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Remifentanil-based fast-track cardiac anesthesia combined with the postoperative serratus anterior plane block for transthoracic device closure of atrial septal defect in pediatric patients

J Card Surg. 2021 Apr 3. doi: 10.1111/jocs.15527. Online ahead of print.

ABSTRACT

BACKGROUND: To evaluate the safety and effectiveness of remifentanil-based fast-track cardiac anesthesia (FTCA) combined with the postoperative serratus anterior plane block (SAPB) for transthoracic device closure of atrial septal defect (ASD) in pediatric patients.

METHODS: A total of 70 children who underwent transthoracic device closure of ASDs from January 2018 to June 2020 were divided into two groups according to different anesthesia strategies administered, namely group F (fast-track anesthesia, n = 38) and group R (routine anesthesia, n = 32), and relevant clinical data were collected and analyzed.

RESULTS: There was no statistically significant difference between the two groups in general preoperative data, intraoperative hemodynamics, and FLACC score 1 h after extubation (p > .05). FLACC score of Group F was significantly lower than that of group R at 4, 8, 12, and 24 h after extubation (p < .05). The number of postoperative PCA press and the dose of PCA infusion in group F were lower than those in group R (p < .05). The mechanical ventilation duration, the length of intensive care unit stay in group F were statistically significantly lower than those in group R (p < .05).

CONCLUSION: Remifentanil-based FTCA combined with the postoperative SAPB for transthoracic device closure of ASD in pediatric patients could effectively reduce postoperative pain of the children.

PMID:33811664 | DOI:10.1111/jocs.15527

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Genotyping of Deltamethrin Resistance in Rhipicephalus (Boophilus) microplus Population in Kerala, South India

Acta Parasitol. 2021 Apr 3. doi: 10.1007/s11686-021-00378-4. Online ahead of print.

ABSTRACT

PURPOSE: Genotyping of Rhipicephalus (Boophilus) microplus for polymorphisms in deltamethrin-resistant loci of sodium channel gene by allele-specific PCR (AS-PCR).

METHODS: Adult R. (B.) microplus ticks were collected from naturally infested cattle in Kerala. The larval packet test (LPT) was performed with deltamethrin and dose response data were analysed by probit method. Adult and larval tick DNA were amplified by PCR and later sequenced to identify mutations, if any, in the domain II S4-5 linker and domain III S6 regions in para voltage-gated sodium channel gene, at loci that were previously documented to be associated with deltamethrin resistance. Allele-specific PCR was performed for the amplification of target gene locus (C190A and T2134C) to genotype 1000 larvae each, at these loci. Genotype frequency was statistically analysed by Chi-square test.

RESULTS: Bioassay using LPT revealed that LC50 and LC95 values of all the R. (B.) microplus isolates in this study were more than double the reported values of reference susceptible strain. Sequence analysis of the PCR amplicons of domain II S4-5 linker of voltage-gated sodium channel gene revealed C190A mutation, A271G mutation as well as A-G mutation at 217th position. AS-PCR done to genotype C190A mutations revealed a frequency of 6%, 15% and 64%, respectively for homozygous-susceptible (SS), heterozygous (RS) and homozygous-resistant (RR) genotypes. In domain III S6 region of the gene, C2121T and A2102T mutations were observed. AS-PCR to genotype the previously reported T2134C mutation revealed 100% SS genotype in R. (B.) microplus isolates of Kerala.

CONCLUSIONS: Genotyping of R. (B.) microplus isolates of Kerala for target site mutations reportedly associated with deltamethrin resistance revealed a significantly high frequency of resistant genotypes at II S4-5 linker of voltage-gated sodium channel gene. This study forms the first report of such mutations in Kerala, south India and demands serious attention in the light of increased prevalence of tick-borne haemoparasitic infection.

PMID:33811625 | DOI:10.1007/s11686-021-00378-4

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Association of TYRP1 with hypoxia and its correlation with patient outcome in uveal melanoma

Clin Transl Oncol. 2021 Apr 3. doi: 10.1007/s12094-021-02597-7. Online ahead of print.

ABSTRACT

PURPOSE: Molecular mechanisms of uveal melanoma development in association with high pigmentation are unclear. Tyrosinase Related Protein (TYRP1) is not only one of the important melanogenesis marker that contributes to melanin synthesis, but can also prevents the melanocyte death. The induction of melanogenesis leads to induction of HIF-1α which can affect the behavior of melanoma cells and its surrounding environment. The aim of our study was to determine the expression of TYRP1 and HIF-1α at the protein and RNA level and determine its prognostic significance.

METHODS: In the present study, the expression of TYRP1 and HIF-1α was investigated on 61 formalin-fixed paraffin-embedded choroidal melanoma samples by immunohistochemistry. Fresh 50 samples were validated by real-time PCR. Results were correlated with clinicopathological parameters and Kaplan-Meier was performed to determine the prognostic significance.

RESULTS: High immunoexpression of TYRP1 and HIF-1α was present in 61 and 54% of patients, respectively. Both TYRP1 and HIF-1α correlated well with high pigmentation and BAP1 (BRCA1 Associated Protein-1) loss (p < 0.05) at IHC level as well as transcriptional level. There was reduced metastatic free survival in patients with necrosis and this was statistically significant (p = 0.010).

CONCLUSION: Our findings indicate that TYRP1 can be used as a potential biomarker in the development of targeted therapy in UM. Further studies on melanogenesis markers associated with TYRP1 could provide us a better understanding in this field.

PMID:33811629 | DOI:10.1007/s12094-021-02597-7

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Computer-Aided Diagnosis System for Alzheimer’s Disease Using Positron Emission Tomography Images

Interdiscip Sci. 2021 Apr 3. doi: 10.1007/s12539-020-00409-0. Online ahead of print.

ABSTRACT

Alzheimer’s disease (AD) is a kind of neurological brain disease. It is an irretrievable, neurodegenerative brain disorder. There are no pills or drugs to cure AD. Therefore, an early diagnosis may help the physician to make accurate analysis and to provide better treatment. With the advent of computational intelligence techniques, machine learning models have made tremendous progress in brain images analysis using MRI, SPECT and PEI. However, accurate analysis of brain scans is an extremely challenging task. The main focus of this paper is to design a Computer Aided Diagnosis (CAD) system using Long-Term Short Memory (LSTM) to improve classification rate and determine suitable attributes that can differentiate AD from Healthy Control (HC) subjects. First, 3D PET images are preprocessed, converted into many groups of 2D images and then grouped into many subsets at certain interval. Subsequently, different features including first order statistical, Gray Level Co-occurrence Matrix and wavelet energy of all sub-bands are extracted from each group, combined and taken as feature vectors. LSTM is designed and employed for classifying PET brain images into HC and AD subjects based on the feature vectors. Finally, the developed system is validated on 18FDG-PET images collected from 188 subjects including 105 HC and 83 AD subjects from ADNI database. Efficacy of the developed CAD system is analyzed using different features. Numerical results revealed that the developed CAD system yields classification accuracy of 98.9% when using combined features, showing outstanding performance.

PMID:33811602 | DOI:10.1007/s12539-020-00409-0

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Dihydroxyeicosatrienoic Acid, a Metabolite of Epoxyeicosatrienoic Acids Upregulates Endothelial Nitric Oxide Synthase Expression Through Transcription: Mechanism of Vascular Endothelial Function Protection

Cell Biochem Biophys. 2021 Apr 3. doi: 10.1007/s12013-021-00978-x. Online ahead of print.

ABSTRACT

The present study aimed to investigate the impacts and underlying mechanisms of 14,15-DHETs on eNOS and vascular endothelial functions. Bovine aortic endothelial cells (BAECs) were treated with various concentrations of 14, 15-DHET. The expressions of eNOS protein and mRNA were observed at different time points. The eNOS expression and phosphorylation were subsequently detected administered with 8,9-DHET, 11,12-DHET, and 14,15-DHET, respectively. Meanwhile, 14,15-DHET action on tube formation was observed in human umbilical vein endothelial cells (HUVECs). Finally, the aorta of male C57BL/6 mice was injected with 14,15-DHET via the tail vein. The impacts of 14,15-DHET (0.4 mg/kg body weight) on the expressions of eNOS protein and mRNA and endothelium-dependent vasodilation (EDV) were detected following 24 h. The expression of eNOS was greatly improved with the 14,15-DHET treatment compared with the BAECs, and eNOS phosphorylation sites at Ser1179, Ser635, and Thr497 were elevated. However, no statistically significant difference was revealed on total eNOS among the 8,9-DHET, 11,12-DHET, and 14,15-DHET treatment groups. Based on the upregulation of eNOS protein, eNOS mRNA levels were increased in BAECs and thoracic aorta of the male C57BL/6 mice treated with 14,15-DHET, suggesting that transcriptional activation was achieved in vascular eNOS. Moreover, 14,15-DHET enhanced tube formation abilities in HUVECs and acetylcholine(ACh)-induced EDV. These findings indicated that 14,15-DHET could improve the vascular endothelial diastolic functions of male C57BL/6 mice, and enhance the ability of tube formation, which might be related to the increase of eNOS expression.

PMID:33811614 | DOI:10.1007/s12013-021-00978-x

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Effects of the Calcium Channel Blocker Otilonium Bromide on Seizure Activity in Rats With Pentylenetetrazole-Induced Convulsions

Neurochem Res. 2021 Apr 3. doi: 10.1007/s11064-021-03310-4. Online ahead of print.

ABSTRACT

Millions of people suffer from drug-resistant epilepsy. New therapeutic approaches for removing this life-affecting disease are required. The activation of T-type calcium channels (TTCC) is one of the epileptogenesis mechanisms that cause epilepsy. So, we researched the effects of Otilonium bromide (OB), an antisposmolytic drug that inhibits TTCC, on seizure activity in rats with pentylenetetrazol (PTZ) induced convulsion. Randomly, 48 rats were divided into two groups; for electroencephalography (EEG) recordings and for behavioral assesment. Rats were treated with either intraperitoneal (IP) OB at two separate doses (25 mg/kg and 50 mg/kg) or placebo, and then pentylenetetrazole (IP), a potent seizure-inducing chemical administered to them. In our model we have measured rat seizure activity with EEG, the convulsion scala of Racine (RCS), the time of first myoclonic jerk (FMJ) and MDA levels to assess if OB has antiepileptic properties. The mean EEG spike wave percentage score reduced from 79.5% (placebo) to 59.2% (lower-dose) and 35.2% (higher-dose). FMJ had increased from a mean of 67.2 s (placebo), to 105.2 (lower-dose), 150.6 (higher-dose). RCS reduced from a mean of 5.12 (placebo) to 4.4 (lower-dose), 3.8 (higher-dose). MDA leves reduced from 84.5 nmol/gr to 51.09 nmol/gr (lower-dose), 33.2 nmol/gr (higher-dose). Compared to placebo, OB reduced significantly seizure activity at both doses, probably through blocking T-type calcium channels. All these results were statistically significant with < 0.0001 p-values. Otilonium bromide reduced seizure activity in rats with PTZ-induced convulsion. Therefore, the clinical role of OB and other TTCC inhibitors as potential anti-seizure drugs should be further investigated.

PMID:33811624 | DOI:10.1007/s11064-021-03310-4

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Impact of Neoadjuvant Chemotherapy and Pretreatment Biliary Drainage for Pancreatic Head Ductal Adenocarcinoma

Dig Dis Sci. 2021 Apr 3. doi: 10.1007/s10620-021-06967-7. Online ahead of print.

ABSTRACT

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related deaths in the USA. Although management strategies have evolved, there are continued controversies about the use of neoadjuvant chemotherapy (NAC) and pretreatment biliary drainage (PBD) in patients with resectable and potentially resectable disease.

AIMS: We aimed to characterize the practice trends and outcomes for NAC and PBD.

METHODS: A single-center cohort study was performed. Electronic medical records were reviewed between 2011 and 2019, and 140 patients who had pancreaticoduodenectomy for PDAC were included. Diagnosis, treatment, and outcome data were captured.

RESULTS: There were no statistically significant temporal trends relating to the use of chemotherapy and PBD. Overall, 41% of patients received NAC and had improved survival, independent of other factors. Of the 71% who received PBD, only 40% had appropriate indications; 30% experienced postprocedure complications, and 34% required reintervention. Factors associated with the application of PBD included preoperative jaundice (OR 70.5, 95% CI 21.4-306.6) and evaluation by non-tertiary therapeutic endoscopists (OR 3.9, 95% CI 1.3-13.6). PBD was associated with a 12-day delay in surgery among those who did not receive NAC (p = 0.005), but there were no differences in surgical complications or mortality.

CONCLUSIONS: Our findings suggest that (1) NAC may confer a survival benefit and (2) PBD should be reserved for individuals with jaundice requiring NAC. Implementation of guidelines by North American gastroenterology societies, multidisciplinary treatment models, and delivery of care at high-volume tertiary centers may help optimize management.

PMID:33811566 | DOI:10.1007/s10620-021-06967-7

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Minimally invasive versus conventional continuous-flow left ventricular assist device implantation for heart failure: a meta-analysis

Heart Fail Rev. 2021 Apr 3. doi: 10.1007/s10741-021-10102-z. Online ahead of print.

ABSTRACT

Many studies have reported various minimally invasive techniques for continuous-flow left ventricular assist device implantation. There is no consensus on whether minimally invasive techniques can bring more benefits for patients compared with the conventional technique, due to the limited number of patients and diverse results in current studies. Our meta-analysis mainly discussed the comparison of minimally invasive and conventional techniques. We searched controlled trials from PubMed, Cochrane Library, and Embase databases until Dec 11, 2020. Perioperative and postoperative outcomes were analyzed among 10 included studies. The protocol has been registered with PROSPERO (CRD42020221532). There were no statistical differences in the 30-day mortality (OR 0.57; 95% CI 0.29 to 1.14), 6-month mortality (OR 0.66; 95% CI 0.41 to 1.05), neurological dysfunction (OR 1.10; 95% CI 0.69 to 1.76), major infection (OR 0.68; 95% CI 0.36 to 1.28), and pump thrombus (OR 1.49; 95% CI 0.63 to 3.52) among the cohorts. Minimally invasive techniques were associated with lower incidences of major bleeding (OR 0.39; 95% CI 0.22 to 0.68), severe right heart failure (OR 0.43; 95% CI 0.23 to 0.81), and less blood-product utilization (SMD -0.44). Sensitivity analysis suggested that minimally invasive techniques were associated with a lower incidence of respiratory failure (OR 0.50; 95% CI 0.26 to 0.96) and shorter mechanical ventilation time (SMD -0.53). Subgroup analysis demonstrated that patients, implanted with a centrifugal pump by minimally invasive techniques, were associated with a shorter length of intensive care unit (ICU) stay (SMD -0.27) and hospital stay (SMD -0.42), and less blood-product utilization (SMD -0.26). In conclusion, minimally invasive techniques can reduce the risks of major bleeding, severe right heart failure, and blood-product utilization, as well as have positive impacts on reducing mechanical ventilation time and the risk of respiratory failure. Minimally invasive centrifugal pump implantation can reduce the length of ICU and hospital stay.

PMID:33811570 | DOI:10.1007/s10741-021-10102-z

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Meta-analysis of nanoparticle albumin-bound paclitaxel used as neoadjuvant chemotherapy for operable breast cancer based on individual patient data (JBCRG-S01 study)

Breast Cancer. 2021 Apr 3. doi: 10.1007/s12282-021-01238-9. Online ahead of print.

ABSTRACT

BACKGROUND: Nanoparticle albumin-bound paclitaxel (nab-PTX), a novel taxane formulation, was developed to avoid cremophor/ethanol-associated toxicities including peripheral neuropathy and hypersensitivity. At least 35 phase II studies using combined nab-PTX and anthracycline in neoadjuvant settings are registered in Japan. We analyzed the efficacy and safety of nab-PTX based on patient characteristics in these studies.

METHODS: We conducted a meta-analysis using individual patient data (IPD) to investigate the average efficacy of nab-PTX-containing regimens as neoadjuvant chemotherapy for operable breast cancer. IPD were provided by principal investigators who agreed to participate. The primary endpoint was pathological complete response (pCR) rate of each breast cancer subtype.

RESULTS: We analyzed the data of 16 studies involving 753 patients. The overall crude frequencies of pCR (ypT0 ypN0, ypT0/is ypN0, and ypT0/is ypNX) were 18.1, 26.0, and 28.6%, respectively. Specifically, the frequencies were 6.7, 10.2, and 13.4% for luminal (n = 343); 40.5, 63.5, and 68.9% for human epidermal growth factor receptor 2 (HER2)-rich, (n = 74); 21.9, 40.6, and 42.7% for luminal/HER2 (n = 96); and 26.3, 31.5, and 32.3% for triple-negative breast cancers (TNBC) (n = 232). The multivariate analyses indicated that HER2 positivity, TNBC, high Ki-67, high nuclear grade, and weekly nab-PTX administration were significantly associated with the pCR. The proportion of hematological toxicities (neutropenia (39.7%) and leukopenia (22.5%)), peripheral sensory neuropathy (9.7%), myalgia (5.7%), and arthralgia (4.7%) was higher than grade 3 adverse events, but most patients recovered.

CONCLUSIONS: Nab-PTX is a safe and acceptable chemotherapeutic agent in neoadjuvant settings, particularly for aggressive cancers. UMIN-CTR#: UMIN000028774.

PMID:33811599 | DOI:10.1007/s12282-021-01238-9

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Critical speed estimated by statistically appropriate fitting procedures

Eur J Appl Physiol. 2021 Apr 3. doi: 10.1007/s00421-021-04675-8. Online ahead of print.

ABSTRACT

PURPOSE: Intensity domains are recommended when prescribing exercise. The distinction between heavy and severe domains is made by the critical speed (CS), therefore requiring a mathematically accurate estimation of CS. The different model variants (distance versus time, running speed versus time, time versus running speed, and distance versus running speed) are mathematically equivalent. Nevertheless, error minimization along the correct axis is important to estimate CS and the distance that can be run above CS (d’). We hypothesized that comparing statistically appropriate fitting procedures, which minimize the error along the axis corresponding to the properly identified dependent variable, should provide similar estimations of CS and d’ but that different estimations should be obtained when comparing statistically appropriate and inappropriate fitting procedure.

METHODS: Sixteen male runners performed a maximal incremental aerobic test and four exhaustive runs at 90, 100, 110, and 120% of their peak speed on a treadmill. Several fitting procedures (a combination of a two-parameter model variant and regression analysis: weighted least square) were used to estimate CS and d’.

RESULTS: Systematic biases (P < 0.001) were observed between each pair of fitting procedures for CS and d’, even when comparing two statistically appropriate fitting procedures, though negligible, thus corroborating the hypothesis.

CONCLUSION: The differences suggest that a statistically appropriate fitting procedure should be chosen beforehand by the researcher. This is also important for coaches that need to prescribe training sessions to their athletes based on exercise intensity, and their choice should be maintained over the running seasons.

PMID:33811559 | DOI:10.1007/s00421-021-04675-8