CMR characterization of patients with heart failure and left bundle branch block.

Aims: We aimed to identify the distinctive cardiovascular magnetic resonance (CMR) features of patients with left bundle branch block (LBBB) and heart failure with reduced ejection fraction (HFrEF) of presumed non-ischaemic aetiology. The secondary aim was to determine whether these individuals exhibit characteristics that could potentially serve as predictors of left ventricular ejection fraction (LVEF) recovery as compared with patients without LBBB. Methods and results: We prospectively recruited patients with HFrEF (LVEF ≤ 40%) on echocardiography who were referred for early CMR examination. Patients with an established diagnosis of coronary artery disease and known structural or congenital heart disease were excluded. LV recovery was defined as achieving ≥10% absolute improvement to ≥40% in LVEF between baseline evaluation to CMR. A total of 391 patients were recruited including 115 (29.4%) with LBBB. Compared with HF patients without LBBB, those with LBBB exhibited larger left ventricles and smaller right ventricles, but no differences were observed with respect to LVEF (35.8 ± 12 vs. 38 ± 12%, P = 0.105). The overall rate of LV recovery from baseline echocardiogram to CMR (70 [42-128] days) was not significantly different between LBBB and non-LBBB patients (27.8% vs. 31.5%, P = 0.47). Reduced LVEF remained an independent predictor of LV non-recovery only in patients with LBBB. Conclusion: Patients presenting with HFrEF and LBBB had larger LV cavities and smaller RV cavities than those without LBBB but no difference in prevalence of scar or ischaemia. The rates of LV recovery were similar between both groups, which supports current guidelines to defer device therapy until 3-6 months of guideline-directed medical therapy, rather than early CMR and device implantation.

Pulmonary transit time is a predictor of outcomes in heart failure: a cardiovascular magnetic resonance first-pass perfusion study.

BACKGROUND: Pulmonary transit time (PTT) can be measured automatically from arterial input function (AIF) images of dual sequence first-pass perfusion imaging. PTT has been validated against invasive cardiac catheterisation correlating with both cardiac output and left ventricular filling pressure (both important prognostic markers in heart failure). We hypothesized that prolonged PTT is associated with clinical outcomes in patients with heart failure. METHODS: We recruited outpatients with a recent diagnosis of non-ischaemic heart failure with left ventricular ejection fraction (LVEF) < 50% on referral echocardiogram. Patients were followed up by a review of medical records for major adverse cardiovascular events (MACE) defined as all-cause mortality, heart failure hospitalization, ventricular arrhythmia, stroke or myocardial infarction. PTT was measured automatically from low-resolution AIF dynamic series of both the LV and RV during rest perfusion imaging, and the PTT was measured as the time (in seconds) between the centroid of the left (LV) and right ventricle (RV) indicator dilution curves. RESULTS: Patients (N = 294) were followed-up for median 2.0 years during which 37 patients (12.6%) had at least one MACE event. On univariate Cox regression analysis there was a significant association between PTT and MACE (Hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.08-1.25, P = 0.0001). There was also significant association between PTT and heart failure hospitalisation (HR 1.15, 95% CI 1.02-1.29, P = 0.02) and moderate correlation between PTT and N-terminal pro B-type natriuretic peptide (NT-proBNP, r = 0.51, P < 0.001). PTT remained predictive of MACE after adjustment for clinical and imaging factors but was no longer significant once adjusted for NT-proBNP. CONCLUSIONS: PTT measured automatically during CMR perfusion imaging in patients with recent onset non-ischaemic heart failure is predictive of MACE and in particular heart failure hospitalisation. PTT derived in this way may be a non-invasive marker of haemodynamic congestion in heart failure and future studies are required to establish if prolonged PTT identifies those who may warrant closer follow-up or medicine optimisation to reduce the risk of future adverse events.

Protein-polysaccharide based double network microbeads improves stability of Bifidobacterium infantis ATCC 15697 in a gastro-Intestinal tract model (TIM-1).

Microencapsulation of probiotics is a main technique employed to improve cell survival in gastrointestinal tract (GIT). The present study investigated the impact of utilizing proteins i.e. Whey Protein Isolates (WPI), Pea Protein Isolates (PPI) or (WPI + PPI) complex based microbeads as encapsulating agents on the encapsulation efficiency (EE), diameter, morphology along with the survival and viability of Bifidobacterium infantis ATCC 15697. Results revealed that WPI + PPI combination had the highest EE% of the probiotics up to 94.09 % and the smoothest surface with less visible holes. WPI based beads revealed lower EE% and smaller size than PPI based ones. In addition, WPI based beads showed rough surface with visible signs of cracks, while PPI beads showed dense surfaces with pores and depressions. In contrast, the combination of the two proteins resulted in compact and smooth beads with less visible pores/wrinkles. The survival in gastrointestinal tract (GIT) was observed through TNO in-vitro gastrointestinal model (TIM-1) and results illustrated that all microbeads shrank in gastric phase while swelled in intestinal phase. In addition, in-vitro survival rate of free cells was very low in gastric phase (18.2 %) and intestinal phase (27.5 %). The free cells lost their viability after 28 days of storage (2.66 CFU/mL) with a maximum log reduction of 6.76, while all the encapsulated probiotic showed more than 106-7 log CFU/g viable cell. It was concluded that encapsulation improved the viability of probiotics in GIT and utilization of WPI + PPI in combination provided better protection to probiotics.

Identification of non-ischaemic fibrosis in male veteran endurance athletes, mechanisms and association with premature ventricular beats.

Left ventricular fibrosis can be identified by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) in some veteran athletes. We aimed to investigate prevalence of ventricular fibrosis in veteran athletes and associations with cardiac arrhythmia. 50 asymptomatic male endurance athletes were recruited. They underwent CMR imaging including volumetric analysis, bright blood (BB) and dark blood (DB) LGE, motion corrected (MOCO) quantitative stress and rest perfusion and T1/T2/extracellular volume mapping. Athletes underwent 12-lead electrocardiogram (ECG) and 24-h ECG. Myocardial fibrosis was identified in 24/50 (48%) athletes. All fibrosis was mid-myocardial in the basal-lateral left ventricular wall. Blood pressure was reduced in athletes without fibrosis compared to controls, but not athletes with fibrosis. Fibrotic areas had longer T2 time (44 ± 4 vs. 40 ± 2 ms, p < 0.0001) and lower rest myocardial blood flow (MBF, 0.5 ± 0.1 vs. 0.6 ± 0.1 ml/g/min, p < 0.0001). On 24-h ECG, athletes with fibrosis had greater burden of premature ventricular beats (0.3 ± 0.6 vs. 0.05 ± 0.2%, p = 0.03), with higher prevalence of ventricular couplets and triplets (33 vs. 8%, p = 0.02). In veteran endurance athletes, myocardial fibrosis is common and associated with an increased burden of ventricular ectopy. Possible mechanisms include inflammation and blood pressure. Further studies are needed to establish whether fibrosis increases risk of malignant arrhythmic events.

Future Innovations in Novel Detection for Atrial Fibrillation (FIND-AF): pilot study of an electronic health record machine learning algorithm-guided intervention to identify undiagnosed atrial fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is associated with a fivefold increased risk of stroke. Oral anticoagulation reduces the risk of stroke, but AF is elusive. A machine learning algorithm (Future Innovations in Novel Detection of Atrial Fibrillation (FIND-AF)) developed to predict incident AF within 6 months using data in primary care electronic health records (EHRs) could be used to guide AF screening. The objectives of the FIND-AF pilot study are to determine yields of AF during ECG monitoring across AF risk estimates and establish rates of recruitment and protocol adherence in a remote AF screening pathway. METHODS AND ANALYSIS: The FIND-AF Pilot is an interventional, non-randomised, single-arm, open-label study that will recruit 1955 participants aged 30 years or older, without a history of AF and eligible for oral anticoagulation, identified as higher risk and lower risk by the FIND-AF risk score from their primary care EHRs, to a period of remote ECG monitoring with a Zenicor-ECG device. The primary outcome is AF diagnosis during ECG monitoring, and secondary outcomes include recruitment rates, withdrawal rates, adherence to ECG monitoring and prescription of oral anticoagulation to participants diagnosed with AF during ECG monitoring. ETHICS AND DISSEMINATION: The study has ethical approval (the North West-Greater Manchester South Research Ethics Committee reference 23/NW/0180). Findings will be announced at relevant conferences and published in peer-reviewed journals in line with the Funder's open access policy. TRIAL REGISTRATION NUMBER: NCT05898165.

Speech Emotion Recognition Using Convolution Neural Networks and Multi-Head Convolutional Transformer.

Speech emotion recognition (SER) is a challenging task in human-computer interaction (HCI) systems. One of the key challenges in speech emotion recognition is to extract the emotional features effectively from a speech utterance. Despite the promising results of recent studies, they generally do not leverage advanced fusion algorithms for the generation of effective representations of emotional features in speech utterances. To address this problem, we describe the fusion of spatial and temporal feature representations of speech emotion by parallelizing convolutional neural networks (CNNs) and a Transformer encoder for SER. We stack two parallel CNNs for spatial feature representation in parallel to a Transformer encoder for temporal feature representation, thereby simultaneously expanding the filter depth and reducing the feature map with an expressive hierarchical feature representation at a lower computational cost. We use the RAVDESS dataset to recognize eight different speech emotions. We augment and intensify the variations in the dataset to minimize model overfitting. Additive White Gaussian Noise (AWGN) is used to augment the RAVDESS dataset. With the spatial and sequential feature representations of CNNs and the Transformer, the SER model achieves 82.31% accuracy for eight emotions on a hold-out dataset. In addition, the SER system is evaluated with the IEMOCAP dataset and achieves 79.42% recognition accuracy for five emotions. Experimental results on the RAVDESS and IEMOCAP datasets show the success of the presented SER system and demonstrate an absolute performance improvement over the state-of-the-art (SOTA) models.

Design of high gain base station antenna array for mm-wave cellular communication systems.

Millimeter wave (mm-Wave) wireless communication systems require high gain antennas to overcome path loss effects and thereby enhance system coverage. This paper presents the design and analysis of an antenna array for high gain performance of future mm-wave 5G communication systems. The proposed antenna is based on planar microstrip technology and fabricated on 0.254 mm thick dielectric substrate (Rogers-5880) having a relative permittivity of 2.2 and loss tangent of 0.0009. The single radiating element used to construct the antenna array is a microstrip patch that has a configuration resembling a two-pronged fork. The single radiator has a realized gain of 7.6 dBi. To achieve the gain required by 5G base stations, a 64-element array antenna design is proposed which has a bore side gain of 21.2 dBi at 37.2 GHz. The 8 × 8, 8 × 16, and 8 × 32 antenna array designs described here were simulated and optimized using CST Microwave Studio, which is a 3D full-wave electromagnetic solver. The overall characteristics of the array in terms of reflection-coefficient and radiation patterns makes the proposed design suitable for mm-Wave 5G and other communication systems.

Cardiovascular magnetic resonance phenotyping of heart failure with mildly reduced ejection fraction.

AIMS: The 2016 European Society of Cardiology Heart Failure Guidelines defined a new category: heart failure with mid-range ejection fraction (HFmrEF) of 40-49%. This new category was highlighted as having limited evidence and research was advocated into underlying characteristics, pathophysiology, and diagnosis. We used multi-parametric cardiovascular magnetic resonance (CMR) to define the cardiac phenotype of presumed non-ischaemic HFmrEF. METHODS AND RESULTS: Patients (N = 300, 62.7 ± 13 years, 63% males) with a clinical diagnosis of heart failure with no angina symptoms, history of myocardial infarction, or coronary intervention were prospectively recruited. Patients underwent clinical assessment and CMR including T1 mapping, extracellular volume (ECV) mapping, late gadolinium enhancement, and measurement of myocardial blood flow at rest and maximal hyperaemia. Of 273 patients in the final analysis, 93 (34%) patients were categorized as HFmrEF, 46 (17%) as heart failure with preserved ejection fraction (HFpEF), and 134 (49%) as heart failure with reduced ejection fraction (HFrEF). Nineteen (20%) patients with HFmrEF had evidence of occult ischaemic heart disease. Diffuse fibrosis and hyperaemic myocardial blood flow were similar in HFmrEF and HFpEF, but HFmrEF showed significantly lower native T1 (1311 ± 32 vs. 1340 ± 45 ms, P < 0.001), ECV (24.6 ± 3.2 vs. 26.3 ± 3.1%, P < 0.001), and higher myocardial perfusion reserve (2.75 ± 0.84 vs. 2.28 ± 0.84, P < 0.001) compared with HFrEF. CONCLUSION: Patients with HFmrEF share most phenotypic characteristics with HFpEF, including the degree of microvascular impairment and fibrosis, but have a high prevalence of occult ischaemic heart disease similar to HFrEF. Further work is needed to confirm how the phenotype of HFmrEF responds to medical therapy.

Antibacterial effectiveness of scaling and root planing with and without photodynamic therapy against Campylobacter rectus counts in the oral biofilm of patients with periodontitis.

BACKGROUND: It is hypothesized that scaling and root planning (SRP) with adjunct photodynamic therapy (PDT) is more effective in reducing Campylobacter rectus (C. rectus) from the oral biofilm (OB) among patients with periodontitis, than SRP alone. The objective was to compare the effectiveness of SRP with and without adjunct PDT in reducing OB C. rectus counts of patients with periodontitis. METHODS: Chronic gastritis patients diagnosed with periodontitis were included. Therapeutically, the patients were divided into 2-groups. Patients in the test- and control-groups underwent SRP with and without adjunct PDT, respectively. In both groups, full-mouth plaque index (PI), bleeding on probing (BOP), probing depth (PD) and marginal bone loss (MBL) were measured and subgingival OB counts of C. rectus were measured at baseline and 12-weeks after treatment. Data normality was assessed and group-comparisons were done using the paired t-test and Man-Whitney U tests. A type-1 error rate of 5 % was used. RESULTS: Thirty patients with periodontitis were included. All patients had Grade-B/Stage-II periodontitis. All participants were male with no significant difference in age. At baseline PI, BOP, PD and MBL were comparable in both groups. Counts of C. rectus in the subgingival OB samples were similar in both groups at baseline. At 12-weeks of follow-up, PI (P < 0.01), GI (P < 0.01) and PD (P < 0.01) were significantly higher in the control- compared with the test-group compared with baseline. The percentages of C. rectus -positive individuals were higher in the control- than the test-group at 12-weeks' (P < 0.01). At 12-weeks' follow-up the percentages of C. rectus -positive patients were comparable with their respective baseline percentages in the control-group. CONCLUSION: Compared with SRP alone, adjuvant use of PDT is more efficient in eliminating C. rectus in the OB and reducing clinical parameters in patients with grade-B/Stage-II periodontitis.

A cohort study examining urgent and emergency treatment for decompensated severe aortic stenosis.

AIMS: We compared strategies in the treatment of decompensated severe aortic stenosis. The hypothesis was that undertaking urgent or emergency transcatheter aortic valve implantation (TAVI) directly in such patients is safer and more effective than urgent or emergency balloon aortic valvuloplasty (BAV) followed by elective TAVI or surgical aortic valve replacement (SAVR). METHODS: This was a single-centre retrospective study including all consecutive patients who underwent urgent or emergency BAV or TAVI for decompensated severe aortic stenosis between September 2014 and February 2018. Primary endpoints were 30-day and 1-year mortality. RESULTS: Fifty-two patients underwent urgent or emergency BAV and 87 underwent TAVI. Baseline characteristics of the two groups were well matched. Significant differences were noted between the two groups in 30-day all-cause mortality (88.5% BAV patients alive at 30 days, 97.7% TAVI patients; P < 0.05) and 1-year all-cause mortality (44.2% BAV patients alive at 1 year, 88.5% TAVI patients; P < 0.001). At 1 year, the estimated hazard ratio for patients undergoing BAV was 11.2 (95% confidence interval: 4.67-26.9; P < 0.001) when adjusted for potential confounding variables. Patients in the BAV group who successfully underwent subsequent TAVI or SAVR all survived for 365 days, but there was no significant 1-year mortality difference compared with those who underwent urgent or emergency TAVI (100 vs. 88.5%; P > 0.155). CONCLUSION: Our results suggest treatment of decompensated severe aortic stenosis with urgent or emergency TAVI may be associated with improved survival outcomes when compared with a strategy of performing BAV as a bridge to subsequent TAVI or SAVR.

Characterization and Comparative Evaluation of Milk Protein Variants from Pakistani Dairy Breeds.

The aim of study was to scrutinize the physicochemical and protein profile of milk obtained from local Pakistani breeds of milch animals such as Nilli-Ravi buffalo, Sahiwal cow, Kajli sheep, Beetal goat and Brela camel. Physicochemical analysis unveiled maximum number of total solids and protein found in sheep and minimum in camel. Buffalo milk contains the highest level of fat (7.45%) while camel milk contains minimum (1.94%). Ash was found maximum in buffalo (0.81%) and sheep (0.80%) while minimum in cow's milk (0.71%). Casein and whey proteins were separated by subjecting milk to isoelectric pH and then analyzed through sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The results showed heterogeneity among these species. Different fractions including αS1, αS2, κ-casein, ß-casein and ß-lactoglobulen (ß-Lg) were identified and quantitatively compared in all milk samples. Additionally, this electrophoretic method after examining the number and strength of different protein bands (αS1, αS2, ß-CN, α-LAC, BSA, and ß-Lg, etc.), was helpful to understand the properties of milk for different processing purposes and could be successfully applied in dairy industry. Results revealed that camel milk was best suitable for producing allergen free milk protein products. Furthermore, based on the variability of milk proteins, it is suggested to clarify the phylogenetic relationships between different cattle breeds and to gather the necessary data to preserve the genetic fund and biodiversity of the local breeds. Thus, the study of milk protein from different breed and species has a wide range of scope in producing diverse protein based dairy products like cheese.

Molecular & biochemical analysis of Pro12Ala variant of PPAR-γ2 gene in type 2 diabetes mellitus.

Diabetes has emerged as a major threat to human life globally. Genomic studies have found a significant link between the Pro12Ala polymorphism of the PPAR-γ2 gene with incidence as well as occurrence of the risk of metabolic syndrome. The present study was aimed at assessing the PPAR-γ2 variant in an Asian Indian cohort of type 2 diabetes patients and its correlation with metabolic parameters. The present case-control study involved 100 type 2 diabetic patients and 100 asymptomatic healthy volunteers enrolled in random. Assessment of demographic factors and biochemical parameters were done for all enrolled. In addition, genotyping for the Pro12Ala (CCA to GCA) polymorphism was done by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) technology. The genotyping study detected the frequency of the CC genotype (Pro12Pro) to be higher in frequency in comparison to the heterozygous CG genotype in both, cases and controls. The homozygous GG genotype (Ala12Ala) was not detected in any of the cases or controls assessed. Biochemical analysis of the levels of malondialdehyde (MDA) detected a significant increase (p < 0.0001). Additionally, increase in levels of fasting and postprandial glucose, total cholesterol, triglycerides, and parameters of the liver and renal function tests were detected. This study detected the PPAR-γ2 to be a significant biomarker for type 2 diabetes mellitus.

Bioavailability, rheology, and sensory evaluation of mayonnaise fortified with vitamin D encapsulated in protein-based carriers.

Vitamin D lost its functionality during processing and storage, thus, encapsulation with proteins is desirable to preserve bioactivity. The aim of the current study was to develop encapsulated vitamin D fortified mayonnaise (VDFM) using whey protein isolates (WPI) and soy protein isolates (SPI) as encapsulating materials in three different formulations, that is, 10% WPI, 10% SPI, and 5/5% WPI/SPI. Increased shear stress decreased the apparent viscosity along with significant effects on the loss modulus of VDFM. WPI encapsulates showed better results as compared to SPI. WPI based VDFM (M1 ) depicted the best results in terms of size and dispersion uniformity of oil droplets. Hue angle and total change differed significantly among treatments. The highest value for overall acceptability was acquired by M3 (5:5%WPI:SPI-encapsulates) thus proceed for in vivo trials. Serum vitamin D level was significantly higher in the encapsulated VDFM rat group (58.14 ± 6.29 nmol/L) than the control (37.80 ± 4.98 nmol/L). Conclusively, WPI and SPI encapsulates have the potential to improve the stability and bioavailability of vitamin D.

In vitro Probiotic Potential and Safety Evaluation (Hemolytic, Cytotoxic Activity) of Bifidobacterium Strains Isolated from Raw Camel Milk.

The present study was designed to isolate Bifidobacterium strains from raw camel milk and to investigate their probiotic characteristics. Among 35 isolates, 8 were identified as Gram-positive, catalase negative, non-spore forming, non-motile and V or Y shaped rods. B-2, B-5, B-11, B-19 and B-28 exhibited good survival at low pH and high bile salt concentration. Most of the isolates were resistant to nalidixic acid, fusidic acid, polymyxin B, neomycin, streptomycin, gentamicin, rifampicin and kanamycin. Furthermore, the production of exopolysaccharides (EPS), adhesion characteristics, antioxidant properties, antagonistic activities, nitrite reduction and cholesterol assimilation were also studied. Isolate B-11 was chosen because it exhibited most of the probiotic properties among all the tested isolates. It is identified as the member of Bifidobacterium longum group through 16S rRNA gene sequencing and named as B. longum B-11. B. longum B-11 was further selected for in vivo attachment to rat intestine and scanning electron micrographs revealed that attachment of a large number of rods shaped bacterial cell. Our findings suggest that B. longum B-11 processes excellent attributes to be used as potential probiotic in the development of functional probiotic food.

Targeting glucose metabolism to suppress cancer progression: prospective of anti-glycolytic cancer therapy.

Most solid tumor cells adapt to their heterogeneous microenvironment by depending largely on aerobic glycolysis for energy production, a phenomenon called the Warburg effect, which is a hallmark of cancer. The altered energy metabolism not only provides cancer cell with ATP for cellular energy, but also generate essential metabolic intermediates that play a pivotal role in the biosynthesis of macromolecules, to support cell proliferation, invasiveness, and chemoresistance. The cellular metabolic reprogramming in cancer is regulated by several oncogenic proteins and tumor suppressors such as hypoxia-inducible factor (HIF-1), Myc, p53, and PI3K/Akt/mTOR pathway. A better understanding of the mechanisms involved in the regulation of aerobic glycolysis can help in developing glycolytic inhibitors as anticancer agents. These metabolic antiglycolytic agents could be more effective if used in drug combinations to combat cancer. Several preclinical and early clinical studies have shown the effectiveness of targeting the glycolytic pathway as a therapeutic approach to suppress cancer progression. This review aimed to present the most recent data on the emerging drug candidate targeting enzymes and intermediates involved in glucose metabolism to provide therapeutic opportunities and challenges for antiglycolytic cancer therapy.

Epidemiological characterization, genetic alterations of Helicobacter pylori infection in chronic gastric disorder and prognostic values of heterozygosity loss in chromosome 3p.

From the literature review, there seem to be no studies conducted on infection caused by Helicobacter pylori in patients with gastric MALT lymphoma in the KSA region. The present research is an attempt to understand the prevalence of patients infected with H. pylori in the selected region and the role of allelic imbalance of chromosome 3p regions to understand the clinical manifestations and features associated with MALT lymphomagenesis. The researcher analyzed the frequency of infection in patients from the region of Saudi Arabia by examining the data collected from hospitals and biopsy tissue samples as per the recommended protocol. The endoscopic diagnosis was performed to collect biopsy samples. Histology and AP-PCR DNA fingerprinting analyses were performed from the endoscopic gastric mucosal biopsies collected from patients with associated gastric MALT lymphoma. The existence of H. pylori was examined based on the results of gastric mucosal biopsies stained with hematoxylin-eosin (H&E) and Steiner's silver stains. MALT, MALT lymphoma tissue samples and H. pylori-positive chronic gastritis were examined for LOH at chromosome 3p24 using standard procedures and techniques. The findings of the paper revealed the H. pylori was found to be positive in 17% of the cases significantly high among the age group of 31-50 years. Patients with MALT, MALT lymphoma, and H. pylori-associated gastritis presented features such as lymphocyte accumulation, vacuolation, Peyer's patch appearance, and lymphatic follicles. H. pylori were found to appear as a dense colored accumulated mass in the gastric epithelial layer. The findings from AP-PCR generated DNA fingerprints revealed intense band including two prominent bands in MALT lymphoma. Among other loci, 3p24 was the only one locus that showed high percentages of LOH as reported earlier in all cancer-related cases. The findings of this research paper empower the fact that allelic imbalances play a vital role in the development of MALT lymphoma. However, future researches should be conducted to identify the chromosome regions of the AP-PCR generated DNA fingerprints of human gastric MALT lymphoma in order to confirm this proposition.

Renal protective effect of SGLT2 inhibitor dapagliflozin alone and in combination with irbesartan in a rat model of diabetic nephropathy.

Considering the complementary mechanisms of SGLT2 inhibitors and angiotensin inhibitors on kidney, it is postulated that combination of both agents could afford greater protection against diabetic renal injury. So, we investigated renal protective effects of SGLT2 inhibitor, dapagliflozin, alone and in combination with irbesartan in a rat model of diabetic nephropathy. Diabetic rats, injected with nicotinamide-streptozotocin, were treated orally for 12 weeks with either vehicle, dapagliflozin 2 mg/kg/day, irbesartan 30 mg/kg/day, or combination of both drugs; respectively. Biochemical analysis included blood glucose, HbA1c, urinary albumin excretion, creatinine clearance, TGF-ß1, sRAGE, oxidative markers, and histopathological examination of kidneys. Treatment with dapagliflozin, irbesartan, and especially their combination, produced significant reduction in albuminuria, improved renal function parameters, increased sRAGE level and improved inflammatory and oxidative markers, together with amelioration of renal histopathological changes. Beside glycemic control, dapagliflozin produced higher sRAGE levels than irbesartan, suggesting that inhibition of AGE-RAGE axis is important in its renoprotective action. Combination of dapagliflozin and irbesartan produced more remarkable protective effects on renal function and structure, than use of either agent alone. It is concluded that, combination of SGLT2 inhibitor, dapagliflozin and ARB, irbesartan could offer more effective renal protection and represent a promising therapeutic option for management of diabetic nephropathy.

Vitamin D enhances antiepileptic and cognitive effects of lamotrigine in pentylenetetrazole-kindled rats.

Despite long use of antiepileptic drugs, it remains a challenge to achieve seizure control while reducing adverse effects and preventing cognitive impairment. Several lines of evidence suggest a role of vitamin D in epilepsy. So this study aimed to investigate the effect of vitamin D on epileptogenesis, cognitive dysfunction and antiepileptic activity of lamotrigine, in a rat model of chemical kindling. Rats were kindled by pentylenetetrazole injections every other day over four weeks, together with daily oral treatment by either vehicle, vitamin D, lamotrigine or combination of vitamin D and lamotrigine. The non-treated kindled rats developed generalized seizures and had poor cognitive performance in water maze, associated with prooxidative status; elevated malondialdehyde and nitric oxide with lowered glutathione levels; in brain tissues. Treatment with either vitamin D, lamotrigine or both leads to significant reduction of seizure activity score, improvement of cognitive performance, and amelioration of the disturbed oxidative stress biomarkers. These findings indicate that, vitamin D has anti-epileptic, cognitive improving and antioxidant effects, on its own and enhance the effects of lamotrigine, in a chronic model of epileptic seizures. Thus, vitamin D supplementation may be a useful addition to antiepileptic drugs improving seizure control and cognitive function in patients with epilepsy.

Neuroprotective effects of vitamin D alone or in combination with lamotrigine against lithium-pilocarpine model of status epilepticus in rats.

Status epilepticus (SE) is considered one of the major serious forms of epilepsy with high mortality rate. Since the currently available antiepileptic drugs have low efficacy and high adverse effects, new more efficient and safe therapies are critically needed. There is increasing evidence supporting dietary and alternative therapies for epilepsy, including the ketogenic diet, modified Atkins diet, and omega-3 fatty acids. Recent studies have shown significant prophylactic and therapeutic potential of vitamin D (vit-D) use in many neurological disorders. Therefore, in the present study, the neuroprotective effects and mechanisms of vit-D alone or in combination with lamotrigine have been evaluated in the lithium-pilocarpine model of SE in rats. Rats were divided into five groups: normal group, SE group, lamotrigine (25 mg/kg/day) pretreated group, vit-D (1.5 mcg/kg/day) pretreated group, and group pretreated with vit-D and lamotrigine for 2 weeks. At the end of treatment, SE was induced by single intraperitoneal injection of LiCl (127 mg/kg), followed 24 h later by pilocarpine (30 mg/kg). Seizures' latency, cognitive performance in Morris water maze, brain oxidative stress biomarkers (glutathione, lipid peroxides, and nitric oxide), brain neurochemistry (γ-aminobutyric acid and glutamate), and brain histopathology have been evaluated. Vit-D prevented pilocarpine-induced behavioral impairments and oxidative stress in the brain; these results were improved in combination with lamotrigine. Vit-D has a promising antiepileptic, neuroprotective, and antioxidant effects. It can be provided to patients as a supportive treatment besides antiepileptic drugs. However, clinical trials are needed to establish its efficacy and safety.