Oral glucose lowering drugs in type 2 diabetic patients with chronic kidney disease

Chronic kidney disease (CKD) represents a challenge in the treatment of type 2 diabetic patients. Renal impairment may affect drug clearance and other pharmacokinetic processes which can increase toxicity and drug to drug interactions or cause ineffective therapy. There are many oral glucose lowering drugs available for the treatment of type 2 diabetes mellitus (T2DM) with different mechanisms of action and different pharmacokinetic profiles. While all classes may be used in patients with mild renal impairment, therapeutic options for patients with moderate to severe CKD are still limited. This review focuses on the pharmacokinetics, metabolism, and safety of oral glucose lowering drugs in patients with T2DM and CKD

Spatial antibunching of photons with parametric down-conversion

The theoretical framework behind a recent experiment by Nogueira et. al. [Phys. Rev. Lett. 86}, 4009 (2001)] of spatial antibunching in a two-photon state generated by collinear type II parametric down-conversion and a birefringent double-slit is presented. The fourth-order quantum correlation function is evaluated and shown to violate the classical Schwarz-type inequality, ensuring that the field does not have a classical analog. We expect these results to be useful in the rapidly growing fields of quantum imaging and quantum information.Comment: 5 pages, 3 figures. Minor changes made, accepted for publication in PR

The Importance Of Monoclonal Proteins Determination For The Correct Diagnosis Of Transthyretin Cardiac Amyloidosis By [Tc-99m]Tc-diphosphonates

EPS-066 Aim/Introduction: To analyze the influence of the determination of free monoclonal proteins in blood and urine in the final diagnosis of Transthyretin Cardiac Amyloidosis (TTRA). Materials and Methods: We have analyzed 200 [99mTc]Tc-diphosphonates scans: 192 performed on 190 patients under suspicion of TTRA and 7 patients with grade II-III radiotracer myocardial deposit as a casual finding (November/2013 - January/2020). Likewise, clinical and laboratory characteristics (heart failure, LVEF, proBNP levels, immunofixation in serum and/or urine for the detection of monoclonal chains and chronic renal failure) have been evaluated. A positive case has been considered for TTRAwt or senile (Score Perugini II-III scan, negative immunofixation in serum and/or urine, negative genetic study), positive case for hereditary TTRA (Score Perugini II-III scan, negative immunofixation and positive genetic study), positive case for secondary amyloidosis (positive immunofixation and presence of hematologic malignancy) and undetermined amyloidosis (immunofixation not performed or positive and absence of haematologic malignancies at follow-up). Results: 59 positive scans have been detected, 47 men (79’7%) and 12 women (20’3%). The mean age of the group of positives was 82’66 years, while that of the negatives was 72’15. The mean proBNP levels in the positives are 7561, compared to 5869 in the negative group. Immunofixation (serum and/or urine for detection of kappa or lambda monoclonal chains at 30 (50.8%) has been performed on these patients. Finally, 37.2% (22/59) resulted in ATTRwt, 3.4% (2/59) hereditary ATTR (genetic study: variant E54Q and mutation c.424> A (p.Va.122Ile) in exon 4 of TTR) and 1.7% (1/59) secondary amyloidosis. The remaining 34/59 (57.7%) cases were undetermined amyloidosis (6 positive immunofixation and 27 without monoclonal proteins determination). Conclusion: Determination of monoclonal bands in blood and urine is mandatory to correctly characterize cases of cardiac amyloidosis and, in presence of monoclonal bands, to assess the existence of underlying haematological malignancies

Generation of spatial antibunching with free propagating twin beams

We propose and implement a novel method to produce a spatial anti-bunched field with free propagating twin beams from spontaneous parametric down-conversion. The method consists in changing the spatial propagation by manipulating the transverse degrees of freedom through reflections of one of the twin beams. Our method use reflective elements eliminating losses from absorption by the objects inserted in the beams.Comment: Submitted for publication in Phys. Rev.

Impact Of Sentinel Lymph Node Biopsy In Breast Cancer Patients Treated With Neoadjuvant Chemotherapy

EPS 196 Aim/Introduction: To analyze how many of the patients undergoing neoadjuvant chemotherapy (NCT) may benefit from SLNB, as well as the impact on patient management, especially in those with early axillary involvement. Materials and Methods: We included patients with breast carcinoma candidates to NCT discussed at the Tumor Committee of our hospital (April/2017-August/2019). All of them were subjected to clinical assessment, ultrasound and, if appropriate, histological analysis, axillary pre and post- NCT. Sentinel lymph node detection was performed after periareolar injection of [99mTc]Tc-nanocoloid (74 MBq) the day before surgery. In some cases, blue dye was injected and/or a pre-NPC metal clip was placed in the affected node. Results: Sixty-two patients were included. NCT achieved a complete breast response in 12 patients, partial in 46 and non-response in 4. Initially, 31 patients were classified as N0 and 31 as N+ (28 N1 and 3 N2), achieving a complete axillary response in 58% of N+ (18). SLNB was performed in 49 patients (79%; 100% in N0 and 58% in N+ from baseline). The gamma detection rate of the sentinel lymph node was 91.8% (93.5% in N0 and 88.9% in N+). 28 lymphadenectomies were undergone (45.2%; 22.5% in N0 and 67.7% in N+), 11 due to positive SLNB (5 N0 and 6 N1), 13 owing to lack of axillary response and 4 caused by the non-localization of the sentinel lymph node. SLNB was performed in 58% of N+ patients, of which 44.4% were negative, avoiding lymphadenectomy. Metal clip and/or blue dye techniques were used in 31 cases (50%). Conclusion: SLNB is viable in a high percentage of patients with previous NCT, with a high detection rate, even in patients with early affected axilla, avoiding lymphadenectomy to patients who achieve a complete response of the axillary lymph node

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020.

Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3–5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes. © 2021, The Author(s), under exclusive licence to Springer Nature Limited

A global analysis of Y-chromosomal haplotype diversity for 23 STR loci

In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed. A considerable number of null, duplicate and off-ladder alleles were revealed. Standard single-locus and haplotype-based parameters were calculated and compared between subsets of Y-STR markers established for forensic casework. The PPY23 marker set provides substantially stronger discriminatory power than other available kits but at the same time reveals the same general patterns of population structure as other marker sets. A strong correlation was observed between the number of Y-STRs included in a marker set and some of the forensic parameters under study. Interestingly a weak but consistent trend toward smaller genetic distances resulting from larger numbers of markers became apparent.Peer reviewe

Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening