Category: Nevin Manimala

Medicines (Basel). 2023 Jan 16;10(1):13. doi: 10.3390/medicines10010013.

ABSTRACT

Background: Edoxaban is a novel oral anticoagulant which may decrease the risk of stroke and systemic embolism in patients suffering from atrial fibrillation (AF). However, the decreased efficacy of edoxaban versus warfarin for the avoidance of stroke and systemic embolism in AF with creatinine clearance (CrCl) > 95 mL/min has been reported. The purpose of this meta-analysis is to further clarify the safety (major bleeding) and efficacy (stroke or systemic embolism) of edoxaban for AF patients with various CrCl. Methods: A systematic search of studies on edoxaban and warfarin in AF patients related to renal function was conducted in PubMed, Medline, Web of Science databases, EBSCO, Embase, and the Cochrane Central Register of Controlled Trials. In this meta-analysis (protocol number: PROSPERO CRD 42021245512), we included studies that provide specific data on three outcomes: ischemic stroke or systemic embolism (S/SE), bleeding, and all-cause mortality. Results: This meta-analysis enrolled two randomized controlled trials (RCTs) studies and two retrospective studies that enrolled 28,065 patients. According to CrCl, subjects are divided into three groups (CrCl 30-50 mL/min, CrCl 50-95 mL/min, CrCl > 95 mL/min). In AF patients with CrCl 30-50 mL/min, edoxaban 30 mg daily is similar to warfarin in the prevention of ischemic S/SE and all-cause mortality, resulting in lower bleeding rate and better net clinical outcome (ischemic S/SE: hazard ratio (HR), 0.85, 95% confidence interval (CI), 0.19-1.87; all-cause mortality: HR, 0.65, 95% CI, 0.35-1.19; bleeding: HR, 0.75, 95% CI, 0.60-0.93; net clinical outcome: HR, 0.75, 95% CI, 0.63-0.90). In the group of CrCl 50-95 mL/min, the net clinical outcome was more favorable with edoxaban 60 mg daily than warfarin (HR, 0.81, 95% CI: 0.68-0.96), and there was no significant difference between edoxaban 60 mg daily and warfarin in terms of prevention of bleeding, ischemic S/SE, and all-cause mortality. For AF patients with CrCl > 95 mL/min, there was a statistically significant difference in lower bleeding rate between edoxaban 60 mg daily and warfarin (bleeding: HR: 0.70, 95% CI: 0.58-0.84). There was no differential safety in ischemic S/SE, all-cause mortality, and net clinical outcome. Conclusion: Overall, edoxaban was superior to warfarin in terms of net clinical outcome in various groups of CrCl with AF patients. Although there was no significant difference in net clinical outcome between edoxaban and warfarin for AF patients with CrCl > 95 mL/min, edoxaban is not inferior to warfarin in safety and effectiveness in the various levels of CrCl. Edoxaban may be a more effective and safe treatment than warfarin for patients with chronic kidney disease (CKD) who require anticoagulation. More high-quality and long-term clinical research are needed to further estimate the effects of edoxaban.

PMID:36662497 | DOI:10.3390/medicines10010013

Medicines (Basel). 2022 Dec 30;10(1):7. doi: 10.3390/medicines10010007.

ABSTRACT

Background: The prevention of preterm delivery (PTD) represents one of the major topics in modern obstetrics. The aim was to design a prospective study and investigate if mid-trimester serum and amniotic fluid levels of MCP-1 could predict the occurence of spontaneous PTD. Methods: The study involved 198 women who underwent genetic amniocentesis and blood sampling in the middle of their trimester. After applying the criteria for inclusion in the study, there were 16 respondents in the study group, and 38 respondents in the control group. Level of MCP-1 in amniotic fluid and serum was measured with commercially available enzyme-linked immunosorbent assays (ELISA) and statistical analysis was conducted. Results: There was no statistically significant difference in serum or amniotic fluid MCP1 levels between PTD and the control groups. Conclusion: The results suggest that MCP-1 is probably not the most relevant marker for predicting PTD. This study provides new normative data for MCP-1 levels in amniotic fluid and maternal sera and is a valuable tool for future diagnostic and comparative studies.

PMID:36662491 | DOI:10.3390/medicines10010007

Bull Math Biol. 2023 Jan 20;85(3):15. doi: 10.1007/s11538-022-01114-3.

ABSTRACT

Targeted vaccination policies can have a significant impact on the number of infections and deaths in an epidemic. However, optimising such policies is complicated, and the resultant solution may be difficult to explain to policy-makers and to the public. The key novelty of this paper is a derivation of the leading-order optimal vaccination policy under multi-group susceptible-infected-recovered dynamics in two different cases. Firstly, it considers the case of a small vulnerable subgroup in a population and shows that (in the asymptotic limit) it is optimal to vaccinate this group first, regardless of the properties of the other groups. Then, it considers the case of a small vaccine supply and transforms the optimal vaccination problem into a simple knapsack problem by linearising the final size equations. Both of these cases are then explored further through numerical examples, which show that these solutions are also directly useful for realistic parameter values. Moreover, the findings of this paper give some general principles for optimal vaccination policies which will help policy-makers and the public to understand the reasoning behind optimal vaccination programs in more generic cases.

PMID:36662446 | DOI:10.1007/s11538-022-01114-3

Environ Sci Pollut Res Int. 2023 Jan 20. doi: 10.1007/s11356-023-25187-2. Online ahead of print.

ABSTRACT

Increased anthropogenic activities have led to the accumulation of certain minerals to ecotoxic levels in the environment, which could influence the secondary metabolism of plants. Shikonin, an exudate from the roots of Onosma dichroantha, is a secondary metabolite involved in plant defense and invasion success; however, the interactive effects of copper (Cu), cadmium (Cd), calcium (Ca), and nitrate (NO₃) in shikonin biosynthesis and accumulation are not known. Here, the individual, curvilinear, and pairwise effects of these elements on shikonin biosynthesis in callus culture of O. dichroantha have been investigated by means of a statistical modeling approach and multivariate regression analyses. Although the main effects of the examined minerals seemed to be suppressive, their combined interactions could enhance callus growth and secondary metabolism of O. dichroantha. Accordingly, maximum values were recorded for the callus growth index (6.85 at 23.25 μM Cu, 70 mM NO₃, 1 mM Ca, 27.50 μM Cd), total phenolics (24.83 mg gallic acid equivalent at 9.75 μM Cu, 70 mM NO₃, 1 mM Ca, 62.50 μM Cd), total flavonoids (6.12 mg quercetin equivalent at 30 μM Cu, 80 mM NO₃, 1.5 mM Ca, 45 μM Cd), and shikonin (24.33 μg g^-1 FW at 9.75 μM Cu, 70 mM NO₃, 2 mM Ca, 27.5 μM Cd). Overall, these data show that increasing concentrations of the examined minerals in culture medium can markedly influence the secondary metabolism of O. dichroantha cells and suggest that a comparable phenomenon may exist in a wider range of medicinal plants, grown on polluted environments, which may affect their invasive capabilities.

PMID:36662436 | DOI:10.1007/s11356-023-25187-2

Environ Sci Pollut Res Int. 2023 Jan 20. doi: 10.1007/s11356-023-25283-3. Online ahead of print.

ABSTRACT

Drought directly impacts the human economy and society, so a proper understanding of its spatiotemporal characteristics in different time scales and return periods can be effective in its evaluation and risk warning. In this research, the spatiotemporal variation of drought characteristics in 70 investigated stations in Iran during 1981-2020 was examined, evaluated, and compared. The Standardized Precipitation Index (SPI) and Standardized Precipitation Evapotranspiration Index (SPEI) have been used on time scales of 1, 3, 6, 9, 12, and 24 months to calculate the meteorological drought. Drought characteristics have been calculated through the run theory method, and the correlation between these characteristics has been checked. Statistical distribution functions have been used to calculate drought characteristics for the 10-, 20-, 50-, and 100-year return periods. Results show that the duration, severity, and peak of the drought in rainy areas increase as the return period increases. The drought features obtained from the SPI and SPEI show that the average value of severity obtained based on the SPI (43.5) is higher than that of the SPEI (40.9) while the average values of the peak are 3.9 and 2.6 for SPI and SPEI, respectively. Extreme drought was identified in 1990 in all regions of Iran. The highest severity in the current study is from 1999 to 2003. At the end of this period, Iran faced wet years. These results are evident on all time scales. The results obtained in this study can identify drought-prone regions and the beneficial use of water resources in the region.

PMID:36662434 | DOI:10.1007/s11356-023-25283-3

Environ Sci Pollut Res Int. 2023 Jan 20. doi: 10.1007/s11356-023-25319-8. Online ahead of print.

ABSTRACT

Accurately determining the spatiotemporal variability of ozone on a regional to intercontinental scale is essential for air quality studies. In the present study, a first systematic evaluation and analysis of long-term (2009-2020) gridded datasets (0.5° × 0.625°) of total columnar ozone (TCO) retrieved from Modern-Era Retrospective Analysis for Research and Applications, version 2 (MERRA-2_TCO) is evaluated for the Indian region. The MERRA-2_TCO is first validated with observations (IMD_TCO) and then further compared with the Atmospheric Infrared Sounder (AIRS_TCO) satellite datasets. For an in-depth comparison and statistical analysis, the dataset has been segregated into seven distinct regions, i.e., Western Himalaya (WH), North East (NE), North Central (NC), North West (NW), West Peninsula India (WPI), East Peninsula India (EPI), and South Peninsula India (SPI). Descriptive statistics (NMSE, FB, R, FA2, and d) reveals a significant correlation of MERRA-2_TCO against IMD_TCO for Delhi with NMSE (0.0013), FB (- 0.029) and Varanasi NMSE (0.0008), FB (- 0.014). The results of simple linear regression analysis show an increasing TCO trend value of 0.31% and 0.44% per decade in both the cities, respectively. A comparison of MERRA-2_TCO with AIRS_TCO shows a significant correlation of 0.62-0.87 in different regions of India. Furthermore, in support of Brewer’s circulation pattern, an increasing shift of columnar ozone from low (SPI) to high (WH) latitudinal regions is observed. Our results show that the MERRA-2 ozone dataset can be effectively used for ozone air quality studies over India and this analysis may strengthen the need for independent, high-quality, and consistent ozone measurements with small uncertainties.

PMID:36662427 | DOI:10.1007/s11356-023-25319-8

Forensic Sci Med Pathol. 2023 Jan 20. doi: 10.1007/s12024-023-00577-7. Online ahead of print.

ABSTRACT

Morphometrics of the hard palate is an important aspect of forensic anthropology and odontology. Palatine triangle is a triangular area in the hard palate formed by the palatine processes of the maxillae, which can aid intraoral bone grafts. We present the osteological measurements of the palatine triangle (maxillary palate) based on sex, compare it with other hard palate parameters, and establish the correlation between them. Seventy-seven male skulls and 36 female skulls were examined. Various morphometric measurements of the hard palate and palatine triangle were performed meticulously. Mean and standard deviation of each parameter were computed for groups using SPSS 16.0. Relationships between all parameters were analyzed using Pearson’s rank correlation test. The mean palatine length was 38.84 ± 3.75 mm in males and 37.22 ± 4.12 mm in females; the mean palatine breadth was 31.36 ± 2.61 mm in males and 29.78 ± 3.07 mm in females. The mean area of the palatine triangle was 600.88 ± 80.16 mm² in male skulls and 547.96 ± 94.28 mm² in the female skulls. Statistically significant difference in various measurements of the palatine triangle and hard palate between the male and female skulls was noted. Leptostaphyline (narrow palate) was the most prominent type of palate. The area of the palatine triangle showed a strong positive correlation between the total length and breadth of the palate for both male and female skulls. A strong positive correlation was also observed between the palate length and the palatine triangle length. Palatine index and palate breadth had a statistically significant moderate linear relationship. The maxillary palate length, breadth, and area of the palatine triangle were higher in males when compared to females in South Indian origin skulls. Most of the skulls had a narrow palate. The results of this metric analysis of the palatine triangle may lead to a new concept of anatomical research into studying the hard palate, which can be used for sexual dimorphism.

PMID:36662407 | DOI:10.1007/s12024-023-00577-7

Breast Cancer Res Treat. 2023 Jan 20. doi: 10.1007/s10549-022-06833-8. Online ahead of print.

ABSTRACT

PURPOSE: Pregnancy-associated breast cancer (PABC) comprises breast cancer diagnosed during the gestational period or within 12 months postpartum. While the incidence of PABC appears to be increasing, data regarding prognosis remain limited.

METHODS: Here we evaluate clinicopathologic features, treatments, and clinical outcomes among women with stage 0-III PABC diagnosed between 1992 and 2020. Comparisons were made between women who were diagnosed with PABC during gestation and those who were diagnosed within 12 months postpartum.

RESULTS: A total of 341 women were identified, with a median age of 36 years (range 25-46). The pregnancy group comprised 119 (35%) women, while 222 (65%) women made up the postpartum group. Clinicopathologic features were similar between groups, with most patients being parous and presenting with stage I and II disease. Treatment delays were uncommon, with a median time from histologic diagnosis to treatment of 4 weeks for both groups. Recurrence-free survival was similar between groups: 67% at 10 years for both. While 10-year overall survival appeared higher in the postpartum group (83% versus 78%, p = 0.02), only the presence of nodal metastases was associated with an increased risk of death (hazard ratio 5.61, 95% CI 2.20-14.3, p < 0.001), whereas timing of diagnosis and receptor profile did not reach statistical significance.

CONCLUSION: Clinicopathologic features of women with PABC are similar regardless of timing of diagnosis. While 10-year recurrence-free survival is similar between groups, 10-year overall survival is higher among women diagnosed postpartum; however, timing of diagnosis may not be the driving factor in determining survival outcomes.

PMID:36662395 | DOI:10.1007/s10549-022-06833-8

Breast Cancer Res Treat. 2023 Jan 20. doi: 10.1007/s10549-022-06827-6. Online ahead of print.

ABSTRACT

PURPOSE: For patients living with metastatic breast cancer (MBC), achieving best possible health-related quality of life, along with maximizing survival, is vital. Yet, we have no systemic way to determine if we achieve these goals. A Core Outcome Set (COS) that allows standardized measurement of outcomes important to patients, but also promotes discussing these outcomes during clinical encounters, is long overdue.

METHODS: An international expert group (EG) of patient advocates, researchers, medical specialists, nurse specialists, and pharmaceutical industry representatives (n = 17) reviewed a list of relevant outcomes retrieved from the literature. A broader group (n = 141: patients/patient advocates (n = 45), health care professionals/researchers (n = 64), pharmaceutical industry representatives (n = 28), and health authority representatives (n = 4)) participated in a modified Delphi procedure, scoring the relevance of outcomes in two survey rounds. The EG finalized the COS in a consensus meeting.

RESULTS: The final MBC COS includes 101 variables about: (1) health-related quality of life (HRQoL, n = 26) and adverse events (n = 24); (2) baseline patient characteristics (n = 9); and (3) clinical variables (n = 42). Many outcome that cover aspects of HRQoL relevant to MBC patients are included, e.g. daily functioning (including ability to work), psychosocial/emotional functioning, sexual functioning, and relationship with the medical team.

CONCLUSION: The COS developed in this study contains important administrative data, clinical records, and clinician-reported measures that captures the impact of cancer. The COS is important for standardization of clinical research and implementation in daily practice and has received accreditation by the International Consortium for Health Outcomes Measurement (ICHOM).

PMID:36662394 | DOI:10.1007/s10549-022-06827-6

Int Urol Nephrol. 2023 Jan 20. doi: 10.1007/s11255-023-03468-6. Online ahead of print.

ABSTRACT

BACKGROUND: In Fabry Disease (FD), although the primary factor initiating kidney damage is glycosphingolipid accumulation, secondary conditions such as increased inflammation and fibrosis may cause this damage to progress. These processes may be induced by immune cells. Therefore, we aimed to investigate the peripheral lymphocyte subgroup analysis of the patients with FD and compare these results with healthy individuals. In addition, we performed T, B, NK, and plasma cell analyses in kidney biopsy materials and compared these kidney biopsy results with the biopsy results of patients whose kidney functions were impaired after 4 years of regular ERT.

MATERIALS AND METHODS: 18 FD and 16 healthy individuals were included in the study. T-B lymphocyte and NK-cell populations were determined. We performed kidney biopsies (KBx) on 13 patients with FD prior to ERT. Of these, 4 patients had rebiopsy after 4 years of regular ERT. Immunohistochemical staining was performed to define immune cell infiltration.

RESULTS: There was no statistically significant difference in terms of total, helper and cytotoxic T-lymphocyte and CD3^–CD16⁺CD56⁺ natural killer (NK)-cell count (p = 0.20; p = 0.12; p = 0.76; p = 0.75, respectively).According to KBx findings prior to ERT, all patients had interstitial fibrosis (IF), podocyte vacuoles (PV), and podocyte inclusion (PI), CD3, CD4, CD8, CD16, and CD56 positivity at different levels. None of the patients had CD19, CD20, and CD138 positivity at the first biopsies. When we compared the first and the second KBx results of the two progressors, we also demonstrated that CD3⁺4⁺T-cells infiltration remained the same, whereas CD8⁺T cells, CD16⁺ and 56⁺NK-cells infiltration were significantly decreased. In contrast, CD20⁺B cells and CD138⁺plasma cell infiltration were significantly increased despite 4 years of ERT (15 fold and sixfold, respectively). The CD20⁺B and CD138⁺ plasma cells and IF were positively correlated with proteinuria.

CONCLUSIONS: The progression of FD nephropathy and proteinuria is increased despite a long-term ERT. Immune cells, primarily B and plasma cells, might cause these unwanted consequences.

PMID:36662386 | DOI:10.1007/s11255-023-03468-6