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Starving infecund widow spiders maintain sexual attractiveness and trade off safety for enhanced prey capture
Get PDFStarving animals must balance their resources between immediate survival and future reproduction. False widow spiders, Steatoda grossa, inhabit indoor settings with scarce prey. Here, we investigated the effects of lengthy starvation on the physiology, web architecture, sexual signaling, and reproductive success of S. grossa females. Compared to well-fed females, starving females (1) lost body mass faster, (2) had lower survival, (3) produced more silk for prey capture than for safety, and (4) deposited less contact pheromone components on their webs but accelerated their hydrolysis to mate-attractant components. As starving females became infecund – but still attracted and copulated with males – they misguided males that would gain reproductive fitness by selecting fecund females. Whether starving females store sperm and potentially regain fecundity upon feeding is still unknown. Our study shows how prey shortage shapes sexual signaling, predation, and reproductive behavior of S. grossa females that seem to engage in deceptive signaling
Sector-Wide Approach (SWAp) in Healthcare—A Mixed-Methods Assessment of Health SWAps in Nepal and Bangladesh
Get PDFBackground: The sector-wide approach (SWAp) is an instrument of cooperation between external development partners (EDPs) and the government of a country. Its main purpose is the coordination, alignment and harmonisation of activities between EDPs and between EDPs and the respective government by covering the entire sector with one major programme. Methods: The main objective of this paper is to analyse the performance of the SWAps in two countries and draw conclusions about the appropriateness of SWAps as financing instruments in the healthcare sector under certain conditions. This paper analyses the development and achievements of the SWAp in healthcare of Bangladesh and Nepal in order to gain insights into the development and relevance of SWAps in the healthcare sectors of low- and lower-middle-income countries in general. We scrutinised the respective documents and conducted qualitative interviews with key stakeholders of the country’s sectors. The design of the questionnaires and the analysis of the interviews were built utilising a framework model reflecting the DAC criteria of development cooperation and the principles of the Declarations of Paris and Accra. Findings: The SWAps in Nepal and Bangladesh began rather early and cover about 20 years of cooperation. The components and interventions of SWAps were quite relevant for the health of the population, and their implementation was effective and efficient. The cohesion between partners strongly improved. However, for both countries, the interview partners do not perceive SWAps as the future of healthcare financing. Conclusions: SWAps were an appropriate instrument of cooperation between the respective governments and EDPs for almost two decades. However, as the share of government budgets in the sector finance has strongly increased and the management capacity of the respective ministries has gone up, there will come a point in time where EDPs can focus more on financing and implementing innovations instead of standard care
Sphingosine‐1‐phosphate receptor type 4 is critically involved in the regulation of peritoneal B‐1 cell trafficking and distribution in vivo
Get PDFB‐1 cells are crucially involved in immune defense and regulation of inflammation and autoimmunity. B‐1 cells are predominantly located in the peritoneal and pleural cavities, although body cavity B‐1 cells recirculate systemically under steady‐state conditions. The chemokines CXCL12 and CXCL13 have been identified as the main regulators of peritoneal B‐cell trafficking. In mice deficient for sphingosine‐1‐phosphate receptor 4 (S1PR4), B‐1a and B‐1b cell numbers are reduced in the peritoneal cavity by an unknown mechanism. In this study, we show that S1PR4‐mediated S1P signaling modifies the chemotactic response of peritoneal B cells to CXCL13 and CXCL12 in vitro. In vivo, S1PR4‐mediated S1P signaling affects both immigration into and emigration from the peritoneal cavity. Long‐term reconstitution experiments of scid mice with wt or s1pr4–/– peritoneal B cells revealed a distinct distributional pattern in secondary lymphoid organs. As a functional consequence, both plasmatic and mucosal IgM levels, the main product of B‐1a cells, are reduced in mice reconstituted with s1pr4–/– peritoneal cells. In summary, our data identify S1PR4 as the second S1P receptor (besides S1PR1), which is critically involved in the regulation of peritoneal B‐1 cell function
How Do Quality of Life (QoL) and Symptom Burden Evolve in Inpatient Palliative Care (PC) Patients following One Week of Care in a Specialized Palliative Care Unit (PCU)? A Comparison of Two Groups, with One Receiving Specialized Outpatient Palliative Care Prior to Admission
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The study aimed to assess changes in quality of life and symptom burden among palliative care patients during one week of inpatient care in a palliative care unit, comparing those who had prior outpatient palliative care with those who did not. Using the EORTC QLQ-C30 instrument, patients were evaluated at admission (T0) and one week later (T1). Patients in both groups showed significant and clinically meaningful improvements in global health/QoL, emotional functioning, nausea, vomiting, pain, and insomnia. The study suggests that even brief inpatient palliative care can substantially enhance the quality of life and reduce symptom burden, benefiting patients regardless of prior outpatient support.
Abstract
Purpose: This study sought to investigate changes in quality of life (QoL) and symptom burden among palliative care patients undergoing one week of inpatient care in a specialized palliative care unit (PCU). The patient population was stratified into two groups, with one group pretreated from pre-admission palliative care (PC) provided by an outpatient multidisciplinary PC team, while the other group did not receive such support prior to admission. Although the average duration of treatment at a PCU in Germany is 1–2 weeks, the question also arises as to whether a significant improvement in symptom burden and QoL can be expected after just one week of PC in a PCU. Methods: PC patients with various cancer entities were prospectively included in a non-randomized study. Patients in group 1 received outpatient specialized PC prior to admission, while patients in group 2 did not. Over an 8-month period, we gathered data from one academic cancer center, utilizing the EORTC QLQ-C30, one of the most widely used patient-reported outcome (PRO) instruments to assess health-related QoL in cancer patients. Patients completed the QLQ-C30 at T0 (admission or one day later) and T1 (one week later), enabling the assessment of potential changes in their QoL and symptom burden over time. Results: A total of 103 patients (51.5% male) were enrolled (group 1: 42%, group 2: 58%). At T0, there were no significant differences regarding QLQ-C30 scores between groups 1 and 2, except from global health/QoL (group 1 mean 20.7, group 2 mean 25.6, p = 0.026). Over the course of one week several significant and clinically relevant changes were found: Emotional functioning demonstrated an uplift in both groups (group 1: mean 41.5 IQR 33 vs. 53.1 IQR 50, p = 0.014, group 2: mean 48.2 IQR 46 vs. 56.8 IQR 58, p = 0.029), as did the global health status (group 1: M 20.7 IQR 17 vs. 36.2 IQR 33, p < 0.001, group 2: M 25.6 IQR 25 vs. 35.3 IQR 33, p < 0.001). Nausea and vomiting showed a reduction (group 1: M 29.9 IQR 17 vs. 6.8 IQR 0, p < 0.001, group 2: M 22.6 IQR 17 vs. 8.2 IQR 0, p < 0.001), along with a notable decline in pain (group 1: M 67.4 IQR 67 vs. 25.3 IQR 17, p < 0.001, group 2: M 73.1 IQR 83 vs. 29.7 IQR 17, p < 0.001). A decrease was observed in insomnia (group 1: M 63.6 IQR 67 vs. 27.6 IQR 33, p < 0.001, group 2: M 60.1 IQR 67 vs. 27.6 IQR 33, p < 0.001). There were no significant differences between groups 1 and 2 in the extent of improvement in the various symptom scales from T0 to T1. Conclusion: The findings of our study demonstrate that QoL and several symptoms prevalent in cancer patients cared for in the PCU experienced significant enhancement over the span of just one week. Both groups, patients receiving specialized outpatient PC prior to admission and those without, equally benefited from inpatient PC. All mentioned changes from T0 to T1 are considered not only significant but clinically relevant
Circulating microRNA miR-425-5p Associated with Brain White Matter Lesions and Inflammatory Processes
Get PDFWhite matter lesions (WML) emerge as a consequence of vascular injuries in the brain. While they are commonly observed in aging, associations have been established with neurodegenerative and neurological disorders such as dementia or stroke. Despite substantial research efforts, biological mechanisms are incomplete and biomarkers indicating WMLs are lacking. Utilizing data from the population-based Study of Health in Pomerania (SHIP), our objective was to identify plasma-circulating micro-RNAs (miRNAs) associated with WMLs, thus providing a foundation for a comprehensive biological model and further research. In linear regression models, direct association and moderating factors were analyzed. In 648 individuals, we identified hsa-miR-425-5p as directly associated with WMLs. In subsequent analyses, hsa-miR-425-5p was found to regulate various genes associated with WMLs with particular emphasis on the SH3PXD2A gene. Furthermore, miR-425-5p was found to be involved in immunological processes. In addition, noteworthy miRNAs associated with WMLs were identified, primarily moderated by the factors of sex or smoking status. All identified miRNAs exhibited a strong over-representation in neurodegenerative and neurological diseases. We introduced hsa-miR-425-5p as a promising candidate in WML research probably involved in immunological processes. Mir-425-5p holds the potential as a biomarker of WMLs, shedding light on potential mechanisms and pathways in vascular dementia
Über mechanistische und kinetische Reaktivitätsstudien an wasserlöslichen, offenschaligen Bisdithiolenkomplexen der VI. Gruppe als Funktionsmodelle mononuklearer Molybdän- und Wolframenzyme
Get PDFDiese Arbeit liefert einen umfangreichen und faszinierenden Einblick in die wässrige Chemie von Bisdithiolenmolybdaten(IV,VI) und -wolframaten(IV,VI) als Funktionsmodelle mononuklearer Molybdän- und Wolframenzyme. Die Komplexität der beobachteten Reaktionspfade entspricht in keiner Weise der geradlinigen, fehlerfreien Reaktivität der biologischen Vorbilder, was die ausgeklügelte Bauweise des aktiven Zentrums dieser Enzymklasse besonders hervorhebt.
Über verschiedene Synthesestrategien wurden unterschiedliche, wasserlösliche Monooxidobisdithiolenmolybdate(IV) und -wolframate(IV) mit zyklisch- oder azyklisch-aliphatischen sowie aromatischen Dithiolenliganden dargestellt. Zudem konnte das erste wasserlösliche Dioxidobisdithiolenwolframat(VI) K2[WO2(vdt)2] erfolgreich isoliert und charakterisiert werden. Durch die spektroskopische und röntgendiffraktometrische Untersuchung der Festphasenstruktur dieser verschiedenen Bisdithiolenkomplexe wurde ein entscheidender Einfluss des Kaliumkations auf die elektronischen Eigenschaften der Metall-Liganden-Bindungen ersichtlich, der zu einer noch größeren Sensitivität gegenüber atmosphärischen Bedingungen führt.
Die Stabilität der Monooxidobisdithiolenkomplexe im wässrigen Medium korreliert sehr streng mit dem pH-Wert, wobei durch spektroskopische und theoretische Untersuchungen die Ursache auf die Protonierung des Oxidoliganden geführt wird. Hieraus resultiert infolge einer langsamen Desoxygenierung die Reorganisation zu Trisdithiolenkomplexen. Im Gegensatz zur Erwartung sind die Dioxidobisdithiolenmolybdate(VI) und -wolframate(VI) im wässrigen Milieu in Abhängigkeit des Ligandensystems nur für kurze Zeit beständig. Grundsätzlich wird durch Hydroxidionen eine Hydrolyse des Komplexes eingeleitet, wobei am Ende das Oxyanion entsteht. Für Verbindungen mit einem elektronenschiebenden Dithiolenliganden steht diese Hydrolyse in Konkurrenz mit der Bildung des neutralen Trisdithiolenkomplexes, welche mit sinkendem pH-Wert zu Gunsten der Trisdithiolenkomplexe ausfällt.
Bei den Untersuchungen zu einem elektrochemisch induzierten, artifiziellen PCET wurden neue Erkenntnisse gewonnen, durch welche das bestehende Reaktionsmodell von einem EC- in einen ECE-Mechanismus ergänzt werden muss. Entsprechend dieser Beobachtungen wird vor der Elektrode in Abhängigkeit der Geschwindigkeit von der chemischen Folgereaktion mit den Hydroxidionen direkt der korrespondierende Dioxidobisdithiolenkomplex erzeugt. An diesem Punkt wird die Stabilität dieser Spezies relevant, weil in Abhängigkeit des Dithiolenliganden verschiedene Folgereaktionen beobachtet werden. In der Folge entsteht vor der Elektrode bevorzugt in einem zweiten Reaktionsschritt entweder durch die Hydrolyse freies Dithiolen, welches oxidativ zum 1,2,5,6-Tetrathiocin umgeformt wird, oder über die Konkurrenzreaktion der Trisdithiolenkomplex.
Anhand dieser Betrachtungen wurde ein mechanistisches Grundkonzept für die Prozesse vor, während und nach der elektrochemisch induzierten Reaktionskaskade von Monooxidobisdithiolenmolybdaten(IV) und -wolframaten(IV) entworfen. Auf Basis dieses Reaktionsmodells kann die Suche nach geeigneten Funktionsmodellen erfolgen, welche als Dioxidobisdithiolenspezies eine ausreichende Stabilität gegenüber den Nebenreaktionen aufweisen und somit für eine erfolgreiche Sauerstoffübertragung auf ein geeignetes Akzeptormolekül in Frage kommen. Damit soll die Grundlage für die Entwicklung der ersten biomimetischen Elektrokatalyse von einer OAT-Reaktion im wässrigen Milieu geliefert werden.
Das Bedeutungsvollste dieser Arbeit lässt sich jedoch durch die kinetischen Untersuchungen des OAT an den Monooxidobisdithiolenwolframaten(IV) in Wasser zusammenfassen. Hierbei wurde einerseits erfolgreich die Sauerstoffübertragung vom Sauerstofftransfermittel TMAO und andererseits die Hydrolyse der Dioxidobisdithiolenwolframate(VI) kinetisch evaluiert. Durch diese Untersuchungen wurden erstmals für verschiedene Funktionsmodelle die Geschwindigkeitskonstanten der OAT-Reaktion in Wasser ermittelt. Zusätzlich konnte durch diese Ergebnisse gezeigt werden, dass die Reaktivität aus dem organischen Milieu nicht auf die wässrigen Bedingungen übertragbar ist, da die wässrige Lösungsmittelumgebung zu einem positiven Einfluss auf die Reaktionsgeschwindigkeit geführt hat.This work provides a comprehensive and fascinating insight into the aqueous chemistry of bisdithiolenemolybdates(IV,VI) and bisdithiolenetungstates(IV,VI) as functional models of mononuclear molybdenum and tungsten-dependent enzymes. The complexity of the observed reaction pathways in no way corresponds to the enzymatic reactivity, what particularly emphasizes the ingenious design of the active centre of this enzyme class.\\
Various water-soluble monooxidobisdithiolenemolybdates(IV) and tungstates(IV) with different dithiolene ligands were synthesized using different synthetic strategies. In addition, the first water-soluble dioxidobisdithiolenetungstate(VI) K2[WO2(vdt)2] was successfully isolated and characterized. The spectroscopic and crystallographic investigations of the solid phase structure for these different bisdithiolene complexes revealed a crucial influence of the potassium cation on the electronic properties of the metal-oxygen bonds. As a result, this leads to an even greater sensitivity to atmospheric conditions in relation to comparable compounds.
The stability of the monooxidobisdithiolene complexes in water correlates very closely with the pH value. The cause can be attributed to the protonation of the oxido ligand based on spectroscopic and theoretical investigations. However, the protonated species shows decreased stability which results in a slow desoxygenation into a trisdithiolene complex.
During the investigations about an electrochemically induced proton-coupled electron transfer, new findings were obtained that require an adjustment of the existing reaction model from an EC- to an ECE-mechanism. According to these observations, the corresponding dioxidobisdithiolene complex is electrochemically generated depending on the rate of the preceding chemical reaction with hydroxide ions. At this point, the stability of this species becomes relevant because different subsequent reactions are observed depending on the dithiolene ligand. This preferably results in either free dithiolene ligands or the trisdithiolene complex via competing reactions. Based on these considerations, a generalized mechanistic concept was developed for the processes before, during and after the electrochemically induced reaction cascade of monooxidobisdithiolene molybdates(IV) and tungstates(IV).
However, the most significant part of this work can be summarised by the kinetic investigations of the OAT in water. Thereby, three monooxidobisdithiolene tungstates(IV) were converted with trimethylamine N-oxide at several pH values. These investigations enabled the determination of the rate constants for the OAT reaction in water for the first time. In addition, the overall rate constant of the subsequent hydrolysis was also evaluated. In summary, the kinetic results for the OAT revealed a positive impact of the aqueous solvent environment on the reaction rate. This influence can be attributed to the interaction of water molecules with the oxido ligand which leads to a thermodynamically favoured reaction
Complement Activation in Nephrotic Glomerular Diseases
Get PDFThe nephrotic syndrome holds significant clinical importance and is characterized by a substantial protein loss in the urine. Damage to the glomerular basement membrane or podocytes frequently underlies renal protein loss. There is an increasing belief in the involvement of the complement system, a part of the innate immune system, in these conditions. Understanding the interactions between the complement system and glomerular structures continually evolves, challenging the traditional view of the blood–urine barrier as a passive filter. Clinical studies suggest that a precise inhibition of the complement system at various points may soon become feasible. However, a thorough understanding of current knowledge is imperative for planning future therapies in nephrotic glomerular diseases such as membranous glomerulopathy, membranoproliferative glomerulonephritis, lupus nephritis, focal segmental glomerulosclerosis, and minimal change disease. This review provides an overview of the complement system, its interactions with glomerular structures, and insights into specific glomerular diseases exhibiting a nephrotic course. Additionally, we explore new diagnostic tools and future therapeutic approaches
3D Map Combined with Transthoracic Echocardiography for Ablation of Premature Ventricular Contractions/Ventricular Arrhythmia from Papillary Muscle: A Technical Report
Get PDFVentricular arrhythmias originating from the papillary muscle of the ventricles are complex clinical problems. Catheter ablation has the potential to cure these arrhythmias. However, the procedure is usually challenging due to the specific anatomy, catheter instability and difficulty in localization of the origin of the arrhythmias. Intracardiac echocardiography (ICE) has been reported to be the suitable imaging method for assessing the location of focus in papillary muscles. We used transthoracic echocardiography (TTE), as a noninvasive cost-effective imaging supporting modality, in combination with 3D mapping to guide the exact localization and successful ablation of papillary muscle-originating premature ventricular contractions (PVCs)
Knockout of the Carbohydrate Responsive Element Binding Protein Enhances Proliferation and Tumorigenesis in Renal Tubules of Mice
Get PDFGlycogen-storing so-called clear cell kidney tubules (CCTs), precursor lesions of renal cell carcinoma, have been described in diabetic rats and in humans. The lesions show upregulation of the Akt/mTOR-pathway and the related transcription factor carbohydrate responsive element binding protein (ChREBP), which is supposedly pro-oncogenic. We investigated the effect of ChREBP-knockout on nephrocarcinogenesis in streptozotocin-induced diabetic and normoglycemic mice. Diabetic, but not non-diabetic mice, showed CCTs at 3, 6 and 12 months of age. Glycogenosis was confirmed by periodic acid schiff reaction and transmission electron microscopy. CCTs in ChREBP-knockout mice consisted of larger cells and occurred more frequently compared to wildtype mice. Progression towards kidney tumors was observed in both diabetic groups but occurred earlier in ChREBP-knockout mice. Proliferative activity assessed by BrdU-labeling was lower in 1-week-old but higher in 12-month-old diabetic ChREBP-knockout mice. Surprisingly, renal neoplasms occurred spontaneously in non-diabetic ChREBP-knockout, but not non-diabetic wildtype mice, indicating an unexpected tumor-suppressive function of ChREBP. Immunohistochemistry showed upregulated glycolysis and lipogenesis, along with activated Akt/mTOR-signaling in tumors of ChREBP-knockout groups. Immunohistochemistry of human clear cell renal cell carcinomas revealed reduced ChREBP expression compared to normal kidney tissue. However, the molecular mechanisms by which loss of ChREBP might facilitate tumorigenesis require further investigation
Comparison of dry and wet electroencephalography for the assessment of cognitive evoked potentials and sensor-level connectivity
Get PDFBackground
Multipin dry electrodes (dry EEG) provide faster and more convenient application than wet EEG, enabling extensive data collection. This study aims to compare task-related time-frequency representations and resting-state connectivity between wet and dry EEG methods to establish a foundation for using dry EEG in investigations of brain activity in neuropsychiatric disorders.
Methods
In this counterbalanced cross-over study, we acquired wet and dry EEG in 33 healthy participants [ n = 22 females, mean age (SD) = 24.3 (± 3.4) years] during resting-state and an auditory oddball paradigm. We computed mismatch negativity (MMN), theta power in task EEG, and connectivity measures from resting-state EEG using phase lag index (PLI) and minimum spanning tree (MST). Agreement between wet and dry EEG was assessed using Bland–Altman bias.
Results
MMN was detectable with both systems in time and frequency domains, but dry EEG underestimated MMN mean amplitude, peak latency, and theta power compared to wet EEG. Resting-state connectivity was reliably estimated with dry EEG using MST diameter in all except the very low frequencies (0.5–4 Hz). PLI showed larger differences between wet and dry EEG in all frequencies except theta.
Conclusion
Dry EEG reliably detected MMN and resting-state connectivity despite a lower signal-to-noise ratio. This study provides the methodological basis for using dry EEG in studies investigating the neural processes underlying psychiatric and neurological conditions