Rapid return to normal activities at a residential summer camp during COVID-19 Pandemic

Aim: Infection prevention and control (IPC) within residential settings is a central focus of the coronavirus disease 2019 (COVID-19) pandemic. Youth residential summer camps are an excellent model for such environments and have thus far had mixed results. The aim of this report is to describe the successful implementation of a seven-week overnight summer camp with rapid return to normal activities from June to August 2020 Subjects and Methods: This retrospective study includes 427 individuals who traveled from 24 US States. All staff and campers were tested by serial nasopharyngeal PCR tests in the context of strict infection prevention and control (IPC) measures including cohorts and masking. The entire camp population was isolated from non-camp personnel with special measures for food, supply, and mail delivery. Results: During the two-week staff session, one staff member tested positive for SARS-CoV-2, was isolated, and sent safely off premises. All other campers and staff had three negative PCR tests: 1-8 days before arrival, upon arrival, and 5-6 days after arrival. After these three negative tests, 6 days into camp, most IPCs, including masking, were successfully lifted and a normal camp experience was possible. Conclusions: These findings indicate that serial PCR-based testing and strict adherence to IPC measures among cohorts can allow for successful assumption of near normal group activities in a residential setting during the COVID-19 pandemic. This result at an overnight summer camp has broad implications for similar residential communities such as boarding schools, other youth education and development programs, as well as nursing homes and military installations

Outcomes from an Addiction Medicine Elective for 2nd Year PCOM DO Students

Introduction: According to the 2020 National Survey on Drug Use and Health, 40.3 million people aged 12 or older had a past-year substance use disorder (SUD). However, the median number of hours of content discussing this clinical issue in medical schools is seven hours. At the PCOM Philadelphia campus, 50 Second Year students (allowable limit) participated in the first Addiction Medicine Elective course in Winter 2022. This was a 6-week long program with one 2-hour session at night (6–8 pm) per week. Classes consisted of sessions with physicians having experience with SUD patients, testimony from those with SUD, Narcan training, direct involvement in a related community experience (e.g., Prevention Point), and as observers in group sessions (e.g., Alcoholics Anonymous). Methods: All students were in good academic standing, and enrolled electively. There were no quizzes or exams but attendance was mandatory. Students were given a pre- and post-survey assessing their understanding of SUD, and their comfort level in talking to patients about their substance use. The survey questions were in the following format: “As a medical student I…” and were asked to give a ‘Yes’ or ‘No’ option; completion was not compulsory. However, submission of a ‘reflection’ paper was mandatory. Students who successfully participated received one course credit for their transcript. Results: All 50 students responded to the survey. Twenty percent stated prior to the course that they felt comfortable in assessing a patient for addiction which increased to 100% at the end. Forty-one percent reported feeling comfortable talking to their patients about their addiction prior to the course which rose to 95% after 6 weeks. In regard to understanding the disease concept of addiction, 66% felt comfortable at the beginning which increased to 100% at the end. On Day 1 of the course, only 2% reported knowing how to access community resources for referral regarding treatment or 12-step programs; after Day 6, 91% indicated that they now knew how to access these community resources. Discussion: The pre- and post-surveys given during this addiction medicine elective showed promising results that it was effective in teaching students about SUD. Students felt more comfortable identifying patients with this serious medical condition, and in talking to their future patients about substance use. They also reported a better understanding of the disease process of addiction. This course is a viable option to increase the knowledge and confidence of future physicians when it comes to treating patients with SUD

Masked-Volume-Wise PCA and "reference Logan" illustrate similar regional differences in kinetic behavior in human brain PET study using [11C]-PIB

<p>Abstract</p> <p>Background</p> <p>Kinetic modeling using reference Logan is commonly used to analyze data obtained from dynamic Positron Emission Tomography (PET) studies on patients with Alzheimer's disease (AD) and healthy volunteers (HVs) using amyloid imaging agent <it>N</it>-methyl [¹¹C]2-(4'-methylaminophenyl)-6-hydroxy-benzothiazole, [¹¹C]-PIB. The aim of the present study was to explore whether results obtained using the newly introduced method, Masked Volume Wise Principal Component Analysis, MVW-PCA, were similar to the results obtained using reference Logan.</p> <p>Methods</p> <p>MVW-PCA and reference Logan were performed on dynamic PET images obtained from four Alzheimer's disease (AD) patients on two occasions (baseline and follow-up) and on four healthy volunteers (HVs). Regions of interest (ROIs) of similar sizes were positioned in different parts of the brain in both AD patients and HVs where the difference between AD patients and HVs is largest. Signal-to-noise ratio (SNR) and discrimination power (DP) were calculated for images generated by the different methods and the results were compared both qualitatively and quantitatively.</p> <p>Results</p> <p>MVW-PCA generated images that illustrated similar regional binding patterns compared to reference Logan images and with slightly higher quality, enhanced contrast, improved SNR and DP, without being based on modeling assumptions. MVW-PCA also generated additional MVW-PC images by using the whole dataset, which illustrated regions with different and uncorrelated kinetic behaviors of the administered tracer. This additional information might improve the understanding of kinetic behavior of the administered tracer.</p> <p>Conclusion</p> <p>MVW-PCA is a potential multivariate method that without modeling assumptions generates high quality images, which illustrated similar regional changes compared to modeling methods such as reference Logan. In addition, MVW-PCA could be used as a new technique, applicable not only on dynamic human brain studies but also on dynamic cardiac studies when using PET.</p

Clinical and Biomarker Changes in Dominantly Inherited Alzheimer's Disease

BACKGROUND: The order and magnitude of pathologic processes in Alzheimer's disease are not well understood, partly because the disease develops over many years. Autosomal dominant Alzheimer's disease has a predictable age at onset and provides an opportunity to determine the sequence and magnitude of pathologic changes that culminate in symptomatic disease. METHODS: In this prospective, longitudinal study, we analyzed data from 128 participants who underwent baseline clinical and cognitive assessments, brain imaging, and cerebrospinal fluid (CSF) and blood tests. We used the participant's age at baseline assessment and the parent's age at the onset of symptoms of Alzheimer's disease to calculate the estimated years from expected symptom onset (age of the participant minus parent's age at symptom onset). We conducted cross-sectional analyses of baseline data in relation to estimated years from expected symptom onset in order to determine the relative order and magnitude of pathophysiological changes. RESULTS: Concentrations of amyloid-beta (Aβ)(42) in the CSF appeared to decline 25 years before expected symptom onset. Aβ deposition, as measured by positron-emission tomography with the use of Pittsburgh compound B, was detected 15 years before expected symptom onset. Increased concentrations of tau protein in the CSF and an increase in brain atrophy were detected 15 years before expected symptom onset. Cerebral hypometabolism and impaired episodic memory were observed 10 years before expected symptom onset. Global cognitive impairment, as measured by the Mini-Mental State Examination and the Clinical Dementia Rating scale, was detected 5 years before expected symptom onset, and patients met diagnostic criteria for dementia at an average of 3 years after expected symptom onset. CONCLUSIONS: We found that autosomal dominant Alzheimer's disease was associated with a series of pathophysiological changes over decades in CSF biochemical markers of Alzheimer's disease, brain amyloid deposition, and brain metabolism as well as progressive cognitive impairment. Our results require confirmation with the use of longitudinal data and may not apply to patients with sporadic Alzheimer's disease. (Funded by the National Institute on Aging and others; DIAN ClinicalTrials.gov number, NCT00869817.)

Analyzing Thioflavin T Binding to Amyloid Fibrils by an Equilibrium Microdialysis-Based Technique

A new approach for the determination of the amyloid fibril – thioflavin T (ThT) binding parameters (the number of binding modes, stoichiometry, and binding constants of each mode) is proposed. This approach is based on the absorption spectroscopy determination of the concentration of free and bound to fibril dye in solutions, which are prepared by equilibrium microdialysis. Furthermore, the proposed approach allowed us, for the first time, to determine the absorption spectrum, molar extinction coefficient, and fluorescence quantum yield of the ThT bound to fibril by each binding modes. This approach is universal and can be used for determining the binding parameters of any dye interaction with a receptor, such as ANS binding to proteins in the molten globule state or to protein amorphous aggregates

NAD-biosynthetic enzyme NMNAT1 reduces early behavioral impairment in the htau mouse model of tauopathy

NAD metabolism and the NAD biosynthetic enzymes nicotinamide nucleotide adenylyltransferases (NMNATs) are thought to play a key neuroprotective role in tauopathies, including Alzheimer’s disease. Here, we investigated whether modulating the expression of the NMNAT nuclear isoform NMNAT1, which is important for neuronal maintenance, influences the development of behavioral and neuropathological abnormalities in htau mice, which express non-mutant human tau isoforms and represent a model of tauopathy relevant to Alzheimer’s disease. Prior to the development of cognitive symptoms, htau mice exhibit tau hyperphosphorylation associated with a selective deficit in food burrowing, a behavior reminiscent to activities of daily living which are impaired early in Alzheimer’s disease. We crossed htau mice with Nmnat1 transgenic and knockout mice and tested the resulting offspring until the age of 6 months. We show that overexpression of NMNAT1 ameliorates the early deficit in food burrowing characteristic of htau mice. At 6 months of age, htau mice did not show neurodegenerative changes in both the cortex and hippocampus, and these were not induced by downregulating NMNAT1 levels. Modulating NMNAT1 levels produced a corresponding effect on NMNAT enzymatic activity but did not alter NAD levels in htau mice. Although changes in local NAD levels and subsequent modulation of NAD-dependent enzymes cannot be ruled out, this suggests that the effects seen on behavior may be due to changes in tau phosphorylation. Our results suggest that increasing NMNAT1 levels can slow the progression of symptoms and neuropathological features of tauopathy, but the underlying mechanisms remain to be established

CD33 Alzheimer’s disease locus: Altered monocyte function and amyloid biology

In our functional dissection of the CD33 Alzheimer’s disease susceptibility locus, we find that the rs3865444C risk allele is associated with greater cell surface expression of CD33 in monocytes (t50 = 10.06, pjoint=1.3×10–13) of young and older individuals. It is also associated with (1) diminished internalization of Aβ42) (2) accumulation of neuritic amyloid pathology and fibrillar amyloid on in vivo imaging and (3), increased numbers of activated human microglia

The origins and genomic diversity of American Civil War Era smallpox vaccine strains

Abstract: Vaccination has transformed public health, most notably including the eradication of smallpox. Despite its profound historical importance, little is known of the origins and diversity of the viruses used in smallpox vaccination. Prior to the twentieth century, the method, source and origin of smallpox vaccinations remained unstandardised and opaque. We reconstruct and analyse viral vaccine genomes associated with smallpox vaccination from historical artefacts. Significantly, we recover viral molecules through non-destructive sampling of historical materials lacking signs of biological residues. We use the authenticated ancient genomes to reveal the evolutionary relationships of smallpox vaccination viruses within the poxviruses as a whole

A pragmatic multi-institutional approach to understanding transplant-associated thrombotic microangiopathy after stem cell transplant

Transplant-associated thrombotic microangiopathy (TA-TMA) is a severe complication of hematopoietic stem cell transplantation (HSCT). A single-center prospective screening study has shown that the incidence of TA-TMA is much higher than prior retrospective studies that did not systematically screen. These data have not been replicated in a multicenter study. Our objective was to determine the incidence and risk factors for TA-TMA and compare outcomes of pediatric HSCT patients with and without TA-TMA. Patients were prospectively screened for TA-TMA at participating centers using a simple to implement and inexpensive strategy from the start of the preparative regimen through day +100. TA-TMA was diagnosed if ≥4 of 7 laboratory/clinical markers diagnostic for TA-TMA were present concurrently or if tissue histology showed TA-TMA. A total of 614 patients (359 males; 58%) received prospective TA-TMA screening at 13 pediatric centers. TA-TMA was diagnosed in 98 patients (16%) at a median of 22 days (interquartile range, 14-44) posttransplant. Patients with TA-TMA had significantly increased bloodstream infections (38% [37/98] vs 21% [107/51], P ≤ .001), mean total hospitalization days (68; 95% confidence interval [CI], 63-74 vs 43; 95% CI, 41-45; P ≤ .001), and number of days spent in the intensive care unit (10.1; 95% CI, 6.4-14; vs 1.6; 95% CI, 1.1-2.2; P ≤ .001) in the first 100 days after HSCT compared with patients without TA-TMA. Overall survival was significantly higher in patients without TA-TMA (93%; 490/516) compared with patients with TA-TMA (78%; 76/98) (P ≤ .001). These data support the need for systematic screening for TA-TMA and demonstrate the feasibility and efficacy of an easy to implement strategy to do so