Author: Nevin Manimala

Vet Comp Oncol. 2021 Mar 27. doi: 10.1111/vco.12696. Online ahead of print.

ABSTRACT

Canine gastrointestinal sarcomas, a group of tumors that includes leiomyosarcomas (LMSAs), gastrointestinal stromal tumors (GISTs), and other rarer sarcomas, comprise about 10-30% of all gastrointestinal tumors. This study aims to characterize the histologic characteristics and clinical behavior in order to identify prognostic factors predictive of outcome. A single institution database search for surgically-treated gastrointestinal sarcomas yielded 47 cases with adequate tissue remaining for histologic analysis and 42 cases available for analysis of clinical outcome. Tumors were then prospectively evaluated for mitotic count, necrosis, hemorrhage, and inflammation, as well as categorized via immunohistochemical (IHC) staining for smooth muscle actin, c-KIT, and DOG-1. IHC analysis defined 32 tumors as GISTs, 14 as LMSAs, and one as a sarcoma not otherwise specified. For both GISTs and LMSAs, the overall median survival time (MST) is 1024 days (range 31-1456), which did not differ statistically between tumor types (p=0.92). The overall metastatic rate of GISTs in this study was 32.1% (n=9) which was not significantly different to that of LMSAs at 15.3% (n=2, p=0.45). In multivariate analysis, mitotic count under 9 in GIST patients and complete surgical excision in all tumor types correlated with improved MST. For patients with GISTs, the intensity of c-KIT staining also correlated positively with survival, with an MST of 250 days in cases with weak staining and an MST of 1418 days in cases with moderate or strong c-KIT staining (p=0.005). This article is protected by copyright. All rights reserved.

PMID:33774909 | DOI:10.1111/vco.12696

Andrologia. 2021 Mar 28:e13935. doi: 10.1111/and.13935. Online ahead of print.

ABSTRACT

Intracytoplasmic sperm injection (ICSI) is increasingly used to treat male-factor infertility when sperm parameters are not proper for intrauterine insemination (IUI) or in vitro fertilization (IVF). Among sperm abnormalities, short tail sperm defect is a rare kind of teratozoospermia, which is a severe cause of male infertility. In this study, we evaluated the ICSI outcomes of infertile men with severely short tail sperm defect. 117 infertile men with primary infertility were included in this study. We evaluated the impact of short tail sperm defect on large ICSI series (228 cycles) outcomes. The fertilisation rate (FR) was 49.0%, the clinical pregnancy rate (PR) was 21.7%, and the delivery rate (DR) was 17.5%. The results of statistical analysis show that there is no relationship between short tail sperm defect and clinical pregnancy. According to the present study, there were patients with successful ICSI outcomes despite the severe defect in their spermatozoa flagella. Our results can be considered in two main aspects: (a) it seems that ICSI could be a proper therapy for infertile men with short-tailed sperm defect and (b) the abnormal sperm morphology (especially in sperm flagellum) is not a reliable predictor for the ICSI outcomes. In conclusion, our study suggests that ICSI should be considered as a proper treatment way for infertile men with severe short tail sperm defect and probably other sperm flagella abnormalities.

PMID:33774863 | DOI:10.1111/and.13935

Med Phys. 2021 Mar 28. doi: 10.1002/mp.14867. Online ahead of print.

ABSTRACT

PURPOSE: Ultrasound-targeted microbubble destruction (UTMD) has been widely applied to enhance chemotherapy of tumors, yet few studies have focused on the metastatic potential induced by UTMD. This study aimed to explore the metastasis of VX2 tumors after treatment with UTMD and chemotherapy.

METHODS: Forty-four New Zealand rabbits bearing subcutaneous VX2 tumors were enrolled for the treatment of UTMD with chemotherapy. For UTMD, the tumors were insonated using two pulsing protocols of diagnostic ultrasound (DUS, VINNO and ECARE) with a mechanical index (MI) of 0.29-0.33, tone burst of 8.0 cycles, and frequencies of 3-4 MHz. A total dose of 2 mL SonoVue^® was injected intermittently during 10 min UTMD exposure. The combination therapy was treated using doxorubicin (DOX, 2 mg/kg) and DUS, while the tumors treated using DOX only served as the control. Tumor size was measured using the tumor volume formula. Survival time was observed until animal death or the end of the study (120 days). Specific organs (lung, liver, kidney, and brain) were removed for metastatic evaluation.

RESULTS: There were no statistical differences in overall metastasis classification and individual organ metastases among all groups (P>0.05). The tumor growth rate only showed inhibition on the 5^th day (P<0.01). The survival time did not demonstrate any significant difference between UTMD and chemotherapy only (P>0.05).

CONCLUSIONS: UTMD using long pulse DUS with commercial microbubbles did not pose a risk of metastasis enhancement in DOX chemotherapy.

PMID:33774845 | DOI:10.1002/mp.14867

J Appl Toxicol. 2021 Mar 28. doi: 10.1002/jat.4162. Online ahead of print.

ABSTRACT

Previously, dibutyltin dichloride (DBTC) was the putative toxophore for dibutyltin bis-alkyl and bis-thio esters. Recent chemical and toxicological data on dioctyltin bis(2-ethylhexyl thioglycolate) suggest the thioglycolate esters of alkyltins do not generate the dichloride toxophore. Our results, using ¹¹⁹ Sn-nuclear magnetic resonance (NMR) spectroscopy, demonstrated that dibutyltin bis(2-ethylhexyl thioglycolate) (DBTE) is hydrolyzed to dibutyltin chloro-(2-ethylhexyl thioglycolate) (DBTEC) under simulated gastric conditions. No DBTC was detected. DBTE was administered orally to presumed-pregnant Sprague-Dawley rats in a corn oil vehicle at 2.5, 8.5, and 25.0 mg/kg/day (Gestation Day 5 [GD5] through GD19). There were no maternal deaths, no treatment-related statistically significant reductions in feed consumption, maternal body weight or weight gain, or adverse gestational outcomes. Maternal thymus weight was significantly reduced in rats at 25 mg/kg. There were no effects on fetal growth, no dose-dependent pattern of external, visceral, or skeletal malformations, and no increase in anatomical variations. Based on the obtained experimental data, it is concluded here that DBTE forms DBTEC, not DBTC, in the stomach, and DBTE was not teratogenic nor fetotoxic in rats, a species sensitive to DBTC. The maternal no-observed-adverse-effect level (NOAEL) was 8.5 mg/kg/day, and the developmental NOAEL was 25 mg/kg/day, the high dose. The maternal LOAEL was 25 mg/kg/day based on reduced maternal thymus weight.

PMID:33774828 | DOI:10.1002/jat.4162

Sports Med. 2021 Mar 28. doi: 10.1007/s40279-021-01452-7. Online ahead of print.

ABSTRACT

BACKGROUND: Cycling has been suggested to be related to risk of all-cause and cardiovascular disease (CVD) mortality. However, a quantitative comprehensive assessment of the dose-response association of cycling with risk of all-cause and CVD mortality has not been reported. We performed a meta-analysis of cohort studies assessing the risk of all-cause and CVD mortality with cycling.

METHODS: PubMed and Embase databases were searched for relevant articles published up to December 13, 2019. Random-effects models were used to estimate the summary relative risk (RR) of all-cause and CVD mortality with cycling. Restricted cubic splines were used to evaluate the dose-response association.

RESULTS: We included 9 articles (17 studies) with 478,847 participants and 27,860 cases (22,415 from all-cause mortality and 5445 from CVD mortality) in the meta-analysis. Risk of all-cause mortality was reduced 23% with the highest versus lowest cycling level [RR 0.77, 95% confidence interval (CI) 0.67-0.88], and CVD mortality was reduced 24% (RR 0.76, 95% CI 0.65-0.89). We found a linear association between cycling and all-cause mortality (P_{non-linearity} = 0.208); the risk was reduced by 9% (RR 0.91, 95% CI 0.86-0.96) with each five metabolic equivalent of task (MET)-h/week increase in cycling. We found an approximately U-shaped association between cycling and CVD mortality (P_{non-linearity} = 0.034), with the lowest risk at approximately 15 MET-h/week of cycling.

CONCLUSIONS: Our findings based on quantitative data suggest that any level of cycling is better than none for all-cause mortality. However, for CVD mortality, one must choose an appropriate level of cycling, with an approximate optimum of 15 MET-h/week (equal to 130 min/week at 6.8 MET).

PMID:33774807 | DOI:10.1007/s40279-021-01452-7

Eur Arch Paediatr Dent. 2021 Mar 27. doi: 10.1007/s40368-021-00603-8. Online ahead of print.

ABSTRACT

PURPOSE: Oral health of children with congenital heart disease (CHD) is of utmost importance. This study aimed to investigate the prevalence of dental caries and attendance to dental care in Finnish heart-operated CHD patients born in 1997-1999.

METHODS: The cohort of children born in 1997-1999 was selected using a national register on all heart-operated children in Finland. Gender, general health problems, diagnosis, type of the heart defect (shunting, stenotic and complex defects), and number of operations were available and included in the analyses. Dental records from primary health care were collected from municipalities with their permission. The data comprised of the number of dental examinations and data on caries status (dt, DT, dmft, DMFT) at the age of 7 (grade 1), 11 (grade 5) and 15 (grade 8) years and at the most recent examination. The control group consisted of dental data on patients born in 1997-1999 provided by the City of Oulu, Finland (n = 3356).

RESULTS: Oral patient records of 215/570 children were obtained. The difference between the defect types was statistically significant both for DT (p = 0.046) and DMFT (p = 0.009) at the age of 15 (grade 8). The prevalence of caries did not differ between the study population and the controls. High present and past caries experiences were not associated with higher number of visits to oral health care, especially to oral hygienist, or with oral health promotion. National obligations concerning dental visits were not implemented in all municipalities.

CONCLUSION: There seems to be a need for oral health promotion and preventive means implemented by oral hygienists among those with CHD.

PMID:33774803 | DOI:10.1007/s40368-021-00603-8

Environ Sci Pollut Res Int. 2021 Mar 28. doi: 10.1007/s11356-021-13576-4. Online ahead of print.

ABSTRACT

Excessive Fe and Mn in groundwater of the Songnen Plain, northeast China, pose a threat to water security. Human activities over recent decades have had significant effects on the water quantity and quality of the Songnen Plain. By adopting the large city of Changchun in the Songnen Plain as a research area, this study analyzed the effects of the natural environment (including characteristics of soil and aquifer, climate, and groundwater level) and human activities (including groundwater salinization, groundwater exploitation, and nitrate effects) on groundwater Fe and Mn using statistical and spatial analysis methods. The results showed that the characteristics of soil and aquifer determine the source of groundwater Fe and Mn. The correlations between Fe and Mn with TDS (total dissolved solids) increased with increasing TDS from southeast to northwest in different microclimate regions. The salinization of groundwater caused by human activities will also lead to the increase of Fe content. The decrease in groundwater Fe and Mn was attributed to an increase in groundwater [Formula: see text], through the use of chemical fertilizers. The variation of Fe concentration in groundwater corresponded well with that of groundwater depth, but the excessive exploitation will lead to the continuous decrease in groundwater level and a corresponding decrease in the concentration of groundwater Fe. This study provides a reference for understanding the influence of human activities and the natural environment on groundwater hydrochemistry in the Songnen Plain.

PMID:33774796 | DOI:10.1007/s11356-021-13576-4

Ir J Med Sci. 2021 Mar 27. doi: 10.1007/s11845-021-02599-y. Online ahead of print.

ABSTRACT

BACKGROUND: The involvement of pharmacists in the provision of specialised care to patients with epilepsy is poor.

OBJECTIVE: To evaluate the impact of pharmaceutical care services on the clinical outcomes of epilepsy.

SETTING: Two selected major referral epilepsy treatment centres in southern Nigeria were used for the study. Patients were recruited from the Neurology and Medical out-patient clinics of the hospitals.

METHOD: An open randomised controlled study was carried out on epilepsy patients receiving clinical care at the selected hospitals. Patients in the intervention group were offered pharmaceutical care services. The impact of the pharmaceutical care services on the clinical outcomes of epilepsy (seizure frequency and severity) was evaluated.

MAIN OUTCOME MEASURE: The effect of pharmaceutical care services on seizure frequency and severity in patients with epilepsy.

RESULTS: There was a statistically significant difference between the usual care (UC) and the pharmaceutical care (PC) group on the clinical outcomes of epilepsy post-PC intervention. Comparison between the groups (UC versus PC) revealed that patients in the PC group had a significantly lower seizure frequency score than those in the UC group at 3 months and 6 months-(pre-intervention: 3.09 versus 3.34; t = -1.685; p = 0.094) (3 months 2.45 versus 1.68; t = 4.494; p = 0.001), (6 months: 1.97 versus 0.92; t = -3.137; p = 0.001). Also, comparisons between the groups (UC versus PC) showed that patients in the PC group had a significantly lower seizure severity score than those in the UC group at 3 months and 6 months-(pre-intervention 18.46 versus 20.38; t = -3.102; p = 0.01) (3 months: 17.51 versus 14.79; t = 4.202; p = 0.001) (6 months 16.41 versus 11.66; t = 8.930; p = 0.001).

CONCLUSION: Pharmaceutical care interventions may significantly reduce seizure frequency and severity in patients with epilepsy.

IMPACT OF FINDINGS ON PRACTICE: These findings provide justification for the integration of pharmaceutical care services with other elements of health care for epilepsy patients.

PMID:33774765 | DOI:10.1007/s11845-021-02599-y

Int J Clin Pharm. 2021 Mar 28. doi: 10.1007/s11096-021-01261-y. Online ahead of print.

ABSTRACT

Background Efficacy of clopidogrel may be diminished due to either co-administration of proton pump inhibitors or carrying CYP2C19 loss-of-function alleles. However, patients may be at greater risk of major adverse cardiovascular events if taking clopidogrel together with proton pump inhibitors and also inherited the CYP2C19 loss-of-function alleles which may cause further reduction of clopidogrel efficacy. This is due to the cumulative effects of drug-drug interactions and drug-gene interactions collectively referred to as multifactorial drug-gene interactions. Aim of the review The aim of this analysis was to estimate aggregated risk of major adverse cardiovascular events for either coronary heart disease or stroke patients with multifactorial drug-gene interactions versus clopidogrel alone with or without drug-gene interactions. Methods Literatures were searched using different resources based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Meta-analysis was performed using RevMan software following either fixed/random effects model based on the levels of heterogeneity. A p value < 0.05 (2-sided) was considered statistically significant. Results In total, five studies consisting 8,802 patients of coronary artery diseases or stroke were included in this meta-analysis in which 3,767 were prescribed clopidogrel alone, 1,931 were concomitantly taking clopidogrel and PPIs, 2,146 were carrying CYP2C19 loss-of-function alleles and 958 were taking both clopidogrel and proton pump inhibitors while also carrying CYP2C19 loss-of-function alleles. It was found that patients with multifactorial drug-gene interactions were associated with significantly increased risk of major adverse cardiovascular events compared to those taking clopidogrel alone without CYP2C19 loss-of-function alleles (12% vs. 5.8%; RR 1.73; 95% CI 1.12-2.67; p = 0.01). Patients with multifactorial drug-gene interactions were also associated with significantly increased risk of major adverse cardiovascular events compared to drug-gene interactions (RR 1.63; 95% CI 1.31-2.03; p < 0.0001). Patients taking clopidogrel with proton pump inhibitors were also associated with 35% significantly increased risk of major adverse cardiovascular events compared to those taking only clopidogrel (RR 1.35; 95% CI 1.11-1.65; p = 0.003). Conclusion Patients inheriting CYP2C19 loss-of-function alleles have significantly increased risk of major adverse cardiovascular events when taking clopidogrel and proton pump inhibitors concurrently.

PMID:33774763 | DOI:10.1007/s11096-021-01261-y

Mol Biol Rep. 2021 Mar 28. doi: 10.1007/s11033-021-06281-5. Online ahead of print.

ABSTRACT

Breast cancer is a heterogeneous disease, which is the most common malignancy in women. The incidence and mortality rates of breast cancer indicate that it is the leading cause of cancer-related with deaths. circRNAs operate as part of competing endogenous RNAs (ceRNAs) mechanisms, which play critical roles in the different biological processes of breast cancer such as proliferation, migration, and apoptosis. The goal of the present study is to identify the potential predictive biomarker for breast cancer diagnosis in the circRNA network by in vitro and in silico analyzes. 40 miRNAs were obtained from the miRWalk database and their combinatorial target genes (potential ceRNAs) were identified with ComiR. We stated that the cancer-specific circRNA genes in MCF-7 cells using the cancer-specific circRNA (CSDC) database, and obtained the ones showing potential ceRNA activity in our previous analysis among them. Identified genes with remarkable expression differences between BCa and normal breast tissue were determined by the GEPIA database. Moreover, the Spearman correlation test in the GEPIA database was used for the statistical analysis of the relationship between DCAF7 and SOGA1, SOGA1 and AVL 9, DCAF7 and AVL 9 gene pairs. And also, DCAF7, SOGA1, and AVL9 gene expression levels were detected in MCF-7 and MCF-10A cells by RT-qPCR method. DCAF7, SOGA1, and AVL9 gene were significantly more expressed to BCa tissue and MCF-7 cells than normal breast tissue and MCF-10 A cells. And also, DCAF7 and SOGA1, SOGA1 and AVL9, DCAF7 and AVL9 genes pairs were found to be significantly correlated with BCa. These genes may be considered as potential predictive biomarkers to discriminate BCa patients from healthy persons. Our preliminary results can supply a new perspective for in vitro and vivo studies in the future.

PMID:33774752 | DOI:10.1007/s11033-021-06281-5