Miracle-dz/UniFAR-FTUs huggingface dataset:
Sitagliptin–Moringa oleifera coadministration did not delay the progression nor ameliorated functional and morphological anomalies in alloxan-induced diabetic nephropathy

OBJECTIVE: Sitagliptin (ST) and Moringa oleifera (MO) Lam (Moringaceae) are used concomitantly by diabetic patients, with no study ascertaining for potential favorable or otherwise renal implications. We investigated the effect of coadministration of ST and MO leaf extract on functional and morphological biomarkers of alloxan-induced diabetic nephropathy (DN). MATERIALS AND METHODS: Diabetes was induced with a single dose of 150 mg/kg of alloxan intraperitoneally. Seven groups of eight rats per group were used, with Groups I, II, and VII as normal (NS), diabetic control (DC), and postprandial controls. Groups III, IV, V, and VI were diabetic rats on ST, MO, ST and MO (SM), for 42 days with 2 weeks delayed treatment in a postprandial hyperglycemic group (PPSM), respectively. Serum urea, albumin, electrolyte levels, lipid profile, and kidney tropism were determined in addition to histological examinations. RESULTS: There was a significant increase (P < 0.05) in kidney tropism comparing all drug-treated groups and DC to normal rats. Significant increases in serum urea were observed (P = 0.02) in DC, MO-treated, and SM-treated rats compared to normal rats and also in serum triglyceride (P < 0.05) in MO-treated and SM-treated rats compared to controls and other drug-treated groups. A mild reduction in severity of pathologic lesions was observed (glomerulosclerosis Grade 1) in SM-treated rats compared to a marked necrosis in DC (Grade 3). CONCLUSION: The coadministration of ST–MO did not delay the progression of functional anomalies and renal injury nor ameliorated the lesions associated with chronic DN in Wistar rats.
Disruption of the methionine cycle and reduced cellular gluthathione levels underlie potex-potyvirus synergism in Nicotiana benthamiana.

Infection caused by the synergistic interaction of two plant viruses is typically manifested by severe symptoms and increased accumulation of either virus. In potex-potyviral synergism, the potyviral RNA silencing suppressor helper component proteinase (HCPro) is known to enhance the pathogenicity of the potexvirus counterpart. In line with this, Potato virus X (PVX; genus Potexvirus) genomic RNA (gRNA) accumulation and gene expression from subgenomic RNA (sgRNA) are increased in Nicotiana benthamiana by Potato virus A (PVA; genus Potyvirus) HCPro expression. Recently, we have demonstrated that PVA HCPro interferes with the host cell methionine cycle by interacting with its key enzymes S-adenosyl-l-methionine synthetase (SAMS) and S-adenosyl-l-homocysteine hydrolase (SAHH). To study the involvement of methionine cycle enzymes in PVX infection, we knocked down SAMS and SAHH. Increased PVX sgRNA expression between 3 and 9 days post-infiltration (dpi) and upregulation of (-)-strand gRNA accumulation at 9 dpi were observed in the SAHH-silenced background. We found that SAMS and SAHH silencing also caused a significant reduction in glutathione (GSH) concentration, specifically in PVX-infected plants between 2 and 9 dpi. Interestingly, HCPro expression in PVX-infected plants caused an even stronger reduction in GSH levels than did SAMS + SAHH silencing and a similar level of reduction was also achieved by knocking down GSH synthetase. PVX sgRNA expression was increased in the GSH synthetase-silenced background. GSH is a major antioxidant of plant cells and therefore GSH shortage may explain the strong oxidative stress and severe symptoms observed during potex-potyvirus mixed infection.
Comparison of Clinical and Radiological Parameters at Knee Osteoarthritis

Introduction: Osteoarthritis (OA) or arthrosis represents an inflammatory disease of joints that develops as a result of interaction of mechanical and biological parameters. With disease development, degenerative changes on joint cartilage can be noticeable that affect and cause pathological changes on other parts of a joint resulting in pain and dysfunction of a joint. A. E. Garrod in 1907 described osteoarthritis as a special clinical entity and separated it from a rheumatoid arthritis. OA is characterized with loss of a joint cartilage, development of new bone tissue under affected cartilage (subchondral bone) and development of osteophytes on joint edge. First sign of a disease is pain after period of relaxation that slowly intensifies. Material and Methods: In this paper, 40 patients have been analyzed with clinical and radiological signs of OA of the knee joint. Radiological classification was done by Ahlback’s classification. Results: In our study female gender was more affected with average age of 63 years. On Ahlback classification, grade II was represented the most. Comparison between clinical and radiological signs showed that there was no significant difference between established grade of OA. Wide spectrum of visible radiological osteoarthritis changes on joints is in correlation with the age of examinees.
Novel Optical Techniques for Imaging Microcirculation in the Diabetic Foot.

BACKGROUND The most severe diabetic foot ulcers are those related with critical ischemia, which is primarily diagnosed with non-invasive diagnostics. However, these diagnostics have several disadvantages. For example, they only provide global indications of the (macro)level of ischemia. A potential solution can be found in novel optical imaging techniques for local assessment of the microcirculation in diabetic foot ulcers. This review provides an overview of these imaging techniques (Laser Doppler Perfusion Imaging, Laser Speckle Contrast Imaging, Photoacoustic Imaging and Hyperspectral Imaging) and their applicability for the diagnostic assessment of microcirculation in diabetic foot ulcers. METHOD For each technique, the following parts are described: a) their technical background; b) general clinical applications; and, c) its application for microcirculation assessment in diabetic foot ulcers. Parts a-b are based on a narrative review of the literature, part c on a systematic review that was performed in the database Scopus, covering the period from January 1, 2000 to November 31, 2017. RESULTS Each of these techniques has specific advantages and disadvantages for imaging microcirculation. Potential clinical use depends on measurement aims, and clinical relevance. However, none of the techniques has a strongly established clinical relevance yet: we found a limited number of publications describing clinical outcomes. Future research is needed to determine which technique is the most clinically relevant for the assessment of microcirculation in diabetic foot ulcers. CONCLUSION Although promising, the currently available novel optical techniques need to be further improved technically and prospective trials are necessary to evaluate their clinical value.
Transplantation of Mesenchymal Stromal Cells in Patients with Amyotrophic Lateral Sclerosis: Results of Phase I/IIa Clinical Trial

Amyotrophic lateral sclerosis (ALS) is a progressive untreatable neurodegenerative disorder, leading to the death of the cortical and spinal motoneurons (MNs). Bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) may represent a new approach to slowing down the progression of ALS by providing neurotrophic support to host MNs and by having an anti-inflammatory effect. We have designed a prospective, nonrandomized, open-label clinical trial (phase I/IIa, EudraCT No. 2011-000362-35) to assess the safety and efficacy of autologous multipotent BM-MSCs in ALS treatment. Autologous BM-MSCs were isolated and expanded under GMP conditions. Patients received 15 ± 4.5 × 106 of BM-MSCs via lumbar puncture into the cerebrospinal fluid. Patients were monitored for 6 months before treatment and then for an 18-month follow-up period. Potential adverse reactions were assessed, and the clinical outcome was evaluated by the ALS functional rating scale (ALSFRS), forced vital capacity (FVC), and weakness scales (WSs) to assess muscle strength on the lower and upper extremities. In total, 26 patients were enrolled in the study and were assessed for safety; 23 patients were suitable for efficacy evaluation. After intrathecal BM-MSC application, about 30% of the patients experienced a mild to moderate headache, resembling the headaches after a standard lumbar puncture. No suspected serious adverse reactions (SUSAR) were observed. We found a reduction in ALSFRS decline at 3 months after application (p < 0.02) that, in some cases, persisted for 6 months (p < 0.05). In about 80% of the patients, FVC values remained stable or above 70% for a time period of 9 months. Values of WS were stable in 75% of patients at 3 months after application. Our results demonstrate that the intrathecal application of BM-MSCs in ALS patients is a safe procedure and that it can slow down progression of the disease.
Plasma Level of Soluble Urokinase-type Plasminogen Activator Receptor Predicts the Severity of Acute Alcohol Pancreatitis

Objectives Systemic levels of soluble urokinase-type plasminogen activator receptor (suPAR) are increased in various inflammatory and infectious diseases. We investigated the activation and prognostic value of plasma suPAR (P-suPAR) in patients experiencing their first acute alcohol pancreatitis (AAP). Methods From prospectively collected data, we measured P-suPAR concentrations in 104 patients with AAP during hospitalization and again after discharge. Results According to the revised Atlanta classification, pancreatitis was moderately severe in 29 (28%) and severe in 6 (6%) patients and these severities were combined for further analysis (non-mild AAP, n = 35; 34%). Median P-suPAR levels were significantly higher in patients with AAP during hospitalization than after discharge (4.8 vs 3.1 ng/mL; P < 0.001) and in non-mild compared to mild AAP (6.2 vs 4.2 ng/mL; P < 0.001). When the analysis was made 1 to 4 days after admission (n = 68), the area under the curve was 0.81 (95% confidence interval, 0.70–0.92). P-suPAR was found to be a better prognostic marker in AAP than C-reactive protein, hematocrit, or creatinine. Conclusions P-suPAR concentrations are elevated in AAP and correlate with the severity of the disease. These results suggest that P-suPAR may have potential to serve as a novel prognostic marker for AAP severity on admission.
Urethral funneling visualized during pelvic floor sonography - analysis of occurrence among urogynecological patients.

OBJECTIVES There are different diagnostic methods used in women with urinary incontinence symptoms such as: medical history, voiding diary, cough test, pad test, urodynamic testing. None of them is optimal. The aim of this study is to analyze the correlation between urethral funneling visualized during pelvic floor sonography and symptoms of stress urinary incontinence. MATERIAL AND METHODS We have performed a retrospective analysis of 657 complete datasets of patients who attended our urogynecological clinic for diagnostics. Women with wet overactive bladder were excluded from the analysis. Tests used in our clinic included: standardized interview and questionnaire, clinical exam, cough test. Pelvic floor sonography with a transvaginal probe in women with filled bladder was performed to assess the urethral length and the urethral funneling during maximal Valsalva maneuver. RESULTS In all patients with clinical SUI symptoms and with a positive cough test the urethral funneling length during Valsalva maneuver was > 50% of urethral length (long urethral funneling). In 83.7% of women without SUI the urethral funneling was absent. In the remaining 16.3% funneling was visible but its relative length was less than 50% of urethral length and urine flow was not observed (short urethral funneling). CONCLUSIONS Long urethral funneling (> 50% of urethral length) seems to be a characteristic sign for SUI in women. The presence of urethral funneling shorter than 50% of urethral length (short urethral funneling) is not a SUI symptom - it is probably a sign of asymptomatic funneling of bladder neck.
Whole Transcriptome Screening Reveals Myelination Deficits in Dysplastic Human Temporal Neocortex

Abstract Focal cortical dysplasias (FCDs) are local malformations of the human neocortex with strong epileptogenic potential. To investigate the underlying pathomechanisms, we performed a whole human transcriptome screening to compare the gene expression pattern of dysplastic versus nondysplastic temporal neocortex. Tissue obtained from FCD IIIa cases (mean age 20.5 years) who had undergone surgical treatment, due to intractable epilepsy, was compared with nondysplastic specimens (mean age 19.9 years) by means of Affymetrix arrays covering 28 869 genes. We found 211 differentially expressed genes (DEX) among which mainly genes important for oligodendrocyte differentiation and myelination were downregulated in FCD IIIa. These findings were confirmed as functionally important by Database for Annotation, Visualization, and Integrated Discovery (DAVID) analysis. The reduced expression of myelin‐associated transcripts was confirmed for FCD Ia, IIa, and IIIa by real‐time RT‐qPCR. In addition, we found that the density of myelin basic protein mRNA‐expressing oligodendrocytes and of 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase‐positive myelin fibers was significantly reduced in dysplastic cortex. Moreover, high‐resolution confocal imaging and 3D reconstruction revealed that the myelin fiber network was severely disorganized in dysplastic neocortex, indicating a disturbance of myelin sheath formation and maintenance in FCD.
Ghrelin Serum Concentrations Are Associated with Treatment Response During Lithium Augmentation of Antidepressants

Abstract Background Lithium augmentation of antidepressants is an effective strategy in treatment-resistant depression. The proteohormone ghrelin is thought to be involved in the pathophysiology of depression. The purpose of this study was to investigate the association of treatment response with the course of ghrelin levels during lithium augmentation. Method Ghrelin serum concentrations and severity of depression were measured in 85 acute depressive patients before and after 4 weeks of lithium augmentation. Results In a linear mixed model analysis, we found a significant effect of response*time interaction (F1.81=9.48; P=.0028): under treatment, ghrelin levels increased in nonresponders and slightly decreased in responders to lithium augmentation. The covariate female gender had a significant positive effect (F1.83=4.69; P=.033), whereas time, response, appetite, and body mass index (kg/m2) did not show any significant effect on ghrelin levels (P>.05). Conclusion This is the first study showing that the course of ghrelin levels separates responders and nonresponders to lithium augmentation. Present results support the hypothesis that ghrelin serum concentrations might be involved in response to pharmacological treatment of depression.
Convergence of the MAC scheme for the compressible stationary Navier-Stokes equations

We prove in this paper the convergence of the Marker and Cell (MAC) scheme for the discretization of the steady state compressible and isentropic Navier-Stokes equations on two or three-dimensional Cartesian grids. Existence of a solution to the scheme is proven, followed by estimates on approximate solutions, which yield the convergence of the approximate solutions, up to a subsequence, and in an appropriate sense. We then prove that the limit of the approximate solutions satisfies the mass and momentum balance equations, as well as the equation of state, which is the main difficulty of this study.
Preservability of bull spermatozoa in Tris-egg yolk extender enriched with different concentrations of butylated hydroxytoluene

Objective: To explore the effect of BHT on cattle spermatozoa during cooling and cryopreservation. Methods: Pooled bull semen were diluted by Tris-Citrate-Fructose egg yolk (TCFY) diluent considered as control (0 BHT) and different concentrations of BHT (1.0, 2.0, 3.0, 4.0, 5.0 and 6.0 mM were prepared in ethanol in prewarmed (37 °C) test tubes. The ethanol was allowed to evaporate so that, a thin crystallized layer of BHT was deposited on the inner surface of the tubes. Then extended semen was added into the tubes and incubated at 37 °C for 5 min to allow uptake of BHT by spermatozoa. The tubes were cooled slowly (approximately for 2 h) up to 5 °C and equilibrated for 4 h. After equilibration, semen freezing process was carried out. Extended semen was subjected to evaluation (motility, alive sperm, intact sperm membrane (HOST) % and acrosome integrity) in both cooled and cryopreserved semen. Results: The result revealed that sperm motility of post-cooled spermatozoa improved (P<0.05) by the use of BHT concentrations (1, 2 and 3 mM) in Tris semen extender if compared to the control (85.00±1.09), (83.33± 0.63), (81.67± 0.63) and (78.33± 0.63), respectively. Alive sperm percent was significantly higher in all concentrations of BHT. Sperm abnormalities percent were significantly lower in concentrations of BHT 1 and 2 (11.2±0.2), (11.8±0.2)and (13.4±0.4), respectively. Sperm membrane integrity were significantly higher in BHT concentrations (1, 2, 3, 4 and 5 mM). It is exhibited that improved sperm motility in post-thawed frozen semen in the concentrations of BHT (1, 2, 3 and 4 mM) if compared to the control. The sperm membrane integrity were significantly improved at all concentrations of BHT. Acrosome integrity was significantly higher at BHT concentration 1 mM (81.80±0.57) and (76.00±2.05), respectively. Conclusions: It could be concluded that some concentrations of BHT improved bull semen quality post-cooling and post-freezing.
Clickotine, A Personalized Smartphone App for Smoking Cessation: Initial Evaluation

Background Tobacco smoking is the leading cause of preventable death in the United States, and the annual economic burden attributable to smoking exceeds US $300 billion. Obstacles to smoking cessation include limited access and adherence to effective cessation interventions. Technology can help overcome these obstacles; many smartphone apps have been developed to aid smoking cessation, but few that conform to the US clinical practice guideline (USCPG) have been rigorously tested and reported in the literature. Clickotine is a novel smartphone app for smoking cessation, designed to deliver the essential features of the USCPG and engineered to engage smokers by personalizing intervention components. Objective Our objective was to assess the engagement, efficacy, and safety of Clickotine in an initial, single-arm study. Outcomes measured were indicators of engagement with the smartphone app (number of app opens, number of interactions with the Clickotine program, and weeks active with Clickotine), cessation outcomes of 7- and 30-day self-reported abstinence from smoking, and negative health events. Methods We recruited US residents between 18 and 65 years of age who owned an iPhone and smoked 5 or more cigarettes daily for the study via online advertising. Respondents were prescreened for eligibility by telephone and, if appropriate, directed to a Web portal to provide informed consent, confirm eligibility, and download the Clickotine app. Participants completed study assessments via the online portal at baseline and after 8 weeks. Data were collected in Amazon S3 with no manual data entry, and access to all data was maximally restrictive, logged, and auditable. Results A total of 416 participants downloaded the app and constituted the intention-to-treat (ITT) sample. On average, participants opened the Clickotine app 100.6 times during the 8-week study (median 69), logged 214.4 interactions with the Clickotine program (median 178), and remained engaged with Clickotine for 5.3 weeks (median 5). Among the ITT sample, 45.2% (188/416) reported 7-day abstinence and 26.2% (109/416) reported 30-day abstinence from smoking after 8 weeks. Completer analysis focused on 365 (87.7%) of the 416 enrolled participants who completed the 8-week questionnaire revealed that 51.5% (188/365) of completers reported 7-day abstinence and 29.9% (109/365) reported 30-day abstinence. Few adverse events, mostly consistent with nicotine withdrawal symptoms, were reported and overall no safety signal was detected. Conclusions In this initial single-arm trial, Clickotine users appeared to demonstrate encouraging indicators of engagement in terms of the number of app opens, number of program interactions, and continued engagement over time. Clickotine users reported encouraging quit rates while reporting few adverse events. Future research is warranted to assess Clickotine’s efficacy in a randomized controlled trial. Trial Registration Clinicaltrials.gov NCT02656745; https://clinicaltrials.gov/ct2/show/NCT02656745 (Archived by WebCite at http://www.webcitation.org/6peTT4x60)
Plasma Lutein and Zeaxanthin Are Associated With Better Cognitive Function Across Multiple Domains in a Large Population-Based Sample of Older Adults: Findings from The Irish Longitudinal Study on Aging

Background Low blood serum or plasma concentrations of the xanthophyll carotenoids lutein and zeaxanthin have been implicated in poorer cognitive health in older adults. However, equivocal results from smaller studies and clinical trials highlight the need for large population-based studies with comprehensive measures of cognitive function and adjustment for multiple confounders to examine such associations in more depth. Methods In the current study, we investigated the association between plasma lutein and zeaxanthin and domain-specific cognitive performance in 4,076 community-dwelling adults aged 50 years or older from The Irish Longitudinal Study on Ageing. Mixed-effects models were fitted with adjustment for demographic and socioeconomic factors, health conditions, and health behaviors. Results Higher plasma lutein and zeaxanthin were independently associated with better composite scores across the domains of global cognition, memory, and executive function. We also found evidence that higher plasma zeaxanthin, but not lutein, was associated with better processing speed. These associations were consistent across domains. Conclusions Further investigation of the prognostic value of carotenoid concentrations, and their changes, on cognition in similar population-based samples longitudinally is warranted.
Stem Cell Factor SALL4 Represses the Transcriptions of PTEN and SALL1 through an Epigenetic Repressor Complex

Background The embryonic stem cell (ESC) factor, SALL4, plays an essential role in both development and leukemogenesis. It is a unique gene that is involved in self-renewal in ESC and leukemic stem cell (LSC). Methodology/Principal Findings To understand the mechanism(s) of SALL4 function(s), we sought to identify SALL4-associated proteins by tandem mass spectrometry. Components of a transcription repressor Mi-2/Nucleosome Remodeling and Deacetylase (NuRD) complex were found in the SALL4-immunocomplexes with histone deacetylase (HDAC) activity in ESCs with endogenous SALL4 expression and 293T cells overexpressing SALL4. The SALL4-mediated transcriptional regulation was tested on two potential target genes: PTEN and SALL1. Both genes were confirmed as SALL4 downstream targets by chromatin-immunoprecipitation, and their expression levels, when tested by quantitative reverse transcription polymerase chain reaction (qRT-PCR), were decreased in 293T cells overexpressing SALL4. Moreover, SALL4 binding sites at the promoter regions of PTEN and SALL1 were co-occupied by NuRD components, suggesting that SALL4 represses the transcriptions of PTEN and SALL1 through its interactions with the Mi-2/NuRD complex. The in vivo repressive effect(s) of SALL4 were evaluated in SALL4 transgenic mice, where decreased expressions of PTEN and SALL1 were associated with myeloid leukemia and cystic kidneys, respectively. Conclusions/Significance In summary, we are the first to demonstrate that stem cell protein SALL4 represses its target genes, PTEN and SALL1, through the epigenetic repressor Mi-2/NuRD complex. Our novel finding provides insight into the mechanism(s) of SALL4 functions in kidney development and leukemogenesis.