The Enterovirus 3C Protease Inhibitor SG85 Efficiently Blocks Rhinovirus Replication and Is Not Cross-Resistant with Rupintrivir

The novel enterovirus protease inhibitor (PI) SG85 effectively inhibits the in vitro replication of 14 rhinoviruses representative of species A and B (median 50% effective concentration, 0.04 μM). A low-level SG85-resistant variant was selected that carried amino acid substitutions S127G and T143A in the 3C protease. Both substitutions are required for low-level resistance to SG85, as demonstrated by reverse genetics. Interestingly, there is no cross-resistance to SG85 and rupintrivir (another PI); a structural explanation is provided for this observation.     

A Practical Application of Data Mining Methods to Build Predictive Models for Autism Spectrum Disorder Based on Biosensor Data From Janssen Autism Knowledge Engine (JAKE®)

Abstract

The Janssen Autism Knowledge Engine (JAKE^®) collects a large number of features from five biosensors across a range of tasks. The application of data mining methods to these data may be a useful approach to enable objective discrimination between autism spectrum disorder (ASD) and typically developing (TD) participants. Following a prospective observational study using JAKE, ASD participants classified as “moderate” or “severe” based on total scores on the Social Responsiveness Scale, and TD participants were used to build models, using repeated cross-validation, to identify biosensor features contributing to diagnosis. Four different models (partial least squares, random forest, elastic net, and C5.0) were chosen to build diagnostic classifiers using the training set, and the fitted models were evaluated on the test set. Model performance on the training set, based on receiver operating characteristics (ROC), was moderate (area under ROC curve = 0.61–0.72), and model performance on the test set based on kappa statistic was between 0.40 and 0.46 across the four models. Data mining methods applied to biosensor data can lead to models that discriminate ASD from TD. This method may prove useful in creating new diagnostic tests for ASD.     

Cost of Contralateral Prophylactic Mastectomy

Purpose

To compare the healthcare costs of women with unilateral breast cancer who underwent contralateral prophylactic mastectomy (CPM) with those of women who did not.

Methods

We conducted a retrospective study of 904 women treated for stage I–III breast cancer with or without CPM. Women were matched according to age, year at diagnosis, stage, and receipt of chemotherapy. We included healthcare costs starting from the date of surgery to 24 months. We identified whether care was immediate or delayed (CPM within 6 months or 6–24 months after initial surgery, respectively). Costs were converted to approximate Medicare reimbursement values and adjusted for inflation. Multivariable regression analysis was performed to evaluate the effect of CPM on total breast cancer care costs adjusting for patient characteristics and accounting for matched pairs.

Results

The mean difference between the CPM and no-CPM matched groups was $3,573 (standard error [SE] $455) for professional costs, $4,176 (SE $1,724) for technical costs, and $7,749 (SE $2,069) for total costs. For immediate and delayed CPM, the mean difference for total costs was $6,528 (SE $2,243) and $16,744 (SE $5,017), respectively. In multivariable analysis, the CPM group had a statistically significant increase of 16.9 % in mean total costs compared with the no-CPM group (p < 0.0001). Human epidermal growth factor receptor 2/neu-positive status, receipt of radiation, and reconstruction were associated with increases in total costs.

Conclusions

CPM significantly increases short-term healthcare costs for women with unilateral breast cancer. These patient-level cost results can be used for future studies that evaluate the influence of costs of CPM on decision making.     

Alexia due to ischemic stroke of the visual word form area

The visual word form area (VWFA) is a region in the posterior left occipitotemporal cortex adjacent to the fusiform gyrus hypothesized to mediate word recognition. Evidence supporting the role of this area in reading comes from neuroimaging studies of normal subjects, case-controlled lesion studies, and studies of patients with surgical resection of the VWFA for tumors or epilepsy. Based on these prior reports, a small discrete lesion to the VWFA would be expected to cause alexia in a literate person without prior brain process, but such a case has not previously been reported to our knowledge. Here, we report the case of a previously-healthy 63-year-old man with the acute onset of alexia without other significant impairments. Magnetic resonance imaging (MRI) of the brain revealed a small ischemic stroke localized to the inferior left occipitotemporal cortex, corresponding to the approximate location of the putative VWFA. Characteristic of pure alexia, testing in the weeks following the stroke revealed a letter-by-letter reading strategy and a word length effect on single word reading. Formal visual field testing was normal. There was no color anomia, or object or face recognition deficits, although a mild agraphia may have been present. This case of acute-onset alexia in a previously normal individual due to a small stroke restricted to the VWFA and sparing occipital cortex and white matter pathways supports the conclusion that the VWFA is crucial for reading.     

Next-of-kin perceptions of physician responsiveness to symptoms of hospitalized patients near death

Many different medical providers visit critically ill patients during a hospitalization, and patients and family members may not feel any physician is truly in charge of care. This study explores whether perceiving that a physician was clearly in charge is associated with reports by surviving next of kin about the responsiveness of physicians to symptoms in hospitalized patients near the end of life. We conducted telephone interviews with surviving next of kin of adult patients (n = 1107) who died in one of five New York City teaching hospitals between April 1998 and June 1999 after a minimum 3-day inpatient stay. Next-of-kin ratings of whether physicians did "all they could" all or most of the time in response to patient pain, dyspnea, and affective distress (confusion, depression or emotional distress) were compared by whether the next of kin reported one or more physicians "clearly in charge" of care, adjusting for patient and next-of-kin characteristics. More than 80% of patients were reported to have experienced often serious pain, dyspnea, or affective distress. Physicians were rated as responsive to pain by 79.1% of respondents, to dyspnea by 84.9%, and to affective distress by 66.6%. Ratings of physician responsiveness to pain (p = 0.001) and affective distress (p = 0.001) were significantly lower among patients for whom no physician was seen as clearly in charge of care. This finding is consistent with the view that ensuring that a physician coordinates the care of seriously ill, hospitalized patients may improve symptom management. Further research is warranted to establish causality and identify optimal models of care.     

Transient neonatal hemolytic anemia due to the novel gamma globin gene mutation HBG2:C.290T>C,p.Leu97Pro (hemoglobin Wareham)

Unstable gamma globin variants can cause transient neonatal hemolytic anemia. We have identified a novel variant in a newborn who presented with jaundice and anemia requiring phototherapy and red blood cell transfusion. The patient was found to be heterozygous for the mutation HGB2:c.290T>C, p.Leu97Pro, which we have termed hemoglobin (Hb) Wareham. This substitution is expected to generate an unstable hemoglobin with increased oxygen affinity based on the homologous mutation previously described in the beta globin gene, which is termed as Hb Debrousse. The patient fully recovered by 9 months of age as expected with the transition from fetal to adult hemoglobin.