Severe anemia in late pregnancy: a retrospective study at a tertiary care rural medical college in Gujarat, India

Background: Anaemia in pregnancy is the commonest medical disorder in developing countries like India. It has multifactorial etiology and is associated with increased maternal and perinatal morbidity and mortality. The study aimed at analyzing the socio-demographic variables and also the maternal and perinatal outcome of pregnant women admitted to labour room with severe anaemia (Hb <7 gm%) late in pregnancy.Methods: This is a retrospective observational study done at a tertiary care rural medical college in Gujarat over a 3 year period from January 2014 to December 2016.Results: Results of the study were analyzed. Out of 3963 deliveries during the study period 225 (5.6%) patients were severely anaemic. There were 177 (78.6%) unbooked patients and 169 (75.1%) were multigravidas. Majority of patients belonged to under 24 yr age group. Maternal complications were in form of preterm labour (44%), pre-eclampsia-ecclampsia (24.8%), cardiac failure (2.2%), PPH (2.2%) maternal death (0.4%). Neonatal outcome was analyzed in terms of prematurity (44%), LBW (24.8%), NICU admission (15.1%), still birth (4.4%), neonatal death (11.5%).Conclusions: Severe anaemia during pregnancy is associated with adverse maternal and perinatal outcome. It is also one of the preventable indirect cause of maternal mortality. Imparting health education to adolescent girls, regular antenatal check-ups, early diagnosis and treatment along with active participation of ASHA workers at grass-root level might help in bringing down the prevalence. A more focused approach is warranted towards pregnant women in rural and underdeveloped areas of India

ASSESSING RISK INTRODUCED THROUGH A CODE CHANGE

Techniques are presented herein that shift the risk assessment focus during a software development process, away from the traditional end-of-process review (when a new feature is delivered, or an application is deployed) to earlier in the process when developers are actively at work. Such an approach allows a developer to assess the risk that a candidate software change is about to introduce prior to the developer committing that change, providing the developer with time (during the early portion of the process) to revisit the software and eliminate the identified risk. Aspects of the presented techniques leverage elements of a continuous integration (CI) and continuous deployment (CD) facility, the results that are available from existing unit and end-to-end tests, and the collection and analysis of OpenTelemetry (OTEL)-based metrics, events, logs, and traces (MELT) data to deliver security insights

IDENTIFYING ENTERPRISE RISK BASED ON BUSINESS CONTEXT WITH THREAT INTELLIGENCE

Presented herein are techniques that facilitate prioritizing risk mitigation efforts for business-critical services and transactions through the incorporation of a business context into threat intelligence scoring. Under aspects of the presented techniques, traditional threat intelligence tools may be employed to evaluate the risk that is associated with an enterprise asset; the results of such an evaluation may then be augmented with an enterprise-assigned business value for the asset to derive the asset’s business risk; and such a business risk may be leveraged to prioritize risk mitigation efforts, may be combined with other business risks, etc. The above-described process may be referred to herein as Business Risk Management (BRM)

PHD2 is a regulator for glycolytic reprogramming in macrophages.

The prolyl-4-hydroxylase domain (PHD) enzymes are regarded as the molecular oxygen sensors. There is an interplay between oxygen availability and cellular metabolism, which in turn has significant effects on the functionality of innate immune cells, such as macrophages. However, if and how PHD enzymes affect macrophage metabolism are enigmatic. We hypothesized that macrophage metabolism and function can be controlled via manipulation of PHD2. We characterized the metabolic phenotypes of PHD2-deficient RAW cells and primary PHD2 knockout bone marrow-derived macrophages (BMDM). Both showed typical features of anaerobic glycolysis, which were paralleled by increased pyruvate dehydrogenase kinase 1 (PDK1) protein levels and a decreased pyruvate dehydrogenase enzyme activity. Metabolic alterations were associated with an impaired cellular functionality. Inhibition of PDK1 or knockout of hypoxia-inducible factor 1 alpha (HIF-1 alpha) reversed the metabolic phenotype and impaired the functionality of the PHD2-deficient RAW cells and BMDM. Taking these results together, we identified a critical role of PHD2 for a reversible glycolytic reprogramming in macrophages with a direct impact on their function. We suggest that PHD2 serves as an adjustable switch to control macropha(g)e behavior

Caste Matters: Perceived Discrimination among Women in Rural India

Purpose: To examine the relationship of caste and class with perceived discrimination among pregnant women from rural western India. Methods: A cross-sectional survey was administered to 170 pregnant women in rural Gujarat, India, who were enrolled in a longitudinal cohort study. Everyday Discrimination Scale and Experiences of Discrimination questionnaires were used to assess perceived discrimination and response to discrimination. Based on self-reported caste, women were classified to three categories with increasing historical disadvantage: General, Other Backward Castes (OBC), and Scheduled Caste or Tribes (SC/ST). Socioeconomic class was determined using standardized Kuppuswamy scale. Regression models for count and binomial data were used to examine association of caste and class with experience of discrimination and response to discrimination. Results: 68% of women experienced discrimination. After adjusting for confounders, there was a consistent trend and association of discrimination with caste but not class. In comparison to General Caste, lower caste (OBC, SC/ST) women were more likely to 1) experience discrimination (OBC OR: 2.2, SC/ST: 4.1; p-trend: 0.01), 2) have a greater perceived discrimination score (OBC IRR: 1.3, SC/ST: 1.5; p-trend: 0.07), 3) accept discrimination (OBC OR: 6.4, SC/ST: 7.6; p-trend: \u3c 0.01), and 4) keep to herself about discrimination (OBC OR: 2.7, SC/ST: 3.6; p-trend: 0.04). Conclusion: The differential experience of discrimination by lower caste women in comparison to upper caste women and their response to such experiences highlight the importance of studying discrimination to understand existing caste-based disparities

Atrial flutter and fibrillation in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension in the ASPIRE registry: comparison of rate versus rhythm control approaches

Background The development of atrial flutter and fibrillation (AFL/AF) in patients with pre-capillary pulmonary hypertension has been associated with an increased risk of morbidity and mortality. Rate and rhythm control strategies have not been directly compared. Methods Eighty-four patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) with new-onset AFL/AF were identified in the ASPIRE registry. First, baseline characteristics and rates of sinus rhythm (SR) restoration of 3 arrhythmia management strategies (rate control, medical rhythm control and DC cardioversion, DCCV) in an early (2009–13) and later (2014–19) cohort were compared. Longer-term outcomes in patients who achieved SR versus those who did not were then explored. Results Sixty (71%) patients had AFL and 24 (29%) AF. Eighteen (22%) patients underwent rate control, 22 (26%) medical rhythm control and 44 (52%) DCCV. SR was restored in 33% treated by rate control, 59% medical rhythm control and 95% DCCV (p < 0.001). Restoration of SR was associated with greater improvement in functional class (FC) and Incremental Shuttle Walk Distance (p both <0.05). It also independently predicted superior survival (3-year survival 62% vs 23% in those remaining in AFL/AF, p < 0.0001). In addition, FC III/IV independently predicted higher mortality (HR 2.86, p = 0.007). Right atrial area independently predicted AFL/AF recurrence (OR 1.08, p = 0.01). DCCV was generally well tolerated with no immediate major complications. Conclusions Restoration of SR is associated with superior functional improvement and survival in PAH/CTEPH compared with rate control. DCCV is generally safe and is more effective than medical therapy at achieving SR

Critical care outcomes in patients with pre-existing pulmonary hypertension: insights from the ASPIRE registry

Pulmonary Hypertension (PH) is a life-shortening condition characterised by episodes of decompensation precipitated by factors such as disease progression, arrhythmias and sepsis. Surgery and pregnancy also place additional strain on the right ventricle. Data on critical care management in patients with pre-existing PH are scarce. We conducted a retrospective observational study of a large cohort of patients admitted to the critical care unit of a national referral centre between 2000–17 to establish acute mortality, evaluate predictors of in-hospital mortality and establish longer-term outcomes in survivors to hospital discharge. 242 critical care admissions involving 206 patients were identified. Hospital survival was 59.3%, 94% and 92% for patients admitted for medical, surgical or obstetric reasons. Medical patients had more severe physiological and laboratory perturbations than patients admitted following surgical or obstetric interventions. Higher APACHE II score, age and lactate, and lower SpO2/FiO2, platelet count and sodium level were identified as independent predictors of hospital mortality. An exploratory risk score, OPALS (Oxygen (SpO2:FiO2), ≤185; Platelets, ≤196×109·L−1; Age, ≥37.5 years; Lactate, ≥2.45 mmol·L−1; Sodium, ≤130.5 mmol·L−1), identified medical patients at increasing risk of hospital mortality. One of nine patients (11%) who were invasively ventilated for medical decompensation and 50% of patients receiving renal replacement therapy left hospital alive. There was no significant difference in exercise capacity or functional class between follow-up and pre-admission in patients who survived to discharge. These data have clinical utility in guiding critical care management of patients with known PH. The exploratory OPALS score requires validation

A Switch from a Gradient to a Threshold Mode in the Regulation of a Transcriptional Cascade Promotes Robust Execution of Meiosis in Budding Yeast

Tight regulation of developmental pathways is of critical importance to all organisms, and is achieved by a transcriptional cascade ensuring the coordinated expression of sets of genes. We aimed to explore whether a strong signal is required to enter and complete a developmental pathway, by using meiosis in budding yeast as a model. We demonstrate that meiosis in budding yeast is insensitive to drastic changes in the levels of its consecutive positive regulators (Ime1, Ime2, and Ndt80). Entry into DNA replication is not correlated with the time of transcription of the early genes that regulate this event. Entry into nuclear division is directly regulated by the time of transcription of the middle genes, as premature transcription of their activator NDT80, leads to a premature entry into the first meiotic division, and loss of coordination between DNA replication and nuclear division. We demonstrate that Cdk1/Cln3 functions as a negative regulator of Ime2, and that ectopic expression of Cln3 delays entry into nuclear division as well as NDT80 transcription. Because Ime2 functions as a positive regulator for premeiotic DNA replication and NDT80 transcription, as well as a negative regulator of Cdk/Cln, we suggest that a double negative feedback loop between Ime2 and Cdk1/Cln3 promotes a bistable switch from the cell cycle to meiosis. Moreover, our results suggest a regulatory mode switch that ensures robust meiosis as the transcription of the early meiosis-specific genes responds in a graded mode to Ime1 levels, whereas that of the middle and late genes as well as initiation of DNA replication, are regulated in a threshold mode