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Abstract Introduction Neurological disorders (ND) have a high incidence in sub-Saharan Africa (SSA). In this region, systemic challenges of conventional medicine (CM) and cultural beliefs have contributed to a large utilization of traditional medicine (TM). Yet, data on TM and those who use it in the treatment of ND in SSA are scarce. Here, we systematically analyze its role as a therapy modality for ND in Mali, the socio-demographic characteristics of its users, and propose next steps to optimize the dual usages of TM and CM for patients with ND. Methods We conducted a questionnaire study in two phases. In phase one, patients with ND answered questions on their usage of and attitudes towards TM. In phase two, the TM therapists who provided care to the patients in phase one answered questions regarding their own practices for treating ND. Patients were recruited from the country's two university neurology departments. Results 3,534 of the 4,532 patients seen in the Departments of Neurology in 2019 met the inclusion criteria. Among these 3,534 patients, 2,430 (68.8%) had previously consulted TM for their present ND. Patients over 60 years of age most often used TM (83.1%). By education, illiterate patients utilized TM the most (85.5%) while those with more than a secondary education used TM the least (48.6%). An income greater than the minimum guaranteed salary was associated with decreased use of traditional medicine (OR 0.29, CI 0.25–0.35, p

Abstract Background Our recent studies have shown headache disorders to be very common in the central and western sub-Saharan countries of Benin and Cameroon. Here we report headache in nearby Mali, a strife-torn country that differs topographically, culturally, politically and economically. The purposes were to estimate headache-attributed burden and need for headache care. Methods We used cluster-random sampling in seven of Mali’s eleven regions to obtain a nationally representative sample. During unannounced household visits by trained interviewers, one randomly selected adult member (18–65 years) from each household was interviewed using the structured HARDSHIP questionnaire, with enquiries into headache in the last year and, additionally, headache yesterday (HY). Headache on ≥ 15 days/month (H15+) was diagnosed as probable medication-overuse headache (pMOH) when associated with acute medication use on ≥ 15 days/month, and as “other H15+” when not. Episodic headache (on

Distributed ledger technologies (DLT) are increasingly considered to enhance payment systems’ and market infrastructures’ functionalities like their accessibility and interoperability. We explore DLT architecture options to enable a new tiered access in the RTGS system of Chile for new payment service providers (PSP). We find that by introducing decentralized apps (DApps) the RTGS system would become more accessible and interoperable by enabling a tiered access to new participants. Our work also suggests that central banks exploring design alternatives for retail Central Bank Digital Currencies (CBDC) could find relevant our approach as a pivot to build a far-reaching PSP network.

Deploying onshore wind energy as a cornerstone of future global energy systems challenges societies and decision-makers worldwide. Expanding wind energy should contribute to a more sustainable electricity generation without harnessing humans and their environment. Opponents often highlight the negative environmental impacts of wind energy to impede its expansion. This study reviews 152 studies to synthesize, summarize, and discuss critically the current knowledge, research gaps, and mitigation strategies on the environmental impacts of onshore wind energy. The investigated effects comprise impacts on the abiotic and biotic environment, with birds and bats in particular, noise and visual impacts. Effects are discussed in the context of social acceptance, other energy technologies, and wind energy expansion in forests. This review illustrates that many effects are highly case-specific and must be more generalizable. Studies are biased regarding the research focus and areas, needing more standardized research methods and long-term measurements. Most studies focus on the direct mortality of birds and bats at wind farms and are concentrated in Europe and North America. Knowledge gaps persist for many impact categories, and the efficacy of mitigation strategies has yet to be proven. More targeted, unbiased research is required that allows for an objective evaluation of the environmental impacts of wind energy and strategies to mitigate them. Impacts, such as those on biodiversity, need to be addressed in the context of other anthropogenic influences and the benefits of wind energy. This forms the basis for a socially acceptable, efficient, and sustainable expansion of wind energy.

Rooftop solar photovoltaics can significantly contribute to global energy transitions by providing clean, decentralized energy without the need for new land, thereby avoiding land-use conflicts. It serves as a valuable complement to other renewable-energy sources and is expected to play a crucial role in future electricity systems. Due to the spatiotemporal variability in the solar radiation on roof surfaces, it is essential to determine the potentials of the rooftop photovoltaics and its variations in specific regions. In Germany, this potential was assessed in 5 km × 5 km zones, as well as at the federal-state and national levels. High-quality satellite and reanalysis data were used to determine the power output of the solar photovoltaics. Additionally, high-resolution (2 m × 2 m) European Settlement Map data, calibrated with solar cadastre data, were utilized to evaluate different scenarios. The results show that the potential is concentrated in larger urban areas and the southwestern part of Germany due to the availability of rooftop space and solar radiation. Overall, the national rooftop areas are substantial across all scenarios, ranging from 2100 to 4500 km2. The applied methods and scenarios provide a straightforward way to reveal the spatiotemporal variability and define realistic ranges of the solar photovoltaic potential without requiring detailed information about each building. However, assessing the rooftop photovoltaic potential remains challenging and uncertain due to the lack of large-scale, high-resolution data on building characteristics and the complexity of the solar radiation distribution in urban environments.

Abstract Objective The boarding of ICU patients in the emergency department (ED) represents a considerable risk to patient safety. This study aims to describe the generation of a rubric to ensure the fidelity of vital, written hand‐off between ED teams. Methods We performed a mixed methods design to develop a scoring rubric to evaluate written hand‐off communication of medical ICU boarders between ED teams during the COVID‐19 pandemic. The primary outcome was the quality of the written hand‐off as agreed upon by the inter‐user agreement. Our secondary outcome included variability in written quality as a function of the number of separate and distinct ED teams at the point of the transition of care. Results There was a moderate inter‐user agreement with rubric scoring (κ = 0.70 [95% confidence interval, 0.66–0.75]). The overall trend noted that several key elements, including code status, performed interventions, and contingency planning, were infrequently documented. Conclusions We effectively created a quality assurance tool for ED ICU boarders that ensures relevant and vital information is relayed between ED teams. Our analysis demonstrated that all relevant information is only sometimes present in the hand‐off.

Intrauterine growth restriction (IUGR) and being small for gestational age (SGA) are two distinct conditions with different implications for short- and long-term child development. SGA is present if the estimated fetal or birth weight is below the tenth percentile. IUGR can be identified by additional abnormalities (pathological Doppler sonography, oligohydramnion, lack of growth in the interval, estimated weight below the third percentile) and can also be present in fetuses and neonates with weights above the tenth percentile. There is a need to differentiate between IUGR and SGA whenever possible, as IUGR in particular is associated with greater perinatal morbidity, prematurity and mortality, as well as an increased risk for diseases in later life. Recognizing fetuses and newborns being “at risk” in order to monitor them accordingly and deliver them in good time, as well as to provide adequate follow up care to ameliorate adverse sequelae is still challenging. This review article discusses approaches to differentiate IUGR from SGA and further increase diagnostic accuracy. Since adverse prenatal influences increase but individually optimized further child development decreases the risk of later diseases, we also discuss the need for interdisciplinary follow-up strategies during childhood. Moreover, we present current concepts of pathophysiology, with a focus on oxidative stress and consecutive inflammatory and metabolic changes as key molecular mechanisms of adverse sequelae, and look at future scientific opportunities and challenges. Most importantly, awareness needs to be raised that pre- and postnatal care of IUGR neonates should be regarded as a continuum.

Traumatic Brain Injury (TBI) represents a significant health concern, necessitating advanced therapeutic interventions. This detailed review explores the critical roles of astrocytes, key cellular constituents of the central nervous system (CNS), in both the pathophysiology and possible rehabilitation of TBI. Following injury, astrocytes exhibit reactive transformations, differentiating into pro-inflammatory (A1) and neuroprotective (A2) phenotypes. This paper elucidates the interactions of astrocytes with neurons, their role in neuroinflammation, and the potential for their therapeutic exploitation. Emphasized strategies encompass the utilization of endocannabinoid and calcium signaling pathways, hormone-based treatments like 17β-estradiol, biological therapies employing anti-HBGB1 monoclonal antibodies, gene therapy targeting Connexin 43, and the innovative technique of astrocyte transplantation as a means to repair damaged neural tissues.

Abstract Water treatment with activated carbon (AC) is an established method for the removal of organic micropollutants and natural organic matter. However, it is not yet possible to predict the removal of individual pollutants. An appropriate material characterization, matching adsorption processes in water, might be the missing piece in the puzzle. To this end, this study examined 25 different commercially available ACs to evaluate their material properties. Frequently reported analyses, including N $$_2$$ 2 adsorption/desorption, CHNS(O), point of zero charge (PZC) analysis, and X-ray photoelectron spectroscopy, were conducted on a selected subset of powdered ACs. Inorganic elements examined using X-ray fluorescence and X-ray diffraction spectroscopy revealed that relative elemental contents were distinctive to the individual AC’s raw material and activation procedure. This study also is the first to use thermogravimetric analysis (TGA) coupled to Fourier-transform infrared spectroscopy (FTIR) to conduct quantitative analyses of functional surface oxygen groups (SOGs: carboxylic acid, anhydride, lactone, phenol, carbonyl, and pyrone groups) on such a large number of ACs. The comparably economical TGA method was found to provide good surrogates for the PZC by pyrolytic mass loss up to 600 $$^{\circ }$$ ∘ C (ML $$_{600}$$ 600 ), for the oxygen content by ML $$_{1000}$$ 1000 and for the carbon content by oxidation. Mass loss profiles depict the AC’s chemistry like fingerprints. Furthermore, we found that SOG contents determined by TGA-FTIR covered a wide individual range and depended on the raw material and production process of the AC. TGA and TGA-FTIR might therefore be used to identify the suitability of a particular AC for a variety of target substances in different target waters. This can help practitioners to control AC use in waterworks or wastewater treatment plants.

Despite a concerted international effort in recent decades that has yielded significant progress in the fight against HIV/AIDS, the disease continues to kill large numbers of people. Although there is still no definitive cure or vaccine, UNAIDS has set an ambitious goal of ending the epidemic by 2030, specifically via its 90-90-90 (‘treatment cascade’) strategy – namely that 90 per cent of those with HIV will know their status, 90 per cent of those who know their status will be on antiretroviral therapy and 90 per cent of those on antiretroviral therapy will have an undetectable viral load. These bold assumptions were put to the test in a five-year pilot project launched in June 2014 by MSF and Kenya’s Ministry of Health in Ndhiwa district, where an initial NHIPS 1 study by Epicentre (MSF’s epidemiology centre) in 2012 revealed some of the world’s highest HIV incidence and prevalence, and a poor treatment cascade. Six years later, a new Epicentre study, NHIPS 2, showed that the 90-90-90 target had been more than met. What explains this ‘success’? And given the still-high incidence, is it truly a success? MSF Deputy Director of Operations Pierre Mendiharat and physician Léon Salumu, Head of MSF France Kenya programmes, discuss the political, scientific and operational challenges of the Ndhiwa project in an interview conducted by Elba Rahmouni.

Introducción: La hipertensión arterial constituye una de las primeras demandas de asistencia en Cuba. La teoría de las representaciones sociales se ha tornado un instrumento esencial en el estudio de las enfermedades y la salud. Resulta necesario acercarse a las creencias, opiniones, actitudes y conocimientos que el paciente hipertenso tiene sobre su enfermedad, debido a que tales elementos influyen sobre su comportamiento. El objetivo del estudio estuvo dirigido a explorar las representaciones sociales sobre hipertensión arterial de personas hipertensas. Método: Se realizó un estudio cualitativo, exploratorio y transversal en el área de salud Julio Antonio Mella, del municipio Guanabacoa, en La Habana, Cuba; durante el año 2017 y sus acciones se extendieron hasta 2019. Participaron 30 personas hipertensas y 10 profesionales de la salud. Como instrumentos se utilizaron la entrevista semiestructurada y el registro etnográfico. La información fue digitalizada, introducida y analizada en el programa de análisis cualitativo NVIVO. Resultados: Los hallazgos reflejaron una acepción negativa otorgada a la enfermedad por los individuos, basado en sus vivencias. Adquirieron conocimientos a partir de su diagnóstico, a la vez que la consideraron como incurable. La mayoría de las personas hipertensas realizaron el tratamiento indicado, en la medida en que ponderaron la efectividad del fármaco por encima de la dieta. Discusión: Se hallaron problemáticas en torno al control de la enfermedad provenientes de los pacientes como comportamientos imprudentes y escaso autocuidado, así como del sistema de salud respecto a deficiencias en el suministro de medicamentos.

To overcome resistance to chemotherapy for colorectal cancer, we propose to validate in vivo a novel terpyridine-platinum (TP) compound radiolabeled with the radio-theranostic isotope 64Cu. In vivo stability, biodistribution, PET imaging, tumor growth delay, toxicity and dosimetry of [64Cu]NOTA-C3-TP were determined. The current experimental studies show that [64Cu]NOTA-C3-TP is stable in vivo, rapidly eliminated by the kidneys and has a promising tumor uptake ranging from 1.8 ± 0.4 to 3.0 ± 0.2 %ID/g over 48 h. [64Cu]NOTA-C3-TP retarded tumor growth by up to 6 ± 2.0 days and improved survival relative to vehicle and non-radioactive [NatCu]NOTA-C3-TP over 17 days of tumor growth observation. This effect was obtained with only 0.4 nmol i.v. injection of [64Cu]NOTA-C3-TP, which delivers 3.4 ± 0.3 Gy tumoral absorbed dose. No evidence of toxicity, by weight loss or mortality was revealed. These findings confirm the high potential of [64Cu]NOTA-TP as a novel radio-theranostic agent.

In modern reconstructive medicine, personalized bone substitutes provide therapeutic hope for patients with non-standard bone defects. The study aims to present a description of a case of using a personalized bone substitute material, taking into account the vascular connections formed after a previous skin transplant. The 29-year-old patient was admitted to the plastic surgery department urgently after being electrocuted with high voltage. Due to extensive scalp burns, a skin graft was performed in the area of previously removed skin along with a charred skull bone vault. After a few months, the patient was qualified for cranioplasty with the use of personalized bone substitutes. The necessity to make cuts around the vascular connections present in the transplanted tissue was the main difficulty in the for the operator. The operation was successful and the recovery was uneventful. The patient was discharged home in good general and local condition. The presented case illustrates the need to take into account creating vascular connections with the use of personalized bone substitutes in patients after skin transplants.

Abstract Purpose The assessment of patient satisfaction during treatment is essential to provide patient-centered high-quality cancer care. Nevertheless, no German instrument assesses patient satisfaction with comprehensive cancer care, which not only includes oncological treatment, but also interpersonal quality of care as well as psychosocial support services. Based on the French REPERES-60, we developed the German Patient Satisfaction with Comprehensive Cancer Care (SCCC) questionnaire. Methods The REPERES-60 was translated and the items were adapted to make it applicable to the German healthcare system and across different tumor entities. Scales of the resulting instrument were extracted via principal axis factoring (PAF). Subsequently, we investigated the reliability (Cronbach’s Alpha, CA), discriminatory power (corrected item-scale correlations) and convergent validity (pre-specified correlations of the SCCC with different outcomes). Results The SCCC consisted of 32 items which were subsequently tested among a sample of 333 patients across different tumor entities (response rate: 47%). Average age was 59 years (standard deviation: 14), 63% were male. PAF revealed four multi-item scales named Competence, Information, Access and Support accounting for 71% of the variance. Two single-items scales assess global satisfaction with medical and psychosocial care, respectively. CA across the multi-item scales ranged from .84 to .96. Discriminatory power was sufficiently high, with all r ≥ .5. Convergent validity was largely verified by negative associations of the four multi-item scales with depressive/anxious symptomatology (r ≥ − .18, p

Se describe un caso de hiperplaia insular localizada, destacándose el carácter funcionante de la misma, que contrasta con los casos más frecuentes sin repercusión funcional.

Spinal Cord Injury (SCI) is a common neurological disorder with devastating psychical and psychosocial sequelae. The majority of patients after SCI suffer from permanent disability caused by motor dysfunction, impaired sensation, neuropathic pain, spasticity as well as urinary complications, and a small number of patients experience a complete recovery. Current standard treatment modalities of the SCI aim to prevent secondary injury and provide limited recovery of lost neurological functions. Stem Cell Therapy (SCT) represents an emerging treatment approach using the differentiation, paracrine, and self-renewal capabilities of stem cells to regenerate the injured spinal cord. To date, multipotent stem cells including mesenchymal stem cells (MSCs), neural stem cells (NSCs), and hematopoietic stem cells (HSCs) represent the most investigated types of stem cells for the treatment of SCI in preclinical and clinical studies. The microenvironment of SCI has a significant impact on the survival, proliferation, and differentiation of transplanted stem cells. Therefore, a deep understanding of the pathophysiology of SCI and molecular mechanisms through which stem cells act may help improve the treatment efficacy of SCT and find new therapeutic approaches such as stem-cell-derived exosomes, gene-modified stem cells, scaffolds, and nanomaterials. In this literature review, the pathogenesis of SCI and molecular mechanisms of action of multipotent stem cells including MSCs, NSCs, and HSCs are comprehensively described. Moreover, the clinical efficacy of multipotent stem cells in SCI treatment, an optimal protocol of stem cell administration, and recent therapeutic approaches based on or combined with SCT are also discussed.

Abstract Background The goal of targeted radiotherapy (TRT) is to administer radionuclides to tumor cells, while limiting radiation exposure to normal tissues. 3′-Deoxy-3′-[18F]-fluorothymidine (18F-FLT) is able to target tumor cells and emits a positron with energy appropriate for local (~ 1 mm range) radiotherapy. In the present work, we investigated the potential of TRT with a local administration of 18F-FLT alone or in combination with 5-fluorouracil (5FU), which acts as a chemotherapeutic agent and radiosensitizer. Treatment efficiency of 18F-FLT combined or not with 5FU was evaluated by intratumoral (i.t.) infusion into subcutaneous HCT116 colorectal tumors implanted in nu/nu mice. The tumor uptake and kinetics of 18F-FLT were determined and compared to 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) by dynamic positron emission tomography (PET) imaging following i.t. injection. The therapeutic responses of 18F-FLT alone and with 5FU were evaluated and compared with 18F-FDG and external beam radiotherapy (EBRT). The level of prostaglandin E2 (PGE2) biosynthesis was measured by liquid chromatography/tandem mass spectrometry (LC/MS/MS) in order to determine the level of inflammation to healthy tissues surrounding the tumor, after i.t. injection of 18F-FLT, and compared to EBRT. Results We found that i.t. administration of 18F-FLT offers (1) the highest tumor-to-muscle uptake ratio not only in the injected tumor, but also in distant tumors, suggesting potential for concurrent metastases treatment and (2) a sixfold gain in radiotherapeutic efficacy in the primary tumor relative to EBRT, which can be further enhanced with concurrent i.t. administration of the radiosensitizer 5FU. While EBRT stimulated PGE2 production in peritumoral tissues, no significant increase of PGE2 was measured in this area following i.t. administration of 18F-FLT. Conclusion Considering the biochemical stability of 18F-FLT and the physical properties of localized 18F, this study shows that TRT via intratumoral infusion of 18F-FLT and 5FU could provide a new effective treatment option for solid tumors. Using this approach in a colorectal tumor model, the tumor and its metastases could be efficiently irradiated locally with much lower doses absorbed by healthy tissues than with i.t. administration of 18F-FDG or conventional EBRT.

Tasmania del Pino-Sedeño,1,2 Wenceslao Peñate,1 Carlos de las Cuevas,3 Cristina Valcarcel-Nazco,2,4 Ascensión Fumero,1 Pedro Guillermo Serrano-Pérez,5,6 Francisco Javier Acosta Artiles,7 Vanesa Ramos García,4 Beatriz León Salas,4 Daniel Bejarano-Quisoboni,8 María M Trujillo-Martín2,4 1Department of Clinical Psychology, Psychobiology and Methodology, University of La Laguna, Canary Islands, Spain; 2Health Services Research on Chronic Patients Network (REDISSEC), Madrid, Spain; 3Department of Internal Medicine, Dermatology and Psychiatry, University of La Laguna, Canary Islands, Spain; 4Canary Islands Foundation of Health Research (FUNCANIS), Canary Islands, Spain; 5Department of Psychiatry, Hospital Universitari Vall d’ Hebron, Catalonia, Spain; 6Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Catalonia, Spain; 7Service of Mental Health, General Health Care Programs Direction, Canary Health Service, Canary Islands, Spain; 8Center for Public Health Research (CSISP-FISABIO), Valencia, Spain Purpose: Depression is a widespread mental disorder which can be treated effectively. However, low adherence to antidepressants is very common. The study of medication adherence in depression (MAPDep study) assesses the effectiveness and cost-effectiveness of a multicomponent strategy to enhance adherence toward medications in patients with depression.Intervention: The intervention is a multicomponent one consisting of an educational program for psychiatrists and/or a collaborative care program for patients and relatives, plus a reminder system that works through the use of an already available high-quality medication reminder application.Study design: MAPDep study is an open, multicenter, four-arm cluster randomized controlled trial. The clusters are mental health units where psychiatrists are invited to participate. The clusters are randomly allocated to one of the three interventions or to usual care (control arm). Patients (18–65 years of age) diagnosed with depressive disorder, those taking antidepressant medication for an existing diagnosis of depression, and mobile phone users are selected. In group 1, only patients and relatives receive intervention; in group 2, only psychiatrists receive intervention; and in group 3, patients/relatives and psychiatrists receive intervention. The primary outcome is adherence to the antidepressant drug. The calculated sample size is 400 patients. To examine changes across time, generalized linear mixed model with repeated measures will be used. A cost-effectiveness analysis will be conducted. The effectiveness measure is quality-adjusted life years. Deterministic sensitivity analyses are planned.Conclusion: MAPDep study aims to assess a multicomponent strategy to improve adherence toward medications in patients with depression, based not only on clinical effectiveness but also on cost-effectiveness. This methodology will enhance the transferability of the expected results beyond mental health services (patients and psychiatrists) to health care policy decision making.Clinical trial identifier: NCT03668457. Keywords: depression, medication adherence, education, behavior modification, mobile phone technology, cost-effectiveness

Motivations for introducing a retail central bank digital currency (CBDC) could range from a rapid decline in the use of physical cash or financial inclusion strategies to an underdeveloped retail payment market. The COVID-19 pandemic and the emergence of global stablecoins proposals have heightened the interest in exploring the introduction of a rCBDC. With the aim of informing these efforts before, during and after its potential implementation, we explore recently launched pilots in three jurisdictions. We aim to provide relevant lessons on the design, operation and implementation of such a new digital form of fiat money. Notably, despite differences among jurisdictions and CBDC pilots, a series of key insights emerge from these experiences that could be useful for those thinking to launch a rCBDC.

La inflamación del sistema nervioso central secundaria a la infección por la familia herpesviridae puede generar un compromiso difuso del parénquima encefálico, la cual puede ser fatal en ausencia de un rápido diagnóstico y tratamiento. Objetivo: revisar las diferentes características biológicas, fisiopatológicas, clínicas, terapéuticas y pronóstico de la meningoencefalitis causada por VHS-1 y 2. Materiales y métodos: revisión de la literatura científica (revisión crítica), llevada a cabo mediante las bases de datos Medline y buscadores específicos IMBIOMED, PUBMEDE, SCIENCEDIRECT, SCIELO, con un total de 150 artículos, se priorizaron 67 los cuales fueron leídos a profundidad. Resultados y discusión: debido el neurotropismo del herpes virus simple puede causar neuroinvasividad, neurotoxicidad y latencia en el SNC. Por sus características semiológicas inespecíficas se requiere un estudio exhaustivo para lograr el diagnóstico acertado. Los métodos actuales tales como neuroimágenes y PCR han aportado al esclarecimiento del diagnóstico etiológico de esta patología. La detección temprana de la entidad y la instauración precoz del tratamiento, se asocian con un aumento en la tasa de supervivencia y a una disminución de las secuelas neurológicas. Conclusión: conocer la biología del virus, su comportamiento, las características clínicas y el tratamiento de la entidad es una estrategia eficaz para disminuir secuelas y desenlaces fatales.

Abstract Background Effectiveness of chemotherapy for treating glioblastoma (GBM) brain tumors is hampered by the blood–brain barrier which limits the entry into the brain of most drugs from the blood. To bypass this barrier, convection-enhanced delivery (CED) was proposed to directly inject drugs in tumor. However, the benefit of CED may be hampered when drugs diffuse outside the tumor to then induce neurotoxicity. Encapsulation of drugs into liposome aims at increasing tumor cells specificity and reduces neurotoxicity. However, the most appropriate liposomal formulation to inject drugs into brain tumor by CED still remains to be determined. In this study, four liposomal carboplatin formulations were prepared and tested in vitro on F98 glioma cells and in Fischer rats carrying F98 tumor implanted in the brain. Impact of pegylation on liposomal surface and relevance of positive or negative charge were assessed. Results The cationic non-pegylated (L1) and pegylated (L2) liposomes greatly improved the toxicity of carboplatin in vitro compared to free carboplatin, whereas only a modest improvement and even a reduction of efficiency were measured with the anionic non-pegylated (L3) and the pegylated (L4) liposomes. Conversely, only the L4 liposome significantly increased the median survival time of Fisher rats implanted with the F98 tumor, compared to free carboplatin. Neurotoxicity assays performed with the empty L4′ liposome showed that the lipid components of L4 were not toxic. These results suggest that the positive charge on liposomes L1 and L2, which is known to promote binding to cell membrane, facilitates carboplatin accumulation in cancer cells explaining their higher efficacy in vitro. Conversely, negatively charged and pegylated liposome (L4) seems to diffuse over a larger distance in the tumor, and consequently significantly increased the median survival time of the animals. Conclusions Selection of the best liposomal formulation based on in vitro studies or animal model can result in contradictory conclusions. The negatively charged and pegylated liposome (L4) which was the less efficient formulation in vitro showed the best therapeutic effect in animal model of GBM. These results support that relevant animal model of GBM must be considered to determine the optimal physicochemical properties of liposomal formulations.

Maximum benefits of chemoradiation therapy with platinum-based compounds are expected if the radiation and the drug are localized simultaneously in cancer cells. To optimize this concomitant effect, we developed the novel chemoradiotherapeutic agent [64Cu]Cu-NOTA-C3-TP by conjugating, via a short flexible alkyl chain spacer (C3), a terpyridine platinum (TP) moiety to a NOTA chelator complexed with copper-64 (64Cu). The decay of 64Cu produces numerous low-energy electrons, enabling the 64Cu-conjugate to deliver radiation energy close to TP, which intercalates into G-quadruplex DNA. Accordingly, the in vitro internalization kinetic and the cytotoxic activity of [64Cu]Cu-NOTA-C3-TP and its derivatives were investigated with colorectal cancer (HCT116) and normal human fibroblast (GM05757) cells. Radiolabeling by 64Cu results in a >55,000-fold increase of cytotoxic potential relative to [NatCu]Cu-NOTA-C3-TP at 72 h post administration, indicating a large additive effect between 64Cu and the TP drug. The internalization and nucleus accumulation of [64Cu]Cu-NOTA-C3-TP in the HCT116 cells were, respectively, 3.1 and 6.0 times higher than that for GM05757 normal human fibroblasts, which is supportive of the higher efficiency of the [64Cu]Cu-NOTA-C3-TP for HCT116 cancer cells. This work presents the first proof-of-concept study showing the potential use of the [64Cu]Cu-NOTA-C3-TP conjugate as a targeted chemoradiotherapeutic agent to treat colorectal cancer.

This study investigates the effects of two mechanism-based treatments for expressive aprosodia. Three participants, two women and one man, had a right hemisphere cerebral infarction resulting in affective aprosodia with greater expressive than receptive deficits. Trained raters determined presence of aprosodia by judging participants' performance on two emotional communication batteries. A single-subject design with replication across three participants was employed. Sentence production with the use of treated and nontreated emotions was measured during baseline and treatment phases. Sentences were scored for accuracy by a trained rater blind to time of testing and analyzed visually and statistically. Effect sizes calculated on the resulting data for each participant and treatment confirmed modest to substantial treatment effects for both treatments in all three participants. Because of a relative paucity of treatment studies investigating expressive aprosodia, these data are among the first to suggest that aprosodia may be amenable to behavioral treatments. [ABSTRACT FROM AUTHOR]

Abstract Northern Uganda hosts a large population of refugees from South Sudan, and malaria is one of the major health problems in the area. In 2015, intermittent preventive treatment for malaria (IPTc) was implemented in two refugee camps among children aged 6 months to 14 years. Three distributions of dihydroartemisinin–piperaquine (DP) were conducted at 8-week intervals. The first dose was directly administered at IPTc distribution sites and the second and third doses were given to caregivers to administer at home. A multi-faceted evaluation was implemented, including coverage surveys, malaria prevalence surveys, reinforced surveillance, and pharmacovigilance. Programme coverage exceeded 90% during all three distributions with a total of 40,611 participants. Compared to same period during the previous year (only available data), the incidence of malaria in the target populations was reduced (IRR 0.73, 95% CI 0.69–0.77 among children under 5 years old; IRR 0.70, 95% CI 0.67–0.72 among children aged 5–14 years). Among those not targeted for intervention, the incidence between the 2 years increased (IRR 1.49, 95% CI 1.42–1.56). Cross-sectional surveys showed a prevalence of parasitaemia (microscopy or PCR) of 12.9–16.4% (95% CI 12.6–19.3) during the intervention, with the highest prevalence among children aged 5–14 years, but with a large increase 8 weeks after the final distribution. A total of 57 adverse events were reported during the intervention period, including one severe adverse event (death from varicella). Adverse events were of mild to moderate severity, and were mainly dermatologic and gastrointestinal. This is the first documentation of an IPTc programme in a refugee camp. The positive impact of DP on the incidence of malaria, together with its favourable safety profile, should lead to further use of IPTc in similar settings. Expanding coverage groups and decreasing intervals between distributions might provide more benefit, but would need to be balanced with the operational implications of a broader, more frequent distribution schedule.

La ecocardiografía transesofágica es un método de diagnóstico por imágenes ampliamente utilizado y recomendado como guía en el cierre percutáneo de una comunicación interauricular tipo ostium secundum. En pacientes de edad pediátrica, se prefiere el uso de una sonda de tamaño apropiado que pueda ser insertada y manipulada con seguridad, y generalmente se aconseja el uso de sondas pediátricas en pacientes con pesos menores a 20 Kg.Estudio de serie de casos y observacional. Entre octubre de 2006 y diciembre de 2014, fueron intervenidos en nuestro Servicio 21 pacientes con comunicaciones interauriculares y pesos entre 15 y 20 kg. En todos ellos se utilizó sonda transesofagica para adultos. Los pacientes tenían una edad promedio de 5,09 años (rango 4-7 años) siendo el 90% de sexo femenino (19 pacientes). El peso promedio al momento del procedimiento fue de 18,37 kg (rango 15,1-20 kg). El tiempo que la sonda transesofágica estuvo colocada fue de 35,5 minutos (rango 21 -75 minutos). Se pudo completar el cierre percutáneo en todos los casos. Durante el procedimiento, a las 24 horas y a mediano-largo plazo, no se registraron complicaciones relacionadas al uso de sondas transesofágicas para adultos en estos pacientes pediátricos.De acuerdo a nuestra experiencia, el monitoreo para cierre percutáneo de una comunicación interauricular tipo ostium secundum con sonda de ecocardiografía transesofágica para adultos en pacientes pediátricos con pesos entre 15 y 20 kg puede realizarse con seguridad y eficacia.

Betrokkenheid is een centraal thema binnen de marketingliteratuur. De theorievorming omtrent betrokkenheid heeft zich echter vooral geconcentreerd op de betrokkenheid vanuit de klant. Veel weten we inmiddels over “customer involvement”. De laatste jaren verschuift de aandacht echter naar “customer engagement” waarin de betrokkenheid van de klant met het product of merk verder gaat dan enkel het eigenbelang, en klanten gemotiveerd blijken om tijd en geld te investeren in bijvoorbeeld referentiegedrag, blogging en hulp bij productverbetering. In een poging tot meer klantenbinding claimen steeds meer (dienstverlenende) organisaties dat ze onderscheidend zijn omdat juist bij hen “de klant centraal staat; er écht toe doet; en de organisatie werkelijk betrokken is met de cliënt”. Hierdoor ontstaat er behoefte aan meer kennis over betrokkenheid vanuit de organisatiekant en dan vooral wat de klant daarvan merkt. In deze studie introduceren we het begrip “corporate engagement” en onderzoeken de invloed hiervan op klantloyaliteit.

The purpose of this paper is to contextualize transnational practices of the southern families of Morocco established in Canaries. It draws on the theoretical proposal of migrant transnationalism and used quantitative and qualitative techniques to determine the presence and features of the phenomenon understudy. The Morocco-Canary migration pattern is characterized by irregular entry of men, which increases during the last decade of the origins of southern Morocco. In 2009 predominantly legal residence with grouping and enhancement of the entry of women. Also correlated with transnational practices: family status, residential southern origin, occupation in destination and timing of arrival. The Moroccan border regions are more transnational which demonstrates the strength of transnational ties in this local context subject to a border political confl ict that has lastedmore than 30 years.

El reflejo mandibular o maseterino posee conexiones nerviosas únicas, diferentes de las exhi­bidas por otros reflejos monosinápticos humanos, y permite evaluar, de forma fácil y eficien­te, el tallo cerebral por medio de la estimulación mecánica, eléctrica o magnética. Diversos estudios han demostrado la participación en este reflejo de las interneuronas del tallo cerebral y su modulación por estructuras supraespinales, que hacen parte fundamental de su integra­ción motora. El reflejo mandibular es útil para evaluar la afectación trigémino-trigeminal en polineuropatías como la diabetes, neuromiopatías como la esclerosis múltiple y en pacientes con trastornos del movimiento, con o sin disfunción oromandibular. La evaluación neuro­funcional de este reflejo craneofacial ayuda a identificar la integración sensorimotora del tallo cerebral y las posibles alteraciones de estas vías reflejas, debidas a anormalidades del sistema nervioso central o del periférico. Su apropiada ejecución e interpretación, clínica y neurológica, permite aplicar de manera más personalizada diversos protocolos de neurorre­habilitación, con el fin de ayudar a mejorar la calidad de vida de los individuos con afectación de estas vías neurales.

En este trabajo se presenta un modelo de programación por metas no lineal devariable binaria para planificar el aprovechamiento de una plantación productora demadera en Cuba, donde se tienen en cuenta tanto objetivos económicos comoecológicos. Se trata de no superar ciertos niveles de volumen extraído, limitar la edad delos rodales a los que se aplica tala rasa, conseguir un bosque lo más equilibrado posiblerespecto a grupos de edad, superar ciertos niveles del valor actualizado neto en cadaperiodo de la planificación así como un umbral global prefijado de captura de carbonopara toda la planificación. Estos objetivos se tratan de superar teniendo en cuenta,además de restricciones técnicas relativas a los tratamientos, restricciones espaciales deadyacencias que limitan la superficie contigua máxima a la que se aplica tala rasa. Elresultado es un problema sumamente complejo, para el que se ha recurrido al métodometaheurístico basado en Scatter Search SSPMO a la hora de tratar su resolución. Conobjeto de contrastar la potencialidad del modelo propuesto, lo hemos aplicado a unaplantación de Pinus Caribaea situada en la provincia cubana de Pinar del Río.

Background. Homeless veterans have complex healthcare needs, but experience many barriers to treatment engagement. While information technologies (IT), especially mobile phones, are used to engage patients in care, little is known about homeless veterans’ IT use. This study examines homeless veterans’ access to and use of IT, attitudes toward health-related IT use, and barriers to IT in the context of homelessness.Methods. Qualitative interviews were conducted with 30 homeless veterans in different housing programs in Boston, MA, ranging from emergency shelters to supportive transitional housing that allow stays of up to 2 years. Interviews were conducted in person, audio recorded and then transcribed. Three researchers coded transcripts. Inductive thematic analysis was used.Results. Most participants (90%) had a mobile phone and were receptive to IT use for health-related communications. A common difficulty communicating with providers was the lack of a stable mailing address. Some participants were using mobile phones to stay in touch with providers. Participants felt mobile-phone calls or text messages could be used to remind patients of appointments, prescription refills, medication taking, and returning for laboratory results. Mobile phone text messaging was seen as convenient, and helped participants stay organized because necessary information was saved in text messages. Some reported concerns about the costs associated with mobile phone use (calls and texting), the potential to be annoyed by too many text messages, and not knowing how to use text messaging.Conclusion. Homeless veterans use IT and welcome its use for health-related purposes. Technology-assisted outreach among this population may lead to improved engagement in care.

Las encefalopatías espongiformes transmisibles (EET) han cobrado gran importancia en los últimos años. Principalmente por el surgimiento de la encefalopatía espongiforme del bovino (EEB) y la nueva variante de la ermedad de Creutzfeldt-Jakob (nvECJ), esta última probablemente adquirida por la ingesta de carne de bovino contaminada. Hasta la fecha se ha informado de 109 casos de la nvECJ en el humano y la gran mayoría de los casos ha ocurrido en el Reino Unido. No se sabe la magnitud real que podrán tener las EET en el humano, sin embargo algunos piensan que nos encontramos en el principio de una pandemia de la nvECJ. En el presente artículo se discuten varios aspectos de las EET y métodos para la prevención de la transmisión de estas enfermedades, tanto en rumiantes como en el humano.