Non-destructive detection of counterfeit and substandard medicines using X-ray diffraction

The prevalence of counterfeit and substandard medicines has been growing rapidly over the past decade, and fast, non-destructive techniques for their detection are urgently needed to counter this trend. In this thesis, both energy-dispersive X-ray diffraction (EDXRD) and pixelated diffraction (“PixD”) combined with chemometric methods were assessed for their effectiveness in detecting poor-quality medicines within their packaging. Firstly, a series of caffeine, paracetamol and cellulose mixtures of known concentrations were pressed into tablets. EDXRD spectra of each tablet were collected both with and without packaging. Principal component analysis (PCA) and partial least-squares regression (PLSR) were used to study the data and construct calibration models for quantitative analysis. The concentration prediction errors for the packaged data were found to be very similar to those obtained in the unpackaged case, and were also on a par with reported values in the literature using higher-resolution angular-dispersive X-ray diffraction (ADXRD). Following this, soft independent modelling by class analogy (SIMCA) classification was used to compare EDXRD spectra from a test set of over-the-counter (OTC) medicines containing various combinations of active pharmaceutical ingredients (APIs) against PCA models constructed using spectra collected for paracetamol and ibuprofen samples. The test samples were selected to emulate different levels of difficulty in authenticating medicines correctly, ranging from completely different APIs (easy) to those with a small quantity of additional API (difficult). This classification study found that the sensitivity and specificity were optimal at data acquisition times on the order of 75~150s, and regardless of whether layers of blister and card packaging surrounded the tablet in question. This experiment was repeated on a novel, compact system incorporating a pixellated detector, which was found to reduce the required data acquisition times for optimal classification by a factor of five

Dopamine transporter (DAT1) and dopamine receptor D4 (DRD4) genotypes differentially impact on electrophysiological correlates of error processing

Peer reviewedPublisher PD

Fatal cerebral edema associated with serine deficiency in CSF

Two young girls without a notable medical history except for asthma presented with an acute toxic encephalopathy with very low serine concentrations both in plasma and cerebrospinal fluid (CSF) comparable to patients with 3-phosphoglycerate dehydrogenase (3-PGDH) deficiency. Clinical symptoms and enzyme measurement (in one patient) excluded 3-PGDH deficiency. Deficiencies in other serine biosynthesis enzymes were highly unlikely on clinical grounds. On basis of the fasting state, ketone bodies and lactate in plasma, urine and CSF, we speculate that reduced serine levels were due to its use as gluconeogenic substrate, conversion to pyruvate by brain serine racemase or decreased L-serine production because of a lack of glucose. These are the first strikingly similar cases of patients with a clear secondary serine deficiency associated with a toxic encephalopathy

Creating, Connecting, and Communicating: A look at social support for postpartum women

The prevalence of postpartum depression underscores the critical need for support systems for new mothers. Virtual support groups, such as the Fourth Trimester Support Group described in this paper, represent a promising avenue for addressing these challenges and providing much-needed support. This article describes the formation, activities, and evaluation of an online support group that leverages technology to foster a sense of community for new mothers. Further, the details within the case study provide a basic model for starting a similar support group

A new record of Munida rugosa (J.C.!Fabricius, 1775) (Decapoda, Anomura, Galatheidae) from the Eastern Aegean Sea, Turkey

[Anstract Not Available

Effects of Dementia Care Mapping on well-being and quality of life of older people with intellectual disability:A quasi-experimental study

BACKGROUND: The ageing of people with intellectual disability, accompanied with consequences like dementia, challenges intellectual disability-care staff and creates a need for supporting methods, with Dementia Care Mapping (DCM) as a promising possibility. This study examined the effect of DCM on the quality of life of older people with intellectual disability.METHODS: We performed a quasi-experimental study in 23 group homes for older people with intellectual disability in the Netherlands, comparing DCM (n = 113) with care-as-usual (CAU; n = 111). Using three measures, we assessed the staff-reported quality of life of older people with intellectual disability.RESULTS: DCM achieved no significantly better or worse quality of life than CAU. Effect sizes varied from 0.01 to -0.22. Adjustments for covariates and restriction of analyses to people with dementia yielded similar results.CONCLUSION: The finding that DCM does not increase quality of life of older people with intellectual disability contradicts previous findings and deserves further study.</p

Absence of Survival Impact from Hepatitis During Immunotherapy in 193 Patients with Advanced Hepatocellular Carcinoma &ndash; An Observational Study from Taiwan

Chi-Han Lin,1,2,&ast; Yung-Chia Kuo,1– 3,&ast; Hsuan-Chih Kuo,1– 3,&ast; Ching-Ting Wang,4 Shi-Ming Lin,1,5 Alan Chao-Wei Lee,1,6 Ming-Chin Yu,1,6,7 Wei-Chen Lee,1,6 Cherry Chiao-Erh Chen,2,3 Jason Chia-Hsun Hsieh1– 3 1College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan; 2Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, 333, Taiwan; 3Division of Hematology-Oncology, Department of Internal Medicine, New Taipei City Municipal TuCheng Hospital, New Taipei City, 236, Taiwan; 4Registered Nurse, Case Manager of Nursing Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, 333, Taiwan; 5Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan; 6Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, 333, Taiwan; 7Department of Surgery, New Taipei City Municipal TuCheng Hospital, New Taipei City, 236, Taiwan&ast;These authors contributed equally to this workCorrespondence: Jason Chia-Hsun Hsieh, Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, No. 5, Fu-Hsin Street, Gueishan District, Taoyuan City, 333, Taiwan, Tel +886-3-3281200 Ext 8825, Email [email protected]: Hepatitis often occurs after initiating immune checkpoint inhibitor (ICI) treatment. The time and grade of hepatitis after ICI starts and the prognostic role of immune-related hepatitis in patients with advanced hepatocellular carcinoma (aHCC) remain unclear.Methods: In this real-world analysis, we enrolled aHCC patients receiving ICIs, documented the highest level of liver enzymes during/after ICIs, and analyzed the survival impact of different hepatitis patterns.Results: One hundred and ninety-three aHCC patients receiving ICIs were recruited. During ICIs, 88.6% of patients experienced aspartate transaminase (AST) elevations (Grade III/IV: 7.8%). For alanine transaminase (ALT), 81.3% had elevated levels (Grade III/IV: 3.6%), and 41.5% of patients had elevated bilirubin levels (Grade 3/4: 6.7%). The median AST, ALT, and total bilirubin values significantly increased after ICI treatment initiated (all p < 0.001) and, similarly, after excluding progressive disease (p = 0.014, p = 0.002, p < 0.001). The median time of hepatitis occurrence is from the 4.0th to 15.9th weeks. Multivariable analysis showed that patterns of liver enzyme change of AST and total bilirubin in patients receiving ICIs significantly correlate to overall survival (OS, p = 0.009 and 0.001, respectively). After ICI termination, patients with elevated bilirubin (p = 0.003) and AST (p = 0.005) would indicate poor survival, with adjustment of viral hepatitis and ICI responses.Conclusion: Hepatitis emerges between the 4th and 20th weeks post-ICI initiation. Changes in liver enzymes during ICI therapy do not directly affect OS, implying the safety of ICI use when corticosteroids are promptly administered if clinically indicated.Keywords: hepatitis, immune checkpoint inhibitor, advanced hepatocellular carcinoma, liver enzymes, overall surviva

Molecular markers of endometrial carcinoma detected in uterine aspirates.

Endometrial cancer (EC) is the most frequent of the invasive tumors of the female genital tract. Although usually detected in its initial stages, a 20% of the patients present with advanced disease. To date, no characterized molecular marker has been validated for the diagnosis of EC. In addition, new methods for prognosis and classification of EC are needed to combat this deadly disease. We thus aimed to identify new molecular markers of EC and to evaluate their validity on endometrial aspirates. Gene expression screening on 52 carcinoma samples and series of real-time quantitative PCR validation on 19 paired carcinomas and normal tissue samples and on 50 carcinoma and noncarcinoma uterine aspirates were performed to identify and validate potential biomarkers of EC. Candidate markers were further confirmed at the protein level by immunohistochemistry and Western blot. We identified ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2 and DCN as differentially expressed in ECs. Furthermore, the differential expression of these biomarkers in primary endometrial tumors is correlated to their expression level in corresponding uterine fluid samples. Finally, these biomarkers significantly identified EC with area under the receiver-operating-characteristic values ranging from 0.74 to 0.95 in uterine aspirates. Interestingly, analogous values were found among initial stages. We present the discovery of molecular biomarkers of EC and describe their utility in uterine aspirates. These findings represent the basis for the development of a highly sensitive and specific minimally invasive method for screening ECs