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Treatment of peritoneal surface malignancies makes physicians face demanding and new-fangled problems, as there are many uncertain aspects considering the outcomes of affected patients’ prognoses. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are associated with favorable long-term outcomes in carefully selected patients with peritoneal metastases (PM). We aim to summarize the current results about the initial malignancies and their peritoneal spreads. The current literature has been scrutinized, and studies between 2016 and 2022 were included wherein long-term, progression-free (PFS), and overall survival (OS) data were considered relevant information. Medline, Embase, and Google Scholar have been the main sources. Hereby, we cover all the primer malignancies: gastric, ovarian, and colorectal cancers with peritoneal metastases (PM), malignant peritoneal mesothelioma, and pseudomyxoma peritonei. Examining the advances in the current peer-reviewed literature about the indications of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), target groups, risk factors, and other influencing elements, we intend to provide a complex state-of-the-art report, establishing the relevant aspects of that emerging treatment method.

Many suggestions for dealing with the so-called replication crisis in psychology revolve around the idea that better and more complex statistical-mathematical tools or stricter procedures are required in order to obtain reliable findings and prevent cheating or publication biases. While these aspects may play an exacerbating role, we interpret the replication crisis primarily as an epistemological crisis in psychology caused by an inadequate fit between the ontic nature of the psyche and the quantitative approach. On the basis of the philosophers of science Karl Popper, Thomas Kuhn, and Imre Lakatos we suggest that the replication crisis is therefore a symptom of a fundamental problem in psychology, but at the same time it is also an opportunity to advance psychology as a science. In a first step, against the background of Popper's Critical Rationalism, the replication crisis is interpreted as an opportunity to eliminate inaccurate theories from the pool of theories and to correct problematic developments. Continuing this line of thought, in an interpretation along the lines of Thomas Kuhn, the replication crisis might signify a model drift or even model crisis, thus possibly heralding a new paradigm in psychology. The reasons for this are located in the structure of academic psychology on the basis of Lakatos's assumption about how sciences operate. Accordingly, one hard core that lies at the very basis of psychology may be found in the assumption that the human psyche can and is to be understood in quantitative terms. For this to be possible, the ontic structure of the psyche, i.e., its very nature, must also in some way be quantitatively constituted. Hence, the replication crisis suggests that the ontic structure of the psyche in some way (also) contains a non-quantitative dimension that can only be grasped incompletely or fragmentarily using quantitative research methods. Fluctuating and inconsistent results in psychology could therefore also be the expression of a mismatch between the ontic level of the object of investigation and the epistemic level of the investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mayrhofer, Büchner and Hevesi.)

Physiological muscle contraction requires an intact ligand gating mechanism of the ryanodine receptor 1 (RyR1), the Ca 2+ -release channel of the sarcoplasmic reticulum. Some mutations impair the gating and thus cause muscle disease. The RyR1 mutation T4706M is linked to a myopathy characterized by muscle weakness. Although, low expression of the T4706M RyR1 protein can explain in part the symptoms, little is known about the function RyR1 channels with this mutation. In order to learn whether this mutation alters channel function in a manner that can account for the observed symptoms, we examined RyR1 channels isolated from mice homozygous for the T4709M (TM) mutation at the single channel level. Ligands, including Ca 2+ , ATP, Mg 2+ and the RyR inhibitor dantrolene were tested. The full conductance of the TM channel was the same as that of wild type (wt) channels and a population of partial open (subconductive) states were not observed. However, two unique sub-populations of TM RyRs were identified. One half of the TM channels exhibited high open probability at low (100 nM) and high (50 μM) cytoplasmic [Ca 2+ ], resulting in Ca 2+ -insensitive, constitutively high P o channels. The rest of the TM channels exhibited significantly lower activity within the physiologically relevant range of cytoplasmic [Ca 2+ ], compared to wt. TM channels retained normal Mg 2+ block, modulation by ATP, and inhibition by dantrolene. Together, these results suggest that the TM mutation results in a combination of primary and secondary RyR1 dysfunctions that contribute to disease pathogenesis., (© 2023. Springer Nature Limited.)

Cardiac diseases are the leading causes of death, with a growing number of cases worldwide, posing a challenge for both healthcare and research. Therefore, the most relevant aim of cardiac research is to unravel the molecular pathomechanisms and identify new therapeutic targets. Cardiac ryanodine receptor (RyR2), the Ca 2+ release channel of the sarcoplasmic reticulum, is believed to be a good therapeutic target in a group of certain heart diseases, collectively called cardiac ryanopathies. Ryanopathies are associated with the impaired function of the RyR, leading to heart diseases such as congestive heart failure (CHF), catecholaminergic polymorphic ventricular tachycardia (CPVT), arrhythmogenic right ventricular dysplasia type 2 (ARVD2), and calcium release deficiency syndrome (CRDS). The aim of the current review is to provide a short insight into the pathological mechanisms of ryanopathies and discuss the pharmacological approaches targeting RyR2.