Distinct trajectories of long-term symptom severity in pediatric obsessive–compulsive disorder during and after stepped-care treatment     

Sanne Jensen  Davíð R.M.A. Højgaard  Katja A. Hybel  Erik Lykke Mortensen  Gudmundur Skarphedinsson  Karin Melin  Tord Ivarsson  Judith Becker Nissen  Bernhard Weidle  Robert Valderhaug  Nor Christian Torp  Kitty Dahl  Scott Compton  Per Hove Thomsen 《Journal of child psychology and psychiatry, and allied disciplines》2020,61(9):969-978

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Gustavo de Alencastro  Francesco Puzzo  Mara Pavel-Dinu  Feijie Zhang  Sirika Pillay  Karim Majzoub  Matthew Tiffany  Hagoon Jang  Adam Sheikali  M. Kyle Cromer  Ruhikanta Meetei  Jan E. Carette  Matthew H. Porteus  Katja Pekrun  Mark A. Kay 《Molecular therapy》2021,29(3):1016-1027

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Arne Sattler  Eva Schrezenmeier  Ulrike A. Weber  Alexander Potekhin  Friederike Bachmann  Henriette Straub-Hohenbleicher  Klemens Budde  Elena Storz  Vanessa Proß  Yasmin Bergmann  Linda M.L. Thole  Caroline Tizian  Oliver Hlsken  Andreas Diefenbach  Hubert Schrezenmeier  Bernd Jahrsdrfer  Tomasz Zemojtel  Katharina Jechow  Christian Conrad  Sren Lukassen  Diana Stauch  Nils Lachmann  Mira Choi  Fabian Halleck  Katja Kotsch 《The Journal of clinical investigation》2021,131(14)

Novel mRNA-based vaccines have been proven to be powerful tools in combating the global pandemic caused by SARS-CoV-2, with BNT162b2 (trade name: Comirnaty) efficiently protecting individuals from COVID-19 across a broad age range. Still, it remains largely unknown how renal insufficiency and immunosuppressive medication affect development of vaccine-induced immunity. We therefore comprehensively analyzed humoral and cellular responses in kidney transplant recipients after the standard second vaccination dose. As opposed to all healthy vaccinees and the majority of hemodialysis patients, only 4 of 39 and 1 of 39 transplanted individuals showed IgA and IgG seroconversion at day 8 ± 1 after booster immunization, with minor changes until day 23 ± 5, respectively. Although most transplanted patients mounted spike-specific T helper cell responses, frequencies were significantly reduced compared with those in controls and dialysis patients and this was accompanied by a broad impairment in effector cytokine production, memory differentiation, and activation-related signatures. Spike-specific CD8⁺ T cell responses were less abundant than their CD4⁺ counterparts in healthy controls and hemodialysis patients and almost undetectable in transplant patients. Promotion of anti-HLA antibodies or acute rejection was not detected after vaccination. In summary, our data strongly suggest revised vaccination approaches in immunosuppressed patients, including individual immune monitoring for protection of this vulnerable group at risk of developing severe COVID-19.  相似文献   

    

Katja Apelt  Susan M. White  Hyun Suk Kim  Jung-Eun Yeo  Angela Kragten  Annelotte P. Wondergem  Martin A. Rooimans  Romn Gonzlez-Prieto  Wouter W. Wiegant  Sebastian Lunke  Daniel Flanagan  Sarah Pantaleo  Catherine Quinlan  Winita Hardikar  Haico van Attikum  Alfred C.O. Vertegaal  Brian T. Wilson  Rob M.F. Wolthuis  Orlando D. Schrer  Martijn S. Luijsterburg 《The Journal of experimental medicine》2021,218(3)

ERCC1-XPF is a multifunctional endonuclease involved in nucleotide excision repair (NER), interstrand cross-link (ICL) repair, and DNA double-strand break (DSB) repair. Only two patients with bi-allelic ERCC1 mutations have been reported, both of whom had features of Cockayne syndrome and died in infancy. Here, we describe two siblings with bi-allelic ERCC1 mutations in their teenage years. Genomic sequencing identified a deletion and a missense variant (R156W) within ERCC1 that disrupts a salt bridge below the XPA-binding pocket. Patient-derived fibroblasts and knock-in epithelial cells carrying the R156W substitution show dramatically reduced protein levels of ERCC1 and XPF. Moreover, mutant ERCC1 weakly interacts with NER and ICL repair proteins, resulting in diminished recruitment to DNA damage. Consequently, patient cells show strongly reduced NER activity and increased chromosome breakage induced by DNA cross-linkers, while DSB repair was relatively normal. We report a new case of ERCC1 deficiency that severely affects NER and considerably impacts ICL repair, which together result in a unique phenotype combining short stature, photosensitivity, and progressive liver and kidney dysfunction.  相似文献   

    

Maarten A.J. De Smet  Alessio Lissoni  Timur Nezlobinsky  Nan Wang  Eef Dries  Marta Prez-Hernndez  Xianming Lin  Matthew Amoni  Tim Vervliet  Katja Witschas  Eli Rothenberg  Geert Bultynck  Rainer Schulz  Alexander V. Panfilov  Mario Delmar  Karin R. Sipido  Luc Leybaert 《The Journal of clinical investigation》2021,131(7)

Cx43, a major cardiac connexin, forms precursor hemichannels that accrue at the intercalated disc to assemble as gap junctions. While gap junctions are crucial for electrical conduction in the heart, little is known about the potential roles of hemichannels. Recent evidence suggests that inhibiting Cx43 hemichannel opening with Gap19 has antiarrhythmic effects. Here, we used multiple electrophysiology, imaging, and super-resolution techniques to understand and define the conditions underlying Cx43 hemichannel activation in ventricular cardiomyocytes, their contribution to diastolic Ca²⁺ release from the sarcoplasmic reticulum, and their impact on electrical stability. We showed that Cx43 hemichannels were activated during diastolic Ca²⁺ release in single ventricular cardiomyocytes and cardiomyocyte cell pairs from mice and pigs. This activation involved Cx43 hemichannel Ca²⁺ entry and coupling to Ca²⁺ release microdomains at the intercalated disc, resulting in enhanced Ca²⁺ dynamics. Hemichannel opening furthermore contributed to delayed afterdepolarizations and triggered action potentials. In single cardiomyocytes, cardiomyocyte cell pairs, and arterially perfused tissue wedges from failing human hearts, increased hemichannel activity contributed to electrical instability compared with nonfailing rejected donor hearts. We conclude that microdomain coupling between Cx43 hemichannels and Ca²⁺ release is a potentially novel, targetable mechanism of cardiac arrhythmogenesis in heart failure.  相似文献   

    

Praiseldy Langi Sasongko  Katja van den Hurk  Marian van Kraaij  Etiënne A. J. A. Rouwette  Vincent A. W. J. Marchau  Mart P. Janssen 《Transfusion》2021,61(8):2356-2367

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Sanna-Mari Manninen  Katja Kero  Katariina Perkonoja  Tero Vahlberg  Pivi Polo-Kantola 《Scandinavian journal of primary health care》2021,39(3):279

Objective Although sexual problems are common, they are rarely brought up in appointments with general practitioners (GPs). We aimed to assess the barriers that hinder GPs from bringing up sexual health issues and to evaluate the need for education on sexual medicine. Design A web-based questionnaire was used. Setting Four fields were included: A) the self-reported competence in discussing sexual health and treating patients with these issues, B) the barriers to bringing up patients’ sexual health problems, C) the source of education on sexual medicine and D) the need for education on sexual medicine. Subjects A random sample of 1000 GPs in Finland (a response rate of 43.5%, n = 402). Main outcome measures GPs’ self-assessed competence in discussing and treating sexual health issues, related barriers to bringing up the topic and the reported need for education. Results The main reasons reported for not bringing up sexual health issues were shortness of the appointment time (85.6%), a lack of knowledge (83.6%) and a lack of experience with sexual medicine (81.8%). The male GPs reported better competence in discussing the issues and treating male patients, whereas the female GPs reported better competence in discussing the issues with female patients. No differences emerged between genders regarding treating female patients. Nearly 90% of the GPs expressed needing more education about sexual medicine. Conclusions Although the GPs reported good competence in discussing sexual health issues with their patients, several barriers to bringing up sexual health issues emerged. Continuing education was desired and could lessen these barriers.

Key points

• Only a few studies have evaluated the competence of general practitioners (GPs) in addressing sexual health issues with their patients.
• In our study, the GPs reported a high competence in discussing patients’ sexual health issues regardless of the patient’s gender.
• However, several barriers to bringing up sexual health issues in appointments emerged.
• A majority of the GPs expressed a need for continuing education about sexual medicine.

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Chris D. Hermann  Benjamin Schoeps  Celina Eckfeld  Enkhtsetseg Munkhbaatar  Lukas Kniep  Olga Prokopchuk  Nils Wirges  Katja Steiger  Daniel Hußler  Percy Knolle  Emily Poulton  Rama Khokha  Barbara T. Grünwald  Ihsan Ekin Demir  Achim Krüger 《The Journal of experimental medicine》2021,218(11)

Sex disparity in cancer is so far inadequately considered, and components of its basis are rather unknown. We reveal that male versus female pancreatic cancer (PC) patients and mice show shortened survival, more frequent liver metastasis, and elevated hepatic metastasis-promoting gene expression. Tissue inhibitor of metalloproteinases 1 (TIMP1) was the secreted factor with the strongest male-biased expression in patient-derived pancreatic tumors. Male-specific up-regulation of systemic TIMP1 was demonstrated in PC mouse models and patients. Using TIMP1-competent and TIMP1-deficient PC mouse models, we established a causal role of TIMP1 in determining shortened survival and increased liver metastasis in males. Observing TIMP1 expression as a risk parameter in males led to identification of a subpopulation exhibiting increased TIMP1 levels (T1^HI males) in both primary tumors and blood. T1^HI males showed increased risk for liver metastasis development not only in PC but also in colorectal cancer and melanoma. This study reveals a lifestyle-independent sex disparity in liver metastasis and may open new avenues toward precision medicine.  相似文献   

    

Rainer Stanek;Eva-Maria Pointner;Katja Canigiani de Cerchi;Gerhard Pomberger;Thomas Benkoe;Thomas Hölzenbein;Mehdi Mousavi; 《Clinical Case Reports》2024,12(8):e9188

Negative pressure wound therapy (NPWT) aided in the management of complex soft tissue injury in a 14-year-old girl by managing moisture, reducing oedema, and stimulating wound granulation less than 2 months after the accident and prepared the skin for skin grafting, thus successfully saving the limb.  相似文献   

    

Stefanie Schreiber MD  Grazyna Debska‐Vielhaber PhD  Susanne Abdulla MD  Judith Machts MSc  Frank Schreiber MSc  Siegfried Kropf PhD  Peter KÖrtvelyessy MD  Sonja KÖrner MD  Katja Kollewe MD  Susanne Petri MD  Reinhard Dengler MD  Wolfram S. Kunz PhD  Peter J. Nestor MD  Stefan Vielhaber MD 《Muscle & nerve》2018,57(2):273-278

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