Efficacy of Transcerebellar Diameter / Abdominal Circumference Ratio Versus Head Circumference/ Abdominal Circumference Ratio in Prediction of Asymmetrical Intrauterine Growth Retardation

INTRODUCTION: The Process of birth is the most dangerous journey an individual undertakes. A healthy newborn is the goal of every expectant mother and her obstetrician. A fetus with an estimated weight below the 10 th percentile for a given gestational age is considered to have fetal growth restriction (FGR) also called as intrauterine growth restriction (IUGR). It is estimated that the incidence of fetal growth restriction is 3-10%. The growth potential of the fetus is dictated, on one hand by the fetal genome and on the other hand by the intrauterine environment. The intrauterine environment is under the influence of both maternal and placental factors. Fetal growth restriction is linked to an increased risk perinatal morbidity and mortality. Growth restricted fetuses are more prone to intrauterine hypoxia / asphyxia. Still birth and hypoxic ischemic encephalopathy (HIE) are more likely to occur in growth restricted fetuses. In addition, it has been also found that these growth restricted infants have increased 1-year infant mortality rate and abnormal neurological development. BACKGROUND: The purpose of the study is to compare the accuracy of transcerebellar diameter (TCD) /abdominal circumference (AC) ratio with head circumference (HC) / abdominal circumference (AC) ratio in predicting asymmetrical intrauterine growth retardation. AIMS AND OBJECTIVES OF THE STUDY To compare the accuracy of trans cerebellar diameter (TCD) / abdominal circumference ratio (AC) ratio with head circumference (HC) / abdominal circumference (AC) ratio in predicting asymmetrical IUGR. MATERIALS AND METHODS: A prospective study consisting of 200 antenatal women. Two groups are chosen control group (contains 100 normal cases) and study group (100 clinically suspected IUGR). TCD/AC ratio and HC/ AC ratio of normal group are calculated. mean and standard deviation are calculated for the normal group. Then the values of the study group is compared with the normal group. The values more than 2SD are labelled as IUGR (sonographically)Then those clinically suspected IUGR cases are followed up to delivery and post-delivery new ballard score and CAN score (clinical assessment of nutritional status at birth) are calculated. Number of ultrasonographically detected IUGR compared with number of true IUGR and accuracy of both TCD/AC ratio and HC/AC ratio is compared. True positive values, False positive values, sensitivity, specificity, positive predictive value, negative predictive value, diagnostic accuracy. Above mentioned are calculated and interpretation is done. RESULTS: Of 100 control group studied mean values and 2SD are calculated. These values are compared with study group. Sensitivity, specificity, PPV, NPV and diagnostic accuracy are compared for TCD/AC ratio and HC/ AC ratio. CONCLUSION: The TCD and AC measurements correlates well with gestational age. The TCD and AC has strong linear relationship, hence the TCD/AC ratio is fairly constant throughout pregnancy. TCD unlike AC is not affected in FGR, because of brain sparing. Hence, TCD/AC ratio can be a screening test to diagnose FGR in the antenatal period. However TCD/AC ratio had a better diagnostic validity and accuracy compared to HC/ AC ratio in predicting asymmetrical IUGR

Longitudinal Study on Sustained Attention to Response Task (SART): Clustering Approach for Mobility and Cognitive Decline

The Sustained Attention to Response Task (SART) is a computer-based go/no-go task to measure neurocognitive function in older adults. However, simplified average features of this complex dataset lead to loss of primary information and fail to express associations between test performance and clinically meaningful outcomes. Here, we combine a novel method to visualise individual trial (raw) information obtained from the SART test in a large population-based study of ageing in Ireland and an automatic clustering technique. We employed a thresholding method, based on the individual trial number of mistakes, to identify poorer SART performances and a fuzzy clusters algorithm to partition the dataset into 3 subgroups, based on the evolution of SART performance after 4 years. Raw SART data were available for 3468 participants aged 50 years and over at baseline. The previously reported SART visualisation-derived feature 'bad performance', indicating the number of SART trials with at least 4 mistakes, and its evolution over time, combined with the fuzzy c-mean (FCM) algorithm, individuated 3 clusters corresponding to 3 degrees of physiological dysregulation. The biggest cluster (94% of the cohort) was constituted by healthy participants, a smaller cluster (5% of the cohort) by participants who showed improvement in cognitive and psychological status, and the smallest cluster (1% of the cohort) by participants whose mobility and cognitive functions dramatically declined after 4 years. We were able to identify in a cohort of relatively high-functioning community-dwelling adults a very small group of participants who showed clinically significant decline. The selected smallest subset manifested not only mobility deterioration, but also cognitive decline, the latter being usually hard to detect in population-based studies. The employed techniques could identify at-risk participants with more specificity than current methods, and help clinicians better identify and manage the small proportion of community-dwelling older adults who are at significant risk of functional decline and loss of independence

Immune responses during COVID-19 infection

Over the past 16 years, three coronaviruses (CoVs), severe acute respiratory syndrome CoV (SARS-CoV) in 2002, Middle East respiratory syndrome CoV (MERS-CoV) in 2012 and 2015, and SARS-CoV-2 in 2020, have been causing severe and fatal human epidemics. The unpredictability of coronavirus disease-19 (COVID-19) poses a major burden on health care and economic systems across the world. This is caused by the paucity of in-depth knowledge of the risk factors for severe COVID-19, insufficient diagnostic tools for the detection of SARS-CoV-2, as well as the absence of specific and effective drug treatments. While protective humoral and cellular immune responses are usually mounted against these betacoronaviruses, immune responses to SARS-CoV2 sometimes derail towards inflammatory tissue damage, leading to rapid admissions to intensive care units. The lack of knowledge on mechanisms that tilt the balance between these two opposite outcomes poses major threats to many ongoing clinical trials dealing with immunostimulatory or immunoregulatory therapeutics. This review will discuss innate and cognate immune responses underlying protective or deleterious immune reactions against these pathogenic coronaviruses

Circulating senescent myeloid cells drive blood brain barrier breakdown and neurodegeneration

Neurodegenerative diseases (ND) are characterized by progressive loss of neuronal function. Mechanisms of ND pathogenesis are incompletely understood, hampering the development of effective therapies. Langerhans cell histiocytosis (LCH) is an inflammatory neoplastic disorder caused by hematopoietic progenitors expressing MAPK activating mutations that differentiate into senescent myeloid cells that drive lesion formation. Some patients with LCH subsequently develop progressive and incurable neurodegeneration (LCH-ND). Here, we show that LCH-ND is caused by myeloid cells that are clonal with peripheral LCH cells. We discovered that circulating BRAF V600E $^{+}$ myeloid cells cause the breakdown of the blood-brain barrier (BBB), enhancing migration into the brain parenchyma where they differentiate into senescent, inflammatory CD11a $^{+}$ macrophages that accumulate in the brainstem and cerebellum. Blocking MAPK activity and senescence programs reduced parenchymal infiltration, neuroinflammation, neuronal damage and improved neurological outcome in preclinical LCH-ND. MAPK activation and senescence programs in circulating myeloid cells represent novel and targetable mechanisms of ND

Early- Onset Stroke and Vasculopathy Associated with Mutations in ADA2

Adenosine deaminase 2 (ADA2) is an enzyme involved in purine metabolism and a growth factor that influences the development of endothelial cells and leukocytes. This study shows that defects in ADA2 cause recurrent fevers, vascular pathologic features, and mild immunodeficiency. Patients with autoinflammatory disease sometimes present with clinical findings that encompass multiple organ systems.(1) Three unrelated children presented to the National Institutes of Health (NIH) Clinical Center with intermittent fevers, recurrent lacunar strokes, elevated levels of acute-phase reactants, livedoid rash, hepatosplenomegaly, and hypogammaglobulinemia. Collectively, these findings do not easily fit with any of the known inherited autoinflammatory diseases. Hereditary or acquired vascular disorders can have protean manifestations yet be caused by mutations in a single gene. Diseases such as the Aicardi-Goutieres syndrome,(2),(3) polypoidal choroidal vasculopathy,(4) sickle cell anemia,(5) livedoid vasculopathy,(6) and the small-vessel vasculitides(7),(8) are examples of systemic ...</p

Early-Onset Stroke and Vasculopathy Associated with Mutations in ADA2

We observed a syndrome of intermittent fevers, early-onset lacunar strokes and other neurovascular manifestations, livedoid rash, hepatosplenomegaly, and systemic vasculopathy in three unrelated patients. We suspected a genetic cause because the disorder presented in early childhood

The Importance of Age in the Prediction of Mortality by a Frailty Index: A Machine Learning Approach in the Irish Longitudinal Study on Ageing

The quantification of biological age in humans is an important scientific endeavor in the face of ageing populations. The frailty index (FI) methodology is based on the accumulation of health deficits and captures variations in health status within individuals of the same age. The aims of this study were to assess whether the addition of age to an FI improves its mortality prediction and whether the associations of the individual FI items differ in strength. We utilized data from The Irish Longitudinal Study on Ageing to conduct, by sex, machine learning analyses of the ability of a 32-item FI to predict 8-year mortality in 8174 wave 1 participants aged 50 or more years. By wave 5, 559 men and 492 women had died. In the absence of age, the FI was an acceptable predictor of mortality with AUCs of 0.7. When age was included, AUCs improved to 0.8 in men and 0.9 in women. After age, deficits related to physical function and self-rated health tended to have higher importance scores. Not all FI variables seemed equally relevant to predict mortality, and age was by far the most relevant feature. Chronological age should remain an important consideration when interpreting the prognostic significance of an FI

SART and Individual Trial Mistake Thresholds: Predictive Model for Mobility Decline

The Sustained Attention to Response Task (SART) has been used to measure neurocognitive functions in older adults. However, simplified average features of this complex dataset may result in loss of primary information and fail to express associations between test performance and clinically meaningful outcomes. Here, we describe a new method to visualise individual trial (raw) information obtained from the SART test, vis-à-vis age, and groups based on mobility status in a large population-based study of ageing in Ireland. A thresholding method, based on the individual trial number of mistakes, was employed to better visualise poorer SART performances, and was statistically validated with binary logistic regression models to predict mobility and cognitive decline after 4 years. Raw SART data were available for 4864 participants aged 50 years and over at baseline. The novel visualisation-derived feature bad performance, indicating the number of SART trials with at least 4 mistakes, was the most significant predictor of mobility decline expressed by the transition from Timed Up-and-Go (TUG) &lt; 12 to TUG ≥ 12 s (OR = 1.29; 95% CI 1.14–1.46; p &lt; 0.001), and the only significant predictor of new falls (OR = 1.11; 95% CI 1.03–1.21; p = 0.011), in models adjusted for multiple covariates. However, no SART-related variables resulted significant for the risk of cognitive decline, expressed by a decrease of ≥2 points in the Mini-Mental State Examination (MMSE) score. This novel multimodal visualisation could help clinicians easily develop clinical hypotheses. A threshold approach to the evaluation of SART performance in older adults may better identify subjects at higher risk of future mobility decline

Dynamic Effect of Bortezomib on Nuclear Factor-B Activity and Gene Expression in Tumor Cells

ABSTRACT Nuclear factor-B (NF-B) influences the initiation, progression, and maintenance of diverse cancer types. Despite current therapeutic efforts to block hyperactive NF-B in cancer cells, the in vivo effects of a drug upon this complex pathway are unclear. We monitored NF-B activity and a fast-expressing reporter level simultaneously in head and neck squamous carcinoma cells by quantitative live microscopy. The real-time single cell assay revealed the tumor necrosis factor-␣-induced oscillation of NF-B was echoed by equally dynamic reporter expression rate. Bortezomib is a proteasome inhibitor whose anticancer action is partly mediated through inhibition of NF-B. When administered to preactivated cells, the drug gave rise to distinct inhibition dynamics, with discrete pulses of reporter induction remaining for hours. These findings suggest that, contrary to a simplistic presumption for a pathway &quot;blockade,&quot; the network dynamics and the intracellular pharmacokinetics of the inhibitor must be critically evaluated in developing strategies for optimal intervention of oncogenic pathways. Recent trends in clinical investigations clearly tend toward molecularly targeted approaches that are based on mechanisms underlying the pathophysiology of the disease. Often, the goal is to block the activity of a specific pathway that has been implicated in the disease process, by targeting a key component with a small molecule or an antibody, for example. It is seldom known whether the desired &quot;blockade&quot; is achieved in the relevant tissue and why paradoxical outcomes occur in certain cases. Here, we show that NF-B activity in tumor cells is altered by the action of a proteasome inhibitor in a complex way that cannot sufficiently be explained by the simplistic notion of pathway blockade. NF-B/Rel is a master regulator of inflammatory processes and has a growing list of cancers and other common diseases that require its aberrant activit