Category: Nevin Manimala

BMC Pregnancy Childbirth. 2022 Aug 26;22(1):664. doi: 10.1186/s12884-022-04978-4.

ABSTRACT

BACKGROUND: Postpartum depression is a common condition in the pregnancy and postpartum cycle. The development of this condition is multifactorial and can be influenced by previous traumas. This study sought to verify whether there is an association between having been exposed to mistreatment during childbirth and presenting symptoms suggestive of postpartum depression.

METHODS: This is a cross-sectional study, with the inclusion of 287 women without complications in childbirth, randomly selected from two maternity hospitals of Porto Alegre, southern Brazil, in 2016. Four weeks after delivery, the postpartum women answered a face-to-face interview about socioeconomic aspects, obstetric history, health history, and childbirth experience (practices and interventions applied) and completed the Edinburgh Postnatal Depression Scale (EPDS). From the perception of women regarding the practices performed in the context of childbirth care, a composite variable was created, using item response theory, to measure the level of mistreatment during childbirth. The items that made up this variable were: absence of a companion during delivery, feeling insecure and not welcome, lack of privacy, lack of skin-to-skin contact after delivery, not having understood the information shared with them, and not having felt comfortable to ask questions and make decisions about their care. To define symptoms suggestive of postpartum depression, reflecting on increased probability of this condition, the EPDS score was set at ≥ 8. Poisson Regression with robust variance estimation was used for modeling.

RESULTS: Women who experienced mistreatment during childbirth had a higher prevalence of symptoms suggestive of postpartum depression (PR 1.55 95% CI 1.07-2.25), as well as those with a history of mental health problems (PR 1.69 95% CI 1.16-2.47), while higher socioeconomic status (A and B) had an inverse association (PR 0.53 95% CI 0.33-0.83).

CONCLUSIONS: Symptoms suggestive of postpartum depression seem to be more prevalent in women who have suffered mistreatment during childbirth, of low socioeconomic status, and with a history of mental health problems. Thus, qualifying care for women during pregnancy, childbirth and postpartum and reducing social inequalities are challenges to be faced in order to eliminate mistreatment during childbirth and reduce the occurrence of postpartum depression.

PMID:36028806 | DOI:10.1186/s12884-022-04978-4

Brief Bioinform. 2022 Aug 26:bbac346. doi: 10.1093/bib/bbac346. Online ahead of print.

ABSTRACT

Anatomical Therapeutic Chemical (ATC) classification for compounds/drugs plays an important role in drug development and basic research. However, previous methods depend on interactions extracted from STITCH dataset which may make it depend on lab experiments. We present a pilot study to explore the possibility of conducting the ATC prediction solely based on the molecular structures. The motivation is to eliminate the reliance on the costly lab experiments so that the characteristics of a drug can be pre-assessed for better decision-making and effort-saving before the actual development. To this end, we construct a new benchmark consisting of 4545 compounds which is with larger scale than the one used in previous study. A light-weight prediction model is proposed. The model is with better explainability in the sense that it is consists of a straightforward tokenization that extracts and embeds statistically and physicochemically meaningful tokens, and a deep network backed by a set of pyramid kernels to capture multi-resolution chemical structural characteristics. Its efficacy has been validated in the experiments where it outperforms the state-of-the-art methods by 15.53% in accuracy and by 69.66% in terms of efficiency. We make the benchmark dataset, source code and web server open to ease the reproduction of this study.

PMID:36027578 | DOI:10.1093/bib/bbac346

J Cardiovasc Pharmacol. 2022 Aug 23. doi: 10.1097/FJC.0000000000001364. Online ahead of print.

ABSTRACT

Only a few meta-analyses evaluated the effect of finerenone on cardiovascular events in type 2 diabetes mellitus (T2DM) with chronic kidney disease (CKD). The main aim of this meta-analysis was to gain more reliable assessments of the efficacy and safety of finerenone for prevention of cardiovascular events in diabetic kidney disease. We searched for finerenone in the treatment of diabetic kidney disease from database (PubMed, Embase and ClinicalTrials.gov) until December 30, 2021. Relative risks (RRs) with 95% confidence intervals (CIs) calculated by the Mantel-Haenszel random-effects model were used as summary statistics for the categorical data. We included four studies that met the inclusion criteria with 13,943 participants. The finerenone group demonstrated a great benefit in reducing the incidence of major adverse cardiac events (MACEs) (RR: 0.88; 95% CI 0.80 – 0.96; P = 0.003), all-cause mortality (RR: 0.89; 95% CI 0.80 – 0.99; P = 0.04), myocardial infarction (RR: 0.79; 95% CI 0.67 – 0.92; P = 0.003) and new-onset hypertension (RR: 0.71; 95% CI 0.62 – 0.81; P < 0.00001). No difference was found in adverse events between the finerenone and placebo groups (RR: 1.00; 95% CI [0.98, 1.01], P = 0.59), whereas, a higher risk of hyperkalemia was observed in the finerenone group than in the placebo group (RR = 2.04, 95% CI 1.80 – 2.32; P < 0.00001). Besides, cerebrovascular events and new-onset atrial fibrillation did not increase in patients taking finerenone. Overall, finerenone treatment showed a great benefit of reducing the risk of MACEs, all-cause mortality, myocardial infarction, and new-onset hypertension events in patients with T2DM and CKD.

PMID:36027585 | DOI:10.1097/FJC.0000000000001364

ACS Appl Bio Mater. 2022 Aug 26. doi: 10.1021/acsabm.2c00434. Online ahead of print.

ABSTRACT

Nanoparticle (NP) internalization by cells is complex, highly heterogeneous, and fundamentally important for nanomedicine. We report powerful probabilistic statistics from single-cell data on quantitative NP uptake of PEG-coated transferrin receptor-targeted gold NPs for cancer-derived and fibroblast cells according to their cell size, receptor expression, and receptor density. The smaller cancer cells had a greater receptor density and more efficient uptake of targeted NPs. However, simply due to fibroblasts being larger with more receptors, they exhibited greater NP uptake. While highly heterogeneous, targeted NP uptake strongly correlated with receptor expression. When uptake was normalized to cell size, no correlation existed. Consequently, skewed population distributions in cell sizes explain the distribution in NP uptake. Furthermore, exposure to the transferrin receptor-targeted NPs alters the fibroblast size and receptor expression, suggesting that the receptor-targeted NPs may interfere with the metabolic flux and nutrient exchange, which could assist in explaining the altered regulation of cells exposed to nanoparticles.

PMID:36027561 | DOI:10.1021/acsabm.2c00434

J Clin Oncol. 2022 Aug 26:JCO2201002. doi: 10.1200/JCO.22.01002. Online ahead of print.

ABSTRACT

PURPOSE: Hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2-) endocrine-resistant metastatic breast cancer is treated with sequential single-agent chemotherapy with poor outcomes. Sacituzumab govitecan (SG) is a first-in-class antibody-drug conjugate with an SN-38 payload targeting trophoblast cell-surface antigen 2, an epithelial antigen expressed in breast cancer.

METHODS: In this global, randomized, phase III study, SG was compared with physician’s choice chemotherapy (eribulin, vinorelbine, capecitabine, or gemcitabine) in endocrine-resistant, chemotherapy-treated HR+/HER2- locally recurrent inoperable or metastatic breast cancer. The primary end point was progression-free survival (PFS) by blinded independent central review.

RESULTS: Patients were randomly assigned to receive SG (n = 272) or chemotherapy (n = 271). The median age was 56 years, 95% had visceral metastases, and 99% had a prior cyclin-dependent kinase 4/6 inhibitor, with three median lines of chemotherapy for advanced disease. Primary end point was met with a 34% reduction in risk of progression or death (hazard ratio, 0.66 [95% CI, 0.53 to 0.83; P = .0003]). The median PFS was 5.5 months (95% CI, 4.2 to 7.0) with SG and 4.0 months (95% CI, 3.1 to 4.4) with chemotherapy; the PFS at 6 and 12 months was 46% (95% CI, 39 to 53) v 30% (95% CI, 24 to 37) and 21% (95% CI, 15 to 28) v 7% (95% CI, 3 to 14), respectively. Median overall survival (first planned interim analysis) was not yet mature (hazard ratio, 0.84; P = .14). Key grade ≥ 3 treatment-related adverse events (SG v chemotherapy) were neutropenia (51% v 38%) and diarrhea (9% v 1%).

CONCLUSION: SG demonstrated statistically significant PFS benefit over chemotherapy, with a manageable safety profile in patients with heavily pretreated, endocrine-resistant HR+/HER2- advanced breast cancer and limited treatment options.

PMID:36027558 | DOI:10.1200/JCO.22.01002

J Hypertens. 2022 Jun 1;40(Suppl 1):e29. doi: 10.1097/01.hjh.0000835528.11250.2d.

ABSTRACT

OBJECTIVE: Hypertension is one of the most important factors for cardiovascular disease. It has been repeatedly proposed as a prognostic factor of severe COVID-19 and has been included in clinical risk scores to predict the occurrence of critical illness in ospitalised with COVID-19. Also, it has been postulated the relation between antihypertensive drugs and the severity of COVID-19. The aims of our study were to analyze whether hypertension and antihypertensive treatment represent an independent risk factor for death or intensive care unit admission in patients with SARS-COV2.

DESIGN AND METHOD: Observational, retrospective, single-center cohort study of all patients admitted to Hospital Virgen Macarena diagnosed with COVID-19 between the months of March and December 2020. A bivariate analysis was performed using Pearson’s chi-square.

RESULTS: 608 patients required admission for COVID-19. A total of 83.7% were hypertensive, specifically 75.9% were under antihypertensive treatment (35.7% with only 1 drug, 29.9% were taking two drugs, 9% with three drugs, and 1.3% with 4 drugs). 26.2% were treated with an ACEI, 24.8% with ARA-II, 16.8% with calcium-antagonists, 30.9% with diuretics, 21.2% with beta-blockers, 0, 5% with alpha-blockers). Hypertension did not show a statistically significant relationship with mortality (p = 0.34), increase in mortality and ICU admissions. Neither treatment with ACEI (p = 0.4), ARB-II (p = 0.45), calcium antagonists (p = 0.53), diuretics (p = 0.68), alpha blockers (p = 0.07) demonstrated relation with those items. Surprisingly, beta-blockers increased the mortality in patients with SARS-COV2 (p = 0.048). Probably this results can be explained as these drugs were indicated for rate control in patients with atrial fibrillation (p = 0.006). The number of antihypertensive drugs used also did not show a statistically significant relationship with an increase in mortality (p = 0.978).

CONCLUSIONS: Hypertension is a highly prevalent pathology in patients ospitalised with COVID-19 infection. However, high blood pressure was not associated with a higher risk for mortality in patients with SARS-COV-2, neither the type or the number of antihypertensive drug used. Only beta-blockers alter outcomes in hypertensive patients with COVID-19, as they were associated with more deaths.

PMID:36027544 | DOI:10.1097/01.hjh.0000835528.11250.2d

J Hypertens. 2022 Jun 1;40(Suppl 1):e28. doi: 10.1097/01.hjh.0000835516.74875.81.

ABSTRACT

OBJECTIVE: The Covid-19 pandemic necessitated a decrease in non-Covid-19 related diagnostic and therapeutic procedures in many countries. We explored the impact on hypertension care in the Excellence Center (EC) network of the European Society of Hypertension.

DESIGN AND METHOD: We conducted an electronic survey regarding 6 key procedures in hypertension care among our ECs.

RESULTS: Overall, 54 ECs from 18 European and 3 non-European countries participated. From 2019 to 2020, there was a significant decrease in the median number per center of ambulatory blood pressure monitorings (ABPMs; 544 vs 289), duplex ultrasound investigations of renal arteries (DUS RA; 88.5 vs 55), computed tomographic investigations of renal arteries (CT RA; 66 vs 19.5), percutaneous renal artery angioplasties (PTA RA; 5 vs 1), laboratory tests for catecholamines (2019: 116 vs 67.5) and for ennin/aldosterone (146 vs 83.5). All comparisons were statistically significant with p < 0.001, respectively (Figure). While the reduction in all diagnostic and therapeutic procedures was observed in all 3-months period comparisons between 2019 and 2020, the most profound decrease occurred from April to June 2020, which was the period of the first wave and the first lockdown in most countries. In this period, as compared to 2019, the median reduction in 2020 was 50.7% (ABPM), 47.1% (DUS RA), 50% (CT RA), 57.1% (PTA RA), 46.9% (catecholamines) and 41% (ennin/aldosterone), respectively. Based on Friedman test, overall differences in reduction between 3 months time intervals were statistically highly significant.

CONCLUSIONS: Diagnostic and therapeutic procedures related to hypertension were dramatically reduced during the first year of the Covid-19 pandemic, with the largest reduction during the first lockdown. The long-term consequences regarding blood pressure control and, ultimately, cardiovascular events remain to be investigated.

PMID:36027541 | DOI:10.1097/01.hjh.0000835516.74875.81

J Hypertens. 2022 Jun 1;40(Suppl 1):e26. doi: 10.1097/01.hjh.0000835508.38962.a6.

ABSTRACT

OBJECTIVE: ACE2, part of the counterregulatory arm of the ennin-angiotensin system, serves both as protective toward oxidative stress and cardiovascular enninling and as key entry for SARS-CoV-2. ACE2 has two isoforms, non-glycosylated and glycosylated, being this latter accountable for the binding with SARS-CoV-2. After the binding, viruses use proteases as cathepsin-L (Cat-L) to entry the cells. Both ACE2 glycosylation and Cat-L activity are pH-dependent. Gitelman and Bartter syndromes (GS/BS), rare genetic tubulopathies, are characterized by electrolytic alterations, activation of the ennin-angiotensin system, yet normo-hypotension, increased levels of ACE2 and metabolic alkalosis with likely increased intracellular pH. We reported that during the first wave of COVID-19 in early 2020 none of our cohort of 128 GS/BS patients from the major hotspots in Northern Italy had been infected or suffered any major COVID-19 symptoms and in a second survey on the same cohort in 2021 we reported only 8 positives, 4 asymptomatic and 4 with very light symptoms This study aims to investigate potential mechanisms as ACE2 glycosylation and Cat-L activity related to patients’ metabolic alkalosis and viral entry/infection.

DESIGN AND METHOD: Mononuclear cells ACE2 glycosylation (Western blot) and blood Cat-L activity (ELISA) from 20 GS/BS patients have been compared to those from 15 heathy subjects.

RESULTS: Non-glycosylated ACE2 was higher in GS/BS (0.82 ± 0.19 d.u. vs 0.67 ± 0.13 p = 0.01); glycosylated ACE2 was not different (0.85 ± 0.28 in GS/BS vs 0.73 ± 0.23 p = 0.19). Cat-L activity was lower in GS/BS (3.90 ± 1.13 r.f.u. vs 5.31 ± 0.8 p < 0.001) and inversely correlated with blood bicarbonate (HCO3-), while a negative correlation between glycosylated ACE2 and HCO3- approaches statistical significance (p = 0.08).

CONCLUSIONS: GS/BS’s metabolic alkalosis, likely by increasing intracellular pH, influences the glycosylation of ACE2 and the activity of Cat-L, providing a mechanistic explanation for the near complete absence of COVID-19 or its symptoms reported in our cohort. These findings provide a rationale for pursuing the identification and/or synthesis of new drugs that specifically target ACE2 glycosylation and/or proteases involved in SARS-CoV-2 infection.

PMID:36027539 | DOI:10.1097/01.hjh.0000835508.38962.a6

J Hypertens. 2022 Jun 1;40(Suppl 1):e22. doi: 10.1097/01.hjh.0000835480.16494.e1.

ABSTRACT

OBJECTIVE: To assess the persistence of BP phenotypes according to office and 24-h ABPM in youth over time.

DESIGN AND METHOD: Retrospective study including 582 children who underwent measurement of both office BP (OBP) and ABPM on the same day. The second office BP and ABPM was performed within 1 year apart. OBP was measured using an oscillometric device validated in children. ABPM was performed using oscillometric SpaceLabs 90207 monitors. OBP and ABPM were classified according to the criteria of the ESH (Lurbe et al J Hypertens 2016). Four phenotypes based on OBP and ABPM were defined: true normotensives, sustained hypertensives, white-coat hypertensives, and masked hypertensives. Persistence and Kappa statistic were used to evaluate the concordance of BP phenotypes. Factors related with persistence on BP phenotypes were evaluated using logistic regression models.

RESULTS: At the initial assessment, the majority of children fell within the category of true normotension (77%), followed by masked hypertension (13%), sustained hypertension (5%) and white coat hypertension (5%). The prevalence of true normotensive increased significantly in the follow-up. The flow through phenotypes is shown in the Figure.Only 38 initial true normotensive patients changed to other categories, mainly masked (12); 63 of initial masked hypertension changed, mainly to normotensive (58); 24 of white coat changed predominantly to normotension (16); finally, 25 of sustained changed, largely to normotension (14), but 9 children migrated to masked. The overall agreement was 74.2% (kappa 0.20). The grade of agreement was slightly higher for boys than for girls. In the multivariable model, higher age showed to be a protective factor, whereas increased office SBP and waist circumference were significant risk factors. The masked hypertensive phenotype carried the highest risk for lack of persistence.

CONCLUSIONS: Children with hypertensive BP phenotypes should be re-evaluated because a large percentage of them will become normotensive. High BP levels and high BMI z-score or waist circumference were significant risk predictors for the lack of persistence on BP phenotypes.

PMID:36027532 | DOI:10.1097/01.hjh.0000835480.16494.e1

J Hypertens. 2022 Jun 1;40(Suppl 1):e23. doi: 10.1097/01.hjh.0000835488.45395.d3.

ABSTRACT

OBJECTIVE: Functional characteristics of the vascular system underly changes associated with aging, such as increasing arterial stiffness. Research suggests that these age-associated changes may be accelerated in the presence of cardiovascular risk factors. So far, normative data on arterial stiffness in unselected adolescents and young adults have been scarce. Recently, measurements of carotid stiffness (cS) parameters have been included in a national health examination survey.

DESIGN AND METHOD: The population-based KiGGS cohort 11-year-follow-up included high-resolution B-mode sonography with semi-automated edge-detection and automatic electrocardiogram-gated real-time quality control. In 4,305 participants aged 14-28 years, distensibility coefficient (DC), stiffness index ß, Young’s (YEM) and Peterson’s elastic modulus (Ep) were assessed. Centiles were modelled by sex, age and height simultaneously, using generalized additive models for location, scale and shape. Log- binomial regression models were used to investigate associations of blood pressure with cS > = 90th centile (P90) as outcomes. Hypertensive blood pressure was defined according to German guidelines (> = P95 systolic or diastolic for age, height and sex according to KiGGS centiles until age 17 and > = 140/90 mmHg from age 18).

RESULTS: Multivariable models show that hypertensive blood pressure in childhood is associated with an increased risk of elevated cS (> = P90 for age, height and sex) eleven years later for all parameters of cS, with the exception of stiffness indexß (no association). Effect estimates for DC, YEM and Ep range from 1.77 [CI 1.28-2.44] for DC to 1.41 [CI 0.99-2.01] for YEM. Cross-sectional associations of blood pressure with cS parameters show even stronger associations (relative risks between 1.3 and 3.3).

CONCLUSIONS: Using state-of-the-art sonography and centiles computed with novel statistical methods, this study confirms that, at the population level, hypertensive blood pressure in childhood is linked to increased carotid stiffness in young adulthood. The results emphasize that healthy lifestyles and healthy living environments in childhood and adolescence represent an early investment in cardiovascular health.

PMID:36027534 | DOI:10.1097/01.hjh.0000835488.45395.d3