Interprofessional Collaboration: Differentiating Netherton Syndrome and Atopic Dermatitis in an African American Infant.

Netherton syndrome is a rare, autosomal recessive disorder that clinically presents with a triad of congenital ichthyosiform erythroderma, hair shaft abnormalities, and immune dysregulation, which is confirmed with genetic testing for mutations in the serine protease inhibitor Kazal-type 5 (SPINK5) gene. This diagnosis was included in our differential due to the patient's recurring and unimproving rash with desquamating skin. While eczema was included in our differential diagnoses, the patient's systemic symptoms, including failure to thrive, prompted our team to consider other diagnoses. This patient endured numerous treatments and diagnostic tests to eliminate underlying immunodeficiencies and autoinflammatory diseases. In this case report, we present a two-month-old male who was originally brought into the outpatient pediatric clinic for severe eczema, periorbital swelling, and failure to thrive. The patient returned with a continuing exudative rash after amoxicillin suspension treatment and was ultimately hospitalized for IV antibiotic treatment. The patient was then transferred to multiple hospitals for treatment and final diagnosis of severe seborrheic dermatitis and atopic dermatitis. Multiple inpatient hospitals and outpatient clinics had to collaborate and communicate effectively to reach a diagnosis. The diagnosis for this patient was found after a true display of the value of interdisciplinary collaboration as several outpatient clinics and inpatient hospitals worked together for this outcome.

Metabolic and behavioral alterations associated with viral vector-mediated toxicity in the paraventricular hypothalamic nucleus.

OBJECTIVE: Combining adeno-associated virus (AAV)-mediated expression of Cre recombinase with genetically modified floxed animals is a powerful approach for assaying the functional role of genes in regulating behavior and metabolism. Extensive research in diverse cell types and tissues using AAV-Cre has shown it can save time and avoid developmental compensation as compared to using Cre driver mouse line crossings. We initially sought to study the impact of ablation of corticotropin-releasing hormone (CRH) in the paraventricular hypothalamic nucleus (PVN) using intracranial AAV-Cre injection in adult animals. METHODS: In this study, we stereotactically injected AAV8-hSyn-Cre or a control AAV8-hSyn-GFP both Crh-floxed and wild-type mouse PVN to assess behavioral and metabolic impacts. We then used immunohistochemical markers to systematically evaluate the density of hypothalamic peptidergic neurons and glial cells. RESULTS: We found that delivery of one specific preparation of AAV8-hSyn-Cre in the PVN led to the development of obesity, hyperphagia, and anxiety-like behaviors. This effect occurred independent of sex and in both floxed and wild-type mice. We subsequently found that AAV8-hSyn-Cre led to neuronal cell death and gliosis at the site of viral vector injections. These behavioral and metabolic deficits were dependent on injection into the PVN. An alternatively sourced AAV-Cre did not reproduce the same results. CONCLUSIONS: Our findings reveal that delivery of a specific batch of AAV-Cre could lead to cellular toxicity and lesions in the PVN that cause robust metabolic and behavioral impacts. These alterations can complicate the interpretation of Cre-mediated gene knockout and highlight the need for rigorous controls.

Metabolic and behavioral alterations associated with viral vector-mediated toxicity in the paraventricular hypothalamic nucleus.

Objective: Combining adeno-associated virus (AAV)-mediated expression of Cre recombinase with genetically modified floxed animals is a powerful approach for assaying the functional role of genes in regulating behavior and metabolism. Extensive research in diverse cell types and tissues using AAV-Cre has shown it can save time and avoid developmental compensation as compared to using Cre driver mouse line crossings. We initially sought to study the impact of ablation of corticotropin-releasing hormone (CRH) in the paraventricular hypothalamic nucleus (PVN) using intracranial AAV-Cre injection in adult animals. Methods: In this study, we stereotactically injected AAV8-hSyn-Cre or a control AAV8-hSyn-GFP both Crh-floxed and wild-type mouse PVN to assess behavioral and metabolic impacts. We then used immunohistochemical markers to systematically evaluate the density of hypothalamic peptidergic neurons and glial cells. Results: We found that delivery of one specific preparation of AAV8-hSyn-Cre in the PVN led to the development of obesity, hyperphagia, and anxiety-like behaviors. This effect occurred independent of sex and in both floxed and wild-type mice. We subsequently found that AAV8-hSyn-Cre led to neuronal cell death and gliosis at the site of viral vector injections. These behavioral and metabolic deficits were dependent on injection into the PVN. An alternatively sourced AAV-Cre did not reproduce the same results. Conclusions: Our findings reveal that delivery of a specific batch of AAV-Cre could lead to cellular toxicity and lesions in the PVN that cause robust metabolic and behavioral impacts. These alterations can complicate the interpretation of Cre-mediated gene knockout and highlight the need for rigorous controls.

T-wave Inversions in Precordial Leads: A Case Study of Arrhythmogenic Right Ventricular Cardiomyopathy in a Patient With Recurrent Syncope.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare sudden cardiac death (SCD) syndrome characterized by ventricular arrhythmias of right ventricular (RV) origin. This case follows the presentation of ARVC in an otherwise healthy 26-year-old male. The patient was observed for one week after being admitted from the emergency department secondary to pre-syncope with pathognomonic findings on his electrocardiogram (EKG), echocardiogram, and cardiac imaging. The patient was started on beta-blockers, which ultimately he could not tolerate due to bradycardia, and the recommendation of an automatic implantable cardioverter-defibrillator (AICD) was refused. He was discharged without any complications or ventricular arrhythmias on telemetry while hospitalized.

The Interplay of COVID-19 and Hereditary Angioedema: Preventing an Acute Attack.

Hereditary angioedema (HAE) is a rare inherited disease that is caused by the inactivation of the C1 esterase inhibitor. In this case report, we present a 51-year-old female previously diagnosed with HAE who tested positive for SARS-Cov-2 (COVID-19). The patient was treated symptomatically. Dexamethasone was used to treat COVID-19 pneumonia. Broad-spectrum antibiotics (vancomycin and meropenem) were utilized to prevent future infection. Although the patient did not experience an acute angioedema attack during her hospital stay, the patient expired due to the exacerbation of COVID-19 pneumonia.

Satisfaction of Search Can Be Ameliorated by Perceptual Learning: A Proof-of-Principle Study.

When searching a visual image that contains multiple target objects of interest, human subjects often show a satisfaction of search (SOS) effect, whereby if the subjects find one target, they are less likely to find additional targets in the image. Reducing SOS or, equivalently, subsequent search miss (SSM), is of great significance in many real-world situations where it is of paramount importance to find all targets in a given image, not just one. However, studies have shown that even highly trained and experienced subjects, such as expert radiologists, are subject to SOS. Here, using the detection of camouflaged objects (or camouflage-breaking) as an illustrative case, we demonstrate that when naïve subjects are trained to detect camouflaged objects more effectively, it has the side effect of reducing subjects' SOS. We tested subjects in the SOS task before and after they were trained in camouflage-breaking. During SOS testing, subjects viewed naturalistic scenes that contained zero, one, or two targets, depending on the image. As expected, before camouflage-training, subjects showed a strong SOS effect, whereby if they had found a target with relatively high visual saliency in a given image, they were less likely to have also found a lower-saliency target when one existed in the image. Subjects were then trained in the camouflage-breaking task to criterion using non-SOS images, i.e., camouflage images that contained zero or one target. Surprisingly, the trained subjects no longer showed significant levels of SOS. This reduction was specific to the particular background texture in which the subjects received camouflage training; subjects continued to show significant SOS when tested using a different background texture in which they did not receive camouflage training. A separate experiment showed that the reduction in SOS was not attributable to non-specific exposure or practice effects. Together, our results demonstrate that perceptual expertise can, in principle, reduce SOS, even when the perceptual training does not specifically target SOS reduction.

Heuristic Vetoing: Top-Down Influences of the Anchoring-and-Adjustment Heuristic Can Override the Bottom-Up Information in Visual Images.

When making decisions under uncertainty, human subjects do not always act as rational decision makers, but often resort to one or more mental "shortcuts", or heuristics, to arrive at a decision. How do such "top-down" processes affect real-world decisions that must take into account empirical, "bottom-up" sensory evidence? Here we use recognition of camouflaged objects by expert viewers as an exemplar case to demonstrate that the effect of heuristics can be so strong as to override the empirical evidence in favor of heuristic information, even though the latter is random. We provided the viewers a random number that we told them was the estimate of a drone reconnaissance system of the probability that the visual image they were about to see contained a camouflaged target. We then showed them the image. We found that the subjects' own estimates of the probability of the target in the image reflected the random information they were provided, and ignored the actual evidence in the image. However, when the heuristic information was not provided, the same subjects were highly successful in finding the target in the same set of images, indicating that the effect was solely attributable to the availability of heuristic information. Two additional experiments confirmed that this effect was not idiosyncratic to camouflage images, visual search task, or the subjects' prior training or expertise. Together, these results demonstrate a novel aspect of the interaction between heuristics and sensory information during real-world decision making, where the former can be strong enough to veto the latter. This 'heuristic vetoing' is distinct from the vetoing of sensory information that occurs in certain visual illusions.