SPING Block Analgesia in Non-Operative Management of Proximal Femur Fractures in Older Adults Living with Frailty: A Retrospective Cohort Study.

: Spinal Phenol IN Glycerol (SPING) block is a novel palliative pain treatment for the non-operative management of proximal femur fractures (PFFs) in older adults living with frailty. Effective pain management that aligns with patient preferences and minimizes opioid use is critical in this setting. This study evaluated the patient, safety, and process outcomes of SPING block in this population.

Gender gap-Gender-specific development in the field of obstetrics and gynecology in Germany in the last 20 years.

Background: Gender Gap refers to differences between men and women in terms of access to medical education, career development, and leadership positions in medical practice and research. Although women now make up most medical school graduates in many countries, they are often underrepresented in higher positions.

Objective: The aim of this study is therefore to analyze the gender-specific development in the field of Obstetrics and Gynecology in Germany over the past 20 years and to survey the current .

Students' and lecturers' perspectives on the implementation of online learning in medical education due to COVID-19 in Germany: a cross-sectional pilot study.

Background: During the coronavirus disease 2019 (COVID-19) crisis, many things changed in universities around the world. In-person learning was not possible. Instead, courses were offered in digital form.

Digital teaching tools in sports medicine: A randomized control trial comparing the effectiveness of virtual seminar and virtual fishbowl teaching method in medical students.

Background: Since the COVID-19 pandemic, the demand for online courses has increased enormously. Therefore, finding new methods to improve medical education is imperative.

Objective: The aim of this study was to compare the self-reports of the individual student-centered virtual teaching techniques (seminar versus fishbowl) in a group of medical students.

Causes of Death in the Seriously Injured -Why do Severely Injured Patients Die Today?

Hintergrund: Trauma ist die häufigste Todesursache bei unter 45-Jährigen und trotzdem gibt es nur wenig Daten zu den genauen Todesursachen Schwerverletzter nach Klinikeinlieferung in Deutschland aus den letzten 10 Jahren. Ziel der Arbeit ist 1. eine Auswertung der Daten der verstorbenen Schwerverletzten eines überregionalen TraumaZentrums aus den letzten 10 Jahren.

[The influence of occupational activity on diseases of the musculoskeletal system of the upper extremity].

Introduction: Diseases of the musculoskeletal system of the upper extremity are the reason for increasing sickness-related absenteeism among the working population.

Objective: The aim of this study is to investigate the influence of occupational dependence on the development of musculoskeletal disorders of the upper extremities and to present health-related risks in addition to occupation-specific factors.

Materials And Methods: We included 1070 patients who underwent surgical rotator cuff (RC) reconstruction for an RC lesion between 2016 and 2019.

Digitization in gynecology and obstetrics in times of COVID-19: Results of a national survey.

Introduction: In the COVID-19 pandemic, many consultations had to be cancelled, postponed, or converted to a virtual format. The use of telemedicine in the management of Women's Health Care could support doctors (tele-gynecology). This study analyses the use and perception of telemedicine applications among gynecologists in Germany.

A novel perspective on pharmaceutical R&D costs: opportunities for reductions.

Introduction: R&D costs as an element of medicines' pricing play a prominent role in the discussions regarding the affordability of medicine. This paper investigates the details of R&D costs and the potential for reductions.

Areas Covered: The manuscript focuses on the constitution of R&D costs in relation to medicines' pricing and its potential developments.

Telemedicine as a Therapeutic Option in Sports Medicine: Results of a Nationwide Cross-Sectional Study among Physicians and Patients in Germany.

Background: Worldwide, the number of treatments in the field of sports medicine is increasing. However, the COVID-19 pandemic has changed everyday life. Many consultations had to be cancelled, postponed, or converted to a virtual format.

A novel sustained-release cysteamine bitartrate formulation for the treatment of cystinosis: Pharmacokinetics and safety in healthy male volunteers.

The strict intake regimen of cysteamine bitartrate formulations, associated with side effects, is a concern for the treatment compliance in cystinosis therapy. Therefore, there is a need for a cysteamine formulation with an improved pharmacokinetic profile. This study investigated the pharmacokinetics, safety and tolerability of a new sustained-release cysteamine dosage form, PO-001, in healthy volunteers.

Cross-reactivity between tumor MHC class I-restricted antigens and an enterococcal bacteriophage.

Intestinal microbiota have been proposed to induce commensal-specific memory T cells that cross-react with tumor-associated antigens. We identified major histocompatibility complex (MHC) class I-binding epitopes in the tail length tape measure protein (TMP) of a prophage found in the genome of the bacteriophage Mice bearing harboring this prophage mounted a TMP-specific H-2K-restricted CD8 T lymphocyte response upon immunotherapy with cyclophosphamide or anti-PD-1 antibodies. Administration of bacterial strains engineered to express the TMP epitope improved immunotherapy in mice.

Phosphorylation of eukaryotic initiation factor-2α (eIF2α) in autophagy.

The integrated stress response is characterized by the phosphorylation of eukaryotic initiation factor-2α (eIF2α) on serine 51 by one out of four specific kinases (EIF2AK1 to 4). Here we provide three series of evidence suggesting that macroautophagy (to which we refer to as autophagy) induced by a variety of distinct pharmacological agents generally requires this phosphorylation event. First, the induction of autophagic puncta by various distinct compounds was accompanied by eIF2α phosphorylation on serine 51.

Immunosuppression by Mutated Calreticulin Released from Malignant Cells.

Mutations affecting exon 9 of the CALR gene lead to the generation of a C-terminally modified calreticulin (CALR) protein that lacks the KDEL endoplasmic reticulum (ER) retention signal and consequently mislocalizes outside of the ER where it activates the thrombopoietin receptor in a cell-autonomous fashion, thus driving myeloproliferative diseases. Here, we used the retention using selective hooks (RUSH) assay to monitor the trafficking of CALR. We found that exon-9-mutated CALR was released from cells in response to the biotin-mediated detachment from its ER-localized hook, in vitro and in vivo.

A Conserved Noncoding Locus Regulates Random Monoallelic Xist Expression across a Topological Boundary.

cis-Regulatory communication is crucial in mammalian development and is thought to be restricted by the spatial partitioning of the genome in topologically associating domains (TADs). Here, we discovered that the Xist locus is regulated by sequences in the neighboring TAD. In particular, the promoter of the noncoding RNA Linx (LinxP) acts as a long-range silencer and influences the choice of X chromosome to be inactivated.

Artificial tethering of LC3 or p62 to organelles is not sufficient to trigger autophagy.

The retention using selective hooks (RUSH) system allows to retain a target protein fused to green fluorescent protein (GFP) and a streptavidin-binding peptide (SBP) due to the interaction with a molar excess of streptavidin molecules ("hooks") targeted to selected subcellular compartments. Supplementation of biotin competitively disrupts the interaction between the SBP moiety and streptavidin, liberating the chimeric target protein from its hooks, while addition of avidin causes the removal of biotin from the system and reestablishes the interaction. Based on this principle, we engineered two chimeric proteins involved in autophagy, namely microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B, best known as LC3) and sequestosome-1 (SQSTM1, best known as p62) to move them as SBP-GFP-LC3 and p62-SBP-GFP at will between the cytosol and two different organelles, the endoplasmic reticulum (ER) and the Golgi apparatus.

Acyl-CoA-Binding Protein Is a Lipogenic Factor that Triggers Food Intake and Obesity.

Autophagy facilitates the adaptation to nutritional stress. Here, we show that short-term starvation of cultured cells or mice caused the autophagy-dependent cellular release of acyl-CoA-binding protein (ACBP, also known as diazepam-binding inhibitor, DBI) and consequent ACBP-mediated feedback inhibition of autophagy. Importantly, ACBP levels were elevated in obese patients and reduced in anorexia nervosa.

Identification of pharmacological inhibitors of conventional protein secretion.

The retention using selective hooks (RUSH) system allows to withhold a fluorescent biosensor such as green fluorescent protein (GFP) fused to a streptavidin-binding peptide (SBP) by an excess of streptavidin molecules that are addressed to different subcellular localizations. Addition of biotin competitively disrupts this interaction, liberating the biosensor from its hook. We constructed a human cell line co-expressing soluble secretory-SBP-GFP (ss-SBP-GFP) and streptavidin within the endoplasmic reticulum (ER) lumen and then used this system to screen a compound library for inhibitors of the biotin-induced release of ss-SBP-GFP via the conventional Golgi-dependent protein secretion pathway into the culture supernatant.

Epigenetic anticancer agents cause HMGB1 release .

A systematic search for anticancer agents that may induce the release of high mobility group box 1 (HMGB1) protein from cells into the extracellular space has led to the identification of several drugs capable of elevating plasma HMGB1 levels , in mice. Such agents include bona-fide immunogenic cell death inducers such as oxaliplatin, as well as a series of epigenetic modifiers, namely azacitidine, decitabine, and suberoylanilide hydroxamic acid (SAHA).

Photodynamic therapy with redaporfin targets the endoplasmic reticulum and Golgi apparatus.

Preclinical evidence depicts the capacity of redaporfin (Redp) to act as potent photosensitizer, causing direct antineoplastic effects as well as indirect immune-dependent destruction of malignant lesions. Here, we investigated the mechanisms through which photodynamic therapy (PDT) with redaporfin kills cancer cells. Subcellular localization and fractionation studies based on the physicochemical properties of redaporfin revealed its selective tropism for the endoplasmic reticulum (ER) and the Golgi apparatus (GA).

Aspirin Recapitulates Features of Caloric Restriction.

The age-associated deterioration in cellular and organismal functions associates with dysregulation of nutrient-sensing pathways and disabled autophagy. The reactivation of autophagic flux may prevent or ameliorate age-related metabolic dysfunctions. Non-toxic compounds endowed with the capacity to reduce the overall levels of protein acetylation and to induce autophagy have been categorized as caloric restriction mimetics (CRMs).

Identification of pharmacological agents that induce HMGB1 release.

The translocation of the protein high mobility group box 1 (HMGB1) from the nucleus to the cytoplasm and its secretion or passive release through the permeabilized plasma membrane, constitutes a major cellular danger signal. Extracellular HMGB1 can interact with pattern recognition receptors to stimulate pro-inflammatory and immunostimulatory pathways. Here, we developed a screening assay to identify pharmacological agents endowed with HMGB1 releasing properties.

Extracellular nucleosides and nucleotides as immunomodulators.

Some anticancer agents induce immunogenic cell death that is accompanied by the emission of danger signals into the tumor microenvironment, thus attracting and activating innate immune effectors and finally inducing anticancer immunity. The release of extracellular nucleosides such as adenosine triphosphate (ATP) from the tumor in response to anticancer therapy plays a pivotal role in the attraction of antigen presenting cells and the activation of inflammasome-mediated proinflammatory cascades. In contrast, the ectonucleotidase-catalyzed phosphohydrolysis of nucleotides to nucleosides reduces the extracellular availability of nucleotides, hence limiting the recruitment and activation of antigen-presenting cells.