Nevin Manimala

PLoS Comput Biol. 2021 Sep 27;17(9):e1009413. doi: 10.1371/journal.pcbi.1009413. Online ahead of print.

ABSTRACT

Persistent destruction of pancreatic β-cells in type 1 diabetes (T1D) results from multifaceted pancreatic cellular interactions in various phase progressions. Owing to the inherent heterogeneity of coupled nonlinear systems, computational modeling based on T1D etiology help achieve a systematic understanding of biological processes and T1D health outcomes. The main challenge is to design such a reliable framework to analyze the highly orchestrated biology of T1D based on the knowledge of cellular networks and biological parameters. We constructed a novel hybrid in-silico computational model to unravel T1D onset, progression, and prevention in a non-obese-diabetic mouse model. The computational approach that integrates mathematical modeling, agent-based modeling, and advanced statistical methods allows for modeling key biological parameters and time-dependent spatial networks of cell behaviors. By integrating interactions between multiple cell types, model results captured the individual-specific dynamics of T1D progression and were validated against experimental data for the number of infiltrating CD8+T-cells. Our simulation results uncovered the correlation between five auto-destructive mechanisms identifying a combination of potential therapeutic strategies: the average lifespan of cytotoxic CD8+T-cells in islets; the initial number of apoptotic β-cells; recruitment rate of dendritic-cells (DCs); binding sites on DCs for naïve CD8+T-cells; and time required for DCs movement. Results from therapy-directed simulations further suggest the efficacy of proposed therapeutic strategies depends upon the type and time of administering therapy interventions and the administered amount of therapeutic dose. Our findings show modeling immunogenicity that underlies autoimmune T1D and identifying autoantigens that serve as potential biomarkers are two pressing parameters to predict disease onset and progression.

PMID:34570760 | DOI:10.1371/journal.pcbi.1009413

Bol Med Hosp Infant Mex. 2021;78(5):385-394. doi: 10.24875/BMHIM.20000301.

ABSTRACT

BACKGROUND: Pulmonary involvement in juvenile systemic sclerosis (JSSc) is rare in children and contributes to morbimortality. This study aimed to describe the pulmonary function and clinical, radiologic, and tomographic findings in JSSc.

METHODS: Patients with JSSc between 5-14 years of age were included. Clinical, functional, and imaging characteristics were assessed. Patients were excluded if they showed lung disease not associated with JSSc: mixed connective tissue disease, overlap syndrome, or acute cardiopulmonary failure at the time of the study. All patients underwent physical examination, electrocardiogram, spirometry, chest X-ray, high-resolution computed tomography (HRCT) of the chest, echocardiography, lung function tests, and the 6-minute walk test (6-MWT). Descriptive statistics were employed for data analysis.

RESULTS: We studied 15 patients with the following characteristics: median age, 11 years; median since symptoms onset, 6 years; median since JSSc diagnosis and the finding of pulmonary involvement, 2 years. Lung disease was detected in 73%, interstitial lung disease (ILD) the most common affection (67%); pulmonary hypertension was found in 6.6%. 6-MWT was positive in 26.6%, forced vital capacity (FVC) was abnormal in 26.6%. No pulmonary involvement was found in four patients.

CONCLUSIONS: The most frequent pulmonary affection in JSSc was ILD. Thus, early JSSc detection and periodic lung monitoring are mandatory to avoid further complications once JSSc is diagnosed.

PMID:34570747 | DOI:10.24875/BMHIM.20000301

Dermatitis. 2021 Sep 27. doi: 10.1097/DER.0000000000000709. Online ahead of print.

ABSTRACT

BACKGROUND: Ethylhexylglycerin (EHG) is a recently recognized contact allergen.

OBJECTIVE: The aims of the study were to characterize individuals with positive patch test reactions to EHG and to analyze reaction strength, clinical relevance, and allergen sources.

METHODS: This study was a retrospective analysis of the patients patch tested to EHG (5% petrolatum) by the North American Contact Dermatitis Group (2013-2018).

RESULTS: Of 15,560 patients tested to EHG, 39 (0.25%) had positive (final interpretation of “allergic”) reactions. Most were female (71.8%) and/or older than 40 years (76.9%). There were no statistically significant differences between age, sex, or atopic history when compared with EHG-negative patients. The most common anatomic sites of dermatitis were the face (28.2%) and scattered generalized distribution (25.6%). Most EHG-positive reactions were + (35.9%) or ++ (33.3%). Current clinical relevance was high (79.5%); none, however, were related to occupation. Personal care products were the most common source of exposure to EHG (59.0%).

CONCLUSIONS: Ethylhexylglycerin is a rare contact allergen; the positive frequency of 0.25% is similar to other low allergenic preservatives including parabens, benzyl alcohol, and phenoxyethanol. The patch test concentration of 5.0% seems to be nonirritating. Although relatively uncommon, EHG reactions were usually clinically relevant (79.5%), often because of moisturizers/lotions/creams.

PMID:34570737 | DOI:10.1097/DER.0000000000000709

Dermatitis. 2021 Sep 27. doi: 10.1097/DER.0000000000000787. Online ahead of print.

ABSTRACT

BACKGROUND: Recently, aluminum chloride hexahydrate (ACH) 10.0% petrolatum (pet) was recommended for patch testing to detect aluminum contact allergy. Aluminum lactate (AL) may be as reliable a test substance as ACH.

OBJECTIVE: We aimed to investigate the frequencies of aluminum allergy when ACH and AL were used in patch testing consecutive patients.

METHODS: Petrolatum preparations of ACH 10.0% and AL 12.0% were added to the baseline series in 2010-2017. Aluminum chloride hexahydrate 10.0% pet was added to the children baseline series from July 1, 2012, to December 31, 2017.

RESULTS: A total of 5448 patients were patch tested with the extended baseline series and 196 children with the extended children baseline series. Forty-eight of the 5448 adults (0.9%) and 10 of the 196 children (5.1%) were diagnosed with aluminum contact allergy. A significant difference was found between the aluminum allergy frequencies in children and adults patch tested with ACH in 2013-2017 (P < 0.001). The difference between the frequencies of contact allergies for the 2 aluminum salts is not statistically significant.

CONCLUSIONS: Patch testing with ACH and AL demonstrated similar contact allergy frequencies. To detect aluminum allergy, patch testing with ACH 10.0% pet is recommended. Aluminum chloride hexahydrate 10.0% pet should be considered for inclusion in baseline series for patch testing adults and children.

PMID:34570735 | DOI:10.1097/DER.0000000000000787

Elife. 2021 Sep 27;10:e64505. doi: 10.7554/eLife.64505.

ABSTRACT

Representations related to past experiences play a critical role in memory and decision-making processes. The rat hippocampus expresses these types of representations during sharp-wave ripple (SWR) events, and previous work identified a minority of SWRs that contain ‘replay’ of spatial trajectories at ∼20x the movement speed of the animal. Efforts to understand replay typically make multiple assumptions about which events to examine and what sorts of representations constitute replay. We therefore lack a clear understanding of both the prevalence and the range of representational dynamics associated with replay. Here, we develop a state space model that uses a combination of movement dynamics of different speeds to capture the spatial content and time evolution of replay during SWRs. Using this model, we find that the large majority of replay events contain spatially coherent, interpretable content. Furthermore, many events progress at real-world, rather than accelerated, movement speeds, consistent with actual experiences.

PMID:34570699 | DOI:10.7554/eLife.64505

Elife. 2021 Sep 27;10:e71969. doi: 10.7554/eLife.71969. Online ahead of print.

ABSTRACT

Neurophysiological studies depend on a reliable quantification of whether and when a neuron responds to stimulation. Simple methods to determine responsiveness require arbitrary parameter choices, such as binning size, while more advanced model-based methods require fitting and hyperparameter tuning. These parameter choices can change the results, which invites bad statistical practice and reduces the replicability. New recording techniques that yield increasingly large numbers of cells would benefit from a test for cell-inclusion that requires no manual curation. Here, we present the parameter-free ZETA-test, which outperforms t-tests, ANOVAs, and renewal-process-based methods by including more cells at a similar false-positive rate. We show that our procedure works across brain regions and recording techniques, including calcium imaging and Neuropixels data. Furthermore, in illustration of the method, we show in mouse visual cortex that 1) visuomotor-mismatch and spatial location are encoded by different neuronal subpopulations; and 2) optogenetic stimulation of VIP cells leads to early inhibition and subsequent disinhibition.

PMID:34570697 | DOI:10.7554/eLife.71969

Arch Argent Pediatr. 2021 Oct;119(5):e435-e440. doi: 10.5546/aap.2021.eng.e435.

ABSTRACT

INTRODUCTION: Hospital readmissions in pediatrics are a severe, potentially avoidable problem of health systems. In our setting, there is little information about this topic.

OBJECTIVE: To estimate the rate of readmissions, the proportion of potentially preventable readmissions, and their associated characteristics.

MATERIAL AND METHODS: Cross-sectional study including hospital readmissions of patients aged 0-18 years, admitted to a tertiary care children’s hospital between January 1st and December 31st, 2018. Readmissions were assessed as potentially preventable based on whether they were or not related to the previous admission.

RESULTS: Out of 8228 hospital admissions recorded in the study period, the rate of readmissions for any cause was 10 % at 30 days and 7.1 % at 15 days. The proportion of readmissions classified as potentially preventable was 47.9 % at 30 days and 47.5 % at 15 days. No statistically significant differences were observed between readmissions at 30 and 15 days in terms of patient age, health insurance, presence of chronic disease or cause of readmission.

CONCLUSION: The rate of hospital readmissions was 10 % at 30 days and 7.1 % at 15 days of discharge; almost half of them were considered potentially preventable.

PMID:34569745 | DOI:10.5546/aap.2021.eng.e435

Arch Argent Pediatr. 2021 Oct;119(5):325-330. doi: 10.5546/aap.2021.eng.325.

ABSTRACT

INTRODUCTION: Infections due to bacteremia in burn patients are a common cause of complications and an extended length of stay. Knowing causative microorganisms and identifying associated risk factors allow to reduce infectious complications, morbidity, mortality, and health care expenditure. This study assesses the extent of the association between risk factors and bacteremia in burn patients and identifies the most common microorganisms found in blood cultures.

POPULATION AND METHODS: Case-control study conducted at the Burn Intensive Care Unit of Hospital de Pediatría S.A.M.I.C. “Prof. Dr. Juan P. Garrahan” between June 1st, 2014 and September 30th, 2019 in patients with bacteremia events and a positive blood culture (cases) and patients with a negative blood culture (controls).

RESULTS: During the study period, 29 cases of bacteremia were identified. The median length of stay at the time of bacteremia was 23 days. The most commonly identified microorganism was Pseudomonas (7 cases). The only risk factor that showed a significant association was the presence of a central venous line for 7 days or more (OR: 3.18; 95 % confidence interval: 1.20- 8.38). The overall mortality rate was 9.1%; 13.8% for cases and 3.4% for controls.

CONCLUSIONS: Central venous lines for more than 7 days are an independent risk factor for bacteremia in critically ill burn children. No statistically significant association was established with other studied risk factors. Pseudomonas, Acinetobacter, and coagulase-negative Staphylococcus were the most common microorganisms found in bacteremia.

PMID:34569740 | DOI:10.5546/aap.2021.eng.325

J Int AIDS Soc. 2021 Sep;24(9):e25815. doi: 10.1002/jia2.25815.

ABSTRACT

INTRODUCTION: In sub-Saharan Africa, less than half of young people know their HIV status. HIV self-testing (HIVST) is a testing strategy with the potential to offer privacy and autonomy. We aimed to understand the uptake and acceptability of different HIV testing options for youth in Harare, Zimbabwe.

METHODS: This study was nested within a cluster randomized trial of a youth-friendly community-based integrated HIV and sexual and reproductive health intervention for youth aged 16-24 years. Three HIV testing options were offered: (1) provider-delivered testing; (2) HIVST on site in a private booth without a provider present; and (3) provision of a test kit to test off site. Descriptive statistics and proportions were used to investigate the uptake of HIV testing in a client sample. A focus group discussion (FGD) with intervention providers alongside in-depth interviews, paired interviews and FGDs with a selected sample of youth clients explored uptake and acceptability of the different HIV testing strategies. Thematic analysis was used to analyse the qualitative data.

RESULTS: Between April and June 2019, 951 eligible clients were tested for HIV: 898 (94.4%) chose option 1, 30 (3.25%) chose option 2 and 23 (2.4%) chose option 3. Option 1 clients cited their trust in the service and a desire for immediate counselling, support and guidance from trusted providers as the reasons for their choice. Young people were not confident in their expertise to conduct HIVST. Concerns about limited privacy, confidentiality and lack of support in the event of an HIV-positive result were barriers for off-site HIVST.

CONCLUSIONS: In the context of supportive, trusted and youth-friendly providers, youth clients overwhelmingly preferred provider-delivered HIV testing over client-initiated HIVST or HIVST off site. This highlights the importance of listening to youth to improve engagement in testing. While young people want autonomy in choosing when, where and how to test, they do not want to necessarily test on their own. They desire quality in-person counselling, guidance and support, alongside privacy and confidentiality. To increase the appeal of HIVST for youth, greater provision of access to private spaces is required, and accessible pre- and post-test counselling and support may improve uptake.

PMID:34569710 | DOI:10.1002/jia2.25815