Unraveling the miRNA Puzzle in Atherosclerosis: Revolutionizing Diagnosis, Prognosis, and Therapeutic Approaches.

PURPOSE OF REVIEW: To eradicate atherosclerotic diseases, novel biomarkers, and future therapy targets must reveal the burden of early atherosclerosis (AS), which occurs before life-threatening unstable plaques form. The chemical and biological features of microRNAs (miRNAs) make them interesting biomarkers for numerous diseases. We summarized the latest research on miRNA regulatory mechanisms in AS progression studies, which may help us use miRNAs as biomarkers and treatments for difficult-to-treat diseases. RECENT FINDINGS: Recent research has demonstrated that miRNAs have a regulatory function in the observed changes in gene and protein expression during atherogenesis, the process that leads to atherosclerosis. Several miRNAs play a role in the development of atherosclerosis, and these miRNAs could potentially serve as non-invasive biomarkers for atherosclerosis in various regions of the body. These miRNAs have the potential to serve as biomarkers and targets for early treatment of atherosclerosis. The start and development of AS require different miRNAs. It reviews new research on miRNAs affecting endothelium, vascular smooth muscle, vascular inflammation, lipid retention, and cholesterol metabolism in AS. A miRNA gene expression profile circulates with AS everywhere. AS therapies include lipid metabolism, inflammation reduction, and oxidative stress inhibition. Clinical use of miRNAs requires tremendous progress. We think tiny miRNAs can enable personalized treatment.

Postoperative pain, recovery and discharge after robot-assisted laparoscopic prostatectomy: A multicentre, single blinded, randomised controlled trial.

BACKGROUND: General anaesthesia is standard of care for patients undergoing robot assisted laparoscopic prostatectomy (RALP). However, postoperative pain and bladder discomfort remains an issue, and optimising pain management could improve recovery and promote earlier home discharge. The main objective of this trial was to evaluate if patients receiving spinal anaesthesia are more frequently home ready at 8 pm on the same day compared with multimodal pain management following RALP under general anaesthesia. METHODS: This pragmatic, randomised controlled, multicentre trial was performed between January 2019 to December 2021. Patients undergoing RALP under general anaesthesia were randomised to either multimodal analgesia using parecoxib and morphine intra-operatively (Group GM) or spinal anaesthesia with bupivacaine and sufentanil (Group GS). The primary aim, home readiness, was assessed using a post-anaesthesia discharge scoring system. RESULTS: Of 202 patients analysed, 27% patients reached home readiness criteria after 12 h, 46% after 24 h and 79% after 48 h, without differences between the groups. Urge to pass urine was greater in group GM than in group GS (p ⟨0.001) and lasted for a median of two hours in both groups. More patients expressed satisfaction with postoperative care in group GS (p ⟨0.001). No other significant differences were found between the groups. DISCUSSION: We found no difference in time to home readiness between the groups. Approximately one-fourth of the patients achieved home readiness the same day after surgery without difference between the groups. Fewer patients had urge, and patient satisfaction was greater in group GS.

Relative dose intensity of taxane-based chemotherapy in breast cancer patients in a tertiary hospital.

INTRODUCTION: Breast cancer (BC) is the most diagnosed tumor among women worldwide. The aim of this study was to investigate the incidence and causes of low relative dose intensity (RDI) < 85% for taxane-based chemotherapy regimens used in the treatment of BC in Sultan Qaboos University Hospital (SQUH). METHODS: This was a retrospective study that included 303 BC patients, treated with taxane-based chemotherapy protocols at SQUH. RDI was calculated for each chemotherapy regimen and causes and predictors of low RDI < 85% were identified. Prophylactic and therapeutic supportive measures for certain toxicities were studied. RESULTS: 50.8% of the patients had neoadjuvant chemotherapy, 38% had adjuvant chemotherapy, and 11.2% of patients were given palliative treatment. AC-T and AC-THP were the most used regimens (40.3% and 17.2%). Mean RDI of used taxane-based chemotherapy regimens was 93.4%. Dose delays, dose reductions, and treatment discontinuation occurred in 36.6%, 14.8%, and 11.5%, respectively. Thirty-eight patients (12.5%) had low RDI < 85% which was reduced to 9.9% after the use of an alternative taxane. Age and chemotherapy intent were significant risk factors. 83.8% received primary granulocyte colony stimulating factor. CONCLUSION: An optimal RDI greater than 85% was achieved in most cases. Furthermore, prophylactic and therapeutic supportive measures were widely used.

Chicken ß-defensin-1 peptide as a candidate anticoccidial agent in broiler chickens.

The current study aimed to investigate the potentiality of using avian ß-defensin-1 peptide as a candidate agent against coccidiosis infection in broiler chicken.We employed an in-silico analysis to study the primary structure of ß-defensin-1 peptide as well as its 3-D and molecular dynamic structures. This will also enable obtaining adequate information about the mode of action of these peptides and the intra-cellular transduction pathways. The results revealed no significant difference among groups of broiler chicken in terms of body weight before the Eimeria challenge.The results of our study indicated a significant reduction in oocyst count in birds administered ß-defensin-1 peptide treatment, vis-a-vis healthy birds. The treated group showed a 2-3 times reduction in oocyst count, compared to the positive control group. The Eimeria oocysts count evaluated for birds administered with ß-defensin-1 after the Eimeria challenge showed a significant difference. The study indicated significant reduction and down-regulation in the level of expression of ß-defensin 1 and 4 in the control and treatment groups.This electrostatic profile and hydrophobicity regulate the functioning of this peptide. The results may help in the development of novel approaches that could be used as alternatives or adjunct to the existing means of coccidiosis control in broilers.

Examination of perceived religion in Muslim women's access to counseling and psychotherapy services: An audit study.

Across the United States and Canada, the marginalization of Muslims has contributed to many Muslim women having mental health difficulties, making it essential that services are available and accessible. An email correspondence audit design research study was used to investigate whether mental health practitioners demonstrate implicit bias in the form of aversive prejudice against Muslim women during a request for counseling/psychotherapy services. A total of 450 counselors or psychologists participated. Practitioners received an email from either a Muslim or non-Muslim woman, signified by name and a religious quotation, requesting an appointment. Based on the Aversive Racism Framework, it was hypothesized that practitioners would (a) respond more frequently to the Muslim woman and (b) respond faster to the Muslim woman but (c) offer services to the Muslim woman at a lesser or similar frequency. All three hypotheses were supported. Findings suggest that aversive prejudice appears active at the forefront of counseling and psychotherapy services for Muslim women, whereby counselors and psychologists are unknowingly acting in a biased manner toward a request for an appointment from a Muslim woman. Suggestions for overcoming this bias are provided. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Development of a validated HPTLC-bioautographic method for evaluation of aromatase inhibitory activity of plant extracts and their constituents.

INTRODUCTION: Aromatase is a CYP450 enzyme that catalyses the conversion of androgens into oestrogens, where the decrease in the production of oestrogens aided by aromatase inhibitors is considered a target in post-menopausal breast cancer therapy. TLC-bioautography is a technique employed for combining chromatographic separations on TLC plates with bioassays. This is the first report to evaluate aromatase inhibitory activity using this technique. OBJECTIVES: The aim of this study is to develop and validate a new TLC-bioautographic method for determination of aromatase inhibitory activity in 14 plant extracts. Two quantitation methods, the peak area method and reciprocal iso-inhibition volume (RIV) method, were compared and investigated to attain reliable results. Factors affecting the enzymatic reaction (temperature, pH, enzyme and substrate concentrations … etc.) were also investigated to attain the optimum parameters. METHODOLOGY: TLC assisted by digital image processing was implemented for quantitative estimation of the aromatase inhibition of 14 plant extracts using chrysin as positive control. The fluorometric substrate dibenzyl fluorescein (DBF) was utilised for the assay, where inhibitory compounds were visualised as dark spots against a blue fluorescent background. Two software programs, Sorbfil® videodensitometer (in the peak area method) and ImageJ® (in the RIV method), were thoroughly validated using the International Council on Harmonisation (ICH) guideline and used for quantitation. RESULTS: The RIV method showed superiority over the peak area method in the quantitation results of the tracks with non-homogenous background with %RSD values of 0.98 and 1.49 compared with 2.86 and 3.58, respectively. Further, the methods allow the comparison of the activity of different unknown inhibitory compounds without the need for a reference or a positive control. CONCLUSION: Using the TLC-bioautographic method by image processing combined with the RIV quantitation method, simultaneous separation and quantitation of aromatase inhibitory components could be applied to estimate the relative activity of various plant extracts.

Impacts of Gum Arabic and Polyvinylpyrrolidone (PVP) with Salicylic Acid on Peach Fruit (Prunus persica) Shelf Life.

Peaches are grown in many Egyptian orchards for local and global fresh market sales. The interior fruit tissue breakdown (IFTB), often resulting in decayed peaches, is a severe problem during marketing. Therefore, to minimize FTB of peaches, in this study, gum arabic (GA) and polyvinylpyrrolidone (PVP) were mixed with different concentrations of salicylic acid (SA) (0, 1, and 2 mM) and were applied as edible coating to extend the shelf life of peach fruits. Mature peaches were selected and harvested when peaches reached total soluble solid content (SSC: 8.5%) and fruit firmness of about 47 N. Fruits were coated and stored at room temperature (26 ± 1 °C and air humidity 51 ± 1%) for 10 days during two seasons: 2020 and 2021. Fruit coated with GA/PVP-SA 2 mM showed a significant (p < 0.05) inhibition in degrading enzyme activities (CWDEs), such as lipoxygenase (LOX), cellulase (CEL), and pectinase (PT), compared to uncoated and coated fruits during the shelf-life period. Hence, cell wall compartments were maintained. Consequently, there was a reduction in browning symptoms in fruits by inhibiting polyphenol oxidase (PPO) and phenylalanine ammonia-lyase (PAL) activities. Thus, the fruit skin browning index showed almost no symptoms. The lipid peroxidation process and ionic permeability declined as well. The result suggests that, by applying GA/PVP-SA 2 mM as an edible coating, fruit tissue breakdown can be minimized, and the shelf life of peach can be extended up to 10 days without symptoms of tissue breakdown.

Antibiotics utilization patterns and dosage appropriateness among patients receiving hemodialysis.

Chronic kidney disease (CKD) is a global health challenge, with a reported prevalence of around 10%. Prescribing for patients receiving hemodialysis (HD) is challenging and complicated by polypharmacy, comorbidities, and changes in clearance of medications. The aim of this study was to evaluate antibiotics utilization patterns and dosage appropriateness in patients receiving HD at a tertiary hospital. A retrospective study was carried on 287 adult inpatients, who received HD and at least one antibiotic in a tertiary hospital in Oman. Data were extracted using the hospital's electronic patient information system. Dosage appropriateness was assessed by identifying the dosage and frequency of prescribed antibiotics and comparing them with international guidelines. The main outcome measures were antibiotics utilization patterns and dosing inappropriateness. The most commonly prescribed parenteral antibiotic was piperacillin + tazobactam (20%), while the most common prescribed oral antibiotic was azithromycin (41.7%). For prophylaxis, cefazolin (54.6%) was the main antibiotic prescribed. The most commonly used antibiotic for external use was mupirocin ointment (38.5%). The overall dosing inappropriateness was 29.5%. Vancomycin was the most common parenteral antibiotic subjected to dosing inappropriateness (19.8%). However, trimethoprim + sulfamethoxazole was more inappropriately prescribed among the oral route (28.6%). In conclusion, the most utilized antibiotic was piperacillin + tazobactam followed by vancomycin. The study reported some inappropriate dosing of antibiotics. Such a study opens the door for the establishment of local guidelines for the improved practice of antibiotics use in HD patients.

Prediction of prognosis in patients with left ventricular dysfunction using three-dimensional strain echocardiography and cardiac magnetic resonance imaging.

BACKGROUND: We evaluated three-dimensional speckle tracking echocardiography (3DSTE) strain and cardiac magnetic resonance (CMR) with delayed contrast enhancement (DCE) for the prediction of cardiac events in left ventricular (LV) dysfunction. METHODS: CMR and 3DSTE in 75 patients with ischaemic and 38 with non-ischaemic LV dysfunction were analysed and temporally correlated to cardiac events during 41 ± 9 months of follow-up. RESULTS: Cardiac events occurred in 44 patients, more in patients with ischaemic LV dysfunction. LV ejection fraction (LVEF), global circumferential and global area strain were reduced more in patients with more cardiac events, whereas 3DSTE LV end-systolic volumes and 3DSTE LV masses were larger. However, the area under the curve using receiver-operating characteristic analysis showed modest sensitivity and specificity for all evaluated parameters. Additionally, DCE did not differ significantly between the two groups. Univariate analysis showed ischaemic aetiology of LV dysfunction, LVEF and LV mass by CMR to be predictors of cardiac events with an increased relative risk of 2.4, 1.6 and 1.5, respectively. By multivariate analysis, only myocardial ischaemia and LVEF ≤ 39% were independent predictors of events (p = 0.004 and 0.005, respectively). Subgroup analysis in ischaemic and non-ischaemic patients showed only 3DSTE LV mass in ischaemic patients to have a significant association (p = 0.033) but without an increased relative risk. CONCLUSION: LVEF calculated by 3DSTE or CMR were both good predictors of cardiac events in patients with LV dysfunction. A reduced LVEF ≤ 39% was associated with a 1.6-fold higher probability of a cardiac event. 3DSTE strain measurements and DCE-CMR did not add to the prognostic value of LVEF.

Antifibrotic effects of bezafibrate and pioglitazone against thioacetamide-induced liver fibrosis in albino rats.

Activation of hepatic stellate cells is a central event in hepatic fibrogenesis that offers multiple potential sites for therapeutic interventions. Peroxisome proliferator-activated receptors are implicated in liver fibrosis. We aimed to evaluate the effect of bezafibrate and pioglitazone on a thioacetamide (TAA) rat model of liver fibrosis and to clarify the possible underlying mechanisms. Rats received intraperitoneal injections of TAA for 6 weeks. Daily oral treatments with bezafibrate or pioglitazone were started with the first day of TAA intoxication. Serum liver function tests, hepatic malondialdehyde (MDA), total nitrite and nitrate (NOx), superoxide dismutase, and hepatic histopathology were assessed to evaluate hepatic damage. Alpha smooth muscle actin (α-SMA) and tissue inhibitor metalloproteinase-1 (TIMP-1) and caspase-3 were also assessed. The TAA group experienced significant deterioration of liver functions, increased oxidative stress, and increased liver tissue NOx. Administration of bezafibrate or pioglitazone resulted in significant improvement of all liver functions and reduced oxidative stress in hepatic tissues. Only administration of bezafibrate significantly reduced NOx levels. Liver tissues from the TAA-treated group showed disrupted normal architecture. Administration of bezafibrate or pioglitazone attenuated this picture. Stronger α-SMA expression was detected in the TAA group. Treatment with bezafibrate or pioglitazone decreased the α-SMA expression.

Clinical studies of single-stage combined ACL and PCL reconstruction variably report graft tensioning, fixation sequence, and knee flexion angle at time of fixation.

PURPOSE: In single-stage ACL-PCL reconstruction, there is uncertainty regarding the order of graft tensioning and fixation, as well as the optimal knee flexion angle(s) for graft fixation. A systematic review of clinical studies of single-stage combined ACL-PCL reconstruction was performed to determine whether a particular fixation sequence and/or knee flexion angle is associated with superior outcomes. METHODS: A systematic review was performed according to PRISMA guidelines. All levels of evidence were included. All outcome measures were extracted, including physical examination values, radiographic measurements, and objective and subjective outcomes. RESULTS: Of the 19 included studies, 17 tensioned and fixed the PCL before the ACL. Only four studies reported the methods/forces used for graft tensioning. Across studies, the ACL was fixed at variable knee flexion angles, from full extension to 70°. Conversely, 3 studies fixed the PCL at a knee flexion angle < 45°, while the remaining 16 studies fixed the PCL at a flexion angle > 70°. Patient-reported outcomes were qualitatively similar between groups. CONCLUSIONS: This systematic review found considerable variability in graft tension, fixation sequence, and knee flexion angle at the time of fixation, with insufficient evidence to support specific surgical practices. Most commonly, the PCL is fixed before the ACL graft, with fixation occurring at a knee flexion angle between 70° and 90° and near full extension, respectively. The methodology for quantifying the forces applied for graft tensioning is rarely described. Given this clinical equipoise, future studies should consistently report these surgical details. Furthermore, prospective, randomized studies on the treatment of multiligament knee injuries are needed to improve outcomes in patients. LEVEL OF EVIDENCE: IV.

Endogenous Avian Leukosis Virus in Combination with Serotype 2 Marek's Disease Virus Significantly Boosted the Incidence of Lymphoid Leukosis-Like Bursal Lymphomas in Susceptible Chickens.

In 2010, sporadic cases of avian leukosis virus (ALV)-like bursal lymphoma, also known as spontaneous lymphoid leukosis (LL)-like tumors, were identified in two commercial broiler breeder flocks in the absence of exogenous ALV infection. Two individual ALV subgroup E (ALV-E) field strains, designated AF227 and AF229, were isolated from two different breeder farms. The role of these ALV-E field isolates in development of and the potential joint impact in conjunction with a Marek's disease virus (MDV) vaccine (SB-1) were further characterized in chickens of an experimental line and commercial broiler breeders. The experimental line 0.TVB*S1, commonly known as the rapid feathering-susceptible (RFS) line, of chickens lacks all endogenous ALV and is fully susceptible to all subgroups of ALV, including ALV-E. Spontaneous LL-like tumors occurred following infection with AF227, AF229, and a reference ALV-E strain, RAV60, in RFS chickens. Vaccination with serotype 2 MDV, SB-1, in addition to AF227 or AF229 inoculation, significantly enhanced the spontaneous LL-like tumor incidence in the RFS chickens. The spontaneous LL-like tumor incidence jumped from 14% by AF227 alone to 42 to 43% by AF227 in combination with SB-1 in the RFS chickens under controlled conditions. RNA-sequencing analysis of the LL-like lymphomas and nonmalignant bursa tissues of the RFS line of birds identified hundreds of differentially expressed genes that are reportedly involved in key biological processes and pathways, including signaling and signal transduction pathways. The data from this study suggested that both ALV-E and MDV-2 play an important role in enhancement of the spontaneous LL-like tumors in susceptible chickens. The underlying mechanism may be complex and involved in many chicken genes and pathways, including signal transduction pathways and immune system processes, in addition to reported viral genes.IMPORTANCE Lymphoid leukosis (LL)-like lymphoma is a low-incidence yet costly and poorly understood disease of domestic chickens. The observed unique characteristics of LL-like lymphomas are that the incidence of the disease is chicken line dependent; pathologically, it appeared to mimic avian leukosis but is free of exogenous ALV infection; inoculation of the nonpathogenic ALV-E or MDV-2 (SB-1) boosts the incidence of the disease; and inoculation of both the nonpathogenic ALV-E and SB-1 escalates it to much higher levels. This study was designed to test the impact of two new ALV-E isolates, recently derived from commercial broiler breeder flocks, in combination with the nonpathogenic SB-1 on LL-like lymphoma incidences in both an experimental egg layer line of chickens and a commercial broiler breeder line of chickens under a controlled condition. Data from this study provided an additional piece of experimental evidence on the potency of nonpathogenic ALV-E, MDV-2, and ALV-E plus MDV-2 in boosting the incidence of LL-like lymphomas in susceptible chickens. This study also generated the first piece of genomic evidence that suggests host transcriptomic variation plays an important role in modulating LL-like lymphoma formation.

Effects of the SGLT-2 Inhibitor Canagliflozin on Adenine-Induced Chronic Kidney Disease in Rats.

BACKGROUND/AIMS: SGLT-2 inhibitors have been shown to be nephroprotective in diabetes. Here, we examined if one of these drugs (canagliflozin) could also ameliorate non-diabetic chronic kidney disease (CKD). METHODS: CKD was induced in rats by feeding them adenine (0.25%w/w for 35 days) and canagliflozin (10 or 25 mg/kg, by gavage) was given with or without adenine. Several conventional and novel plasma and urine biomarkers and tissues morphology were used to investigate the canagliflozin effect on kidney structure and function. RESULTS: Rats fed adenine showed the typical features of CKD that included elevation of blood pressure, decreased food intake and growth, increased water intake and urine output, decrease in creatinine clearance, and increase in urinary albumin/creatinine ratio, liver-type fatty acid binding protein, N-acetyl-beta-D-glucosaminidase, and plasma urea, creatinine, uric acid, calcium, indoxyl sulfate and phosphorus concentrations. Adenine also increased concentrations of several biomarkers of inflammation such as neutrophil gelatinase-associated lipocalin, interleukin-6, tumor necrosis factor alpha, clusterin, cystatin C and interleukin-1ß, and decreased some oxidative biomarkers in kidney homogenate, such as superoxide dismutase, catalase, glutathione reductase, total antioxidant activity, and also urinary 8-isoprostane and urinary 8-hydroxy-2-deoxy guanosine. Adenine significantly increased the renal protein content of Nrf2, caused renal tubular necrosis and fibrosis. Given alone, canagliflozin at the two doses used did not significantly alter any of the parameters mentioned above. When canagliflozin was given concomitantly with adenine, it significantly and dose - dependently ameliorated all the measured adenine - induced actions. CONCLUSION: Canagliflozin ameliorated adenine - induced CKD in rats, through reduction of several inflammatory and oxidative stress parameters, and other indices such as uremic toxins, and by antagonizing the increase in the renal content of the transcription factor Nrf2. The drug caused no overt or significant untoward effects, and its trial in patients with CKD may be warranted.

Metabolites profiling of date palm (Phoenix dactylifera L.) commercial by-products (pits and pollen) in relation to its antioxidant effect: a multiplex approach of MS and NMR metabolomics.

INTRODUCTION: Phoenix dactylifera L. (date palm) is one of the most valued crops worldwide for its economical and nutraceutical applications of its date fruit (pericarp). Currently date pits, considered as a waste product, is employed as coffee substitute post roasting. Whereas, pollen represents another valuable by-product used as a dietary supplement. OBJECTIVES: In this study, a large-scale comparative metabolomics approach was performed for the first characterization and standardization of date palm by-products viz., date pits and pollen. Moreover, roasting impact on date pit metabolite composition was also assessed. METHODS: Metabolites profiling of pits and pollen was determined via a multiplex approach of UPLC-MS and NMR, coupled to multivariate analysis, in relation to its antioxidant activities. RESULTS: Chemical analyses led to the identification of 67 metabolites viz., phenolic acids, flavonols, fatty acids, sphingolipids, steroids and saponins of which 10 are first time to be reported. The enrichment of steroids in date pollen accounts for its fertility promoting properties, whereas date pit was found a rich source for antioxidant polyphenols using metabolomics.

Does intra-operative flexible endoscopy reduce anastomotic complications following left-sided colonic resections? A systematic review and meta-analysis.

AIM: Postoperative anastomotic leakage (AL) or bleeding (AB) significantly impacts on patient outcome following colorectal resection. To minimize such complications, surgeons can utilize different techniques perioperatively to assess anastomotic integrity. We aim to assess published anastomotic complication rates following left-sided colonic resection, comparing the use of intra-operative flexible endoscopy (FE) against conventional tests used to assess anastomotic integrity. METHODS: PubMed/MEDLINE and Embase online databases were searched for non-randomized and randomized case-control studies that investigated postoperative AL and/or AB rates in left-sided colonic resections, comparing intra-operative FE against conventional tests. Data from eligible studies were pooled, and a meta-analysis using Review Manager 5.3 software was performed to assess for differences in AL and AB rates. RESULTS: Data from six studies were analysed to assess the impact of FE on postoperative AL and AB rates (1084 and 751 patients respectively). Use of FE was associated with reduced postoperative AL and AB rates, from 6.9% to 3.5% and 5.8% to 2.4% respectively. Odds ratios favoured intra-operative FE: 0.37 (95% CI 0.21-0.68, P = 0.001) for AL and 0.35 (95% CI 0.15-0.82, P = 0.02) for AB. CONCLUSION: This meta-analysis showed that the use of intra-operative FE is associated with a reduced rate of postoperative AL and AB, compared to conventional anastomotic testing methods.

Sensory Metabolite Profiling in a Date Pit Based Coffee Substitute and in Response to Roasting as Analyzed via Mass Spectrometry Based Metabolomics.

Interest in developing coffee substitutes is on the rise, to minimizing its health side effects. In the Middle East, date palm (Phoenix dactylifera L.) pits are often used as a coffee substitute post roasting. In this study, commercially-roasted date pit products, along with unroasted and home-prepared roasted date pits, were subjected to analyses for their metabolite composition, and neuropharmacological evaluation in mice. Headspace SPME-GCMS and GCMS post silylation were employed for characterizing its volatile and non-volatile metabolite profile. For comparison to roasted coffee, coffee product was also included. There is evidence that some commercial date pit products appear to contain undeclared additives. SPME headspace analysis revealed the abundance of furans, pyrans, terpenoids and sulfur compounds in roasted date pits, whereas pyrroles and caffeine were absent. GCMS-post silylation employed for primary metabolite profiling revealed fatty acids' enrichment in roasted pits versus sugars' abundance in coffee. Biological investigations affirmed that date pit showed safer margin than coffee from its LD50, albeit it exhibits no CNS stimulant properties. This study provides the first insight into the roasting impact on the date pit through its metabolome and its neuropharmacological aspects to rationalize its use as a coffee substitute.

Increased natural killer cell subsets with inhibitory cytokines and inhibitory surface receptors in patients with recurrent miscarriage and decreased or normal subsets in kidney transplant recipients late post-transplant.

Patients with recurrent miscarriage (RM) show up-regulated cytotoxic natural killer (NK) cells that are suspected to play a causal role in abortion. In the present study, we investigated counter-regulating inhibitory mechanisms and compared the results in RM patients with those of healthy controls (HC), patients with end-stage renal disease (ESRD) and kidney transplant recipients late post-transplant (TX). NK, NK T and T cell subsets were analysed in the peripheral blood of 31 RM, 14 female ESRD and nine female TX patients as well as 21 female HC using eight-colour fluorescence flow cytometry. Compared with HC, RM patients showed significantly higher absolute numbers of CD56+ NK cells co-expressing the phenotype interferon (IFN)-γR+ , IL-4+ , transforming growth factor (TGF)-ß+ , IL-4+ human leucocyte antigen D-related (HLA-DR)+ , TGF-ß+ HLA-DR+ , IL-4+ TGF-ß+ , IL-4+ TGF-ß- , IFN-γ+ and/or IL-10- IFN-γ+ (all P ≤ 0·01), more IL-17+ CD56bright (P = 0·028) NK cells and more CD56dim CD16+ NK cells co-expressing IFN-γR, IFN-γ, IL-4 and/or TGF-ß (all P ≤ 0·01). When the same cell subsets were analysed in ESRD or TX patients, cytokine-producing NK cell subsets were not significantly different from those of HC. RM patients showed significantly higher absolute numbers of CD158a+ , CD158b+ , CD158a- CD158e+ (all P < 0·05), NKG2D+ NKG2A+ , NKG2D + NKG2A- , NKG2D+ and/or NKG2A+ (all P ≤ 0·01) CD56+ NK cells and higher CD158a+ , CD158b+ (all P < 0·05), NKG2D+ and/or NKG2A+ (all P < 0·01) CD56dim+ CD16+ NK cells than HC. In contrast, ESRD patients had normal and TX recipients had lower CD158a+ and NKG2D+ NKG2A- CD56+ NK cells and lower CD158a+ CD56dim+ CD16+ NK cells (all P < 0·05) than HC. RM patients have abnormally high circulating NK cells expressing inhibitory cytokines and inhibitory surface receptors which might contribute to the pathogenesis of RM.

Lanthanide complexes of spiropyran photoswitch and sensor: spectroscopic investigations and computational modelling.

A number of novel lanthanide (Gd3+, Sm3+, and Tb3+) complexes of the 1',3'-dihydro-8-methoxy-1',3',3'-trimethyl-6-nitrospiro[2H-1-benzopyran-2,2'-(2H)-indole] (spiropyran; SP), a widely studied molecular photoswitch, were investigated. Comparative spectroscopic (absorption and fluorescence) and kinetic investigations of the stimulated photochromic and solvatochromic behavior were carried out in different media. SP embedded in a rigid thin film of poly(methylmethacrylate) might be exploited profitably as an optical sensor for the identification of a solvent's nature. Furthermore, thermodynamic parameters, in particular, Gibbs' free energy change (ΔG°), were derived using density functional theory quantum chemical calculations with the SP and merocyanine coloured form. The model used was the B3LYP/6-31G(d,p)/SCRF = (SMD, solvent) and its time-dependent extension procedure was used to quantitatively explain the structural isomerization in response to a variety of stimuli, such as light, solvent nature, lanthanide(iii) ions, and macromolecular support. These findings might be useful for the design of photoswitchable and energy transfer materials and their related fields.

Elective Primary or Secondary Delayed Sternal Closure Improves Outcome in Severely Compromised Patients.

BACKGROUND: Delayed sternal closure (DSC) in patients with severely compromised preoperative hemodynamics can be helpful as the chest sometimes cannot be able to contain both lungs and heart. We report our experience to evaluate the midterm results of this strategy in an adult population. MATERIALS AND METHODS: From May 2009 till July 2015, 33 patients had DSC as first treatment of severe hemodynamic deterioration after cardiac surgery. Surgical procedures were valvular (9.27%) or coronary artery bypass grafting + others (24.73%). Stepwise logistic regression (SLR) showed that patients with lower ejection fraction, dilated right ventricle, and severe pulmonary hypertension were more likely to need DSC. Patients were divided in two groups: group A (n = 17), when the sternum was reopened before any hemodynamic collapse, or was never closed, and group B (n = 16), when the sternum was reopened after hemodynamic collapse. RESULTS: Inhospital mortality was 39% (n = 13), 18% in group A and 62% in group B (p < 0.0001). In 28 patients where the sternum was reopened, cardiac index increased from 1.7 (1.6, 1.9) L/m2 to 2.8 (2.4, 3) L/m2, p < 0.0001. The sternum was closed in 28 patients (85%), 94% in group A and 75% in group B (p = 0.13), after a median of 4 (2.5) days. SLR showed that only group B (p < 0.0001) was a risk factor for early death. Two-year survival was 48 ± 9%, higher in group A (71 ± 13) than in group B (25 ± 11), p < 0.0001. Cox's analysis showed that group B (p < 0.0001) and redo (p < 0.0001) were risk factors for lower survival. CONCLUSION: Elective DSC represents a useful strategy in severely compromised patients, entailing an improvement of hemodynamics and a higher survival.

Synthesis, antitumor activity evaluation, and DNA-binding study of coumarin-based agents.

A novel series of coumarin-thiadiazole heterocycle derivatives was synthesized by the nucleophilic substitution reaction. The synthesized compounds were structurally verified by IR, 1 H NMR, 13 C NMR, mass spectra, and elemental analyses. The antitumor activity of the synthesized compounds was evaluated through DNA binding assays and the 60-cell line panel according to the US NCI-DTP protocol or a selection of human tumor cell lines: breast cancer (MCF-7), liver cancer (HepG-2), and colorectal cancer (HCT-116). Most of the compounds had better DNA/ethidium bromide fluorescence quenching rather than methyl green displacement, suggesting superior DNA intercalation over DNA groove binding. Compounds 8 and 14b showed the best quenching effect with KSV = 4.27 × 105 M-1 . Moreover, the results for compounds 8, 4c, and 4e revealed a possible dual DNA binding mode with the intercalation to be superior, with KSV 4.27 × 105 , 3.96 × 105 , and 3.51 × 105 M-1 , respectively, compared to 42%, 45%, and 43% methyl green displacement, respectively. Out of the 60-cell line panel, the leukemia HL-60 cell line was the most susceptible to growth inhibition when treated with 14a, resulting in 61% growth, followed by the lung carcinoma cell line NCI-H522 showing 67% growth when treated with 9. Moreover, compound 10c had an IC50 value of 24.9 µg/mL against the HepG-2 cell line.