Authors

RNA quality control in miRNA expression analysis Application Not

SEX-RELATED DIFFERENCES IN THE PHARMACOLOGICAL TREATMENT OF MAJOR DEPRESSION - ARE WOMEN AND MEN TREATED DIFFERENTLY?

Background: In the last decade, sex-related medicine has become an increasingly important area of research as insights in this field can improve treatment strategies and recovery. The aim of this study was to investigate sex-related differences in the prescription and kinds of psychopharmacological treatment in individuals with unipolar affective disorder. Subjects and methods: Data collected on 388 patients attending a psychiatric rehabilitation clinic (194 females, 194 males, mean age 52.3 years, standard deviation 7.8 years), who were matched by age and severity of depression, were analyzed. Depression severity and information on drug type and quantity were assessed at the beginning of the rehabilitation program and compared between women and men. Results: A significant difference between females and males was found in the frequency of prescribing bupropion (females: 3.61%, males: 12.89%; p=0.001) and mirtazapine (females: 5.15%, males: 13.40%; p=0.005). In terms of polypharmacy, the results showed that over 53% of the patients were taking two or more psychotropic substances as a long-term therapy and that 34% of them were taking three to five different substances. No sex-related differences were found concerning the number of psychotropic drugs taken by the patients. Conclusion: The higher frequency of prescriptions for bupropion and mirtazapine in men might be explained by the adverse drug reactions of the drugs (e.g., fewer sexually adverse drug reactions, weight gain) and a known interaction with oral contraception. It remains unclear whether these aspects are taken into consideration for each patient in terms of their special needs and conditions or whether it is a decision based on the patient’s sex. Given a similar severity of depression, men and women are prescribed a similar number of psychotropic substances. However, the high number of psychotropic drugs prescribed on average should be noted. Well-trained healthcare professionals should focus on regularly assessing and optimizing treatment regimens

Combining targeted and systematic prostate biopsy improves prostate cancer detection and correlation with the whole mount histopathology in biopsy naïve and previous negative biopsy patients

OBJECTIVE: Guidelines for previous negative biopsy (PNB) cohorts with a suspicion of prostate cancer (PCa) after positive multiparametric (mp) magnetic-resonance-imaging (MRI) often favour the fusion-guided targeted prostate-biopsy (TB) only approach for Prostate Imaging-Reporting and Data System (PI-RADS) ≥3 lesions. However, recommendations lack direct biopsy performance comparison within biopsy naïve (BN) vs. PNB patients and its prognostication of the whole mount pathology report (WMPR), respectively. We suppose, that the combination of TB and concomitant TRUS-systematic biopsy (SB) improves the PCa detection rate of PI-RADS 2, 3, 4 or 5 lesions and the International Society of Urological Pathology (ISUP)-grade predictability of the WMPR in BN- and PNB patients. METHODS: Patients with suspicious mpMRI, elevated prostate-specific-antigen and/or abnormal digital rectal examination were included. All PI-RADS reports were intramurally reviewed for biopsy planning. We compared the PI-RADS score substratified TB, SB or combined approach (TB/SB) associated BN- and PNB-PCa detection rate. Furthermore, we assessed the ISUP-grade variability between biopsy cores and the WMPR. RESULTS: According to BN (n = 499) vs. PNB (n = 314) patients, clinically significant (cs) PCa was detected more frequently by the TB/SB approach (62 vs. 43%) than with the TB (54 vs. 34%) or SB (57 vs. 34%) (all p < 0.0001) alone. Furthermore, we observed that the TB/SB strategy detects a significantly higher number of csPCa within PI-RADS 3, 4 or 5 reports, both in BN and PNB men. In contrast, applied biopsy techniques were equally effective to detect csPCa within PI-RADS 2 lesions. In case of csPCa diagnosis the TB approach was more often false-negative in PNB patients (BN 11% vs. PNB 19%; p = 0.02). The TB/SB technique showed in general significantly less upgrading, whereas a higher agreement was only observed for the total and BN patient cohort. CONCLUSION: Despite csPCa is more frequently found in BN patients, the TB/SB method always detected a significantly higher number of csPCa within PI-RADS 3, 4 or 5 reports of our BN and PNB group. The TB/SB strategy predicts the ISUP-grade best in the total and BN cohort and in general shows the lowest upgrading rates, emphasizing its value not only in BN but also PNB patients

The epidemiology of pertussis in Germany: past and present

<p>Abstract</p> <p>Background</p> <p>Current and past pertussis epidemiology in the two parts of Germany is compared in the context of different histories of vaccination recommendations and coverage to better understand patterns of disease transmission.</p> <p>Methods</p> <p>Available regional pertussis surveillance and vaccination coverage data, supplemented by a literature search for published surveys as well as official national hospital and mortality statistics, were analyzed in the context of respective vaccination recommendations from 1964 onwards.</p> <p>Results</p> <p>Routine childhood pertussis vaccination was recommended in the German Democratic Republic (GDR) from 1964 and in former West German states (FWG) from 1969, but withdrawn from 1974–1991 in FWG. Pertussis incidence declined to <1 case/100.000 inhabitants in GDR prior to reunification in 1991, while in FWG, where pertussis was not notifiable after 1961, incidence was estimated at 160–180 cases/100.000 inhabitants in the 1970s-1980s. Despite recommendations for universal childhood immunization in 1991, vaccination coverage decreased in former East German States (FEG) and increased only slowly in FWG. After introduction of acellular pertussis vaccines in 1995, vaccination coverage increased markedly among younger children, but remains low in adolescents, especially in FWG, despite introduction of a booster vaccination for 9–17 year olds in 2000. Reported pertussis incidence increased in FEG to 39.3 cases/100.000 inhabitants in 2007, with the proportion of adults increasing from 20% in 1995 to 68% in 2007. From 2004–2007, incidence was highest among 5–14 year-old children, with a high proportion fully vaccinated according to official recommendations, which did not include a preschool booster until 2006. Hospital discharge statistics revealed a ~2-fold higher pertussis morbidity among infants in FWG than FEG.</p> <p>Conclusion</p> <p>The shift in pertussis morbidity to older age groups observed in FEG is similar to reports from other countries with longstanding vaccination programs and suggests that additional booster vaccination may be necessary beyond adolescence. The high proportion of fully vaccinated cases in older children in FEG suggests waning immunity 5–10 years after primary immunisation in infancy. The higher incidence of pertussis hospitalisations in infants suggests a stronger force of infection in FWG than FEG. Nationwide pertussis reporting is required for better evaluation of transmission patterns and vaccination policy in both parts of Germany.</p

Grey wolf genomic history reveals a dual ancestry of dogs

The grey wolf (Canis lupus) was the first species to give rise to a domestic population, and they remained widespread throughout the last Ice Age when many other large mammal species went extinct. Little is known, however, about the history and possible extinction of past wolf populations or when and where the wolf progenitors of the present-day dog lineage (Canisfamiliaris) lived(1-8). Here we analysed 72 ancient wolf genomes spanning the last 100,000 years from Europe, Siberia and North America. We found that wolf populations were highly connected throughout the Late Pleistocene, with levels of differentiation an order of magnitude lower than they are today. This population connectivity allowed us to detect natural selection across the time series, including rapid fixation of mutations in the gene IFT8840,000-30,000 years ago. We show that dogs are overall more closely related to ancient wolves from eastern Eurasia than to those from western Eurasia, suggesting a domestication process in the east. However, we also found that dogs in the Near East and Africa derive up to half of their ancestry from a distinct population related to modern southwest Eurasian wolves, reflecting either an independent domestication process or admixture from local wolves. None of the analysed ancient wolf genomes is a direct match for either of these dog ancestries, meaning that the exact progenitor populations remain to be located.Peer reviewe

Status of the BELLE II Pixel Detector

The Belle II experiment at the super KEK B-factory (SuperKEKB) in Tsukuba, Japan, has been collecting $e^+e^−$ collision data since March 2019. Operating at a record-breaking luminosity of up to $4.7×10^{34} cm^{−2}s^{−1}$, data corresponding to $424 fb^{−1}$ has since been recorded. The Belle II VerteX Detector (VXD) is central to the Belle II detector and its physics program and plays a crucial role in reconstructing precise primary and decay vertices. It consists of the outer 4-layer Silicon Vertex Detector (SVD) using double sided silicon strips and the inner two-layer PiXel Detector (PXD) based on the Depleted P-channel Field Effect Transistor (DePFET) technology. The PXD DePFET structure combines signal generation and amplification within pixels with a minimum pitch of $(50×55) μm^2$. A high gain and a high signal-to-noise ratio allow thinning the pixels to $75 μm$ while retaining a high pixel hit efficiency of about $99$. As a consequence, also the material budget of the full detector is kept low at $≈0.21$$\frac{X}{X_0}$ per layer in the acceptance region. This also includes contributions from the control, Analog-to-Digital Converter (ADC), and data processing Application Specific Integrated Circuits (ASICs) as well as from cooling and support structures. This article will present the experience gained from four years of operating PXD; the first full scale detector employing the DePFET technology in High Energy Physics. Overall, the PXD has met the expectations. Operating in the intense SuperKEKB environment poses many challenges that will also be discussed. The current PXD system remains incomplete with only 20 out of 40 modules having been installed. A full replacement has been constructed and is currently in its final testing stage before it will be installed into Belle II during the ongoing long shutdown that will last throughout 2023

Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMPV families with the pathogenic variants in the FOXF1 locus that arose on paternal chromosome 16. Interestingly, a combination of the severe cardiac defects, including hypoplastic left heart, and single umbilical artery were observed only in children with deletion CNVs involving FOXF1 and its upstream enhancer. Our data demonstrate that genomic imprinting at 16q24.1 plays an important role in variable ACDMPV manifestation likely through long-range regulation of FOXF1 expression, and may be also responsible for key phenotypic features of maternal uniparental disomy 16. Moreover, in one family, WES revealed a de novo missense variant in ESRP1, potentially implicating FGF signaling in the etiology of ACDMPV