One month to one day? : can we really reduce the detection time of tubercu[l]osis that much?

Mycobacterium tuberculosis (Mtb) remains important to clinicians and patients because it can be highly infectious and challenging to diagnose. The CDC reports that there were 10,528 cases of TB in the U.S. in 2011, and 529 deaths due to TB in 2009. The rapid diagnosis of Mtb is essential for early disease management. Equally important for clinicians is the exclusion of Mtb from the differential diagnosis. Per the University of Missouri Infection Control Manual, precautions for a patient with suspected infectious pulmonary tuberculosis include a private room with a closed door, negative air pressure, and a 'stop sign alert on the door'. This is inconvenient for patients and care providers and adds expense to the hospital stay. Patients suspected of having TB should have 3 sputum samples tested with acid fast bacilli smears and culture, and one sample should undergo nucleic acid amplification testing. Unfortunately, standard culture techniques can take a month to detect Mtb. Here we present a commercially available assay validated in our lab that reduces detection time to less than two hours

A Three Monoclonal Antibody Combination Potently Neutralizes Multiple Botulinum Neurotoxin Serotype E Subtypes.

Human botulism is most commonly caused by botulinum neurotoxin (BoNT) serotypes A, B, and E. For this work, we sought to develop a human monoclonal antibody (mAb)-based antitoxin capable of binding and neutralizing multiple subtypes of BoNT/E. Libraries of yeast-displayed single chain Fv (scFv) antibodies were created from the heavy and light chain variable region genes of humans immunized with pentavalent-toxoid- and BoNT/E-binding scFv isolated by Fluorescence-Activated Cell Sorting (FACS). A total of 10 scFv were isolated that bound one or more BoNT/E subtypes with nanomolar-level equilibrium dissociation constants (KD). By diversifying the V-regions of the lead mAbs and selecting for cross-reactivity, we generated three scFv that bound all four BoNT/E subtypes tested at three non-overlapping epitopes. The scFvs were converted to IgG that had KD values for the different BoNT/E subtypes ranging from 9.7 nM to 2.28 pM. An equimolar combination of the three mAbs was able to potently neutralize BoNT/E1, BoNT/E3, and BoNT/E4 in a mouse neutralization assay. The mAbs have potential utility as therapeutics and as diagnostics capable of recognizing multiple BoNT/E subtypes. A derivative of the three-antibody combination (NTM-1633) is in pre-clinical development with an investigational new drug (IND) application filing expected in 2018

The roles of intolerance of uncertainty, anxiety sensitivity and distress tolerance in hoarding disorder compared with OCD and healthy controls

Background: It is suggested that the different psychological vulnerability factors of intolerance of uncertainty (IU), anxiety sensitivity (AS) and distress tolerance (DT) may be in important in hoarding disorder (HD). However, the extent to which these factors are specific to HD compared with other disorders remains unclear. Aims: The current study aimed to investigate differences in IU, AS and DT in three groups: HD (n=66), obsessive compulsive disorder (OCD; n=59) and healthy controls (HCs; n=63). Method: Participants completed an online battery of standardised self-report measures to establish the independent variable of group membership (HD, OCD and HC) and the dependent variables (IU, AS and DT). Results: A MANOVA analysis indicated statistically significant differences in IU, AS and DT between the clinical groups and HCs. Follow-up analyses showed no statistically significant differences between the HD and OCD group for any of the three constructs. The results remained the same when examining the effects of co-morbid HD and OCD. An unexpected finding was the trend for IU, AS and DT to be more severe when HD and OCD were co-morbid. Conclusions: The evidence suggests the absence of a specific relationship between IU, AS or DT in HD and instead is consistent with existing research which suggests that these psychological vulnerability factors are transdiagnostic constructs across anxiety disorders. The implications of the findings are discussed

A Single Tri-Epitopic Antibody Virtually Recapitulates the Potency of a Combination of Three Monoclonal Antibodies in Neutralization of Botulinum Neurotoxin Serotype A.

The standard of treatment for botulism, equine antitoxin, is a foreign protein with associated safety issues and a short serum half-life which excludes its use as a prophylactic antitoxin and makes it a less-than-optimal therapeutic. Due to these limitations, a recombinant monoclonal antibody (mAb) product is preferable. It has been shown that combining three mAbs that bind non-overlapping epitopes leads to highly potent botulinum neurotoxin (BoNT) neutralization. Recently, a triple human antibody combination for BoNT/A has demonstrated potent toxin neutralization in mouse models with no serious adverse events when tested in a Phase I clinical trial. However, a triple antibody therapeutic poses unique development and manufacturing challenges. Thus, potentially to streamline development of BoNT antitoxins, we sought to achieve the potency of multiple mAb combinations in a single IgG-based molecule that has a long serum half-life. The design, production, and testing of a single tri-epitopic IgG1-based mAb (TeAb) containing the binding sites of each of the three parental BoNT/A mAbs yielded an antibody of nearly equal potency to the combination. The approach taken here could be applied to the design and creation of other multivalent antibodies that could be used for a variety of applications, including toxin elimination

The impact of believing you have had COVID-19 on self-reported behaviour: Cross-sectional survey.

OBJECTIVES: To investigate whether people who think they have had COVID-19 are less likely to report engaging with lockdown measures compared with those who think they have not had COVID-19. DESIGN: On-line cross-sectional survey. SETTING: Data were collected between 20th and 22nd April 2020. PARTICIPANTS: 6149 participants living in the UK aged 18 years or over. MAIN OUTCOME MEASURES: Perceived immunity to COVID-19, self-reported adherence to social distancing measures (going out for essential shopping, nonessential shopping, and meeting up with friends/family; total out-of-home activity), worry about COVID-19 and perceived risk of COVID-19 to oneself and people in the UK. Knowledge that cough and high temperature / fever are the main symptoms of COVID-19. We used logistic regression analyses and one-way ANOVAs to investigate associations between believing you had had COVID-19 and binary and continuous outcomes respectively. RESULTS: In this sample, 1493 people (24.3%) thought they had had COVID-19 but only 245 (4.0%) reported having received a positive test result. Reported test results were often incongruent with participants' belief that they had had COVID-19. People who believed that they had had COVID-19 were: more likely to agree that they had some immunity to COVID-19; less likely to report adhering to lockdown measures; less worried about COVID-19; and less likely to know that cough and high temperature / fever are two of the most common symptoms of COVID-19. CONCLUSIONS: At the time of data collection, the percentage of people in the UK who thought they had already had COVID-19 was about twice the estimated infection rate. Those who believed they had had COVID-19 were more likely to report leaving home. This may contribute to transmission of the virus. Clear communications to this growing group are needed to explain why protective measures continue to be important and to encourage sustained adherence

Sustained Medication Reduction Following Unilateral VIM Thalamic Stimulation for Essential Tremor

Background: Deep brain stimulation (DBS) is an increasingly utilized therapeutic modality for the management of medication refractory essential tremor (ET). The aim of this study was to determine whether DBS allowed for anti-tremor medication reduction within the year after the procedure was performed. Methods: We conducted a retrospective chart review and telephone interviews on 34 consecutive patients who had been diagnosed with ET, and who had undergone unilateral DBS surgery. Results: Of the 34 patients in our cohort, 31 patients (91%) completely stopped all anti-tremor medications either before surgery (21 patients, 62%) or in the year following DBS surgery (10 patients, 29%). Patients who discontinued tremor medications before DBS surgery did so because their tremors either became refractory to anti-tremor medication, or they developed adverse events to tremor medications. Patients who stopped tremor medications after DBS surgery did so due to sufficient tremor control. Only three patients (9%) who were taking tremor medications at the time of surgery continued the use of a beta-blocker post-operatively for the purpose of hypertension management in all cases. Discussion: The data from this study indicate that medication cessation is common following unilateral DBS for ET