilial, nonimmune mediated, transient or persistent acantholytic dermatosis. Herein, we present a 72-year-old man who had clinical and histopathologic findings of GD following two weeks of treatment with vemurafenib without MEK inhibitor. The patient was successfully treated with topical emollients and a high-potency corticosteroid. Meanwhile, vemurafenib was temporarily discontinued. Drug-induced GD has increasingly been reported in patients on BRAF inhibitor monotherapy as an immune-related adverse event. The cutaneous side effects seem to arise secondary to a paradoxical activation of the mitogen-activated protein kinase signaling of BRAF inhibitor treatment, leading to keratinocyte proliferation. Although the pathogenesis of GD has not been delineated, there is suggestion of activation of T lymphocytes, particularly helper cells under the action of pro-inflammatory cytokines, resulting in proliferation of keratinocytes. Combination therapy with a MEK inhibitor appears to prevent BRAF-induced GD. Given that there is a higher prevalence of GD in patients with hematologic malignancy, a direct causal relationship between the initiation of vemurafenib therapy and development of GD in this case may be difficult to establish.

Mechanisms underlying simultaneous brightness contrast: Early and innate.

In the phenomenon of simultaneous brightness contrast, two patches, one on a dark background and the other on a light one, appear to have different brightness despite being physically equi-luminant. Elucidating the phenomenon's underlying mechanisms is relevant for the larger question of how the visual system makes photometric judgments in images. Accounts over the past century have spanned low-, mid- and high-level visual processes, but a definitive resolution has not emerged. We present three studies that collectively demonstrate that the computations underlying this phenomenon are low-level, instantiated prior to binocular fusion, and available innately, without need for inferential learning via an individual's visual experience. In our first two studies, we find that strong brightness induction is obtained even when observers are unaware of any luminance differences in the neighborhoods of the probe patches. Results with dichoptic displays reveal that eye of origin, although not evident consciously, has a marked influence on the eventual brightness percept of the probe patches, thereby localizing brightness estimation to a site preceding binocular fusion. The third study uses conventional simultaneous brightness contrast displays, but an unusual group of participants: Congenitally blind children whom we were able to treat surgically. The results demonstrate an immediate susceptibility to the simultaneous brightness illusion after sight onset. Together, these data strongly constrain the search for mechanisms underlying a fundamental brightness phenomenon.

Why Does the Cortex Reorganize after Sensory Loss?

A growing body of evidence demonstrates that the brain can reorganize dramatically following sensory loss. Although the existence of such neuroplastic crossmodal changes is not in doubt, the functional significance of these changes remains unclear. The dominant belief is that reorganization is compensatory. However, results thus far do not unequivocally indicate that sensory deprivation results in markedly enhanced abilities in other senses. Here, we consider alternative reasons besides sensory compensation that might drive the brain to reorganize after sensory loss. One such possibility is that the cortex reorganizes not to confer functional benefits, but to avoid undesirable physiological consequences of sensory deafferentation. Empirical assessment of the validity of this and other possibilities defines a rich program for future research.

Multiplex real-time RT-PCR for the simultaneous detection and quantification of GI, GII and GIV noroviruses.

Noroviruses are important causes of acute gastroenteritis and are classified into six genogroups with GI, GII and GIV containing human pathogens. This high genetic diversity represents a significant challenge for diagnostic assay development. Genogroup specific monoplex and multiplex real time RT-PCR assays are widely used for the detection of GI and GII noroviruses. On the other hand, GIV norovirus detection is not part of routine laboratory diagnosis. This study describes the development and evaluation of a one tube, real time RT-PCR assay for the simultaneous detection and quantification of GI, GII and GIV noroviruses, including both GIV.1 (human) and GIV.2 (animal) strains. Assay performance was evaluated on a panel of norovirus positive clinical samples by comparison of monoplex and multiplex standard curves and Ct values. The multiplex assay demonstrated equal sensitivity and specificity to the monoplex assays and was able to detect all GI, GII and GIV noroviruses with Ct values equal to that of the monoplex assays. The multiplex assay described in this study will be instrumental for the better understanding of GIV norovirus epidemiology, including their possible zoonotic nature.