A new long-term lifetime distribution induced by a latent complementary risk framework

In this paper, we proposed a new three-parameter long-term lifetime distribution induced by a latent complementary risk framework with decreasing, increasing and unimodal hazard function, the long-term complementary exponential geometric distribution. The new distribution arises from latent competing risk scenarios, where the lifetime associated scenario, with a particular risk, is not observable, rather we observe only the maximum lifetime value among all risks, and the presence of long-term survival. The properties of the proposed distribution are discussed, including its probability density function and explicit algebraic formulas for its reliability, hazard and quantile functions and order statistics. The parameter estimation is based on the usual maximum-likelihood approach. A simulation study assesses the performance of the estimation procedure. We compare the new distribution with its particular cases, as well as with the long-term Weibull distribution on three real data sets, observing its potential and competitiveness in comparison with some usual long-term lifetime distributions.

A bayesian network meta-analysis on comparisons of enamel matrix derivatives, guided tissue regeneration and their combination therapies

Aims: Guided tissue regeneration (GTR) and enamel matrix derivatives (EMD) are two popular regenerative treatments for periodontal infrabony lesions. Both have been used in conjunction with other regenerative materials. We conducted a Bayesian network meta-analysis of randomized controlled trials on treatment effects of GTR, EMD and their combination therapies. Material and Methods: A systematic literature search was conducted using the Medline, EMBASE, LILACS and CENTRAL databases up to and including June 2011. Treatment outcomes were changes in probing pocket depth (PPD), clinical attachment level (CAL) and infrabony defect depth. Different types of bone grafts were treated as one group and so were barrier membranes. Results: A total of 53 studies were included in this review, and we found small differences between regenerative therapies which were non-significant statistically and clinically. GTR and GTR-related combination therapies achieved greater PPD reduction than EMD and EMD-related combination therapies. Combination therapies achieved slightly greater CAL gain than the use of EMD or GTR alone. GTR with BG achieved greatest defect fill. Conclusion: Combination therapies performed better than single therapies, but the additional benefits were small. Bayesian network meta-analysis is a promising technique to compare multiple treatments. Further analysis of methodological characteristics will be required prior to clinical recommendations.

SLEEP QUALITY OF OBESE WORKERS OF A TEACHING HOSPITAL: ACUPUNCTURE AS A COMPLEMENTARY THERAPY

The objective of this study was to verify the effect of acupuncture on the sleep quality of obese workers in a teaching hospital. Data were collected from July to October 2009, focusing on 37 workers who attended eight weekly acupuncture sessions. The Pittsburgh Sleep Quality Index was used to assess their sleep quality before and after the intervention. Results show that before the intervention, five (13.5%) people experienced good quality of sleep whereas at the end of the study 14 (37.8%) showed this condition. Statistic significance (p=0.0001) was found in comparing the mean scores obtained before and after acupuncture. Acupuncture had effects on the quality of sleep in the studied sample, presenting itself as a complementary technique for treating sleep disorders and consequently improving the quality of life in this population.

An economic evaluation of antihypertensive therapies based on clinical trials

OBJECTIVE: Hypertension is a major issue in public health, and the financial costs associated with hypertension continue to increase. Cost-effectiveness studies focusing on antihypertensive drug combinations, however, have been scarce. The cost-effectiveness ratios of the traditional treatment (hydrochlorothiazide and atenolol) and the current treatment (losartan and amlodipine) were evaluated in patients with grade 1 or 2 hypertension (HT1-2). For patients with grade 3 hypertension (HT3), a third drug was added to the treatment combinations: enalapril was added to the traditional treatment, and hydrochlorothiazide was added to the current treatment. METHODS: Hypertension treatment costs were estimated on the basis of the purchase prices of the antihypertensive medications, and effectiveness was measured as the reduction in systolic blood pressure and diastolic blood pressure (in mm Hg) at the end of a 12-month study period. RESULTS: When the purchase price of the brand-name medication was used to calculate the cost, the traditional treatment presented a lower cost-effectiveness ratio [US$/mm Hg] than the current treatment in the HT1-2 group. In the HT3 group, however, there was no difference in cost-effectiveness ratio between the traditional treatment and the current treatment. The cost-effectiveness ratio differences between the treatment regimens maintained the same pattern when the purchase price of the lower-cost medication was used. CONCLUSIONS: We conclude that the traditional treatment is more cost-effective (US$/mm Hg) than the current treatment in the HT1-2 group. There was no difference in cost-effectiveness between the traditional treatment and the current treatment for the HT3 group.

In search of mechanisms associated with mesenchymal stem cell-based therapies for acute kidney injury

Acute kidney injury (AKI) is classically described as a rapid loss of kidney function. AKI affects more than 15% of all hospital admissions and is associated with elevated mortality rates. Although many advances have occurred, intermittent or continuous renal replacement therapies are still considered the best options for reversing mild and severe AKI syndrome. For this reason, it is essential that innovative and effective therapies, without side effects and complications, be developed to treat AKI and the end-stages of renal disease. Mesenchymal stem cell (MSC) based therapies have numerous advantages in helping to repair inflamed and damaged tissues and are being considered as a new alternative for treating kidney injuries. Numerous experimental models have shown that MSCs can act via differentiation-independent mechanisms to help renal recovery. Essentially, MSCs can secrete a pool of cytokines, growth factors and chemokines, express enzymes, interact via cell-to-cell contacts and release bioagents such as microvesicles to orchestrate renal protection. In this review, we propose seven distinct properties of MSCs which explain how renoprotection may be conferred: 1) anti-inflammatory; 2) pro-angiogenic; 3) stimulation of endogenous progenitor cells; 4) anti-apoptotic; 5) anti-fibrotic; 6) anti-oxidant; and 7) promotion of cellular reprogramming. In this context, these mechanisms, either individually or synergically, could induce renal protection and functional recovery. This review summarises the most important effects and benefits associated with MSC-based therapies in experimental renal disease models and attempts to clarify the mechanisms behind the MSC-related renoprotection. MSCs may prove to be an effective, innovative and affordable treatment for moderate and severe AKI. However, more studies need to be performed to provide a more comprehensive global understanding of MSC-related therapies and to ensure their safety for future clinical applications.

Equine and human mutual welfare: a whole subject? Critical aspects and possible strategies in equine-assisted activities and therapies

General aim of the study is equine welfare, particularly concerning different husbandry methodic and inter-specific relational factors. Specific aim is the evaluation of possible mutual (to humans and to equines) benefits and the analysis of critical factors/strength points, of human-horse relationship within Therapeutic Riding context (TR). The peculiarities of human-horse relationship (compared to the bond with “Pet”) are analyzed, concerning their socio-anthropological, psychological, psycho-dynamic distinctive characteristics. 8 European representative therapeutic riding centers (TRC) were therefore selected (on the basis of their different animals’ husbandry criteria, and of the different rehabilitative methodologies adopted). TRC were investigated through 2 different questionnaires, specifically settled to access objective/subjective animal welfare parameters; the quality of human-horse relationship; technicians’ emotional experienced. 3 Centers were further selected, and behavioral (145 hours of behavioral recording) and physiological parameters (heart rate and heart rate variability) were evaluated, aimed to access equine welfare and horses’ adaptive responses/coping (towards general environment and towards TR job). Moreover a specific “handling-task” was ideated and experimented, aimed to measure the quality of TR technicians-horses relationship. We did therefore evaluate both the individual horses’ responses and the possible differences among Centers. Data collected highlight the lack of univocal standardized methodic, concerning the general animals’ management and the specific methodologies (aimed to improve animal welfare and to empower TR efficacy). Some positive and some critical aspects were detected concerning TR personnel-horse relationship. Another experimental approach did evaluate the efficacy (concerning the mutual benefits’ empowerment) of an “ethologically-fitted” TR intervention, aimed to educate children to and through the relationship with horses. Our data evidenced that the improvement of human horse relationship, through structured educational programs for TR personnel might have important consequences both to human and equine welfare.

Sahaja Yoga im Vergleich mit der Progressiven Muskelrelaxation nach Jacobson

Fragestellung: In der vorliegenden Arbeit wird erstmals das Sahaja Yoga (SY) bezüglich seiner Effektivität in der komplementären Behandlung von Patienten mit Mamma- oder Prostatakarzinom untersucht und mit der Progressiven Muskelrelaxation nach Jacobson (PMR) verglichen. Methoden: Zu diesem Zweck wurden 16 Patienten mit Prostatakarzinom und 21 Patientinnen mit Mammakarzinom im Rahmen einer stationären Anschlußheilbehandlung (AHB) rekrutiert und jeweils mittels Zufallstabelle entweder einer SY-Gruppe oder einer PMR-Gruppe zugeteilt. Die Patienten übten während des dreiwöchigen Aufenthalts zusätzlich zu den jeweiligen physikalischen und physiotherapeutischen Therapien die entsprechenden Entspannungsverfahren (SY oder PMR) insgesamt acht mal und wurden dazu angehalten, die Verfahren auch in Eigenregie fortzuführen. Die Patienten füllten zu Beginn ihres Aufenthaltes (t1), nach 3 Wochen (Ende der AHB, t2) sowie 2 Monate nach dem Beenden der AHB (t3) folgende Fragebögen aus: den SF-36 von Bullinger et al. (1995) zur Erfassung von gesundheitsbezogener Lebensqualität, die HADS von Hermann et al. (1995) zur Erfassung von Angst und Depressivität und zwei vom Autor selbstkonzipierte Fragebögen, mit denen die Anzahl und Dauer der durchgeführten Übungen registriert wurden. Den MDBF von Steyer et al. (1997) (für aktuelle Befindlichkeit) füllten die Patienten jeweils direkt vor und nach der ersten (t1v und t1n) und letzten (t2v und t2n) Entspannungsübung und zum Zeitpunkt t3 aus. Ergebnisse: Fast alle Testwerte des Gesundheitsfragebogens SF-36 steigen (teils statistisch signifikant) bei beiden Gruppen von dem Zeitpunkt t1 über t2 zu t3 an. Es scheinen zwar die Verbesserungen der SY-Gruppe gegenüber der PMR-Gruppe etwas zu überwiegen, statistisch konnte dies jedoch nicht belegt werden. Bei den Subskalen der HADS (Angst und Depression) fallen die Werte bei beiden Gruppen von Zeitpunkt t1 über t2 zu t3 ab, statistisch signifikant ist der Abfall jedoch nur von t1 zu t2 bei den Werten der HADS-D (Depression) bei der SY-Gruppe. Die Testwerte sinken bei der SY-Gruppe im Verlauf etwas steiler ab als die Testwerte der PMR-Gruppe, signifikanten Unterschiede zwischen den Gruppen lassen sich jedoch nicht finden. Die Testwerte des MDBF (Kurzform A) steigen von dem Zeitpunkt t1v über t2v zu t3 bei beiden Gruppen (bei der SY-Gruppe etwas steiler, jedoch ohne signifikanten Unterschied zur PMR-Gruppe) nur zum Teil signifikant an. Die Werte vor und nach den jeweiligen Anwendungen (Zeitpunkt t1v zu t1n und t2v zu t2n) unterscheiden sich signifikant bei beiden Gruppen. Bezüglich der Dauer und Anzahl der durchgeführten Anwendungen zeigen sich keine statistisch signifikanten Unterschiede zwischen den Gruppen. Schlußfolgerungen: Die Patienten konnten beide Verfahren gleich gut annehmen. Bezüglich der gesundheitsbezogenen Lebensqualität, Angst und Depressivität sowie der aktuellen Befindlichkeit scheint sowohl das SY als auch die PMR (in dieser Studie) relevante Effekte zu haben. Diese Effekte scheinen sich auch nach 2 Monaten weiter positiv auszuwirken. Statistisch ließen sich zwischen beiden Verfahren keine Unterschiede hinsichtlich ihrer Wirkung belegen. Die Ergebnisse müssen allerdings durch weitere Untersuchungen mit größerer Probandenzahl genauer geprüft werden.

Generation and characterization of mouse models of Small cell lung cancer and Basal cell carcinoma for the preclinical evaluation of new therapies

Background. Human small cell lung cancer (SCLC) accounting for approximately 15-20% of all lung cancers, is an aggressive tumor with high propensity for early regional and distant metastases. Although the initial tumor rate response to chemotherapy is very high, SCLC relapses after approximately 4 months in ED and 12 months in LD. Basal cell carcinoma (BCC) is the most prevalent cancer in the western world, and its incidence is increasing worldwide. This type of cancer rarely metastasizes and the death rate is extraordinary low. Surgery is curative for most of the patients, but for those that develop locally advanced or metastatic BCC there is currently no effective treatment. Both types of cancer have been deeply investigated and genetic alterations, MYCN amplification (MA) among the most interesting, have been found. These could become targets of new pharmacological therapies. Procedures. We created and characterized novel BLI xenograft orthotopic mouse models of SCLC to evaluate the tumor onset and progression and the efficacy of new pharmacological strategies. We compared an in vitro model with a transgenic mouse model of BCC, to investigate and delineate the canonical HH signalling pathway and its connections with other molecular pathways. Results and conclusions. The orthotopic models showed latency and progression patterns similar to human disease. Chemotherapy treatments improved survival rates and validated the in vivo model. The presence of MA and overexpression were confirmed in each model and we tested the efficacy of a new MYCN inhibitor in vitro. Preliminar data of BCC models highlighted Hedgehog pathway role and underlined the importance of both in vitro and in vivo strategies to achieve a better understanding of the pathology and to evaluate the applicability of new therapeutic compounds

Nuove tecniche per il trattamento della malattia paranale di Crohn

Studio prospettico su 75 pazienti con malattia paranale di Crohn che ha come obiettivo quello di confrontare i risultati tra le nuove terapie medico-chirurgiche emergenti. La prima procedura è comune a tutti i pazienti e consiste in un intervento di incisione degli ascessi, fistulectomia e posizionamento di setoni di drenaggio nei tramiti fistolosi per il controllo della sepsi.Successivamente i pazienti vengono divisi in cinque gruppi e sottoposti ai trattamenti per la chiusura dei tramiti fistolosi: terapia sistemica con Infliximab,terapia sistemica con Adalimumab,confezionamento di Flap endoanale, instillazione di colla di fibrina o posizionamento di protesi biologiche. Abbiamo osservato una chiusura completa dei tramiti fistolosi nel 60% dei pazienti trattati con Infliximab, 53% di quelli trattati con Adalimumab, 40% di quelli in terapia con colla di fibrina, 80% di quelli sottoposti a Flap endoanale e 60% di quelli trattati con protesi biologiche. Gli ottimi risultati raggiunti in con le diverse metodiche di trattamento chirurgico locale rappresentano una valida alternativa alla terapia con farmaci biologici. Tali nuove metodiche risultano anzi fondamentali per il trattamento di quei pazienti che dopo una terapia con farmaci biologici non hanno raggiunto una completa risoluzione del quadro (rescue therapy). Terapia biologica e nuove tecniche chirurgiche risultano pertanto complementari, la prima contribuendo al miglioramento della qualità della mucosa del canale anale e del retto basso sulla quale risulta quindi più agevole agire con le seconde con una percentuale di successo sempre maggiore.

Prozessevaluation einer kognitiv-verhaltenstherapeutischen Gruppentherapie bei Diabetes und Depression : Entwicklung und Validierung der Patienten- und Therapeuten- Gruppentherapiestundenbögen (GTS-P, GTS-T, GTS-TP) zur Vorhersage des Therapieerfolgs

Untersucht werden Prozess-Ergebnis-Zusammenhänge einer kognitiv-verhaltenstherapeutischen Gruppentherapie für Diabetes und Depression im Rahmen der DAD-Studie. rnAufgrund des Mangels an geeigneten Erhebungsinstrumenten der validen, ökonomischen und komplementären Sitzungsbewertung von Gruppenpatienten und -therapeuten wurden angelehnt an einen Patienten- (GTS-P) zwei Therapeutenstundenbögen entwickelt: der GTS-T zur Bewertung der Gesamtgruppe und der GTS-TP zur Bewertung einzelner Patienten. Die GTS-Bögen zeigen bei der Überprüfung der Testgüte insgesamt gute Itemparameter und Reliabilitäten. Das in den exploratorischen Faktorenanaylsen des GTS-P identifizierte zweifaktorielle Modell (1. wahrgenommene Zuversicht hinsichtlich der Gruppentherapie, 2. wahrgenommene persönliche Beteiligung) kann in den konfirmatorischen Faktorenanalysen bestätigt werden. Dazu wurden GTS-P-Daten aus einer Untersuchung mit Patienten mit somatoformen Störungen (Schulte, 2001) einbezogen. Den Ergebnissen der Item- und Faktorenanalysen folgend, wurden zwei Items des GTS-P und zwei weitere Items des GTS-T aus den Instrumenten ausgeschlossen. Für den GTS-T zeigt sich eine einfaktorielle, für den GTS-TP eine zum GTS-P parallele zweifaktorielle Struktur. rnIn den Mehrebenenanalysen zur Vorhersage des Therapieergebnisses (Post-Depressionssymptomatik) zeigt sich die Skala Zuversicht des GTS-P zu Therapiebeginn (1.-4. Sitzung) kontrolliert an der Skala Beteiligung und der Prä-Symptomatik, als valider Prädiktor. Das Item 5 „Anregungen“ (Skala Zuversicht) und Item 2 „Aktive Mitwirkung“ (Skala Beteiligung) sind am stärksten an diesem Effekt beteiligt, da diese Itemkombination das Therapieergebnis ebenfalls valide vorhersagen kann. Die Prognose ist schon durch die Werte der ersten Gruppentherapiesitzungen in der Remoralisierungsphase (Howard et al., 1993) möglich und verbessert sich nicht bei Berücksichtigung aller 10 Gruppensitzungen. Die Therapeutenbögen zeigen keine prädiktive Validität. Bedeutsame Zusammenhänge der Patienten- und Therapeutenbewertungen finden sich lediglich für den GTS-P und GTS-TP. Weitere Prädiktoren, wie der Diabetestyp, Diabeteskomplikationen und die Adhärenz, konnten nicht zur Verbesserung der Vorhersage beitragen. Für sekundär überprüfte Kriterien gelang die Prognose lediglich für ein weiteres Maß der Depressionssymptomatik und für eine Gesamtbewertung der Gruppentherapie durch die Patienten zu Therapieende. Bei der deskriptiven Betrachtung der Prozessqualität der DAD-Gruppentherapien zeigen sich positive, über den Verlauf der Gruppe zunehmende und nach Therapiephasen differenzierbare Bewertungsverläufe. rnDie Ergebnisse der Studie sprechen für die Relevanz von unspezifischen Wirkfaktoren für das Therapieergebnis von kognitiv-behavioralen Gruppentherapien. Die von den Gruppenpatienten wahrgenommene Zuversicht und Beteiligung als Zeichen der Ansprechbarkeit auf die Therapie sollte mit Hilfe von Stundenbögen, wie den GTS-Bögen, von Gruppentherapeuten zur Prozessoptimierung und Prävention von Therapieabbrüchen und Misserfolgen beachtet werden. rn

Complementary mass spectrometric techniques for the characterization of the organic fraction in atmospheric aerosols

Aerosol particles are strongly related to climate, air quality, visibility and human health issues. They contribute the largest uncertainty in the assessment of the Earth´s radiative budget, directly by scattering or absorbing solar radiation or indirectly by nucleating cloud droplets. The influence of aerosol particles on cloud related climatic effects essentially depends upon their number concentration, size and chemical composition. A major part of submicron aerosol consists of secondary organic aerosol (SOA) that is formed in the atmosphere by the oxidation of volatile organic compounds. SOA can comprise a highly diverse spectrum of compounds that undergo continuous chemical transformations in the atmosphere.rnThe aim of this work was to obtain insights into the complexity of ambient SOA by the application of advanced mass spectrometric techniques. Therefore, an atmospheric pressure chemical ionization ion trap mass spectrometer (APCI-IT-MS) was applied in the field, facilitating the measurement of ions of the intact molecular organic species. Furthermore, the high measurement frequency provided insights into SOA composition and chemical transformation processes on a high temporal resolution. Within different comprehensive field campaigns, online measurements of particular biogenic organic acids were achieved by combining an online aerosol concentrator with the APCI-IT-MS. A holistic picture of the ambient organic aerosol was obtained through the co-located application of other complementary MS techniques, such as aerosol mass spectrometry (AMS) or filter sampling for the analysis by liquid chromatography / ultrahigh resolution mass spectrometry (LC/UHRMS).rnIn particular, during a summertime field study at the pristine boreal forest station in Hyytiälä, Finland, the partitioning of organic acids between gas and particle phase was quantified, based on the online APCI-IT-MS and AMS measurements. It was found that low volatile compounds reside to a large extent in the gas phase. This observation can be interpreted as a consequence of large aerosol equilibration timescales, which build up due to the continuous production of low volatile compounds in the gas phase and/or a semi-solid phase state of the ambient aerosol. Furthermore, in-situ structural informations of particular compounds were achieved by using the MS/MS mode of the ion trap. The comparison to MS/MS spectra from laboratory generated SOA of specific monoterpene precursors indicated that laboratory SOA barely depicts the complexity of ambient SOA. Moreover, it was shown that the mass spectra of the laboratory SOA more closely resemble the ambient gas phase composition, indicating that the oxidation state of the ambient organic compounds in the particle phase is underestimated by the comparison to laboratory ozonolysis. These observations suggest that the micro-scale processes, such as the chemistry of aerosol aging or the gas-to-particle partitioning, need to be better understood in order to predict SOA concentrations more reliably.rnDuring a field study at the Mt. Kleiner Feldberg, Germany, a slightly different aerosol concentrator / APCI-IT-MS setup made the online analysis of new particle formation possible. During a particular nucleation event, the online mass spectra indicated that organic compounds of approximately 300 Da are main constituents of the bulk aerosol during ambient new particle formation. Co-located filter analysis by LC/UHRMS analysis supported these findings and furthermore allowed to determine the molecular formulas of the involved organic compounds. The unambiguous identification of several oxidized C 15 compounds indicated that oxidation products of sesquiterpenes can be important compounds for the initial formation and subsequent growth of atmospheric nanoparticles.rnThe LC/UHRMS analysis furthermore revealed that considerable amounts of organosulfates and nitrooxy organosulfates were detected on the filter samples. Indeed, it was found that several nitrooxy organosulfate related APCI-IT-MS mass traces were simultaneously enhanced. Concurrent particle phase ion chromatography and AMS measurements indicated a strong bias between inorganic sulfate and total sulfate concentrations, supporting the assumption that substantial amounts of sulfate was bonded to organic molecules.rnFinally, the comprehensive chemical analysis of the aerosol composition was compared to the hygroscopicity parameter kappa, which was derived from cloud condensation nuclei (CCN) measurements. Simultaneously, organic aerosol aging was observed by the evolution of a ratio between a second and a first generation biogenic oxidation product. It was found that this aging proxy positively correlates with increasing hygroscopicity. Moreover, it was observed that the bonding of sulfate to organic molecules leads to a significant reduction of kappa, compared to an internal mixture of the same mass fractions of purely inorganic sulfate and organic molecules. Concluding, it has been shown within this thesis that the application of modern mass spectrometric techniques allows for detailed insights into chemical and physico-chemical processes of atmospheric aerosols.rn

Improving adoptive T cell therapies of cancer by ectopic expression of miR181a to repress inhibitory phosphatases

Adoptive T cell therapy using antigen-specific T lymphocytes is a powerful immunotherapeutic approach against cancer. Nevertheless, many T cells against tumor-antigens exhibit only weak anti-tumoral response. To overcome this barrier it is necessary to improve the potency and anti-tumoral efficacy of these T cells. Activation and activity of T cells are tightly controlled to inhibit unwanted T cell responses and to reduce the risk of autoimmunity. Both are regulated by extrinsic signals and intrinsic mechanisms which suppress T cell activation. The intrinsic mechanisms include the expression of phosphatases that counteract the activation-inducing kinases. Modifying the expression of these phosphatases allows the targeted modulation of T cell reactivity. MicroRNAs (miRNAs) are regulatory small noncoding RNA molecules that control gene expression by targeting messenger RNAs in a sequence specific manner. Gene-specific silencing plays a key role in diverse biological processes, such as development, differentiation, and functionality. miR181a has been shown to be highly expressed in immature T cells that recognize low-affinity antigens.rnThe present study successfully shows that ectopic expression of miR181a is able to enhance the sensitivity of both murine and human T cells. In CD4+ T helper cells as well as in CD8+ cytotoxic T cells the overexpression of miR181a leads to downregulation of multiple phosphatases involved in the T cell receptor signaling pathway. Overexpression of miR181a in human T cells achieves a co-stimulatory independent activation and has an anti-apoptotic effect on CD4+ T helper cells. Additionally, increasing the amount of miR181a enhances the cytolytic activity of murine CD8+ TCRtg T cells in an antigen-specific manner.rnTo test miR181a overexpressing T cells in vivo, a mouse tumor model using a B cell lymphoma cell line (A20-HA) expressing the Influenza hemagglutinin (Infl.-HA) antigen was established. The expression of model antigens in tumor cell lines enables targeted elimination of tumors using TCRtg T cells. The transfer of miR181a overexpressing Infl.-HA TCRtg CD8+ T cells alone has no positive effect neither on tumor control nor on survival of A20-HA tumor-bearing mice. In contrast, the co-transfer of miR181a overexpressing Infl.-HA TCRtg CD8+ and CD4+ T cells leads to improved tumor control and prolongs survival of A20-HA tumor-bearing mice. This effect is characterized by higher amounts of effector T cells and the expansion of Infl.-HA TCRtg CD8+ T cells.rnAll effects were achieved by changes in expression of several genes including molecules involved in T cell differentiation, activation, and regulation, cytotoxic effector molecules, and receptors important for the homing process of T cells in miR181a overexpressing T cells. The present study demonstrates that miR181a is able to enhance the anti-tumoral response of antigen-specific T cells and is a promising candidate for improving adoptive cell therapy.

Differences in the quality of interpersonal care in complementary and conventional medicine

The study was part of a nationwide evaluation of complementary and alternative medicine (CAM) in Swiss primary care. The aim of the study was to compare patient-physician relationships and the respective patient-reported relief of symptoms between CAM and conventional primary care (COM).