Tag: nevin manimala

PLoS One. 2022 Nov 8;17(11):e0276813. doi: 10.1371/journal.pone.0276813. eCollection 2022.

ABSTRACT

INTRODUCTION: The receptor activator NF-κB ligand (RANKL) and Osteoprotegrin (OPG) single nucleotide polymorphisms (SNPs) have been associated with the risk of breast cancer to bone metastasis. This study was designed to investigate the association of RANKL and OPG gene polymorphisms with breast to bone metastasis in Pashtun population of Khyber Pakhtunkhwa, Pakistan.

MATERIALS AND METHODS: A total of 215 participants were enrolled containing 106 breast cancer patients, 58 breast to bone metastasis and 51 age and gender matched healthy controls. RANKL (rs9533156) and OPG (rs2073618, rs3102735) polymorphisms were genotyped in genomic DNA, using Tetra-ARMS PCR protocol. The results were analyzed among the three groups and P-value less then 0.05 were considered statistically significant.

RESULTS: Our results displayed significant association of OPG (rs3102735) risk allele and corresponding genotypes in breast cancer vs healthy controls, bone metastasis vs healthy controls and breast cancer vs breast to bone metastasis as a disease risk. However, there was no association observed for OPG (rs2073618) risk allele and corresponding genotypes with the diseases risk. Similarly, RANKL (rs9533156) risk allele and corresponding genotypes in breast cancer vs healthy controls, bone metastasis vs healthy controls and breast cancer vs breast to bone metastasis exhibited significant association except for the risk allele carrying genotypes in breast to bone metastasis.

CONCLUSION: OPG (rs3102735) and RANKL (rs9533156) exhibited significant association with breast to bone metastasis while OPG (rs2073618) didn’t show significant association with breast to bone metastasis in Pashtun population of Pakistan. However, this study unlocks more questions to investigate the exact scenario of genetic predisposition of breast to bone metastasis.

PMID:36346787 | DOI:10.1371/journal.pone.0276813

PLoS One. 2022 Nov 8;17(11):e0277340. doi: 10.1371/journal.pone.0277340. eCollection 2022.

ABSTRACT

Due to the high prevalence of patients attending with urinary tract infection (UTI) symptoms, the use of flow-cytometry as a rapid screening tool to avoid unnecessary cultures is becoming a widely used system in clinical practice. However, the recommended cut-points applied in flow-cytometry systems differ substantially among authors, making it difficult to obtain reliable conclusions. Here, we present FlowUTI, a shiny web-application created to establish optimal cut-off values in flow-cytometry for different UTI markers, such as bacterial or leukocyte counts, in urine from patients with UTI symptoms. This application provides a user-friendly graphical interface to perform robust statistical analysis without a specific training. Two datasets are analyzed in this manuscript: one composed of 204 urine samples from neonates and infants (≤3 months old) attended in the emergency department with suspected UTI; and the second dataset including 1174 urines samples from an elderly population attended at the primary care level. The source code is available on GitHub (https://github.com/GuillermoMG-HUVR/Microbiology-applications/tree/FlowUTI/FlowUTI). The web application can be executed locally from the R console. Alternatively, it can be freely accessed at https://covidiario.shinyapps.io/flowuti/. FlowUTI provides an easy-to-use environment for evaluating the efficiency of the urinary screening process with flow-cytometry, reducing the computational burden associated with this kind of analysis.

PMID:36346782 | DOI:10.1371/journal.pone.0277340

Braz J Cardiovasc Surg. 2022 Nov 8;37(5):654-662. doi: 10.21470/1678-9741-2021-0560.

ABSTRACT

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) for temporary cardiopulmonary support is one of the most intense and technologically complex therapies offered in medicine. It is a high-risk procedure that requires specific knowledge and technical skills to perform it with good results.

OBJECTIVE: The main goal of this study is to describe our extracorporeal membrane oxygenation (ECMO) training program based on the study of specialized nurses and physicians of a simulation teaching experience, conducted in a pediatric cardiac intensive care unit. The program was developed as a theoretical-practical course with final exam and annual maintenance training sessions, caring for ECMO patients, its implementation and results.

METHODS: A descriptive study for registered nurses, intensivists, and cardiac surgeons. A self-administered, anonymous, and voluntary survey was conducted to assess the long-term perception about the program. Demographic data to describe the population was required, and questions about satisfaction and confidence in acquired skills and competences were asked. A descriptive statistical analysis was performed; patient survival and complications were compared before and after ECMO program using chi-square test, and P<0.05 was considered statistically significant.

RESULTS: Twenty-four training courses were performed for 68 professionals. More than 88% of the professionals considered the course components to be adequate and complete; and 94% felt trained to manage the ECMO circuit. Most valued activities were workshops and clinical cases. Since the implementation of the training program, 88 patients were assisted, with a survival rate at discharge of 58%, higher than in the previous period (P=0.03).

CONCLUSION: More than 80% of the professionals considered the workshops and simulations as the most useful components. Reliance on the circuit care was higher than in training problem scenarios. Since 2013 we assisted 88 patients on ECMO, with a survival rate at discharge of 58%, within international standards results.

PMID:36346772 | DOI:10.21470/1678-9741-2021-0560

Matern Child Health J. 2022 Nov 8. doi: 10.1007/s10995-022-03512-4. Online ahead of print.

ABSTRACT

BACKGROUND: Preterm delivery is a stressful event and stress can affect adaptation to maternal role. The purpose of this study is to determine the effect of supportive-educational interventions on stress and adaptation to the maternal role among women with premature infants hospitalized in the neonatal intensive care unit.

METHODS: This quasi-experimental study was conducted on 60 women with premature infants hospitalized in the neonatal intensive care unit. A control group (n = 30) was initially selected from eligible female participants. Sampling was stopped for three weeks and then the intervention group was sampled. The entire sampling process was carried out from December 2018 to June 2019. The control group received usual care at the hospital and the intervention group (n = 30) received three sessions of supportive-educational intervention in addition to routine care. Data were collected through the perceived stress and the maternal role adaptation questionnaires completed by both groups at the time of infant discharge, and also at the follow-up period (one month after discharge).

RESULTS: The results showed that maternal stress score changed considerably over time and a significant difference between the two groups was observed (P < 0.05). Additionally, adaptation to the maternal role changed substantially over time and the difference between the two groups was statistically significant (P < 0.05).

CONCLUSION: The supportive-educational program reduced the stress of mothers with premature infants hospitalized in the neonatal intensive care unit and increased their adaptation to the maternal role.

PMID:36346564 | DOI:10.1007/s10995-022-03512-4

Intern Emerg Med. 2022 Nov 8. doi: 10.1007/s11739-022-03147-x. Online ahead of print.

ABSTRACT

Hospital-acquired anemia is defined as a new-onset anemia in hospitalized patients who have a normal hemoglobin level at admission. Its prevalence is unknown and most studies published on this topic have been conducted in intensive care unit patients with limited applicability to less acute settings, such as internal medicine wards. We conducted a retrospective study and enrolled 129 patients who were admitted to an Internal Medicine Unit between October 2021 and February 2022. The median value of phlebotomy during hospitalization was 46 ml (IQR 30-72 ml), whereas the median length of hospital stay was 9 days (IQR 5-13 days). The median value of hemoglobin reduction was -0.63 g/dl (p < 0.001) and the maximum value of drop in hemoglobin value was -2.6 g/dl. All patients who experienced a phlebotomy > 85 ml had a hemoglobin reduction > 0.6 g/dl. 20.9% of patients developed anemia during the hospital stay (7% moderate and 13.9% mild). No cases of severe anemia were observed. The volume of blood drawn during the hospital stay and the Hb value on admission were the only two variables statistically associated with the development of anemia, whereas gender, age, and chronic diseases, such as diabetes, history of cancer, or heart failure, were not. Strategies, such as elimination of unnecessary laboratory tests and the use of smaller tubes for blood collection, are needed to reduce the volume of iatrogenic blood loss and avoid blood wastage occurring during hospitalization in internal medicine patients.

PMID:36346557 | DOI:10.1007/s11739-022-03147-x

CNS Drugs. 2022 Nov 8. doi: 10.1007/s40263-022-00958-6. Online ahead of print.

ABSTRACT

BACKGROUND: Levodopa remains the gold standard for the treatment of Parkinson’s disease, but its long-term use is associated with motor complications whose management is still a significant challenge. Safinamide is a multimodal drug with proven efficacy as an adjunct to levodopa.

OBJECTIVE: The objective of this study was to investigate the efficacy and safety of safinamide as an add-on to levodopa in Chinese patients with Parkinson’s disease with motor fluctuations.

METHODS: The XINDI study was a phase III, randomized, double-blind, placebo-controlled, multicenter study, with a 2-week screening period and a 16-week treatment period. The starting dose of safinamide (or placebo) was 50 mg once daily, increased to 100 mg once daily at day 15. Patients aged ≥ 18 years, with idiopathic Parkinson’s disease of >3 years duration, Hoehn and Yahr stage 1-4, and daily OFF time ≥ 1.5 h, were eligible. Patients should follow a stable oral levodopa regimen and may receive concomitant treatment with stable doses of other anti-Parkinson drugs, except monoamine oxidase-B inhibitors. Patients with severe disabling peak-dose or biphasic dyskinesia, unpredictable or widely swinging fluctuations, other forms of parkinsonism, a history of dementia or severe cognitive dysfunction, major psychiatric illnesses, and/or clinically significant medical illnesses were excluded. The primary efficacy endpoint was the change from baseline to week 16 in the mean daily OFF time. Secondary efficacy endpoints included the Unified Parkinson’s Disease Rating Scale, the Numerical Rating Scale, the Clinical Global Impression scale, and the 39-Item Parkinson’s Disease Questionnaire scale. The statistical analysis of the efficacy parameters was conducted using an analysis of co-variance, except for the Clinical Global Impression scale scores that were assessed using the Wilcoxon-Mann-Whitney test. Safety was evaluated through the frequency of adverse events and serious adverse events, physical examination, vital signs, 12-lead electrocardiograms, and laboratory exams. All safety endpoints were summarized using descriptive statistics.

RESULTS: The trial enrolled 307 patients. At week 16, the difference in the change of the mean total daily OFF time between safinamide and placebo groups was 1.10 h (p < 0.0001). This change was significantly greater in the safinamide group starting from week 2, suggesting a rapid onset of drug efficacy. ON time, Unified Parkinson’s Disease Rating Scale, Clinical Global Impression scale, and the 39-Item Parkinson’s Disease Questionnaire showed statistically significant improvements. There were no significant between-group differences for adverse events or serious adverse events.

CONCLUSIONS: Safinamide, as add-on therapy to levodopa, significantly reduced motor fluctuations and improved motor symptoms and quality of life of Chinese patients with idiopathic Parkinson’s disease. The improvements observed in the Unified Parkinson’s Disease Rating Scale total and motor scores were also clinically significant. No safety concerns were identified, confirming the good tolerability profile of the drug.

CLINICAL TRIAL REGISTRATION: NCT03881371, registered on 19 March, 2019, https://clinicaltrials.gov/NCT03881371 .

PMID:36346534 | DOI:10.1007/s40263-022-00958-6

Environ Sci Pollut Res Int. 2022 Nov 8. doi: 10.1007/s11356-022-23863-3. Online ahead of print.

ABSTRACT

Bisphenol A (BPA) is an endocrine disruptor that is present in freshwater and marine environments. However, conclusive evidence for the toxicity of chronic BPA exposure to marine fishes remains lacking. Therefore, we investigated the influence of BPA on male marine medaka (Oryzias melastigma). BPA exposure induced formation of testis-ova at 2610 µg/L, and male-type anal fins became more female type in a concentration-dependent manner. Some males with female-type anal fins had normal testes, indicating that anal fin shape is more sensitive to BPA. Gonadal soma-derived factor (gsdf) expression decreased after BPA exposure in the 746 and 2610 µg/L exposure groups, although the changes were not statistically significant. Additionally, liver vitellogenin (vtg) expression increased in a dose-dependent manner and was significantly higher in all exposure groups. vtg and gsdf are likely to be useful biomarkers for the impact of estrogenic endocrine disrupters in O. melastigma.

PMID:36346516 | DOI:10.1007/s11356-022-23863-3

EJNMMI Res. 2022 Nov 8;12(1):71. doi: 10.1186/s13550-022-00944-5.

ABSTRACT

BACKGROUND: Antiepileptic drugs, levetiracetam (LEV) and brivaracetam (BRV), bind to synaptic vesicle glycoprotein 2A (SV2A). In their anti-seizure activity, speed of brain entry may be an important factor. BRV showed faster entry into the human and non-human primate brain, based on more rapid displacement of SV2A tracer ¹¹C-UCB-J. To extract additional information from previous human studies, we developed a nonlinear model that accounted for drug entry into the brain and binding to SV2A using brain ¹¹C-UCB-J positron emission tomography (PET) data and the time-varying plasma drug concentration, to assess the kinetic parameter K₁ (brain entry rate) of the drugs.

METHOD: Displacement (LEV or BRV p.i. 60 min post-tracer injection) and post-dose scans were conducted in five healthy subjects. Blood samples were collected for measurement of drug concentration and the tracer arterial input function. Fitting of nonlinear differential equations was applied simultaneously to time-activity curves (TACs) from displacement and post-dose scans to estimate 5 parameters: K₁ (drug), K₁(¹¹C-UCB-J, displacement), K₁(¹¹C-UCB-J, post-dose), free fraction of ¹¹C-UCB-J in brain (f_ND(¹¹C-UCB-J)), and distribution volume of ¹¹C-UCB-J (V_T(UCB-J)). Other parameters (K_D(drug), K_D(¹¹C-UCB-J), f_P(drug), f_P(¹¹C-UCB-J, displacement), f_P(¹¹C-UCB-J, post-dose), f_ND(drug), k_off(drug), k_off(¹¹C-UCB-J)) were fixed to literature or measured values.

RESULTS: The proposed model described well the TACs in all subjects; however, estimates of drug K₁ were unstable in comparison with ¹¹C-UCB-J K₁ estimation. To provide a conservative estimate of the relative speed of brain entry for BRV vs. LEV, we determined a lower bound on the ratio BRV K₁/LEV K₁, by finding the lowest BRV K₁ or highest LEV K₁ that were statistically consistent with the data. Specifically, we used the F test to compare the residual sum of squares with fixed BRV K₁ to that with floating BRV K₁ to obtain the lowest possible BRV K₁; the same analysis was performed to find the highest LEV K₁. The lower bound of the ratio BRV K₁/LEV K₁ was ~ 7.

CONCLUSIONS: Under appropriate conditions, this advanced nonlinear model can directly estimate entry rates of drugs into tissue by analysis of PET TACs. Using a conservative statistical cutoff, BRV enters the brain at least sevenfold faster than LEV.

PMID:36346513 | DOI:10.1186/s13550-022-00944-5

Dig Dis Sci. 2022 Nov 8. doi: 10.1007/s10620-022-07734-y. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Several studies showed muscularis macrophages (MMφ) are associated with GI motility disorders. The purpose of this study was to preliminary explore the association between MMφ and achalasia.

METHODS: Tissue samples of the lower esophageal sphincter (LES) high-pressure zone were obtained from 27 achalasia patients and 10 controls. Immunohistochemistry for MMφ, interstitial cells of Cajal (ICC), neuronal nitric oxide synthase (nNOS), and glial cells were conducted. Histological characteristics were compared between groups, and correlation analysis was performed.

RESULTS: Fewer ICC was found in achalasia compared with controls (P = 0.018), and the level of M1 macrophages was higher than that in controls no matter in terms of the number or the proportion of M1(P = 0.026 for M1 and 0.037 for M1/MMφ). Statistical differences were found between two groups in terms of proportion of M2 and ratio of M1 to M2 (P = 0.048 for M2/ MMφ and < 0.001 for M1/M2). For the correlation analysis, significant correlations were detected between levels of nNOS, ICC, and glial cells in patients with achalasia (P = 0.026 for nNOS and ICC, 0.001 for nNOS and glial cells, 0.019 for ICC and glial cells). There were significant correlations between M2/MMφ and levels of ICC (P = 0.019), glial cells (P = 0.004), and nNOS (P = 0.135).

CONCLUSION: Patients with achalasia had a higher level of M1/M2 ratio in LES and significant correlations were found between M2/MMφ and numbers of ICC and glial cells, which suggested that MMφ were probably associated with occurrence and development of achalasia.

PMID:36346489 | DOI:10.1007/s10620-022-07734-y

Breast Cancer Res Treat. 2022 Nov 8. doi: 10.1007/s10549-022-06781-3. Online ahead of print.

ABSTRACT

PURPOSE: The status of human epidermal growth factor receptor 2 (HER2) is important for treatment decision-making of breast cancer and was commonly determined by core needle biopsy (CNB). The concordance of CNB with surgical excision biopsy (SEB) has been verified, but remain unclear according to the newly developed classification of HER2 status. Our study aimed to re-evaluate the diagnostic value of CNB for determining HER2 status in breast cancer, especially in the HER2-low population.

METHODS: Eligible breast cancer patients in West China Hospital between January 1, 2007 and December 31, 2021 were enrolled consecutively and data were extracted from the Hospital Information System. The agreement of HER2 status between CNB and SEB was calculated by concordance rate and κ statistics, as well as the sensitivity, specificity, positive, and negative predictive values (PPV & NPV). Logistic models were used to explore potential factors associated with the discordance between both tests.

RESULTS: Of 1829 eligible patients, 1097 (60.0%) and 1358 (74.2%) were consistent between CNB and SEB by pathological and clinical classifications, respectively, with κ value being 0.46 (0.43-0.49) and 0.57 (0.53-0.60). The sensitivity (50.9%-52.7%) and PPV (50.5%-55.2%) of CNB were especially low among IHC 1+ and 2+/ISH – subgroups by pathological classifications; however, it showed the highest sensitivity (77.5%) and the lowest specificity (73.9%) in HER2-low population by clinical classifications. Advanced N stages might be a stable indicator for the discordance between both tests.

CONCLUSION: The diagnostic value of CNB was limited for determining HER2 status in breast cancer, especially in HER2-low population.

PMID:36346486 | DOI:10.1007/s10549-022-06781-3