Miracle-dz/UniFAR-FTUs huggingface dataset:
Correlation between myoclonus and the 3-glucuronide metabolites in patients treated with morphine or hydromorphone: a pilot study.

BACKGROUND The 3-glucuronide metabolites of morphine and hydromorphone have been implicated as a causative factor for patients exhibiting myoclonus. OBJECTIVE The primary goal of this study was to determine plasma levels of morphine-3-glucuronide (M3G) or hydromorphone-3-glucuronide (H3G) in patients demonstrating myoclonus and identify any trends or associations between the two. SETTING Patients were recruited from San Diego Hospice and the Institute for Palliative Medicine's inpatient unit. DESIGN A prospective convenience sample comprised of 17 subjects, 12 with myoclonus and 5 without myoclonus. Analysis included demographic, metabolic and clinical variables. Plasma was assayed via high performance liquid chromatography for morphine, M3G, and morphine-6-glucuronide or hydromorphone and hydromorphone-3-glucuronide. RESULTS No trends or associations were identified between plasma levels of M3G or H3G and myoclonus. Ratio levels of 3-glucuronide metabolite to their corresponding parent opioid were dramatically lower than anticipated. CONCLUSION In this small pilot study, it appears that the serum levels of metabolites M3G and H3G do not correlate with myoclonus.
Application of diffusion tensor imaging (DTI) and MR-tractography in the evaluation of peripheral nerve tumours: state of the art and review of the literature

Peripheral nerves can be affected by a variety of benign and malignant tumour and tumour-like lesions. Besides clinical evaluation and electrophysiologic studies, MRI is the imaging modality of choice for the assessment of these soft tissue tumours. Conventional MR sequences, however, can fail to assess the histologic features of the lesions. Moreover, the precise topographical relationship between the peripheral nerve and the tumor must be delineated preoperatively for complete tumour resection minimizing nerve damage. Using Diffusion tensor imaging (DTI) and tractography, it is possible to obtain functional information on tumour and nerve structures, allowing the assess anatomy, function and biological features. In this article, we review the technical aspects and clinical application of DTI for the evaluation of peripheral nerve tumours. (www.actabiomedica.it)
Pharmacokinetics of a New Carbapenem, DA-1131, after Intravenous Administration to Rats with Uranyl Nitrate-Induced Acute Renal Failure

ABSTRACT Because the physiological changes that occur in patients with acute renal failure could alter the pharmacokinetics of the drugs used to treat the disease, the pharmacokinetics of DA-1131, a new carbapenem antibiotic, were investigated after 1-min intravenous administration of the drug (50 mg/kg of body weight) to control rats and rats with uranyl nitrate-induced acute renal failure (U-ARF rats). The impaired kidney function was observed in U-ARF rats on the basis of physiological parameters observed by microscopy of the kidney and obtained by chemical analysis of the plasma. After a 1-min intravenous infusion of DA-1131, the concentrations in plasma and the total area under the plasma concentration-time curve from time zero to time infinity increased significantly in U-ARF rats compared with those in control rats (13,000 versus 4,400 μg · min/ml). This was due to the significantly slower total body clearance (CL) of DA-1131 (3.84 versus 11.4 ml/min/kg) from U-ARF rats than from control rats. The significantly slower CL of DA-1131 from U-ARF rats was due to both significantly slower renal clearance (0.000635 versus 4.95 ml/min/kg because of a significant decrease in the 8-h urinary excretion of unchanged DA-1131 [1.54 versus 43.8% of the intravenous dose] due to impaired kidney function, as proved by the significant decrease in creatinine clearance [0.0159 versus 4.29 ml/min/kg]) and significantly slower nonrenal clearance (3.80 versus 6.34 ml/min/kg because of a significant decrease in the metabolism of DA-1131 in the kidney) in U-ARF rats. The amounts of DA-1131 recovered from all tissues studied (except the kidneys) were significantly higher for U-ARF rats than for control rats; however, the ratios of the amount in tissue to the concentration in plasma (except those for the kidney, small intestine, and spleen) were not significantly different between the two groups of rats, indicating that the affinity of DA-1131 for rat tissues was not changed considerably in U-ARF rats.
Identification of Putative Regulatory Alterations Leading to Changes in Gene Expression in Chronic Obstructive Pulmonary Disease

Various genetic and environmental factors are known to be associated with chronic obstructive pulmonary disease (COPD). We identified COPD-related differentially expressed genes (DEGs) using 189 samples accompanying either adenocarcinoma (AC) or squamous cell carcinoma (SC), comprising 91 normal and 98 COPD samples. DEGs were obtained from the intersection of two DEG sets separately identified for AC and SC to exclude the influence of different cancer backgrounds co-occurring with COPD. We also measured patient samples named group ‘I’, which were unable to be determined as normal or COPD based on alterations in gene expression. The Gene Ontology (GO) analysis revealed significant alterations in the expression of genes categorized with the ‘cell adhesion’, ‘inflammatory response’, and ‘mitochondrial functions’, i.e., well-known functions related to COPD, in samples from patients with COPD. Multi-omics data were subsequently integrated to decipher the upstream regulatory changes linked to the gene expression alterations in COPD. COPD-associated expression quantitative trait loci (eQTLs) were located at the upstream regulatory regions of 96 DEGs. Additionally, 45 previously identified COPD-related miRNAs were predicted to target 66 of the DEGs. The eQTLs and miRNAs might affect the expression of ‘respiratory electron transport chain’ genes and ‘cell proliferation’ genes, respectively, while both eQTLs and miRNAs might affect the expression of ‘apoptosis’ genes. We think that our present study will contribute to our understanding of the molecular etiology of COPD accompanying lung cancer.
Expression of the c‐Met in advanced epithelial ovarian cancer and its prognostic significance

The purpose of this study was to evaluate the prognostic significance of c-Met expression in advanced cases of epithelial ovarian carcinoma. Paraffin-embedded tissues from 41 stage IIIC primary ovarian adenocarcinoma were stained immunohistochemically for c-Met expression. The expression of c-Met was correlated with conventional clinicopathologic parameters and with overall survival of the patients. c-Met expression was found in 60.9% of cases. This clinicopathologic study showed that epithelial ovarian carcinomas with c-Met expression had higher histologic tumor grade and were more frequently associated with para-aortic lymph node metastasis (P < 0.05). In multivariate analysis, c-Met expression remained as a statistically significant predictor for survival with histologic grade. The patients with stage IIIC epithelial ovarian cancers whose tumors expressed c-Met were more likely to have high-grade tumors, have more para-aortic lymph node involvement, and have a significantly worse overall survival than those whose tumors were c-Met negative. In conclusion, c-Met expression might be a potential prognostic marker for patients with advanced-stage epithelial ovarian cancers.
Conjunctival Melanomas Harbor BRAF and NRAS Mutations—Letter

In their recent study, Griewank and colleagues proposed that new therapies effective in cutaneous melanoma could hold promise in the management of conjunctival melanoma due to oncogenic BRAF and NRAS mutations and similarities in chromosomal gains and losses ([1][1]). Specifically, 27% of 78 primary
Volatile and semi-volatile components of jetsam ambergris

Abstract Volatile and semi-volatile compounds account for the odors, long valued in the perfumery industry, of the natural product, ambergris. Here we demonstrate application of solid phase micro extraction (SPME) and gas chromatography-mass spectrometry (GC-MS) to headspace analysis of the volatiles and semi-volatiles of jetsam ambergris. The samples collected in 2017/2018, ranged from a black, sticky material from New Zealand, likely recently ejected from a sperm whale, to a white solid found on a beach in Chile and radiocarbon-dated previously to be about 1000 years old. The traces of volatile/semi-volatile compounds extracted included, odorous γ-dihydroionone and odor-free pristane (2,6,10,14-tetramethylpentadecane), as the major constituents. The ratios of these to one another and to many other minor constituents, varied, depending on sample color and age.
Surgical closure of PDA in low-weight premature infants

Low-weight premature neonates (LWPNs) frequently have haemodynamically significant patent ductus arteriosus (PDA) responsible for serious complications. Cyclooxygenase inhibitors are used for ductal closure. If the medical treatment fails, the PDA can be legated surgically. We present our experience, since 2006, on PDA surgical closure. Material and methods. From 2006 to 2009, of the 518 LWPNs, PDA was present in 109 (21%) infants. The mean gestational age was 29.1 weeks. All patients underwent a medical treatment for PDA closure. Because of the failure of medical treatment, 19 patients (17%) underwent surgical closure. The shift from medical to surgical treatment was related to clinical condition and the echocardiographic appearance of PDA. At operation, the mean age was 17 days (9–42 days). The operation was performed through a left lateral thoracotomy in third intercostal space. PDA was clipped with metallic haemoclipps. Results. No LWPN died as a result of operation (0% early mortality). Post-operative period required inotrophic and diuretic infusion and a more aggressive ventilatory management. Discussion. In LWPNs, surgical PDA closure is usually given when medical treatment fails. The shift from medical to surgical closure should be based on clinical conditions being surgical PDA closure in the neonatal intensive care unit safe and effective also in extremely LWPNs.
Sprint mechanical differences at maximal running speed: Effects of performance level

ABSTRACT As the effect of performance level on sprinting mechanics has not been fully studied, we examined mechanical differences at maximal running speed (MRS) over a straight-line 35 m sprint amongst sprinters of different performance levels. Fifty male track and field sprinters, divided in Slow, Medium and Fast groups (MRS: 7.67 ± 0.27 m∙s−1, 8.44 ± 0.22 m∙s−1, and 9.37 ± 0.41 m∙s−1, respectively) were tested. A high-speed camera (250 Hz) recorded a full stride in the sagittal plane at 30–35 m. MRS was higher (p < 0.05) in Fast vs. Medium (+11.0%) and Slow (+22.1%) as well as in Medium vs. Slow (+10.0%). Twelve, eight and seven out of 21 variables significantly distinguished Fast from Slow, Fast from Medium and Medium from Slow sprinters, respectively. Propulsive phase was signiﬁcantly shorter in Fast vs. Medium (−17.5%) and Slow (−29.4%) as well as in Medium vs. Slow (−14.4%). Fast sprinters had significantly higher vertical and leg stiffness values than Medium (+44.1% and +18.1%, respectively) and Slow (+25.4% and +22.0%, respectively). MRS at 30–35 m increased with performance level during a 35-m sprint and was achieved through shorter contact time, longer step length, faster step rate, and higher vertical and leg stiffness.
Somatic genetic alterations in a large cohort of pediatric thyroid nodules

There is a rise in the incidence of thyroid nodules in pediatric patients. Most of them are benign tissues, but part of them can cause papillary thyroid cancer (PTC). The aim of this study was to detect the mutations in commonly investigated genes as well as in novel PTC-causing genes in thyroid nodules and to correlate the found mutations with clinical and pathological data. The cohort of 113 pediatric samples consisted of 30 benign lesions and 83 PTCs. DNA from samples was used for next-generation sequencing to identify mutations in the following genes: HRAS, KRAS, NRAS, BRAF, IDH1, CHEK2, PPM1D, EIF1AX, EZH1 and for capillary sequencing in case of the TERT promoter. RNA was used for real-time PCR to detect RET/PTC1 and RET/PTC3 rearrangements. Total detection rate of mutations was 5/30 in benign tissues and 35/83 in PTCs. Mutations in RAS genes (HRAS G13R, KRAS G12D, KRAS Q61R, NRAS Q61R) were detected in benign lesions and HRAS Q61R and NRAS Q61K mutations in PTCs. The RET/PTC rearrangement was identified in 18/83 of PTCs and was significantly associated with higher frequency of local and distant metastases. The BRAF V600E mutation was identified in 15/83 of PTCs and significantly correlated with higher age of patients and classical variant of PTC. Germline variants in the genes IDH1, CHEK2 and PPM1D were found. In conclusion, RET/PTC rearrangements and BRAF mutations were associated with different clinical and histopathological features of pediatric PTC. RAS mutations were detected with high frequency in patients with benign nodules; thus, our results suggest that these patients should be followed up intensively.
Ecological momentary assessments among patients with cancer: A scoping review

Abstract Introduction Ecological momentary assessment (EMA) is an emerging method to assess an individual's current thoughts, affect, behaviour, physical states and contextual factors as they occur in real‐time and in their natural environment. Whereas EMA is frequently used in mental health, little is known about the added value of EMA in oncology research. This review aimed to synthesise methodological information and results of studies that applied EMA among patients with cancer to inform future researchers about the opportunities and challenges. Methods We included full‐text articles on studies that: (a) were conducted among adult cancer patients; and (b) examined cancer and treatment‐related experiences by EMA. Information from selected studies was synthesised: study designs, EMA data collection methods, response‐related results and main findings. Results Twelve studies were included, which all applied an observational design. The EMA data collection methods varied considerably and the reporting of response‐related results were poor. Nevertheless, EMA was found feasible as no systematic patterns of problems were reported and reported response‐related results were acceptable. Furthermore, EMA was found useful as it facilitated examination of real‐time experiences and behaviour. Conclusion Ecological momentary assessment is useful and feasible in oncology research. Future studies would benefit from guidelines for designing and reporting EMA studies.
Fluoride influences nickel-titanium orthodontic wires' surface texture and friction resistance

Objectives: The aim of this study was to investigate the effects exerted by the acidulated fluoride gel on stainless steel and nickel-titanium (Ni-Ti) orthodontic wires. Materials and Methods: Sixty stainless steel and Ni-Ti orthodontic archwires were distributed into forty archwires used for in vitro study and twenty for in situ study. Fluoride was applied for 1 h in the in vitro experiment while it was applied for 5 min in the in situ experiment. The friction resistance of all wires with ceramic brackets before/after topical fluoride application was measured using a universal testing machine at 1 min intervals of moving wire. Moreover, surface properties of the tested wires before/after fluoride application and before/after friction test were examined by a scanning electron microscope (SEM). Dunnett′s t-test was used to compare frictional resistance of as-received stainless steel wires and Ni-Ti wires to the wires treated by fluoride in vitro and in situ (P < 0.05). Two-way ANOVA was used to compare the effect of fluoride application and type of wire on friction resistance in vitro and in situ (P < 0.05). Results: Ni-Ti wires recorded significantly high friction resistance after fluoride application when compared to stainless steel wires in vitro, P < 0.05. Fluoride application did not significantly affect the friction resistance of the tested wires in situ, P < 0.05. SEM observation revealed deterioration of the surface texture of the Ni-Ti wires after fluoride application in vitro and in situ. Conclusions: The in vitro fluoride application caused an increase in friction resistance of Ni-Ti wires when compared to stainless steel wires. In vitro and in situ fluoride application caused deterioration in surface properties of Ni-Ti wires.
HIF Inactivation of p53 in Ovarian Cancer Can Be Reversed by Topotecan, Restoring Cisplatin and Paclitaxel Sensitivity

Ovarian cancer growth under hypoxic conditions results in hypoxia-inducible factor-1α (HIF1α) stabilization. HIF1α is an adverse prognostic factor that may contribute to worse outcomes via its capacity to bind to p53, potentially blocking p53-mediated apoptosis. We determined whether HIF1α-p53 binding occurred in hypoxic ovarian cancer cell lines, and if this blocked p53 transcriptional activity. Topotecan (TPT), used in the treatment of ovarian cancer, inhibits HIF1α translation via a topoisomerase-1 (TOPO1)–dependent mechanism. We examined if TPT knockdown of HIF1α restored p53 transcriptional function. TPT effects on HIF1α and p53-related transcriptional targets were assessed by PCR. Associations between TPT effects and TOPO1 expression levels were examined by Western blots and knockdown by siRNA. RNA-binding protein immunoprecipitation was used to assess if TOPO1 was resident on HIF1α mRNA. We determined if sublethal doses of TPT, used to knockdown HIF1α, reversed hypoxia-related cisplatin and paclitaxel resistance (XTT assay). Flow cytometry was used to assess HIF1α-mediated upregulation of ABCB1 and ABCB5 efflux pump expression. We found that HIF1α binding to, and inhibition of, p53 transcriptional activity in hypoxic ovarian cancer cells was associated with drug resistance. TPT-mediated downregulation of HIF1α in hypoxic cells required TOPO1 resident on HIF1α mRNA, restored p53 transcriptional activity, downregulated ABCB1/ABCB5 cell surface expression, and reversed hypoxia-related cisplatin and paclitaxel resistance. Implications: TPT-mediated reduction of HIF1α accumulation in hypoxic ovarian cancer cell lines restores p53 tumor-suppressor function, offering a novel approach to reverse chemoresistance. Further clinical investigation is warranted.
EHMT2 and SETDB1 protect the maternal pronucleus from 5mC oxidation

Significance The most important task of the mammalian zygote is to globally remodel its epigenome. Chromosomes that carried out sperm or oocyte functions are remodeled toward directing the unique totipotent state that characterizes the healthy preimplantation-stage embryo. The guiding differences in cell functions are marked on the chromosomes by interdependent epigenetic modifications including histone and DNA methylation, which both undergo global changes in the zygote. By performing genetic experiments, we found that two maternally supplied histone methyltransferase enzymes play important roles in the zygote in specifying the process of global DNA remodeling by 5-methylcytosine oxidation. Genome-wide DNA “demethylation” in the zygote involves global TET3-mediated oxidation of 5‐methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) in the paternal pronucleus. Asymmetrically enriched histone H3K9 methylation in the maternal pronucleus was suggested to protect the underlying DNA from 5mC conversion. We hypothesized that an H3K9 methyltransferase enzyme, either EHMT2 or SETDB1, must be expressed in the oocyte to specify the asymmetry of 5mC oxidation. To test these possibilities, we genetically deleted the catalytic domain of either EHMT2 or SETDB1 in growing oocytes and achieved significant reduction of global H3K9me2 or H3K9me3 levels, respectively, in the maternal pronucleus. We found that the asymmetry of global 5mC oxidation was significantly reduced in the zygotes that carried maternal mutation of either the Ehmt2 or Setdb1 genes. Whereas the levels of 5hmC, 5fC, and 5caC increased, 5mC levels decreased in the mutant maternal pronuclei. H3K9me3-rich rings around the nucleolar-like bodies retained 5mC in the maternal mutant zygotes, suggesting that the pericentromeric heterochromatin regions are protected from DNA demethylation independently of EHMT2 and SETDB1. We observed that the maternal pronuclei expanded in size in the mutant zygotes and contained a significantly increased number of nucleolar-like bodies compared with normal zygotes. These findings suggest that oocyte-derived EHMT2 and SETDB1 enzymes have roles in regulating 5mC oxidation and in the structural aspects of zygote development.
Effect of Glyphaea brevis twigs extract on cell viability, apoptosis induction and mitochondrial membrane potential in TM3 Leydig cells

Glyphaea brevis twigs (Spreng) Monach. (GBT) are used by local herb healers to manage male sexual fertility disorders. The aim of this study was to examine the effects of G. brevis twigs on TM3 Leydig cells. GBT was extracted using methanol solvent, and Leydig cells were exposed to the respective concentrations of GBT extract (0.1, 1, 10, 100 and 1,000 μg/ml) for 24 and 72 hr respectively. Parameters evaluated include cell morphology, viability (MTT assay), mitochondrial membrane potential (TMRE dye), apoptosis (Annexin V Alexa Fluor 488 binding) and RT‐qPCR analyses of the mRNA expression. Results revealed that GBT had no cytotoxic effect on cell viability and the cell morphology. GBT also revealed a considerable elevation (p < 0.05) in fluorescence intensity, accompanied by intact mitochondria in TM3 Leydig cells. Furthermore, GBT resulted in the reduction of necrotic and apoptotic cells. The mRNA StAR was upregulated markedly with the effect prominent at 100 μg/ml. This study showed that GBT might be useful for managing male infertility ailments.
Shared Medical Appointments: An Innovative Model to Reduce Health Disparities Among Latinxs With Type-2 Diabetes

In the United States, diabetes is epidemic. A study of Latinxs with diabetes evaluated a behavioral shared medical appointment (SMA) intervention. This quasi-experimental study included nonrandomized matched control group participants receiving usual care. The nonprobability convenience sample consisted of 90 participants (SMA = 30; control = 60) receiving primary care at an FQHC (Federally Qualified Health Center) clinic. At 6 months, the percentage of participants achieving target A1C goals was greater in the intervention group (59%) than in the control group (31%; χ2 = 4.462, p ≤ .05). In a multiple regression model, the SMA intervention group, compared to the control group had an A1C decline at 3 months of 0.55% (b = - 0.55, t = - 1.48, p=.14) and an A1C decline at 6 months of 0.83% (b= - 0.83, t= - 2.25, p = .03). Therefore, the results showed 3- and 6-month declines that were greater in the SMA group than in the control group. Underserved, underinsured Latinxs in the ALDEA program achieved significant A1C reductions; the program succeeded in empowering Latino patients and improving glycemic control.
Scaling of adult human bone and skeletal muscle mass to height in the US population

The scaling of structural components to body size is well studied in mammals, although comparable human observations in a large and diverse sample are lacking. The current study aimed to fill this gap by examining the scaling relationships between total body (TB) and regional bone and skeletal muscle (SM) mass with body size, as defined by stature, in a nationally representative sample of the US population.