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Hybridization and reticulate evolution in Diphasiastrum (flat-branched clubmosses, Lycopodiaceae) – New data from the island of Taiwan and Vietnam
Get PDFIn the species groups related to Diphasiastrum multispicatum and D. veitchii, hybridization was investigated in samples from northern and southern Vietnam and the island of Taiwan, including available herbarium specimens from southeast Asia. The accessions were analyzed using flow cytometry (living material only), Sanger sequencing and multiplexed inter-simple sequence repeat genotyping by sequencing. We detected two cases of ancient hybridization involving different combinations of parental species; both led via subsequent duplication to tetraploid taxa. A cross D. multispicatum × D. veitchii from Malaysia represents D. wightianum, a tetraploid taxon according to reported DNA content measurements of dried material (genome formulas MM, VV and MMVV, respectively). The second case involves D. veitchii and an unknown diploid parent (genome formula XX). Three hybridogenous taxa (genome formulas VVX, VVXX, VVVX) were discernable by a combination of flow cytometry and molecular data. Taxon I (VVX, three clones found on Taiwan island) is apparently triploid. Taxon II represents another genetically diverse and sexual tetraploid species (VVXX) and can be assigned to D. yueshanense, described from Taiwan island but occurring as well in mainland China and Vietnam. Taxon III is as well most likely tetraploid (VVVX) and represented by at least one, more likely two, clones from Taiwan island. Taxa I and III are presumably asexual and new to science. Two independently inherited nuclear markers recombine only within, not between these hybrids, pointing towards reproductive isolation. We present an evolutionary scheme which explains the origin of the hybrids and the evolution of new and fully sexual species by hybridization and subsequent allopolyploidization in flat-branched clubmosses
Molecular mechanisms of Sig-dependent gene regulation in Bacillus subtilis
Get PDFUnderstanding the intricate regulatory networks governing stress responses in Bacillus subtilis is crucial for elucidating its adaptive strategies. The general stress response serves as an essential reaction to various stress and starvation conditions in B. subtilis. Physiological adaptation, mediated
by the induction of more than 150 general stress genes by the master regulator SigB, offers both
specific protection against acute stressors and a prospective shield against potential future stress factors or nutrient limitations. The activity of the alternative sigma factor SigB is tightly controlled and
stimulated by physical stress stimuli such as heat, cold, ethanol, osmotic and oxidative stress, as well as energy deficiency. Despite extensive research, many aspects of the molecular mechanisms regulating subsets of the SigB regulon and their integration into the highly complex gene regulatory network of the cell still remain unclear. This study aims to contribute significantly to answer these important questions by investigating three distinct SigB-dependent molecular mechanisms for differential gene expression in B. subtilis in response to different stressors:
1. The first light or radiation induced phenotype in B. subtilis was described and the regulatory mechanism of the interplay of the master regulator SigB and ComK on a molecular level was elucidated.
2. A distinct and conserved cis regulatory operator sequences was identified, responsive to the modulator of the general stress response MgsR with respect to secondary oxidative stress.
3. A novel role of the ClpX ATPase as a major player for CtsR functionalization and thus CtsR dependent gene regulation under heat stress conditions was discovered.Um ein besseres Verständnis von den komplexen regulatorischen Netzwerken der Stressantworten
von B. subtilis zu bekommen, ist es von entscheidender Bedeutung, die entsprechenden
Anpassungsstrategien umfassend zu untersuchen. Die allgemeine Stressantwort dient als essentielle
Reaktion auf verschiedene Stress- und Hungerbedingungen in B. subtilis. Die physiologische
Adaptation, vermittelt durch die Induktion von über 150 allgemeinen Stressgenen durch den
Masterregulator SigB, bietet sowohl spezifischen Schutz vor akuten Stressoren als auch einen
protektiven Schutzmechanismus gegen zukünftige Stressfaktoren oder Nährstoffmangel. Die Aktivität
des alternativen Sigmafaktors SigB wird strikt kontrolliert und durch physikalische Stressoren wie Hitze,
Kälte, Ethanol, osmotischer und oxidativer Stress sowie Energieknappheit stimuliert. Trotz jahrelanger
Forschung zur allgemeinen Stressantwort in B. subtilis sind wichtige Aspekte noch immer nicht
verstanden. Dies trifft besonders auf die molekularen Mechanismen, die die Untergruppen des SigBRegulons
regulieren, und deren Integration in das komplexe Genregulationsnetzwerk der Zelle zu.
Daher war die Zielsetzung im Rahmen dieser Doktorarbeit einen wesentlichen Beitrag zur
Untersuchung von drei verschiedenen molekularen Mechanismen der SigB-abhängigen Genregulation
in B. subtilis als Reaktion auf unterschiedlichen Stressoren zu leisten:
1. Aufklärung des ersten licht- und strahlungsinduzierten Phänotyps in B. subtilis und
Charakterisierung des Zusammenspiels der Masterregulatoren SigB und ComK auf molekularer
Ebene (zur Veröffentlichung angenommen in mBio).
2. Charakterisierung einer konservierten cis-regulatorischen Operatorsequenz, die als
potenzielle Bindestelle für den Modulator der generellen Stressantwort MgsR als Reaktion auf
sekundären oxidativen Stress dient (eingereicht in Nucleic Acids Research).
3. Beschreibung einer neuen Rolle der ClpX ATPase als zentraler Bestandteil der CtsRFunktionalisierung
und damit der CtsR-abhängigen Genregulation unter
Hitzestressbedingungen (unveröffentlichte Arbeit)
Impact of advanced age on the gastric emptying of water under fasted and fed state conditions
Get PDFAlthough older people are the main users of oral medications, few studies are reported on the influence of advanced age on gastric emptying rate of non-caloric liquids. This study aimed at evaluating the gastric emptying of 240 ml water in healthy older and young adults in fasted and fed state conditions using the established method of salivary caffeine kinetics. The gastric emptying of water was evaluated in 12 healthy older volunteers (mean age: 73 ± 6 years) and 12 healthy younger volunteers (mean age: 25 ± 2 years) with the ingestion of a rapid disintegrating tablet containing 20 mg of 13C3-caffeine. The gastric emptying of water was assessed indirectly by calculating the AUC ratios of salivary caffeine concentrations in specific time segments. Comparison of the AUC ratios showed no statistically significant difference between young and older volunteers in both fasted and fed state conditions (p > 0.05). Advanced age itself seems to have no relevant effect on gastric emptying of water in either fasted or fed state conditions and the phenomenon of Magenstrasse appears to follow a similar pattern in healthy older adults as in healthy younger adults
Prognostische Bedeutung kardiopulmonaler Funktionsdaten bei Patienten mit interstitieller Lungenerkrankung
Get PDFDas Ziel dieser Arbeit war die Überprüfung, welche klinischen und kardiopulmonalen Funktionsparameter bei Patienten mit interstitieller Lungenerkrankung (ILD) eine prognostische Aussage haben.
Alle zwischen 2006 und 2019 im Register der Universitätsmedizin Greifswald aufgeführten Patienten mit einer ILD und erfolgter Spiroergometrie fanden Einschluss.
Zusätzlich wurden Daten wie Komorbiditäten, Alter, Größe, Gewicht sowie Ergebnisse aus weiteren Funktionsuntersuchungen (Echokardiographie, Lungenfunktionsuntersuchung, Rechtsherzkatheter) miteinbezogen.
Es erfolgte eine retrospektive Auswertung der Daten von 183 Patienten (32 % Frauen, 68 % Männer) mit verschiedenen Formen der ILD (UIP/IPF, EAA, CPFE, Sarkoidose, Sonstige-ILD). Die mediane Follow-Up-Zeit betrug 3 ± 2,5 Jahre. Die 3- und 5-Jahres-Überlebensraten lagen bei 68 und 50 Prozent.
Als Parameter mit prognostisch signifikantem Einfluss erwiesen sich VO2 peak (%pred.), VE/VCO2 an der VT1, VE/VCO2 slope, VO2 peak/HF max, petCO2 peak, Dyslipidämie, pulmonale Hypertonie (PH), TAPSE, PAP syst., FEV1 (%pred.), DLCO (%pred.), KCO (%pred.). Innerhalb von drei erstellten Modellen hinsichtlich des Überlebens in der Gesamtgruppe der ILD-Patienten ergab sich die beste C-Statistik (0,869) für ein Modell mit Komorbiditäten, Spiroergometrie- und Lungenfunktionsparametern. Für Modelle hinsichtlich des Überlebens in der größten einheitlichen Untergruppe der UIP/IPF-Patienten präsentierten sich C-Statistiken von 0,869 (Spiroergometrieparameter) und 0,928 (Komorbiditäten, Echokardiographie- und Lungenfunktionsparameter).
Bei den Cut-off-Werten und Youden-Indexen für die Mortalität sind in der Gesamtgruppe vor allem die VO2 peak (%pred.) (Youden-Index von 0,39, Cut-off-Wert von 61,1 Prozent der Norm) und der KCO (%pred.) (Youden-Index von 0,39, Cut-off-Wert von 47,5 Prozent der Norm) hervorzuheben. In der Untergruppe der UIP/IPF-Patienten sind ebenfalls der KCO (%pred.)(Youden-Index von 0,41 und Cut-off-Wert von 69,8 Prozent der Norm) und die VO2 peak (%pred.)(Youden-Index von 0,35 und Cut-off-Wert von 68,8 Prozent der Norm) erwähnenswert. Der höchste Youden-Index (0,50) zeigte sich in dieser Gruppe bei der DLCO (%pred.) mit einem Cut-off-Wert von 42,1 Prozent der Norm.
Ein „Prognose-Tool“ mit Spiroergometrie-, Lungenfunktions-, allgemeinen Patientendaten und Vorerkrankungen ist am besten zur prognostischen Beurteilung geeignet
Revisiting a decade of inequality in healthcare financial burden in Cambodia, 2009–19: trends, determinants and decomposition
Get PDFBackground
Out-of-pocket healthcare expenditure (OOPHE) without adequate social protection often translates to inequitable financial burden and utilization of services. Recent publications highlighted Cambodia’s progress towards Universal Health Coverage (UHC) with reduced incidence of catastrophic health expenditure (CHE) and improvements in its distribution. However, departing from standard CHE measurement methods suggests a different storyline on trends and inequality in the country.
Objective
This study revisits the distribution and impact of OOPHE and its financial burden from 2009–19, employing alternative socio-economic and economic shock metrics. It also identifies determinants of the financial burden and evaluates inequality-contributing and -mitigating factors from 2014–19, including coping mechanisms, free healthcare, and OOPHE financing sources.
Methods
Data from the Cambodian Socio-Economic Surveys of 2009, 2014, and 2019 were utilized. An alternative measure to CHE is proposed: Excessive financial burden (EFB). A household was considered under EFB when its OOPHE surpassed 10% or 25% of total consumption, excluding healthcare costs. A polychoric wealth index was used to rank households and measure EFB inequality using the Erreygers Concentration Index. Inequality shifts from 2014–19 were decomposed using the Recentered Influence Function regression followed by the Oaxaca-Blinder method. Determinants of financial burden levels were assessed through zero-inflated ordered logit regression.
Results
Between 2009–19, EFB incidence increased from 10.95% to 17.92% at the 10% threshold, and from 4.41% to 7.29% at the 25% threshold. EFB was systematically concentrated among the poorest households, with inequality sharply rising over time, and nearly a quarter of the poorest households facing EFB at the 10% threshold. The main determinants of financial burden were geographic location, household size, age and education of household head, social health protection coverage, disease prevalence, hospitalization, and coping strategies. Urbanization, biased disease burdens, and preventive care were key in explaining the evolution of inequality.
Conclusion
More efforts are needed to expand social protection, but monitoring those through standard measures such as CHE has masked inequality and the burden of the poor. The financial burden across the population has risen and become more unequal over the past decade despite expansion and improvements in social health protection schemes. Health Equity funds have, to some extent, mitigated inequality over time. However, their slow expansion and the reduced reliance on coping strategies to finance OOPHE could not outbalance inequality
B cell academy of the gut: an update on gut associated germinal centre B cell dynamics
Get PDFBackground
The gut is an environment in which the immune system closely interacts with a vast number of foreign antigens, both inert such as food and alive, from the viral, bacterial, fungal and protozoal microbiota. Within this environment, germinal centres, which are microanatomical structures where B cells affinity-mature, are chronically present and active.
Main Body
The functional mechanism by which gut-associated germinal centres contribute to gut homeostasis is not well understood. Additionally, the role of T cells in class switching to immunoglobulin A and the importance of B cell affinity maturation in homeostasis remains elusive. Here, we provide a brief overview of the dynamics of gut-associated germinal centres, T cell dependency in Immunoglobulin A class switching, and the current state of research regarding the role of B cell selection in germinal centres in the gut under steady-state conditions in gnotobiotic mouse models and complex microbiota, as well as in response to immunization and microbial colonization. Furthermore, we briefly link those processes to immune system maturation and relevant diseases.
Conclusion
B cell response at mucosal surfaces consists of a delicate interplay of many dynamic factors, including the microbiota and continuous B cell influx. The rapid turnover within gut-associated germinal centres and potential influences of an early-life window of immune system imprinting complicate B cell dynamics in the gut
Prolongation of the gastric residence time of caffeine after administration in fed state: Comparison of effervescent granules with an extended release tablet
Get PDFThe aim of the present study was to investigate the gastroretentive capacity of different formulation principles. This was indirectly determined by the absorption behavior of caffeine from the dosage forms. A slow and continuous appearance of caffeine in the saliva of healthy volunteers was used as a parameter for a prolonged gastric retention time. For this purpose, a four-way study was conducted with twelve healthy volunteers using the following test procedures: (1) Effervescent granules with 240 mL of still water administered in fed state, (2) effervescent granules with 20 mL of still water in fed state, (3) extended release (ER) tablet with 240 mL of still water in fed state, and (4) effervescent granules with 240 mL of still water in fasted state. The initial rise of the caffeine concentrations was more pronounced after the intake of the effervescent granules in the fed state compared to that of the ER tablets. However, tmax tended to be shorter in the fed study arms following administration of the ER tablet compared to the granules. Overall, the application of active pharmaceutical ingredients formulated as effervescent granules seems to be a promising approach to increase their gastric residence time after intake in fed state
Daily Time-Use Patterns and Quality of Life in Parents: Protocol for a Pilot Quasi-Experimental, Nonrandomized Controlled Trial Using Ecological Momentary Assessment
Get PDFBackground
The gender gap in time use and its impact on health and well-being are still prevalent. Women work longer hours than men when considering both paid and unpaid (eg, childcare and chores) work, and this gender disparity is particularly visible among parents. Less is known about factors that could potentially mediate or moderate this relationship (eg, work-family conflict and gender role beliefs). Ecological momentary assessment (EMA) allows for the documentation of changes in momentary internal states, such as time use, stress, or mood. It has shown particular validity to measure shorter-term activities (eg, unpaid work) and is thus useful to address gender differences.
Objective
The feasibility of the daily EMA surveys in a parent sample will be examined. The associations between time use, well-being, and stress will be examined, along with potential moderating and mediating factors such as gender, gender role beliefs, and work-family conflict. Finally, the act of monitoring one’s own time use, well-being, and stress will be examined in relation to, for example, the quality of life.
Methods
We conducted a quasi-experimental, nonrandomized controlled trial with 3 data collection methods, namely, online questionnaires, EMA surveys, and qualitative interviews. The intervention group (n=64) will participate in the online questionnaires and EMA surveys, and a subsample of the intervention group (n=6-17) will also be invited to participate in qualitative interviews. Over a period of 1 week, participants in the intervention group will answer daily EMA surveys (4 times per day). In contrast, the control group (n=17) will only participate in the online questionnaires at baseline and after 1 week. The following constructs were surveyed: sociodemographic background (eg, age, gender, and household composition; baseline questionnaire); mediators and moderators (eg, gender role beliefs and work-family conflict; baseline and follow-up questionnaires); well-being, quality of life, and trait mindfulness (baseline and follow-up questionnaires); momentary activity and well-being, as well as state mindfulness (EMA); and feasibility (baseline and follow-up questionnaires as well as interviews). We anticipate that participants will regard the daily EMA as feasible. Particular daily time-use patterns (eg, high paid and unpaid workload) are expected to be related to lower well-being, higher stress, and health-related quality of life. These associations are expected to be moderated and mediated by factors such as gender, gender role beliefs, work-family conflict, and social support. Participants in the intervention group are expected to show higher values of mindfulness, well-being, health-related quality of life, and lower stress.
Results
Patient recruitment started in November 2023 and ended in mid April 2024. Data analysis commenced in mid April 2024.
Conclusions
This study aims to provide valuable insights into the feasibility of using EMAs and the potential benefits of activity tracking in various aspects of daily life.
Trial Registration
Open Science Framework 8qj3d; https://osf.io/8qj3d
International Registered Report Identifier (IRRID)
PRR1-10.2196/5472
Dementia and Physical Activity: Exploring the Effects of Physical Activity on Cognitive Function in Persons with Dementia and Investigating Mediating Factors for Successful Implementation of Physical Activity Strategies
Get PDFBackground and aim: The aging population and rising dementia cases highlight concerns for individuals' well-being. Lifestyle factors and vascular disorders play significant roles in dementia onset, prompting a focus on physical activity (PA) in prevention strategies due to its potential to slow cognitive decline affordably. However, uncertainties persist regarding optimal PA implementation methods, largely due to study design limitations and low adherence rates among individuals with dementia or at elevated risk. Therefore, this dissertation aims to address these uncertainties by examining PA intervention's effectiveness on cognition in dementia, exploring PA changes and influencing factors in at-risk older adults over a 24-month period, and identifying critical factors for successful PA program implementation. This research aims to provide valuable insights for future dementia prevention and care strategies.
Method: This dissertation offers a thorough evidence synthesis, incorporating various methodological approaches to explore effective implementation methods for PA in PwD or those at increased risk. It encompasses a systematic review and meta-analysis, quantitative analyses, and qualitative interviews.
Results: This study addresses three key research questions. Firstly, regarding the effectiveness of PA interventions on cognitive function in PwD, we found that PA interventions hold potential for improving cognitive function in PwD, but addressing methodological challenges and adherence issues is still crucial for future research. Secondly, concerning the mediating factors associated with PA engagement at 24 months follow-up among individuals at increased dementia risk, we identified that self-efficacy and targeted interventions are essential for promoting PA engagement, with demographic and health factors also playing significant roles. Lastly, regarding the mediating factors influencing the successful implementation of PA initiatives for PwD, findings underscore the critical need for tailored approaches, strong support systems, and flexibility in implementing PA interventions for PwD, alongside inclusive policies, to address challenges and ensure long-term sustainability.
Conclusion: This dissertation provides essential insights and strategies for effectively implementing PA programs for PwD and those an increased risk, bridging gaps in research and informing both practice and policy.Hintergrund und Ziel: Die alternde Bevölkerung und die steigenden Demenzfälle werfen Bedenken hinsichtlich des Wohlbefindens der Individuen auf. Lebensstilfaktoren und vaskuläre Störungen spielen eine wesentliche Rolle beim Beginn von Demenz, was den Fokus auf körperliche Aktivität (KA) in Präventionsstrategien lenkt, aufgrund ihres Potentials, den kognitiven Rückgang kostengünstig zu verlangsamen. Es bestehen jedoch nach wie vor Unsicherheiten hinsichtlich der optimalen Implementierung von KA, hauptsächlich aufgrund von Einschränkungen im Studiendesign und niedrigen Teilnahmequoten bei Menschen mit Demenz oder einem erhöhten Risiko. Daher zielt diese Dissertation darauf ab, diese Unsicherheiten zu adressieren, indem die Wirksamkeit von KA-Interventionen auf die Kognition bei Demenz untersucht wird, Veränderungen der KA und einflussnehmende Faktoren bei älteren Erwachsenen mit erhöhtem Risiko über einen Zeitraum von 24 Monaten analysiert werden und kritische Faktoren für die erfolgreiche Implementierung von KA-Programmen identifiziert werden. Diese Forschung soll wertvolle Erkenntnisse für zukünftige Demenzpräventions- und Versorgungsstrategien liefern.
Methode: Diese Dissertation bietet eine gründliche Evidenzsynthese, die verschiedene methodologische Ansätze umfasst, um effektive Implementierungsmethoden für KA bei Menschen mit Demenz oder erhöhtem Risiko zu untersuchen. Sie beinhaltet eine systematische Überprüfung und Meta-Analyse, quantitative Analysen und qualitative Interviews.
Ergebnisse: Diese Studie beantwortet drei zentrale Forschungsfragen. Erstens, hinsichtlich der Wirksamkeit von KA-Interventionen auf die kognitive Funktion bei Menschen mit Demenz, fanden wir, dass KA-Interventionen das Potenzial haben, die kognitive Funktion bei Menschen mit Demenz zu verbessern, jedoch sind die Lösung von methodischen Herausforderungen und die Verbesserung der Adhärenz nach wie vor entscheidend für zukünftige Forschungen. Zweitens, hinsichtlich der vermittelnden Faktoren, die mit der KA-Teilnahme bei der 24-Monats-Follow-up unter Individuen mit erhöhtem Demenzrisiko verbunden sind, identifizierten wir, dass Selbstwirksamkeit und gezielte Interventionen entscheidend sind, um die KA-Teilnahme zu fördern, wobei demografische und gesundheitliche Faktoren ebenfalls eine bedeutende Rolle spielen. Schließlich, hinsichtlich der vermittelnden Faktoren, die die erfolgreiche Umsetzung von KA-Initiativen für Menschen mit Demenz beeinflussen, unterstreichen die Ergebnisse die dringende Notwendigkeit maßgeschneiderter Ansätze, starker Unterstützungssysteme und Flexibilität bei der Umsetzung von KA-Interventionen für Menschen mit Demenz, zusammen mit inklusiven politischen Maßnahmen, um Herausforderungen zu adressieren und langfristige Nachhaltigkeit zu gewährleisten.
Fazit: Diese Dissertation liefert wesentliche Erkenntnisse und Strategien für die effektive Implementierung von KA-Programmen für Menschen mit Demenz und solche mit erhöhtem Risiko, überbrückt Forschungslücken und informiert sowohl die Praxis als auch die Politik
Congenital mesocolic hernia—a case report
Get PDFAbstract
Internal hernias are defined as protrusions of viscera through congenital or acquired aperture within the peritoneal cavity without an exit from the abdomen. The entity is broadly diversified with a wide variety of forms and severity of symptoms. A 10-day-old, full-term infant with poor feeding, bilious vomiting, and faecal retention for 3 days presented at our hospital. In the abdominal ultrasound, a whirl-pool sign was detected and laparotomy indicated. Intraoperatively, a malrotation of the small bowel with herniation of the jejunum into a mesocolic hernia was detected