A simple methodology was developed to quantify penicillamine (PA) in pharmaceutical samples, using the selective interaction of the drug with Cu-modified graphene quantum dots (Cu-GQDs). The proposed strategy combines the advantages of carbon dots (over other nanoparticles) with the high affinity of PA for the proposed Cu-GQDs, resulting in a significant and selective quenching effect. Under the optimum conditions for the interaction, a linear response (in the 0.10–7.50 μmol/L PA concentration range) was observed. The highly fluorescent GQDs used were synthesized using uric acid as single precursor and then characterized by high resolution transmission electron microscopy, Raman spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, fluorescence, and absorption spectroscopy. The proposed methodology could also be extended to other compounds, further expanding the applicability of GQDs.

A simple methodology was developed to quantify penicillamine (PA) in pharmaceutical samples, using the selective interaction of the drug with Cu-modified graphene quantum dots (Cu-GQDs). The proposed strategy combines the advantages of carbon dots (over other nanoparticles) with the high affinity of PA for the proposed Cu-GQDs, resulting in a significant and selective quenching effect. Under the optimum conditions for the interaction, a linear response (in the 0.10–7.50 μmol/L PA concentration range) was observed. The highly fluorescent GQDs used were synthesized using uric acid as single precursor and then characterized by high resolution transmission electron microscopy, Raman spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, fluorescence, and absorption spectroscopy. The proposed methodology could also be extended to other compounds, further expanding the applicability of GQDs.

Primary leptomeningeal lymphoma (PLML) is a rare entity, representing 7% of all cases of primary central nervous system lymphoma and approximately 0.1% of primary central nervous system tumours.1-4 Patients can present with symptoms of raised intracranial pressure, or cranial or spinal polyradiculopathies.1-3 Even with extensive investigations, diagnosis in up to a third of patients can only be confirmed with meningeal biopsy. In this Imaging Highlights, we describe a patient who presented with multiple cranial nerve palsies with corresponding MRI nerve enhancement, and subsequent meningeal biopsy proven lymphoma.

Background Epidemiological surveys showed that the types of bacteria are different in the conjunvical sac from different nationalities,which possibly is associated with living environment.To characterize the types of conjunctival bacteria involved is important for the prevention and treatment of infectious eye diseases.Objective The present survey was to obtain data about bacterial species in the conjunctival sac in the Tibetan minority population aged over 40 years old and compared with the matched Han nationality population.Methods The standardized training and protocol were performed before this survey.A total of 290 eyes of 145 individuals from the Tibetan minority and 346 eyes of 173 subjects from the Han nationality were enrolled in this study in Ganzi Autonomous Prefecture,who had received questionnaire surveys and ophthalmological examinations.The secretion of the inferior palpebral conjunctival sac was embrocated and inoculated and grown on blood plates for 48-72 hours.The bacteria were isolated and identified.This study was approved by the Medical Ethic Committee of the Sichuan People Hospital.Oral informed consent was obtained from the subjects.Results No significant differences were seen in the constituent ratio of the gender as well as the age between the Tibetan minority and Han nationality in this study (x2 =0.987,P=0.3202;t=1.142,P=0.254).There was a significant difference in the proportions of farmers and herdsmen between the two groups(x2 =8.557,P =0.000).The positive rate of bacterial cultivation in Tibetan individuals was 50.74％,showing a statistically significant decrease in comparison with the Han people(60.4％)(x2=6.042,P=0.014).There was no statistical difference in the multiple bacterial species between the two groups (11.0％ in Tibetan,11.6％ in Han people)(x2 =0.0271,P =0.869).The rate of staphylococcus epidemics was 26.6％ in the Tibetan minority and that of Han population was 33.2％,without a significant difference between them (x2 =3.350,P=0.060).No significant difference was seen in the ratio of corynbacterium infection between the two population(15.9％ vs.17.3％)(x2 =0.248,P =0.618).Conclusions The ratio of bacterial cultivation in Tibetans is statistically lower than that of the Han people.The types and distribution of bacteria are similar in the Tibetan and Han nationality.

PURPOSE: Trabectedin induces synthetic lethality in tumor cells carrying defects in homologous recombinant DNA repair. We evaluated the effect of concomitant inhibition of nucleotide-excision repair and poly (ADP-ribose) polymerase (PARP) activity with trabectedin and PARP inhibitors, respectively, and whether the synthetic lethality effect had the potential for a synergistic effect in breast cancer cell lines. Additionally, we investigated if this approach remained effective in BRCA1-positive breast tumor cells. METHODS: We have evaluated the in vitro synergistic effect of combinations of trabectedin and three different PARP inhibitors (veliparib, olaparib, and iniparib) in four breast cancer cell lines, each presenting a different BRCA1 genetic background. Antiproliferative activity, DNA damage, cell cycle perturbations and poly(ADP-ribosyl)ation were assessed by MTT assay, comet assay, flow cytometry and western blot, respectively. RESULTS: The combination of trabectedin and olaparib was synergistic in all the breast cancer cell lines tested. Our data indicated that the synergy persisted regardless of the BRCA1 status of the tumor cells. Combination treatment was associated with a strong accumulation of double-stranded DNA breaks, G2/M arrest, and apoptotic cell death. Synergistic effects were not observed when trabectedin was combined with veliparib or iniparib. CONCLUSION: Collectively, our results indicate that the combination of trabectedin and olaparib induces an artificial synthetic lethality effect that can be used to kill breast cancer cells, independent of BRCA1 status.
Blotting, Western ; BRCA1 Protein ; Breast Neoplasms* ; Breast* ; Cell Cycle ; Cell Death ; Cell Line* ; Comet Assay ; DNA Breaks, Double-Stranded ; DNA Damage ; DNA, Recombinant ; Drug Combinations ; Flow Cytometry

Introduction: Early femoral stem subsidence has been a concern as a predictor of the beginning of implant loosening, especially on cementless hip arthroplasty implants. This study aimed to determine the factors that affect femoral stem subsidence and outcome following hemiarthroplasty in the geriatric population. Materials and Methods: This is a retrospective study of 179 patients who underwent cementless bipolar hemiarthroplasty during the 2011-2019 period at an orthopaedic and traumatology hospital. Data on the patient's demography, pre-operative American Society Anaesthesiologist (ASA) score, body mass index (BMI), canal flare index (CFI), Dorr classification, and stem alignment were obtained. The primary outcomes were post-operative femoral stem subsidence, post-operative pain, and functional outcome using Harris Hip Score (HHS). Statistical analysis was conducted to identify risk factors associated with the primary outcome. Results: The mean femoral stem subsidence was 2.16 ±3.4 mm. The mean post-operative Visual Analog Score (VAS) on follow-up was 1.38 ± 1. Mean HHS on follow-up was 85.28±10.3. American Society Anaesthesiologist score 3 (p = 0.011, OR = 2.77) and varus alignment (p=0.039, OR = 6.963) were related to worse stem subsidence. Otherwise, neutral alignment (p = 0.045 and OR = 0.405) gave protection against femoral stem subsidence. The female gender (p = 0.014, OR 2.53) was associated with postoperative pain onset. Neutral alignment had significant relationship with functional outcomes (p = 0.01; OR 0.33). Conclusion: A higher ASA score and varus stem alignment were related to a higher risk of femoral stem subsidence. Meanwhile, neutral stem alignment had a protective effect on the femoral stem subsidence and outcome.

Objective: This study aims to assess the correlation of ferritin serum level and PELOD-2 score, and determine the effectiveness of ferritin serum level as early indicator of organ dysfunction. Methods: This was a cross-sectional study carried out to pediatric patients with sepsis in the Pediatric Intensive Care Unit Haji Adam Malik and Universitas Sumatera Utara hospital from June 2021 – January 2022. Complete blood work was done, and ferritin serum level and PELOD-2 score were measured on the first and third day of hospital stay of all the sixty participants aged 1-18 years old with sepsis. The correlation was measured using Spearman test, with p<0.05 indicating a significant correlation. Results: The median level of serum ferritin level was 480 (24.7 – 22652) ng/mL. There were 20% patients with ferritin level <200 ng/mL, 26.7% with ferritin level 200-500 ng/mL, and 53.3% patients with ferritin >500 ng/mL. The median score of PELOD-2 was 4. There was a significant correlation of serum ferritin and PELOD-2 score on day 1 of hospital stay. Conclusion The ferritin serum level is effective as an early indicator of organ dysfunction until PELOD-2 score is established. There is a positive correlation between serum ferritin and PELOD-2 score. There is a link between elevated ferritin and worse disease prognosis.
Ferritins ; Sepsis ; Infections

The chronic indeterminate phase of Chagas’ disease is asymptomatic despite positive test results for antibodies specific to Trypanosoma cruzi. CD62P-APC (P-selectin) and PAC-1 FITC (GpIIb/IIIa) may improve diagnosis as biomarkers of platelet activity. Nine asymptomatic seropositive subjects, previously untreated, were selected from a blood bank within a year of Chagas’ disease detection, in addition to a control group of four. All subjects were evaluated by flow cytometry for CD62P, PAC-1 and CD41, and in a complementary study, by Tissue Doppler Echocardiography for isovolumic relaxation times (IVRT) and E/A ratios. The subjects were classified as positive or negative for CD62P and PAC-1 by a cut off obtained from their mean±2SD. For IVRT and E/A ratios, cut offs were obtained from the American Society of Echocardiography and the European Association of Cardiovascular Imaging recommendations. Fisher’s exact test was used for associated findings. Pre-test and post-test probability, sensitivity, specificity, positive and negative predictive values and likelihood ratios were calculated. Abnormalities were expressed as platelet hyperactivity and ventricular dysfunction in CD62P, PAC-1, IVRT and E/A ratios. CD62P appears to have greater sensitivity (0.75) and PAC-1, more accurate specificity (0.75), which may explain thrombotic events in Chagas’ disease. We recommend the use of CD62P and PAC-1 as biomarkers of platelet hyperactivity in patients in the chronic indeterminate phase of Chagas’ disease.