Comparison of Noninvasive Oscillometric and Intra-Arterial Blood Pressure Measurements in Children Admitted to the Pediatric Intensive Care Unit.

Intra-arterial blood pressure (IABP) measurement, although considered the gold standard in critically ill children, is associated with certain risks and lacks widespread availability. This study was conducted to determine the differences and agreements between oscillometric non-invasive blood pressure (NIBP) and invasive IABP measurements in children. Inclusion criteria consisted of children (from 1 month to 18 years) admitted to the pediatric intensive care unit (PICU) of a teaching hospital who required arterial catheter insertion for blood pressure (BP) monitoring. The comparison between IABP and NIBP was studied using paired t -test, Bland-Altman analysis, and Pearson's correlation coefficient. In total, 4,447 pairs of simultaneously recorded hourly NIBP and IABP measurements were collected from 65 children. Mean differences between IABP and NIBP were -3.6 ± 12.85, -4.7 ± 9.3, and -3.12 ± 9.30 mm Hg for systolic, diastolic, and mean arterial BP, respectively ( p < 0.001), with wide limits of agreement. NIBP significantly overestimated BP ( p < 0.001) in all three BP states (hypotensive, normotensive, and hypertensive), except systolic blood pressure (SBP) during hypertension where IABP was significantly higher. The difference in SBP was most pronounced during hypotension. The difference in SBP was significant in children <10 years ( p < 0.001), with the maximum difference being in infants. It was insignificant in adolescents ( p = 0.28) and underweight children ( p = 0.55). NIBP recorded significantly higher BP in all states of BP except SBP in the hypertensive state. SBP measured by NIBP tended to be the most reliable in adolescents and underweight children. NIBP was the most unreliable in infants, obese children, and during hypotension.

Genome replication in asynchronously growing microbial populations.

Biological cells replicate their genomes in a well-planned manner. The DNA replication program of an organism determines the timing at which different genomic regions are replicated, with fundamental consequences for cell homeostasis and genome stability. In a growing cell culture, genomic regions that are replicated early should be more abundant than regions that are replicated late. This abundance pattern can be experimentally measured using deep sequencing. However, a general quantitative theory linking this pattern to the replication program is still lacking. In this paper, we predict the abundance of DNA fragments in asynchronously growing cultures from any given stochastic model of the DNA replication program. As key examples, we present stochastic models of the DNA replication programs in budding yeast and Escherichia coli. In both cases, our model results are in excellent agreement with experimental data and permit to infer key information about the replication program. In particular, our method is able to infer the locations of known replication origins in budding yeast with high accuracy. These examples demonstrate that our method can provide insight into a broad range of organisms, from bacteria to eukaryotes.

Opposing Responses to Scarcity Emerge from Functionally Unique Sociality Drivers.

AbstractFrom biofilms to whale pods, organisms across taxa live in groups, thereby accruing numerous diverse benefits of sociality. All social organisms, however, pay the inherent cost of increased resource competition. One expects that when resources become scarce, this cost will increase, causing group sizes to decrease. Indeed, this occurs in some species, but there are also species for which group sizes remain stable or even increase under scarcity. What accounts for these opposing responses? We present a conceptual framework, literature review, and theoretical model demonstrating that differing responses to sudden resource shifts can be explained by which sociality benefit exerts the strongest selection pressure on a particular species. We categorize resource-related benefits of sociality into six functionally distinct classes and model their effect on the survival of individuals foraging in groups under different resource conditions. We find that whether, and to what degree, the optimal group size (or correlates thereof) increases, decreases, or remains constant when resource abundance declines depends strongly on the dominant sociality mechanism. Existing data, although limited, support our model predictions. Overall, we show that across a wide diversity of taxa, differences in how group size shifts in response to resource declines can be driven by differences in the primary benefits of sociality.

Speed variations of bacterial replisomes.

Replisomes are multi-protein complexes that replicate genomes with remarkable speed and accuracy. Despite their importance, their dynamics is poorly characterized, especially in vivo. In this paper, we present an approach to infer the replisome dynamics from the DNA abundance distribution measured in a growing bacterial population. Our method is sensitive enough to detect subtle variations of the replisome speed along the genome. As an application, we experimentally measured the DNA abundance distribution in Escherichia coli populations growing at different temperatures using deep sequencing. We find that the average replisome speed increases nearly fivefold between 17 °C and 37 °C. Further, we observe wave-like variations of the replisome speed along the genome. These variations correlate with previously observed variations of the mutation rate, suggesting a common dynamical origin. Our approach has the potential to elucidate replication dynamics in E. coli mutants and in other bacterial species.

Search and Localization Dynamics of the CRISPR-Cas9 System.

The CRISPR-Cas9 system acts as the prokaryotic immune system and has important applications in gene editing. The protein Cas9 is one of its crucial components. The role of Cas9 is to search for specific target sequences on the DNA and cleave them. In this Letter, we introduce a model of facilitated diffusion for Cas9 and fit its parameters to single-molecule experiments. Our model confirms that Cas9 search for targets by sliding, but shows that its sliding length is rather short. We then investigate how Cas9 explores a long stretch of DNA containing randomly placed targets. We solve this problem by mapping it into the theory of Anderson localization in condensed matter physics. Our theoretical approach rationalizes experimental evidence on the distribution of Cas9 molecules along the DNA.

Comparison of Clinical Features and Outcome of Dengue Fever and Multisystem Inflammatory Syndrome in Children Associated With COVID-19 (MIS-C).

OBJECTIVE: To identify clinical and laboratory features that differentiate dengue fever patients from MIS-C patients and determine their outcomes. Methods: This comparative cross-sectional study was done at a tertiary care teaching institute. We enrolled all hospitalized children aged 1 month - 18 years and diagnosed with either MIS-C and/or dengue fever according to WHO criteria between June and December, 2020. Clinical and laboratory features and outcomes were recorded on a structured proforma. RESULTS: During the study period 34 cases of MIS-C and 83 cases of Dengue fever were enrolled. Mean age of MIS-C cases (male, 86.3%) was 7.89 (4.61) years. MIS-C with shock was seen in 15 cases (44%), MIS-C without shock in 17 cases (50%) and Kawasaki disease-like presentation in 2 cases (6%). Patients of MIS-C were younger as compared to dengue fever (P=0.002). Abdominal pain and erythematous rash were more common in dengue fever. Of the inflammatory markers, mean C reactive protein was higher in MIS-C patients [100.2 (85.1) vs 16.9 (29.3) mg/dL] (P<0.001). In contrast, serum ferritin levels were higher in dengue fever patients (P=0.03). Mean hospital stay (patient days) was longer in MIS- C compared to dengue fever (8.6 vs 6.5 days; P=0.014). CONCLUSION: Clinical and laboratory features can give important clues to differentiate dengue fever and MIS-C and help initiate specific treatment.

Role of montelukast in multitrigger wheezers attending chest clinic in Punjab, India.

BACKGROUND: Wheeze is seen in 40% of preschool children, one-third of these may develop recurrent wheeze. Montelukast is an oral, once a day, easy to give therapy but there is no definite evidence to support its use in a recent meta-analysis. Present study was done to evaluate role of daily montelukast and various factors affecting the outcome after therapy in multitrigger wheeze (MTW). METHODS: A prospective study conducted in Pediatric chest clinic over 18 months at DMCH, Ludhiana. Children from 6 months to 5 years, diagnosed cases of MTW were started on montelukast. Diagnosis based on symptoms of recurrent wheeze triggered by various allergens/precipitants was made by pediatrician in charge of chest clinic. Children were followed up at 1 and 3 months. They were labeled as controlled, partially controlled, or uncontrolled as per global initiative for asthma guidelines. Data were used to compare the outcome related to various factors. RESULTS: Total 139 out of 150 children came for regular follow-up. At the end of 3 months, 94 (67.7%) were controlled, 8 (5.7%) partially controlled, and 37 (26.6%) children remained uncontrolled on montelukast. Factors associated with poor control were onset of symptoms at younger age (<6 months of age), family history of allergies, prior multiple visits or hospitalizations due to MTW, use of MDI in the past. No significant side effects were reported by parents. CONCLUSION: Symptomatically two-third of children became better after starting montelukast. There were few factors which resulted in poorer control in subset of patients.

Extended Residual-State Creep Test and Its Application for Landslide Stability Assessment.

This paper contains the results of a newly developed residual-state creep test performed to determine the behavior of a selected geomaterial in the context of reactivated landslides. Soil and rock creep is a time-dependent phenomenon in which a deformation occurs under constant stress. Based on the examination results, it was found that the tested clayey material (from Kobe, Japan) shows tertiary creep behavior only under shear stress higher than the residual strength condition and primary and secondary creep behavior under shear stress lower or equal to the residual strength condition. Based on the data, a model for predicting the critical or failure time is introduced. The study traces the development of the limit state based on the contact model corresponding to Blair's body. The time to occurrence of the conditions necessary for unlimited creep on the surface is estimated. As long-term precipitation and infiltrating water in the area of the landslides are identified as the key phenomena initiating collapse, the work focuses on the prediction of landslides with identified surfaces of potential damage as a result of changes in the saturation state. The procedure outlined is applied to a case study and considerations as to when the necessary safety work should be carried out are presented.

Oral cyclophosphamide therapy in 100 children with steroid-sensitive nephrotic syndrome: experience from a developing country.

BACKGROUND: Oral cyclophosphamide (CYP) is an important therapeutic agent in treatment of steroid-sensitive nephrotic syndrome having a steroid-dependent (SD) or frequent relapsing (FR) course. This retrospective observational study aimed to determine response to oral CYP and factors associated with positive response in these patients. METHODS: We studied 100 children (male; 75) with FR (19%) and SD (81%) NS treated with CYP in the Pediatric Nephrology clinic. Responders were defined as children in whom steroids were stopped for at least 6 months following CYP and factors affecting response were analysed. Relapse-free survival was estimated by Kaplan-Meier method. RESULTS: Median age at onset of NS was 3 years (IQR 2-5.2). Median age at CYP was 5.7 years (IQR 3.7-7.9). Fifty percent of patients were in the responder group at 6 months of CYP. Relapse-free survival post CYP therapy was 31% at 1 year, 11% at 2 years. Factors predicting good response were age at onset of NS > 3 years with 61.2% response at 6 months (p = 0.028) and older age at CYP initiation (> 5 years) with 61% response (p = 0.008). Multivariate regression analysis showed age at start of CYP > 5 years was an independent factor for good response (p = 0.044, OR = 2.903, CI -1.03 to 8.18). CONCLUSIONS: Judicious selection of patients, especially with age of onset of NS more than 3 years and initiation of CYP after age of 5 years, can predict better response in this group of patents.

A Case Report of An Iris Epithelial Cyst Masquerading As Iris Cysticercosis.

INTRODUCTION: Iris cysts can be primary or secondary. It is common to mistake a parasitic cyst for a benign pigment epithelial cyst. However, we report a case where a benign cyst was mistaken for a parasitic cyst. CASE: A 50-year-old gentleman was seen in our OPD with gradual, progressive, painless diminution of vision in the right eye over past 5 Months. He was found to have a cystic lesion in the iris encroaching upon the pupil. OBSERVATIONS: Ultrasound biomicroscopy showed features characteristic of cysticercosis. In-toto excision of the cyst was done and was sent for histopathological examination. Histopathology failed to reveal features consistent with cysticercosis and instead showed characteristics of epithelial cyst of the iris. CONCLUSION: Histopathological examination should be done for all cystic lesions of the iris to confirm diagnosis.

Nonuniversal opinion dynamics driven by opposing external influences.

We study the opinion dynamics of a generalized voter model in which N voters are additionally influenced by two opposing news sources whose effect is to promote political polarization. As the influence of these news sources is increased, the mean time to reach consensus scales nonuniversally as N^{α}. The parameter α quantifies the influence of the news sources and increases without bound as the news sources become increasingly influential. The time to reach a politically polarized state, in which roughly equal fractions of the populations are in each opinion state, is generally short, and the steady-state opinion distribution exhibits a transition from near consensus to a politically polarized state as a function of α.

Utilization of the renal angina index in PICU of a developing country for prediction of subsequent severe acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is independently associated with worsened morbidity and increased mortality in the pediatric intensive care unit (PICU). AKI risk score, termed renal angina index (RAI) is used in developed countries to predict subsequent severe AKI. Very few studies have investigated application of RAI in the PICU of a developing country. This prospective observational study aimed to predict severe subsequent AKI in children admitted to PICU using RAI. METHODS: Over 1 year, children admitted to PICU aged 1 month-18 years old, with no previous kidney disease, were included. RAI was assessed from 8 to 12 h of PICU admission (day 0). RAI was calculated from product of the renal risk and renal injury score. Renal angina positivity was defined as RAI ≥ 8. On day 3, serum creatinine was estimated and estimated glomerular filtrration rate (eGFR) calculated. RAI was correlated with presence/absence of subsequent (day 3) severe AKI. RAI positivity was also correlated with duration of PICU stay, need for dialysis, mechanical ventilation, and mortality. RESULTS: RAI positivity was seen in 16.7% cases, of which 36.2% developed AKI at 4 days vs. 2.3% in RAI-negative cases (p < 0.001). Mean duration of PICU stay in the RAI-positive group was 7.19 ± 5.13 days vs. 4.72 ± 2.71 days in the RAI-negative group (p < 0.001). Mortality was seen in 31.9% of RAI-positive cases vs. 2% in RAI-negative cases (p < 0.001). CONCLUSIONS: RAI could be used as a simple and important bedside tool to predict patients at risk of severe AKI.

Multidimensional impact on families of children with steroid-sensitive nephrotic syndrome.

AIM: Children with nephrotic syndrome (NS) have prolonged disease course with relapses requiring frequent visits and prolonged steroid therapy with their long-term concerns. All these factors affect the child and their families in many domains of functioning. The objective of this study was to assess multidimensional impact on families of children with nephrotic syndrome using (PedsQL) Family Impact Module (FIM). METHODS: This cross-sectional study was conducted in a paediatric nephrology clinic of a tertiary care hospital. Fifty cases of steroid-sensitive nephrotic syndrome between age group of 2-18 years were included, and equal age-sex matched healthy children were taken as controls. Baseline demographic factors including age, gender and education status, modified Kuppuswamy's socio-economic status were collected and clinical variables of NS cases were recorded. FIM is a parent-reported instrument that measures the impact of paediatric chronic health conditions on care giver's HRQOL and their family function. Mean FIM scores were compared among the cases and controls, and different predictive factors affecting family impact (FI) were analysed. RESULTS: The FI total score showed significantly lower scores in cases (mean score: 60.76 ± 15.66) as compared to controls (mean 100). Among the individual groups, lowest scores were found in two domains, namely 'worry' and 'emotional function' with mean scores of 46.20 ± 20.66 and 46.80 ± 24.61, respectively, although other domains were also significantly affected. CONCLUSION: FI score should be evaluated in all cases of NS as parenting such children may significantly affect all domains of family functioning.

Transport of organelles by elastically coupled motor proteins.

Motor-driven intracellular transport is a complex phenomenon where multiple motor proteins simultaneously attached on to a cargo engage in pulling activity, often leading to tug-of-war, displaying bidirectional motion. However, most mathematical and computational models ignore the details of the motor-cargo interaction. A few studies have focused on more realistic models of cargo transport by including elastic motor-cargo coupling, but either restrict the number of motors and/or use purely phenomenological forms for force-dependent hopping rates. Here, we study a generic model in which N motors are elastically coupled to a cargo, which itself is subjected to thermal noise in the cytoplasm and to an additional external applied force. The motor-hopping rates are chosen to satisfy detailed balance with respect to the energy of elastic stretching. With these assumptions, an (N + 1) -variable master equation is constructed for dynamics of the motor-cargo complex. By expanding the hopping rates to linear order in fluctuations in motor positions, we obtain a linear Fokker-Planck equation. The deterministic equations governing the average quantities are separated out and explicit analytical expressions are obtained for the mean velocity and diffusion coefficient of the cargo. We also study the statistical features of the force experienced by an individual motor and quantitatively characterize the load-sharing among the cargo-bound motors. The mean cargo velocity and the effective diffusion coefficient are found to be decreasing functions of the stiffness. While the increase in the number of motors N does not increase the velocity substantially, it decreases the effective diffusion coefficient which falls as 1/N asymptotically. We further show that the cargo-bound motors share the force exerted on the cargo equally only in the limit of vanishing elastic stiffness; as stiffness is increased, deviations from equal load sharing are observed. Numerical simulations agree with our analytical results where expected. Interestingly, we find in simulations that the stall force of a cargo elastically coupled to motors is independent of the stiffness of the linkers.

Outcome of children with acute disseminated encephalomyelitis in a tertiary care center in India.

Acute disseminated encephalomyelitis (ADEM) is an immune-mediated disease of the brain that follows viral infection or vaccination, or even appears spontaneously. The objective of the study was to evaluate the clinical, neuroimaging and laboratory profiles of children with ADEM. Seventeen children admitted to the Pediatric Department of Dayanand Medical College and Hospital, Ludhiana, whose cases were consistent with the diagnosis of ADEM, were included. Their clinical and neuroimaging profiles and outcomes were studied. The most common presenting features were fever (71%), altered sensorium (59%) and headache and convulsions (41%). Brain MRI identified lesions in subcortical white matter (75%) and periventricular white matter (38%). Most patients were treated with corticosteroids. A favorable outcome was seen in 88% of patients. Although 59% of patients had neurologic sequelae at discharge, only one patient had a major neurological deficit at follow-up. Prognosis for survival and outcome was good in the majority of patients. Neurological sequelae at discharge do not predict poor outcome.

Memory, bias, and correlations in bidirectional transport of molecular-motor-driven cargoes.

Molecular motors are specialized proteins that perform active, directed transport of cellular cargoes on cytoskeletal filaments. In many cases, cargo motion powered by motor proteins is found to be bidirectional, and may be viewed as a biased random walk with fast unidirectional runs interspersed with slow tug-of-war states. The statistical properties of this walk are not known in detail, and here, we study memory and bias, as well as directional correlations between successive runs in bidirectional transport. We show, based on a study of the direction-reversal probabilities of the cargo using a purely stochastic (tug-of-war) model, that bidirectional motion of cellular cargoes is, in general, a correlated random walk. In particular, while the motion of a cargo driven by two oppositely pulling motors is a Markovian random walk, memory of direction appears when multiple motors haul the cargo in one or both directions. In the latter case, the Markovian nature of the underlying single-motor processes is hidden by internal transitions between degenerate run and pause states of the cargo. Interestingly, memory is found to be a nonmonotonic function of the number of motors. Stochastic numerical simulations of the tug-of-war model support our mathematical results and extend them to biologically relevant situations.