Die multimodale Therapie des lokal fortgeschrittenen Mundhöhlenkarzinoms unter Berücksichtigung der prognostischen Relevanz einer Podoplanin Expression.

Hintergrund: Die vorliegende retrospektive Auswertung untersucht 80 Patient:innen mit Mundhöhlenplattenepithelkarzinom (MHPC) der Stadien I-IV nach Abschluss multimodaler Tumortherapien. Die Tumorpräparate wurden bezüglich der Expression von p16, Podoplanin, SMR3a und Moesin, sowie EGFR, COX-2 und PKM2 auf die klinischen Endpunkte Gesamtüberleben (GÜ) und erkrankungsfreies Überleben (EFÜ) analysiert. Methoden: Die Behandlungen wurden zwischen 10/2002 - 06/2005 durchgeführt. Die Patient:innen erhielten eine radikale Tumorresektion in der Abteilung für Mund-, Kiefer und Gesichtschirurgie des Universitätsklinikum zu Köln in kurativer Intention gefolgt von Radiatio oder Radiochemotherapie mit Carboplatin AUC1 d1-5 und d29-33 in Abhängigkeit der Indikationsstellung. Die Tumorpräparate wurden histopathologisch analog UICC-6 untersucht und das Vorliegen einer p16 Expression beurteilt. Die relevanten Biomarker wurden immunhistochemisch ausgewertet und in vier Gruppen „fehlende, schwache, moderate und starke Expression“ unterteilt. Das 2- und 5-Jahres GÜ und EFÜ wurde mittels Kaplan–Meier Methode untersucht und prognostische Faktoren mit univariaten und multivariaten Analysen identifiziert (SPSS, IBM - Version 26). Ergebnisse: Risikoadjustierte adjuvante Therapien kompensieren das Risiko für Therapieversagen eines fortgeschrittenen MHPC nur teilweise. Indikationen zur Adjuvanz zeigten sich bei Vorliegen einer Lymphgefäßinvasion (p=0.023), Lymphknotenbefall (p=0.000), extranodaler Extension (p=0.012), R1-Resektion (p=0.081), sowie hoher T- (p<0.001) und UICC-Stadien (p<0.001). Die Expression von p16 führte im vorliegenden MHPC-Kollektiv nicht zu einem Unterschied im GÜ (p=0.748) und EFÜ (p=0.519). Für EGFR, VEGF, COX-2 und PKM2 lassen sich keine Einflüsse bezüglich der erhobenen klinischen Endpunkte nachweisen. Allerdings lassen sich für Podoplanin, SMR3A und Moesin mit steigenden Expressionsgraden Entwicklungen von De-differenzierung, lokaler Invasion, hoher UICC-Stadien, Lymphknotenmetastasen und extranodaler Extension aufzeigen. In der multiplen linearen Regressionsanalyse resultieren hohe Expressionslevel von Podoplanin (p=0.004), SMR3A (p=0.002) und Moesin (p=0.024) als unabhängige Variabeln zu signifikant verkürztem Gesamtüberleben. Podoplanin (p<0.001) und Moesin (p=0.023) zeigen dabei klinisch aggressivere Verläufe mit signifikant verkürztem erkrankungsfreiem Überleben. Zusammenfassung: Trotz multimodaler Therapien ist die Prognose fortgeschrittener MHPC insgesamt ungünstig. Im vorliegenden Kollektiv mit MHPC lassen sich für p16 keine Unterschiede in Bezug auf das GÜ und EFÜ feststellen. Die isolierte Betrachtung des p16-Status scheint zur prognostischen Beurteilung fortgeschrittener MHPC im Gegensatz zum Oropharynxkarzinom unzureichend. Das Vorliegen multipler Noxen und biomolekularer Faktoren und deren Einfluss auf die in der Pathogenese, Prognose und Therapieansprechen des MHCP sollte untersucht werden, um Risikokollektive mit aggressivem Verlauf sowie Optionen zur Therapiedeeskalation oder Therapieintensivierung frühzeitig detektieren zu können. Immunhistochemische Nachweise von Podoplanin, SMR3a und Moesin könnten dazu geeignet sein, frühzeitig ungünstige klinische Verläufe mit dem Risiko für Therapieversagen zu detektieren und sollten in weiteren Studien spezifisch untersucht werden

3D printed chitosan dressing crosslinked with genipin for potential healing of chronic wounds

Recently, various additive manufacturing (3D printing) approaches have been employed to fabricate dressings such as film scaffolds that possess well defined architecture and orientation at the micro level. In this study, crosslinked chitosan (CH) based film matrices were prepared using 3D printing with genipin (GE) as a crosslinker, with glycerol (GLY) and poly ethylene glycol (PEG) as plasticizer. The 3D printed films were functionally characterized using (tensile, fluid handling, mucoadhesion, drug dissolution, morphological properties and cell viability as well physico-chemical characterization using scanning electron microscopy, Fourier transform infrared spectroscopy and X-ray diffraction. CH-GE-PEG600 3D printed films having the ratio of 1:1 polymer: plasticizer was selected due to their appropriate flexibility. Fourier transform infrared results showed intermolecular interaction between CH, GE and PEG which was confirmed by X-ray diffraction showing amorphous matrix structure. In vitro mucoadhesion studies of CH-GE-PEG600 films showed the capability of the 3D printed film to adhere to the epithelial surface. Scanning electron microscopy images showed that the surface of the plasticised films were smooth indicating content uniformity of CH, GE and PEG whilst micro cracks in unplasticised films confirmed their brittle nature. Plasticised films also showed high swelling capacity which enhanced water absorption. Cytotoxicity (MTT) assay using human skin fibroblast cell lines demonstrated that more than 90% of cells were viable after 48 h confirming non-toxic nature of the 3D printed CH-GE-PEG600 films and therefore promising dressing for chronic wound healing applications

A review of hot-melt extrusion: process technology to pharmaceutical products [Review article]

Over the last three decades industrial adaptability has allowed hot-melt extrusion (HME) to gain wide acceptance and has already established its place in the broad spectrum of manufacturing operations and pharmaceutical research developments. HME has already been demonstrated as a robust, novel technique to make solid dispersions in order to provide time controlled, modified, extended, and targeted drug delivery resulting in improved bioavailability as well as taste masking of bitter active pharmaceutical ingredients (APIs). This paper reviews the innumerable benefits of HME, based on a holistic perspective of the equipment, processing technologies to the materials, novel formulation design and developments, and its varied applications in oral drug delivery systems

Climate Change Awareness and Coping Strategies of Cocoa Farmers in Rural Ghana

The study assessed the perception of farmers on the awareness, causes and impact of climate change on their farming activities. The study further identifies and describes the various coping strategies adopted by farmers and ways of improving upon them to effectively tackle change in climatic conditions. The collected data were analyzed using descriptive statistics, such as frequencies, and percentages. The other key technique that was employed to address the objective includes the Chi square analysis. The findings indicates that, the ( ) calculated (25.846) is greater than critical (18.307); implying that, respondents (cocoa farmers) in all the cocoa growing regions in the country are much aware of climate change and its impact on their farming activities ranging from the time of planting cocoa to the time of harvesting and drying cocoa beans. Main causes of climate change by farmers’ perception include God’s plan signifying the end of time, usage of heavy machines on land, air and water, deforestation, indiscriminate bush burning before farming or in search of game, farming alongside river bodies and illegal mining. Amongst the coping strategies identified include the soil fertility strategy, shade management strategy, land preparation strategy, farm size strategy and lining and pegging strategy.  It evident that the existing agencies and government bodies have not been responsive enough in addressing the climatic problems, forecasting skills and opportunities facing cocoa farmers as crucial factors of risk posed by climate change. The study advocates that government and stakeholders should put up educational programmes tailored to meet the climatic information needs of farmers especially the causes to enable them cope with the emerging challenges to enhance their production. This could be realized through effective extension services. Keywords: Cocoa Farmers, Climate Change, Chi square, Coping strategies, Rural Ghana.

An evolutionary study of production of electricity in Ghana (1900–1960s)

The literature on the history of electricity production have studied the evolution of electricity in both developed and developing countries and its impact on their economies. Some have laid foundations upon which other works are carried out. A close examination of historiography and multidisciplinary research on electricity production in Ghana shows that more efforts are required to improve the electric power landscape in Ghana. From the colonial era, the increasing demand for electricity has been the biggest challenge plaguing the energy sector. Respective governments have made significant strides in ensuring reliable and universal access to electricity throughout Ghana, yet such efforts have been accompanied by different levels of challenges. The study uses a qualitative and exploratory research approach to trace the activities that helped, in many other ways to the creation of a sustainable electric power provision to household and industry in Ghana, particularly in two of Ghana’s cities; Accra and Kumasi, within the period 1900 to the1960s. The work focused mainly on archival sources in its quest to arrive at how indigenous Ghanaians provided power for industrial activities and for household purposes. Results from the study show that local and cottage industries relied predominantly on wood, fuel, and biomass for their operations even before the introduction of the more sophisticated means of power generation. Also, the study revealed that in finding solutions to the challenges of electricity production, policymakers have focused more on current issues with little or no effort to trace the historical foundation of electricity production. This notwithstanding, the little efforts that have been made examined the history of energy production, with a limited focus on the immediate post-independence era

Evaluations of the downward velocity of soil water movement in the unsaturated zone in a groundwater recharge area using δ18 O tracer: the Kumamoto region, southern Japan

Water and substances from the surface infiltrate the unsaturated zone before reaching groundwater. Yet, little study has been done on the unsaturated zone due to the difficulty of sampling. A lot of studies have been carried out on the top soil down to a depth of one metre and on shallow aquifers because they are easily accessible for sampling. The unsaturated zone of the Kumamotoregion recharge areas is important due to concerns about groundwater pollution from agriculture. The aim of this study was to estimate the downward velocity of soil water movement through the unsaturated zone and the recharge rate using δ18O as a tracer. Five sampling sites were selected and a core was taken from each site. The cores were cut into 0.1 m pieces and soil water was extracted from each to analyze for δD and the δ18O content. Average δD and δ18O compositions of soil water were similar to the isotopic compositions of summer precipitation. Annual average recharge rate and the downward velocity of soil water in each site were estimated by fitting a vertical δ18O profile pattern to a precipitation δ18O time series as a theoretical water displacement flow model for recharge. An estimated annual average recharge rate in the recharge area ranged from 745 to 1058 mm/yr with the annual average downward velocity of 1.37 to 2.34 m/yr. Based on the estimated downward velocity, the infiltration time for soilwater to reach the aquifer was determined as ranging from 9 to 24 years, which corresponds with previous groundwater age estimations presented in an earlier published study on the same area. It was assumed that contaminants will reach aquifers in 9 to 25 years if the effects of diffusion and microbiological reaction are not taken into account

Development and optimization of ketoconazole oral strips by means of continuous hot-melt extrusion processing

Objectives The aim of this study was to develop mucoadhesive oral strips using hot-melt extrusion as a continuous manufacturing process. Methods Powder blends of ketoconazole, a water-insoluble drug – either hydroxypropyl methylcellulose (HPMC) or soluplus (SOL), sorbitol (SRB) and magnesium aluminometasilicate (MAS) were extruded to manufacture thin strips with 0.5-mm thickness. The presence of the inorganic metasilicate facilitated smooth processing of the extruded strips as it worked as an absorbent directly impacting on the extensive mixing of the drug/excipients inside the extruder barrel. Key findings The use of MAS also favoured the rapid hydration, swelling and eventual disintegration of the strips. Differential scanning calorimetry and transmission X-ray diffraction analysis revealed the existence of the amorphous drug within the extruded strips. Scanning electron microscopy and energy dispersive X-ray undertaken on the formulations showed a homogeneous drug distribution within the extruded strips. Conclusion The strips produced via continuous hot-melt extrusion processing showed significantly faster release of ketoconazole compared to the bulk drug substance

Women and Medicine: A Historical and Contemporary Study on Ghana

Women have always been central concerning the provision of healthcare. The transitions into the modern world have been very slow for women because of how societies classify women. Starting from lay care, women provided healthcare for their family and sometimes to the members of the community in which they lived. With no formal education, women served as midwives and served in other specialised fields in medicine. They usually treated their fellow women because they saw ‘women’s medicine’ as women’s business. They were discriminated against by the opposite sex and by the church, which regarded it as a taboo to allow women to practice medicine. This study points to a Ghanaian context on how the charismas of women have made them excel in their efforts to provide healthcare for their people. The study also focused on the role of indigenous practitioners who are mostly found in the rural areas and modern practitioners who are mostly found in the peri-urban, urban areas and larger cities in Ghana

A linguistic landscape of the central business district of Accra

Using the mixed method research approach, this study investigated the linguistic landscape of the central business district of Accra, Ghana. The study employed both the Ethnolinguistic Vitality Theory (EV) and the Place Semiotics Theory to explore the types of signage displayed by shop owners in the Makola market, the languages used on these signs, the dominant language(s) on the signs and how the use of language reflects the ethnolinguistic vitality of the local languages used in Accra. The findings present a very busy linguistic landscape where shop owners use the names of their companies and the products they sell as a marketing strategy through a variety of modes including signboards, billboards, taglines, and signposts to attract customers. There was also a preponderance of English in the linguistic landscape of Accra, which establishes English as a powerful tool for inter-ethnic communication and national integration, giving an implicit impression of low vitality of indigenous languages in the space