A Pfs48/45-based vaccine to block Plasmodium falciparum transmission: phase 1, open-label, clinical trial.

BACKGROUND: The stalling global progress in malaria control highlights the need for novel tools for malaria elimination, including transmission-blocking vaccines. Transmission-blocking vaccines aim to induce human antibodies that block parasite development in the mosquito and mosquitoes becoming infectious. The Pfs48/45 protein is a leading Plasmodium falciparum transmission-blocking vaccine candidate. The R0.6C fusion protein, consisting of Pfs48/45 domain 3 (6C) and the N-terminal region of P. falciparum glutamate-rich protein (R0), has previously been produced in Lactococcus lactis and elicited functional antibodies in rodents. Here, we assess the safety and transmission-reducing efficacy of R0.6C adsorbed to aluminium hydroxide with and without Matrix-M™ adjuvant in humans. METHODS: In this first-in-human, open-label clinical trial, malaria-naïve adults, aged 18-55 years, were recruited at the Radboudumc in Nijmegen, the Netherlands. Participants received four intramuscular vaccinations on days 0, 28, 56 and 168 with either 30 µg or 100 µg of R0.6C and were randomised for the allocation of one of the two different adjuvant combinations: aluminium hydroxide alone, or aluminium hydroxide combined with Matrix-M1™ adjuvant. Adverse events were recorded from inclusion until 84 days after the fourth vaccination. Anti-R0.6C and anti-6C IgG titres were measured by enzyme-linked immunosorbent assay. Transmission-reducing activity of participants' serum and purified vaccine-specific immunoglobulin G was assessed by standard membrane feeding assays using laboratory-reared Anopheles stephensi mosquitoes and cultured P. falciparum gametocytes. RESULTS: Thirty-one participants completed four vaccinations and were included in the analysis. Administration of all doses was safe and well-tolerated, with one related grade 3 adverse event (transient fever) and no serious adverse events occurring. Anti-R0.6C and anti-6C IgG titres were similar between the 30 and 100 µg R0.6C arms, but higher in Matrix-M1™ arms. Neat participant sera did not induce significant transmission-reducing activity in mosquito feeding experiments, but concentrated vaccine-specific IgGs purified from sera collected two weeks after the fourth vaccination achieved up to 99% transmission-reducing activity. CONCLUSIONS: R0.6C/aluminium hydroxide with or without Matrix-M1™ is safe, immunogenic and induces functional Pfs48/45-specific transmission-blocking antibodies, albeit at insufficient serum concentrations to result in transmission reduction by neat serum. Future work should focus on identifying alternative vaccine formulations or regimens that enhance functional antibody responses. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov under identifier NCT04862416.

Enhanced dynamic nuclear polarization via swept microwave frequency combs.

Dynamic nuclear polarization (DNP) has enabled enormous gains in magnetic resonance signals and led to vastly accelerated NMR/MRI imaging and spectroscopy. Unlike conventional cw-techniques, DNP methods that exploit the full electron spectrum are appealing since they allow direct participation of all electrons in the hyperpolarization process. Such methods typically entail sweeps of microwave radiation over the broad electron linewidth to excite DNP but are often inefficient because the sweeps, constrained by adiabaticity requirements, are slow. In this paper, we develop a technique to overcome the DNP bottlenecks set by the slow sweeps, using a swept microwave frequency comb that increases the effective number of polarization transfer events while respecting adiabaticity constraints. This allows a multiplicative gain in DNP enhancement, scaling with the number of comb frequencies and limited only by the hyperfine-mediated electron linewidth. We demonstrate the technique for the optical hyperpolarization of 13C nuclei in powdered microdiamonds at low fields, increasing the DNP enhancement from 30 to 100 measured with respect to the thermal signal at 7T. For low concentrations of broad linewidth electron radicals [e.g., TEMPO ((2,2,6,6-tetramethylpiperidin-1-yl)oxyl)], these multiplicative gains could exceed an order of magnitude.

Two new species of threadlike blood flukes (Aporocotylidae), with a molecular revision of the genera Ankistromeces Nolan & Cribb, 2004 and Phthinomita Nolan & Cribb, 2006.

Ankistromeces Nolan & Cribb, 2004 and Phthinomita Nolan & Cribb, 2006 are sister genera of threadlike blood flukes (Trematoda: Aporocotylidae) infecting teleost fishes of the tropical Indo-west Pacific. Here, we report new collections of these genera from Australia, Indonesia, and Japan. A new species of Ankistromeces, Ankistromeces kawamurai n. sp., is described from Siganus spinus (Linnaeus) off Okinawa, Japan, and a new species of Phthinomita, Phthinomita abdita n. sp., from Choerodon cephalotes (Castelnau), in Moreton Bay, Australia; the new species are morphologically cryptic within their respective genera and are delineated by molecular and ecological data. Ankistromeces olsoni Nolan & Cribb, 2006 is reported from Siganus fuscescens (Houttuyn) off Heron Island (southern Great Barrier Reef), Lizard Island (northern Great Barrier Reef), and Okinawa and Wakayama Prefectures, Japan and from Siganus spinus (Linnaeus) from off Bali, Indonesia. Ankistromeces mariae Nolan & Cribb, 2004 is re-reported from the type-host, Meuschenia freycineti (Quoy & Gaimard), from a new location, Gypsy Bay, Tasmania. Phthinomita poulini Nolan & Cribb, 2006 is re-reported from its type-locality, Lizard Island, from a range of mullids, including five new host species, and its range is extended to include Moreton Bay. Phthinomita symplocos Nolan & Cribb, 2006 is reported from Bali and P. hallae Nolan & Cribb, 2006, P. jonesi Nolan & Cribb, 2006, P. littlewoodi Nolan & Cribb, 2006, and P. munozae Nolan & Cribb, 2006 are each re-reported from their type-host and type-localities. New cox1 mtDNA data were generated for all known species of these two genera from new and archival material. Analyses of these data enabled an evaluation of all known Phthinomita species; P. robertsthomsoni Nolan & Cribb, 2006 is synonymised with P. adlardi Nolan & Cribb, 2006, and P. brooksi Nolan & Cribb, 2006 is synonymised with P. sasali Nolan & Cribb, 2006. We highlight the failure of ITS2 data to delineate closely related aporocotylid species. In contrast, cox1 sequence data are proving reliable and effective in this context and we recommend their incorporation in future studies of blood fluke taxonomy.

Hepatitis C treatment uptake and adherence among injecting drug users in the Czech Republic.

BACKGROUND: Injecting drug users (IDUs) represent a major subpopulation of hepatitis C virus (HCV)-infected people in developed countries. Yet their uptake to treatment is generally low despite well-documented effectiveness of HCV treatment among former and active IDUs. The present study represents the first attempt to describe the HCV treatment coverage among IDUs and identify factors that affect treatment uptake in the Czech Republic. METHODS: From January to March 2011, a questionnaire survey was conducted among viral hepatitis treatment centres in the Czech Republic. RESULTS: From a total of 76 identified hepatitis treatment centres existing in the country, 39 provided HCV treatment to (mainly former or abstaining) IDUs in 2010. Most clinicians reported being cautious in initiating HCV treatment in IDUs. Abstinence, a screening phase before treatment initiation, opioid substitution treatment and an external evaluation by a specialist were often prerequisites for skrting treatment. However, HCV treatment centres rarely provided drug-use specific services. Financial constraints were also reported, further limiting the inclusion of IDUs into treatment, as non-users are widely preferred to active drug users. Clinicians reported no difference in treatment uptake and adherence between drug users and non-users, nor between opioid and methamphetamine users. CONCLUSION: A number of system- and provider-related factors limit HCV treatment in IDUs in the Czech Republic, despite permissive national clinical guidelines. Targeting these factors is crucial to reduce HCV prevalence at population level.

[Internet presence of psychiatrists in private practice. Status, chances and legal framework]. / Internetauftritte niedergelassener Psychiater. Status quo, Möglichkeiten und gesetzliche Vorgaben.

BACKGROUND: Physicians increasingly use home pages to call attention to their practice. Based on predefined criteria, this study examines the web presence of psychiatrists and medical psychotherapists in private practice. METHODS: All registered psychiatrists and psychotherapists of six northern German states were examined in May 2010 with regards to existence and quality of their web presence. Homepages were evaluated by means of a standardized criteria catalogue with 42 items. Statistical analysis comprised descriptive and analytic approaches (ANOVA, linear models). RESULTS: The analysis included 956 physicians, 168 of whom (17.6%) had a web presence. More physicians in city states had a web presence as compared to those in states with larger territories. However, there was no difference between eastern and western states. Male as compared to female physicians more often possessed an Internet presence. The average score was 19 (± 5.2) out of 42 items, with practices with more than one physician scoring higher than single physician practices. Websites often contained general information about the practice, medical services and diseases, and rarely online services, professional information about the physician, access for disabled, emergency services and holiday substitution. Legal requirements were not sufficiently considered by more than half of the physicians. CONCLUSION: Only a smaller number of psychiatrists and psychotherapists in private practice make use of their own web presence. The quality of information varies. The criteria catalogue used in this study may offer a guideline for development of a good quality Internet presence. A consensus Internet guideline with participation of physician chambers and medical societies would be of use to establish quality standards.

Quality of life profiles and changes in the course of maintenance treatment among 1,015 patients with severe opioid dependence.

INTRODUCTION: Studies indicate that different areas of mental, physical, social and daily life functioning need to be considered in order to improve intervention outcomes in substance user patients. The aim of the study was to assess health-related quality of life (HRQOL) in patients diagnosed with opioid dependence as compared to healthy controls and patients diagnosed with depression and schizophrenia. METHODS: A total of 1,015 outpatients diagnosed with opioid dependence were investigated during 12 months of maintenance treatment. HRQOL (MSQoL), addiction (EUROP-ASI), and sociodemographic characteristics were assessed. RESULTS: HRQOL in opioid dependence improved significantly (p < .001), but was lower as compared to that of healthy controls and patients diagnosed with schizophrenia. HRQOL in opioid dependence comprises addiction-specific aspects, most importantly low material satisfaction, physical health, and social stability. CONCLUSIONS: HRQOL measurement provides valuable information for course and outcome in opioid dependence treatment.

[Cerebral amyloid angiopathy: an easily missed diagnosis in patients with transient neurological deficits]. / Cerebrale amyloïdangiopathie.

Cerebral amyloid angiopathy (CAA) is a degenerative neurovascular disease in which the protein amyloid-beta accumulates in the vessel wall of cortical and leptomeningeal arteries. This may lead to acute lobar cerebral haemorrhage, which in case of CAA is fatal in 10-30% of cases. CAA may also present with transient focal neurological episodes (TFNE), the symptoms of which may mimic a transient ischaemic attack (TIA). Distinction between the two has important implications for therapy, as antithrombotics are relatively contra-indicated in CAA, but indicated after a TIA. We describe a patient with transient focal neurological deficits who was initially treated with antithrombotic therapy for a suspected TIA. Eventually, the diagnosis CAA was made and antithrombotic treatment was ceased. This case stresses the importance of considering the diagnosis CAA with TFNE in patients presenting with transient neurological deficits, in order to avoid an unnecessarily increased risk of symptomatic and possibly fatal cerebral haemorrhage.

Low-field microwave-mediated optical hyperpolarization in optically pumped diamond.

The emergence of a new class of optically polarizable electronic spins in diamond, nitrogen vacancy (NV) defect centers, has opened interesting new avenues for dynamic nuclear polarization. Here we review methods for the room-temperature hyperpolarization of lattice 13C nuclei using optically pumped NV centers, focusing particular attention to a polarization transfer via rotating-frame level anti-crossings. We describe special features of this optical DNP mechanism at low-field, in particular, its deployability to randomly oriented diamond nanoparticles. In addition, we detail methods for indirectly obtaining high-resolution NV ESR spectra via hyperpolarization readout. These mechanistic features provide perspectives for interesting new applications exploiting the optically generated 13C hyperpolarization.

Is heroin-assisted treatment effective for patients with no previous maintenance treatment? Results from a German randomised controlled trial.

BACKGROUND/AIMS: Until now, the medical prescription of diamorphine (heroin) has been suggested as suitable for patients who have failed previous maintenance treatments. The aim of this paper is to assess the effects of diamorphine on opioid-dependent patients with no previous maintenance treatment experience (NPME). METHODS: The German heroin trial compared diamorphine versus methadone maintenance treatment and included 107 patients with NPME. This paper is a sub-analysis of these patients. RESULTS: When comparing this subsample with the rest of the participants in the study, large baseline differences were found, showing a more severe drug use profile in patients with NPME. However, no differences were found in terms of treatment outcome and treatment retention. In the subsample with NPME, outcome measures on the reduction of illicit drug use were significantly better under diamorphine compared to methadone treatment, while there was no difference in health outcomes. CONCLUSION: Controlled studies are now necessary to examine whether diamorphine treatment could be considered as one of several options in treating severely opioid-dependent patients, regardless of previous maintenance treatment experience.

Effects of psychiatric comorbidity on treatment outcome in patients undergoing diamorphine or methadone maintenance treatment.

BACKGROUND: Comorbid psychiatric disorders among opioid-dependent patients are associated with several negative outcome factors. However, outcomes of maintenance treatment have not been sufficiently established, and no evidence is available with respect to heroin-assisted treatment (HAT). METHODS: For patients in the German heroin trial outcome measures were analyzed for HAT versus methadone maintenance treatment (MMT) both for patients with and without a comorbid diagnosis according to CIDI. RESULTS: 47.2% of the sample had at least one comorbid psychiatric diagnosis, mainly neurotic, stress-related or somatoform (F4) or affective (F3) disorders. HAT had a better outcome than MMT concerning improvement of health and reduction of illicit drug use in both comorbid and non-comorbid patients, but weaker effects were found in the comorbid group. CONCLUSIONS: The better outcome of HAT also in comorbid patients suggests that psychiatric comorbidity should be an inclusion criterion for HAT. The weaker advantage of HAT may be due to pharmacological or methodological reasons.

[Prison health is public health! Problems in adapting and implementing health services for prisoners in Germany. A review]. / Prison Health is Public Health! Angleichungs- und Umsetzungsprobleme in der gesundheitlichen Versorgung Gefangener im deutschen Justizvollzug Ein Ubersichtsbeitrag.

On the basis of international standards, health care in German prisons has been oriented along the principle of equivalence (equity of health care delivery for inmates compared with the health care delivery in the community). Against this background, selected health problems demonstrate not only isolated problems in adaptation and implementation of health care delivery, but also structural problems resulting from the parallel system of prison health care, which is separated from the general German health care insurance system. This review serves as a basis to present suggestions to rethink and reorganize prison-based health care services.

[Status quo of opioid agonist maintenance therapy in Germany]. / Zum Stand der Substitutionstherapie in Deutschland.

Neurobiological evidence and clinical experience indicate that opioid dependence is a chronic relapsing disorder. Crisis intervention, abstinence-oriented treatment (including detoxification and relapse prevention), and agonist maintenance treatment are the current treatment options depending on the individually pursued treatment goals. Agonist maintenance therapy is considered the first-line treatment for severe chronic opioid dependence. Numerous studies demonstrated evidence of a growing number of different agonist maintenance agents, such as methadone, buprenorphine and also new options like slow-release morphine, intravenous, inhalable and oral diamorphine. Despite the proven effectiveness of agonist maintenance therapy, the number of comprehensive care facilities nationwide is still not adequate. The growing number of patients in maintenance-treatment has not been accompanied by an increase in the number of specialized German physicians actively taking part in substitution treatment. Further efforts are needed to ensure adequate health care provision for opiate addicts in Germany.

Intraperitoneal injection of sodium pentobarbital has the potential to elicit pain in adult rats (Rattus norvegicus).

An effective and pain-free killing method is required to achieve the goal of euthanasia, a "good death". Overdose of sodium pentobarbital (PB) by intraperitoneal (IP) injection is a widely accepted technique in laboratory rats, but questions remain regarding pain associated with administration. As PB rapidly causes sedation and loss of consciousness, most studies have relied on indirect evidence of pain. The objective of this study was to assess pain associated with IP PB using an appropriate vehicle control. Adult male and female Sprague Dawley (SD) and female Wistar rats (N = 84) were block randomised by sex and strain to receive one of three treatments: 1) 800 mg/kg PB (pH 11), 2) saline or 3) vehicle controls (pH 11 or 12.5). Behavior (Rat Grimace Scale (RGS), writhing, back arching) was evaluated at baseline, before loss of righting reflex (LORR, PB group), and at 80s, 151s and 10 min post-injection (PI; saline and vehicle control groups). In the PB group, mean time to LORR was 78 ± 7.9 seconds. In the vehicle control groups, RGS scores were increased at 151s PI (SD: p = 0.0002, 95%CI 0.73 to 0.20) from baseline, as was relative frequency of writhing (SD: p < 0.0001; Wistar; p = 0.0004). RGS scores remained elevated 10 mins PI (SD: p = 0.0005, 95%CI 0.71 to 0.18; Wistar: p = 0.0234, 95%CI 0.91 to 0.07) but the relative frequency of writhing did not (p > 0.999). The RGS scores and the relative frequency of writhing remained low in the PB and saline groups (p > 0.05). These results show that, vehicle controls for IP PB result in signs associated with pain, pain may not be experienced following IP PB when LORR occurs quickly, and that the effects of PB limit behavioral pain assessments.

Room temperature "optical nanodiamond hyperpolarizer": Physics, design, and operation.

Dynamic Nuclear Polarization (DNP) is a powerful suite of techniques that deliver multifold signal enhancements in nuclear magnetic resonance (NMR) and MRI. The generated athermal spin states can also be exploited for quantum sensing and as probes for many-body physics. Typical DNP methods require the use of cryogens, large magnetic fields, and high power microwave excitation, which are expensive and unwieldy. Nanodiamond particles, rich in Nitrogen-Vacancy (NV) centers, have attracted attention as alternative DNP agents because they can potentially be optically hyperpolarized at room temperature. Here, unraveling new physics underlying an optical DNP mechanism first introduced by Ajoy et al. [Sci. Adv. 4, eaar5492 (2018)], we report the realization of a miniature "optical nanodiamond hyperpolarizer," where 13C nuclei within the diamond particles are hyperpolarized via the NV centers. The device occupies a compact footprint and operates at room temperature. Instrumental requirements are very modest: low polarizing fields, low optical and microwave irradiation powers, and convenient frequency ranges that enable miniaturization. We obtain the best reported optical 13C hyperpolarization in diamond particles exceeding 720 times of the thermal 7 T value (0.86% bulk polarization), corresponding to a ten-million-fold gain in averaging time to detect them by NMR. In addition, the hyperpolarization signal can be background-suppressed by over two-orders of magnitude, retained for multiple-minute long periods at low fields, and deployed efficiently even to 13C enriched particles. Besides applications in quantum sensing and bright-contrast MRI imaging, this work opens possibilities for low-cost room-temperature DNP platforms that relay the 13C polarization to liquids in contact with the high surface-area particles.

Management and assessment of prognosis after gastrocnemius disruption in Thoroughbred foals: 28 cases (1993-2007).

REASONS FOR PERFORMING STUDY: Few studies have evaluated the athletic prognosis of foals affected by gastrocnemius disruption. OBJECTIVE: To examine the diagnosis and management of gastrocnemius disruption in Thoroughbred (TB) foals, determine short-term survival rate and assess future racing performance. The hypothesis was that Thoroughbred foals with gastrocnemius disruption are able to perform as racehorses comparably to their age matched maternal siblings. METHODS: The medical records of foals diagnosed with gastrocnemius muscle disruption were reviewed. Information on training and racing was acquired from published works and race records. Paired t tests were utilised to compare performance variables of affected racehorses to their maternal siblings in starts, earnings and earnings/start for their 2- and 3-year-old racing seasons. Fisher's exact tests were employed to determine the association between sex, limb affected, age on admission, degree of caudal reciprocal apparatus dysfunction, concurrent disease, antibiotic therapy, complications, abscess formation and likelihood of entering training or starting a race. RESULTS: Sample size was too small to detect significant differences in performance variables between affected horses and controls. Of 28 foals, 17 (61%) presented with concomitant illness; foals without concurrent disease were more likely to achieve race training or start a race (P = 0.04); 23 (82%) were short-term survivors defined as survival to discharge. Of these 23 survivors, 7 were aged <2 years at the time of the study. Eighty-one percent (13/16) of the survivors that were of racing age were in training or had started a race. CONCLUSIONS: In this population, 82% of TB foals affected with gastrocnemius disruption were able to achieve training or start a race. Foals presenting for gastrocnemius disruption have a high prevalence of concurrent disease processes. POTENTIAL RELEVANCE: The assessment of athletic prognosis and treatment complications provides useful information to clinicians treating gastrocnemius muscle disruption in foals and making recommendations to clientele.

Wide dynamic range magnetic field cycler: Harnessing quantum control at low and high fields.

We describe the construction of a fast field cycling device capable of sweeping a 4-order-of-magnitude range of magnetic fields, from ∼1 mT to 7 T, in under 700 ms, and which is further extendable to a 1 nT-7 T range. Central to this system is a high-speed sample shuttling mechanism between a superconducting magnet and a magnetic shield, with the capability to access arbitrary fields in between with high resolution. Our instrument serves as a versatile platform to harness the inherent dichotomy of spin dynamics on offer at low and high fields-in particular, the low anisotropy, fast spin manipulation, and rapid entanglement growth at low field as well as the long spin lifetimes, spin specific control, and efficient inductive measurement possible at high fields. Exploiting these complementary capabilities in a single device opens up applications in a host of problems in quantum control, sensing, and information storage, besides in nuclear hyperpolarization, relaxometry, and imaging. In particular, in this paper, we focus on the ability of the device to enable low-field hyperpolarization of 13C nuclei in diamond via optically pumped electronic spins associated with nitrogen vacancy defect centers.

Hyperpolarized relaxometry based nuclear T1 noise spectroscopy in diamond.

The origins of spin lifetimes in quantum systems is a matter of importance in several areas of quantum information. Spectrally mapping spin relaxation processes provides insight into their origin and motivates methods to mitigate them. In this paper, we map nuclear relaxation in a prototypical system of [Formula: see text] nuclei in diamond coupled to Nitrogen Vacancy (NV) centers over a wide field range (1 mT-7 T). Nuclear hyperpolarization through optically pumped NV electrons allows signal measurement savings exceeding million-fold over conventional methods. Through a systematic study with varying substitutional electron (P1 center) and [Formula: see text] concentrations, we identify the operational relaxation channels for the nuclei at different fields as well as the dominant role played by [Formula: see text] coupling to the interacting P1 electronic spin bath. These results motivate quantum control techniques for dissipation engineering to boost spin lifetimes in diamond, with applications including engineered quantum memories and hyperpolarized [Formula: see text] imaging.

Acculturation and mental distress among Russian and Iranian migrants in Germany.

Several studies have stressed a correlation between difficulties in acculturation and mental distress or even mental disorders. The stress related to the process of acculturation can lead to depressive symptoms by way of changes in the activity of the HPA axis. However, it remains difficult to measure acculturation stress, as difficulties in acculturation strongly depend on subjective interpretations of every day experiences. The association between acculturation stress and mental distress was examined in two different migrant groups in Germany, 202 migrants of Russian and 100 of Iranian origin. In both migrant groups a significant correlation between acculturation stress and mental distress was found, yet no significant association between acculturation stress and length of residency in Germany. These findings will have to be replicated with representative samples and also with other migrant groups, both in and out of treatment. Considering the fact that the Russian sample was younger and nonetheless had relatively high acculturation stress scores, prevention of future mental health problems among migrants will have to focus on easing the process of integration into the host society.

Switching from cyclosporine to tacrolimus leads to improved disease-specific quality of life in patients after kidney transplantation.

BACKGROUND: Advances in transplantation medicine are linked to improved efficacy of immunosuppressive agents. At the same time, these agents endanger medical success by side effects that may impair survival and quality of life (QOL). This study examined whether conversion to tacrolimus-based immunosuppression due to cyclosporine-related side effects improved. QOL in patients after kidney transplantation. METHODS: In total 64 patients (29 men) with an average age of 51 years (SD+/-12) who had received a kidney allograft an average of 5.6 years (SD+/-4) before conversion participated. The reasons for conversion were cardiovascular/metabolic (n=26) or periodontal/dermatological side effects (n=38) of cyclosporine therapy. QOL was assessed before conversion and in average 7 months thereafter by a global (SF-36) and a disease-specific instrument (ESRD-SCL). RESULTS: Disease-specific QOL (ESRD-SCL, global index) improved significantly (P<.001, explanation of variance [EV]=16.6%) after conversion from cyclosporine to tacrolimus. In detail, cardiac and renal dysfunction (P<.01, EV=12.9%) as well as increased growth of gum and hair (P<.0001, EV=53.2%) were significantly reduced at end of the study. However, global QOL (SF-36) remained unchanged. CONCLUSION: Regardless of the indication (cardiovascular or cosmetic), switching to tacrolimus due to cyclosporine-related side effects improved disease-specific QOL within the short term.