Comparison of the Panther Fusion and BD MAX GBS Assays for Detection of Group B Streptococcus in Prenatal Screening Specimens.

Streptococcus agalactiae, or Group B Streptococcus (GBS) is the cause of early and late-onset GBS disease in neonates and can present as septicemia, meningitis, and pneumonia. Our objective was to compare the performance of two FDA-approved nucleic acid amplification tests (NAATs), the Panther Fusion and BD MAX™ systems, for detection of group B Streptococcus (GBS) in vaginal-rectal screening specimens. A total of 510 vaginal-rectal prepartum specimens were tested simultaneously in both NAATs following broth enrichment. Assay agreement was calculated using the kappa statistics. Overall agreement between assays was 99.0% (505/510; 95% CI: 0.951 to 0.997; kappa = 0.974). Discordant results were re-tested with both assays and by standard culture. The assays were also compared for workflow characteristics, including time to first results (TFR), total turnaround time (TAT), number of return visits to load additional specimens, and hands-on time (HoT).Using a standard run size of 60 specimens/day, the Panther Fusion assay had a longer time to TFR (2.4 vs. 2.0 hours), but showed a shorter overall TAT for all 60 samples (3.98 vs. 7.18 hours) due to an increased initial sample loading capacity, required less labor (35.0 vs. 71.3 sec/sample) and fewer return visits for loading additional specimens (0 vs. 2). The Panther Fusion system also had a larger sample loading capacity (120 vs. 24 samples) and greater 8-hour throughput (335 vs. 96 samples). In summary, the Panther Fusion GBS assay has comparable clinical performance to the BD MAX GBS assay, but provides a faster TAT, less HoT, and higher throughput

Predictors of Stunting, Wasting and Underweight among Tanzanian Children Born to HIV-Infected Women.

Children born to human immunodeficiency virus (HIV)-infected women are susceptible to undernutrition, but modifiable risk factors and the time course of the development of undernutrition have not been well characterized. The objective of this study was to identify maternal, socioeconomic and child characteristics that are associated with stunting, wasting and underweight among Tanzanian children born to HIV-infected mothers, followed from 6 weeks of age for 24 months. Maternal and socioeconomic characteristics were recorded during pregnancy, data pertaining to the infant's birth were collected immediately after delivery, morbidity histories and anthropometric measurements were performed monthly. Multivariate Cox proportional hazards methods were used to assess the association between potential predictors and the time to first episode of stunting, wasting and underweight. A total of 2387 infants (54.0% male) were enrolled and followed for a median duration of 21.2 months. The respective prevalence of prematurity (<37 weeks) and low birth weight (<2500 g) was 15.2% and 7.0%; 11.3% of infants were HIV-positive at 6 weeks. Median time to first episode of stunting, wasting and underweight was 8.7, 7.2 and 7.0 months, respectively. Low maternal education, few household possessions, low infant birth weight, child HIV infection and male sex were all independent predictors of stunting, wasting and underweight. In addition, preterm infants were more likely to become wasted and underweight, whereas those with a low Apgar score at birth were more likely to become stunted. Interventions to improve maternal education and nutritional status, reduce mother-to-child transmission of HIV, and increase birth weight may lower the risk of undernutrition among children born to HIV-infected women

Neighbourhoods as relational places for people living with dementia

An increase in the number of people living independently with dementia across the developed world has focused attention on the relevance of neighbourhood context for enabling or facilitating social health and wellbeing. Taking the lived experiences and daily realities of people living with dementia as a starting point, this paper contributes new understanding about the relevance of local places for supporting those living with the condition in the community. The paper outlines findings from a study of the neighbourhood experiences, drawing on new data collected from a creative blend of qualitatively-driven mixed methods with people living in a diverse array of settings across three international settings. The paper details some of the implications of neighbourhoods as sites of social connection for those living with dementia from material from 67 people living with dementia and 62 nominated care-partners. It demonstrates how neighbourhoods are experienced as relational places and considers how people living with dementia contribute to the production of such places through engagement and interactions in ways that may be beneficial to social health. We contend that research has rarely focused on the subjective, experiential and ‘everyday’ social practices that contextualise neighbourhood life for people living with dementia. In doing so, the paper extends empirical and conceptual understanding of the relevance of neighbourhoods as sites of connection, interaction, and social engagement for people living with dementia

Acetylcholinesterase inhibition ameliorates deficits in motivational drive

<p>Abstract</p> <p>Background</p> <p>Apathy is frequently observed in numerous neurological disorders, including Alzheimer's and Parkinson's, as well as neuropsychiatric disorders including schizophrenia. Apathy is defined as a lack of motivation characterized by diminished goal-oriented behavior and self-initiated activity. This study evaluated a chronic restraint stress (CRS) protocol in modeling apathetic behavior, and determined whether administration of an anticholinesterase had utility in attenuating CRS-induced phenotypes.</p> <p>Methods</p> <p>We assessed behavior as well as regional neuronal activity patterns using FosB immunohistochemistry after exposure to CRS for 6 h/d for a minimum of 21 d. Based on our FosB findings and recent clinical trials, we administered an anticholinesterase to evaluate attenuation of CRS-induced phenotypes.</p> <p>Results</p> <p>CRS resulted in behaviors that reflect motivational loss and diminished emotional responsiveness. CRS-exposed mice showed differences in FosB accumulation, including changes in the cholinergic basal forebrain system. Facilitating cholinergic signaling ameliorated CRS-induced deficits in initiation and motivational drive and rescued immediate early gene activation in the medial septum and nucleus accumbens.</p> <p>Conclusions</p> <p>Some CRS protocols may be useful for studying deficits in motivation and apathetic behavior. Amelioration of CRS-induced behaviors with an anticholinesterase supports a role for the cholinergic system in remediation of deficits in motivational drive.</p

Sex Differences in The effects of Maternal Vitamin Supplements on Mortality and Morbidity among Children Born to HIV-Infected women in Tanzania.

We examined whether there are sex differences in the effect of vitamin supplements on birth outcomes, mortality and morbidity by 2 years of age among children born to HIV-infected women in Tanzania. A randomised placebo-controlled trial was conducted among 959 mother-infant pairs. HIV-infected pregnant women were randomly assigned to receive a daily oral dose of one of four regimens: multivitamins (vitamins B-complex, C and E), vitamin A plus beta-carotene, multivitamins including vitamin A plus beta-carotene or placebo. Supplements were administered during pregnancy and continued after delivery. The beneficial effect of multivitamins on decreasing the risk of low birth weight was stronger among girls (relative risks (RR) = 0.39, 95 % CI 0.22, 0.67) than among boys (RR = 0.81, 95 % CI 0.44, 1.49; P for interaction = 0.08). Maternal multivitamin supplements resulted in 32 % reduction in mortality among girls (RR = 0.68, 95 % CI 0.47, 0.97), whereas no effect was found among boys (RR = 1.20, 95 % CI 0.80, 1.78; P for interaction = 0.04). Multivitamins had beneficial effects on the overall risks of diarrhoea that did not differ by sex. Vitamin A plus beta-carotene alone increased the risk of HIV transmission, but had no effects on mortality, and we found no sex differences in these effects. Sex differential effects of multivitamins on mortality may be due to sex-related differences in the immunological or genetic factors. More research is warranted to examine the effect of vitamins by sex and better understand biological mechanisms mediating such effects

The Queen Square Encephalitis Multidisciplinary Team Meeting - experience over three years, pre and post the COVID-19 pandemic

Background: Patients with suspected encephalitis continue to represent a diagnostic and therapeutic challenge, even in highly resourced centres. In February 2018, we set up a monthly in-person multidisciplinary team meeting (MDT). We describe the experience and outcomes of the MDT over three years. Methods: A retrospective analysis was performed to summarise patient demographics, MDT outcomes and final diagnoses. Results: Over the three-year period, 324 discussions of 238 patients took place. Cases were diverse; approximately 40% related to COVID-19 or brain infection, 40% autoimmune or other inflammatory disorders and 20% encephalitis mimics or uncertain aetiologies. Feedback from an online survey sent to referring teams and attendees highlighted the value of the MDT; 94% reported the discussion was useful and 69% reported resulting change in patient management. Conclusions: Multidisciplinary input is crucial in this challenging area, ensuring that all diagnostic avenues are explored and opening doors to novel diagnostics and therapeutics. It also supports clinicians dealing with unwell patients, including in centres where less specialist input is available, and when decisions have to be made where there is little or no evidence base

Bioluminescent Reporting of In Vivo IFN-γ Immune Responses during Infection and Autoimmunity

IFN-γ is a key cytokine of innate and adaptive immunity. It is important to understand temporal changes in IFN-γ production and how these changes relate to the role of IFN-γ in diverse models of infectious and autoimmune disease, making the ability to monitor and track IFN-γ production in vivo of a substantial benefit. IFN-γ ELISPOTs have been a central methodology to measure T cell immunity for many years. In this study, we add the capacity to analyze IFN-γ responses with high sensitivity and specificity, longitudinally, in vitro and in vivo. This allows the refinement of experimental protocols because immunity can be tracked in real-time through a longitudinal approach. We have generated a novel murine IFN-γ reporter transgenic model that allows IFN-γ production to be visualized and quantified in vitro and in vivo as bioluminescence using an imaging system. At baseline, in the absence of an inflammatory stimulus, IFN-γ signal from lymphoid tissue is detectable in vivo. Reporter transgenics are used in this study to track the IFN-γ response to Pseudomonas aeruginosa infection in the lung over time in vivo. The longitudinal development of the adaptive T cell immunity following immunization with Ag is identified from day 7 in vivo. Finally, we show that we are able to use this reporter transgenic to follow the onset of autoimmune T cell activation after regulatory T cell depletion in an established model of systemic autoimmunity. This IFN-γ reporter transgenic, termed “Gammaglow,” offers a valuable new modality for tracking IFN-γ immunity, noninvasively and longitudinally over time

Pilot phenotype and natural history study of hereditary neuropathies caused by mutations in the HSPB1 gene

Mutations in HSPB1 are one of the commonest causes of distal Hereditary Motor Neuropathy (dHMN). Transgenic mouse models of the disease have identified HDAC6 inhibitors as promising treatments for the condition paving the way for human trials. A detailed phenotype and natural history study of HSPB1 neuropathy is therefore required in order to inform the duration and outcome measures of any future trials. Clinical and neurophysiological data and lower limb muscle MRI were collected both prospectively and retrospectively from patients with mutations in HSPB1. The natural history was assessed by recording the weighted Charcot-Marie-Tooth Examination Score (CMTES) at annual intervals in a subset of patients. 20 patients from 14 families were recruited into the study. The average age of onset was in the 4th decade. Patients presented with a length dependent neuropathy but with early ankle plantar flexion weakness. Neurophysiology confirmed a motor neuropathy but also showed sensory nerve involvement in most patients. Cross sectional muscle MRI revealed soleus and medial gastrocnemius fat infiltration as an early signature of mutant HSPB1 disease. In this study neither semi quantitative muscle MRI, the CMTES nor neurophysiology were able to detect disease progression in HSPB1 neuropathy over 1 or 2 years. Further studies are therefore required to identify a suitable biomarker before clinical trials in HSPB1 neuropathy can be undertaken

Cryptosporidium, Enterocytozoon, and Cyclospora Infections in Pediatric and Adult Patients with Diarrhea in Tanzania.

Cryptosporidiosis, microsporidiosis, and cyclosporiasis were studied in four groups of Tanzanian inpatients: adults with AIDS-associated diarrhea, children with chronic diarrhea (of whom 23 of 59 were positive [+] for human immunodeficiency virus [HIV]), children with acute diarrhea (of whom 15 of 55 were HIV+), and HIV control children without diarrhea. Cryptosporidium was identified in specimens from 6/86 adults, 5/59 children with chronic diarrhea (3/5, HIV+), 7/55 children with acute diarrhea (0/7, HIV+), and 0/20 control children. Among children with acute diarrhea, 7/7 with cryptosporidiosis were malnourished, compared with 10/48 without cryptosporidiosis (P < .01). Enterocytozoon was identified in specimens from 3/86 adults, 2/59 children with chronic diarrhea (1 HIV+), 0/55 children with acute diarrhea, and 4/20 control children. All four controls were underweight (P < .01). Cyclospora was identified in specimens from one adult and one child with acute diarrhea (HIV-). Thus, Cryptosporidium was the most frequent and Cyclospora the least frequent pathogen identified. Cryptosporidium and Enterocytozoon were associated with malnutrition. Asymptomatic fecal shedding of Enterocytozoon in otherwise healthy, HIV children has not been described previously

Defining Meyer's loop-temporal lobe resections, visual field deficits and diffusion tensor tractography

Anterior temporal lobe resection is often complicated by superior quadrantic visual field deficits (VFDs). In some cases this can be severe enough to prohibit driving, even if a patient is free of seizures. These deficits are caused by damage to Meyer's loop of the optic radiation, which shows considerable heterogeneity in its anterior extent. This structure cannot be distinguished using clinical magnetic resonance imaging sequences. Diffusion tensor tractography is an advanced magnetic resonance imaging technique that enables the parcellation of white matter. Using seed voxels antero-lateral to the lateral geniculate nucleus, we applied this technique to 20 control subjects, and 21 postoperative patients. All patients had visual fields assessed with Goldmann perimetry at least three months after surgery. We measured the distance from the tip of Meyer's loop to the temporal pole and horn in all subjects. In addition, we measured the size of temporal lobe resection using postoperative T1-weighted images, and quantified VFDs. Nine patients suffered VFDs ranging from 22% to 87% of the contralateral superior quadrant. In patients, the range of distance from the tip of Meyer's loop to the temporal pole was 24–43 mm (mean 34 mm), and the range of distance from the tip of Meyer's loop to the temporal horn was –15 to +9 mm (mean 0 mm). In controls the range of distance from the tip of Meyer's loop to the temporal pole was 24–47 mm (mean 35 mm), and the range of distance from the tip of Meyer's loop to the temporal horn was –11 to +9 mm (mean 0 mm). Both quantitative and qualitative results were in accord with recent dissections of cadaveric brains, and analysis of postoperative VFDs and resection volumes. By applying a linear regression analysis we showed that both distance from the tip of Meyer's loop to the temporal pole and the size of resection were significant predictors of the postoperative VFDs. We conclude that there is considerable variation in the anterior extent of Meyer's loop. In view of this, diffusion tensor tractography of the optic radiation is a potentially useful method to assess an individual patient's risk of postoperative VFDs following anterior temporal lobe resection