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The objective of regulatory authorities is to ensure a favourable risk-benefit balance for medicines in their licenced indication, without seeking to establish their place in the therapeutic armamentarium beyond that. The licenced indication covers heterogeneous subpopulations and often does not sufficiently specify the characteristics of the patients who may benefit. The regulatory information does not always show the benefit over the standard treatment(s); moreover, it only reacts to the conditions specified in the developer's application, and lacks an assessment of the clinical relevance of the benefit and its uncertainties. Many cases highlight the need to establish a more specific therapeutic benefit scenario than the licenced indication. For example, abemaciclib was approved in the adjuvant setting for high-risk patients with early breast cancer, but the appropriate level of risk and how to assess it needs to be specified. Also, pembrolizumab is approved for neoadjuvant plus adjuvant treatment in lung cancer; but it remains to be analysed whether it is superior to nivolumab in neoadjuvant treatment alone, which involves less treatment and economic burden. As therapeutic positioning is always a necessary decision, whether made at a national, regional, local, or individual level, it must be made in the most appropriate way. The absence of a multidisciplinary discussion and consensus, relying only on individual decisions to determine positioning from the outset, underestimates information gaps, inter-individual variability, and the influence of drug promotion. It can be harmful and costly. To properly manage the introduction of new medicines, it is essential to establish their benefit scenario in a multidisciplinary way. This, together with consideration of the clinical benefit provided versus the appropriate alternatives and the uncertainties of the benefit, constitutes the objective of the clinical assessment and the basis for designing a well-focused economic analysis. This allows policy-makers to make the most appropriate decisions on pricing and funding new treatments. In an ideal situation, the benefit scenario considered for the new medicine would coincide with the one established for funding, but costs that are difficult to bear may lead to restrictions and affect the final positioning after the economic and budgetary impact assessment., Competing Interests: Declaration of competing interest Manuel Jesús Cárdenas Aranzana has served on advisory boards for Merck Serono and Incyte., (Copyright © 2024. Publicado por Elsevier España, S.L.U.)

Objetivo: Estimar el riesgo de morir por SARS-CoV-2 en el periodo febrero de 2020 a junio de 2022, en función de las desigualdades socioterritoriales existentes en la Ciudad de México. Material y métodos. Análisis retrospectivo de los datos de defunciones por SARS-CoV-2 en la población de la Ciudad de México entre febrero de 2020 y junio de 2022, según la colonia de residencia clasificada en muy bajo, bajo, medio, alto y muy alto desarrollo social, a partir del Índice de Desarrollo Social (IDS) propuesto por el Consejo de Evaluación de la Ciudad de México., Resultados: Las defunciones por Covid-19 en las colonias con muy bajo y bajo desarrollo social representaron casi la mitad de los fallecimientos. La población residente en los territorios con peores condiciones socioterritoriales falleció, en promedio, 10 años más joven que la del estrato con mejor IDS., Conclusiones: Las diferencias en el riesgo de morir por SARS-CoV-2 se asociaron a las condiciones socioterritoriales en las que residía la población fallecida. El riesgo de muerte por SARS-CoV-2 fue más alto para las personas residentes en colonias con muy bajo y bajo IDS. Estas diferencias se redujeron a partir de la tercera ola, lo que posiblemente se deba al inicio de la vacunación masiva en la Ciudad de México.

This clinical report presents a conservative approach to restoring aesthetic function in anterior maxillary teeth using digital dental technologies. A 40-year-old female patient sought treatment to enhance the aesthetics of her anterior maxillary teeth. The clinical examination revealed wear on the incisal surfaces and gingival asymmetry. Utilizing a digital workflow, intraoral and extraoral data were acquired through clinical photographs and an intraoral scanner. The patient's restorative needs were assessed using the 3Shape Smile Design system (3Shape, Copenhagen, Denmark). Minimal-thickness ceramic restorations were designed and fabricated using Computer-Aided Design-Computer-Aided Manufacturing (CAD-CAM) technologies. Lithium disilicate was selected for its strong mechanical properties and adhesive capabilities. The restorations were then placed using an adhesive cementation protocol under magnification. Digital technologies facilitated precise diagnosis, planning, and execution of the treatment. The ceramic restorations provided excellent aesthetic outcomes, aligning with the patient's expectations. The minimal thickness of the restorations ensured the preservation of natural tooth structure while maintaining structural integrity and adhesion performance. This case underscores the advantages of a digital workflow in achieving optimal restorative outcomes. The digital dental workflow demonstrated in this case report provides a reliable, efficient, and patient-centric approach to minimal thickness restorations, highlighting the potential for future advancements in restorative dentistry., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Osorio-Vélez et al.)

The objective of regulatory authorities is to ensure a favorable risk-benefit balance for medicines in their licensed indication, without seeking to establish their place in the therapeutic armamentarium beyond that. The licensed indication covers heterogeneous subpopulations and often does not sufficiently specify the characteristics of the patients who may benefit. The regulatory information does not always show the benefit over the standard treatments; moreover, it only reacts to the conditions specified in the developer's application, and lacks an assessment of the clinical relevance of the benefit and its uncertainties. Many cases highlight the need to establish a more specific therapeutic benefit scenario than the licensed indication. For example, abemaciclib was approved in the adjuvant setting for high-risk patients with early breast cancer, but the appropriate level of risk and how to assess it needs to be specified. Also, pembrolizumab is approved for neoadjuvant plus adjuvant treatment in lung cancer; but it remains to be analyzed whether it is superior to nivolumab in neoadjuvant treatment alone, which involves less treatment and economic burden. As therapeutic positioning is always a necessary decision, whether made at a national, regional, local or individual level, it must be made in the most appropriate way. The absence of a multidisciplinary discussion and consensus, relying only on individual decisions to determine positioning from the outset, underestimates information gaps, inter-individual variability and the influence of drug promotion. It can be harmful and costly. To properly manage the introduction of new medicines, it is essential to establish their benefit scenario in a multidisciplinary way. This, together with consideration of the clinical benefit provided versus the appropriate alternatives and the uncertainties of the benefit, constitutes the objective of the clinical assessment and the basis for designing a well-focused economic analysis. This allows policy makers to make the most appropriate decisions on pricing and funding new treatments. In an ideal situation, the benefit scenario considered for the new medicine would coincide with the one established for funding, but costs that are difficult to bear may lead to restrictions and affect the final positioning after the economic and budgetary impact assessment., (Copyright © 2024. Publicado por Elsevier España, S.L.U.)

Pituicytoma is a rare low degree tumor that arises from pituicytes in the infundibulum and posterior pituitary gland. As they do not have characteristic radiological features, they can be misdiagnosed as pituitary adenoma, meningioma, or craniopharyngioma. Clinically, patients can present with hormonal disturbances, headaches and visual field defects. A 46 year old male who presented with visual field defects and symptoms suggestive of panhypopituitarism for the past 3 years, is described. As a personal history, he had neurofibromatosis type 1 and his daughter, with the same disease, who has been operated of astrocytoma. Upon clinical assessment, the patient's ophthalmic examination was bitemporal hemianoptia, and hormonal evaluation confirmed hypopituitarism. Pituitary magnetic resonance imaging showed a suprasellar homogeneous enhancing post-gadolinium mass causing chiasmatic displacement. Transnasal transsphenoidal resection was performed. Postoperatively, the patient developed diabetes insipidus. Histopathology showed patterns consistent with pituicytoma. and immunohistochemistry confirmed it. Total resection remains the goal of treatment.

The Unified Identification Protocol (UIP) is an innovation which empowers patients and legal guardians to generate their unique digital identity for cross-border healthcare. This digital identity seamlessly links to local identifiers across different territories and organizations, bridging the gap between disparate systems. Combined with the International Patient Summary (IPS) - endorsed by the G7 and the EU - UIP is pioneering a new paradigm in telehealth services. Championing a user-centric approach in line with Web 3.0 principles, UIP places data control directly in the hands of patients and their legal guardians. This ensures accurate identification, streamlined access to health data, and robust privacy protection. When harmonized with tools like the SMART-On-FHIR API, FHIR Contract, DID Documents, and blockchain certification, UIP lays down transparent, user-approved guidelines for sharing healthcare data across borders. This framework guarantees that data is securely exchanged, encrypted specifically for the intended recipients upon user consent, adhering to international standards, and in full compliance with prevailing regulations. Furthermore, UIP facilitates certification of health courses and competences for patients, caregivers, and practitioners, enhancing healthcare understanding and management.

Quality of processes and products is based on traceability and review of both components, material processing and product flow throughout the manufacturing and supply chain. Blockchain technology enables cross-border audit trail and traceability while reducing costs. Donors are the providers of biological raw material (starting material). They can share their health records when donating by using an IPS document or a FHIR Questionnaire-response resource. It allows health personnel to retrieve and verify relevant clinical information when donating. Additionally, health personnel can generate an anonymized and de-identified digital twin of the donor for research purposes, and it can be updated over time. The starting material can include a reference to a digital twin of an unknown supplier, which improves the data quality and enhances research possibilities. Adverse reactions and events can be also recorded on blockchain to improve safety, transparency, traceability, medical research and product quality.

All the information stored in the different information systems is issued in a format that allows the holder (the information owner) to disclose only certain information to a third party, which will act as a requester, receiver and verifier of the information disclosed by the holder. We define the Interoperable Universal Resource Identifier (iURI) as a harmonized method of representing a claim (minimum piece of verifiable information) using disparate encoding systems, agnostic to the original encoding system and data format. Encoding systems are represented in Reverse Domain Name Resolution (Reverse-DNS) format for HL7 FHIR, OpenEHR, and other data formats. The iURI can then be used in JSON Web Token for Selective Disclosure (SD-JWT) and Verifiable Credential (VC), among others. The method enables a person to demonstrate data that already exists in different information systems in disparate data formats, and even an information system, to verify certain claims, in a harmonized way.

In Web 3.0 the user owns the information. Decentralized Identity Documents (DID documents) allow users to create their own digital identity and decentralized cryptographic material resistant to quantum computing. A patient's DID document also contains a unique identifier for cross-border healthcare, endpoints for receiving DIDComm messages and for SOS services, and additional identifiers (passport, etc.). We propose a blockchain for cross-border healthcare to store the evidence of different electronic, physical identities, and identifiers, but also the rules approved by the patient or legal guardians to access patient data. The International Patient Summary (IPS) is the de facto standard for cross-border healthcare and includes an index of information classified into sections (HL7 FHIR Composition) that healthcare professionals and services can update and read on the patient's SOS service, then retrieving all the necessary patient information from the different FHIR API endpoints of different healthcare providers according to the approved rules.

Background: Microbial interactions are fundamental for Earth's ecosystem functioning and biogeochemical cycling. Nevertheless, they are challenging to identify and remain barely known. Omics-based censuses are helpful in predicting microbial interactions through the statistical inference of single (static) association networks. Yet, microbial interactions are dynamic and we have limited knowledge of how they change over time. Here, we investigate the dynamics of microbial associations in a 10-year marine time series in the Mediterranean Sea using an approach inferring a time-resolved (temporal) network from a single static network., Results: A single static network including microbial eukaryotes and bacteria was built using metabarcoding data derived from 120 monthly samples. For the decade, we aimed to identify persistent, seasonal, and temporary microbial associations by determining a temporal network that captures the interactome of each individual sample. We found that the temporal network appears to follow an annual cycle, collapsing, and reassembling when transiting between colder and warmer waters. We observed higher association repeatability in colder than in warmer months. Only 16 associations could be validated using observations reported in literature, underlining our knowledge gap in marine microbial ecological interactions., Conclusions: Our results indicate that marine microbial associations follow recurrent temporal dynamics in temperate zones, which need to be accounted for to better understand the functioning of the ocean microbiome. The constructed marine temporal network may serve as a resource for testing season-specific microbial interaction hypotheses. The applied approach can be transferred to microbiome studies in other ecosystems. Video Abstract., (© 2023. The Author(s).)

Abstract: The expanded application of radiologic imaging resulted in an increased incidence of renal masses in the recent decade. Clinically, it is difficult to determine the malignant potential of the renal masses, thus resulting in complex management. Image-guided biopsies are the ongoing standard of care to identify molecular variance but are limited by tumor accessibility and heterogeneity. With the evolving importance of individualized cancer therapies, radiomics has displayed promising results in the identification of tumoral mutation status on routine imaging. This article discusses how magnetic resonance imaging features can guide a radiologist toward identifying renal mass characteristics., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Pneumonia is a lung parenchyma acute infection usually treated with antibiotics. Increasing bacterial resistances force the review and control of antibiotic use criteria in different health departments., Objective: Evaluate the adequacy of antibiotic treatment in community-acquired pneumonia in patients initially attended at the emergency department and then admitted to the internal medicine service of the Alto Deba Hospital-Osakidetza Basque Country Health Service (Spain)., Methods: Observational, retrospective study, based on the review of medical records of patients with community-acquired pneumonia attended at the hospital between January and May 2021. The review was made considering the following items: antimicrobial treatment indication, choice of antibiotic, time of administration of the first dose, adequacy of the de-escalation-sequential therapy, duration of treatment, monitoring of efficacy and adverse effects, and registry in the medical records. The review was made by the research team (professionals from the emergency department, internal medicine, and pharmacy services)., Results: Fifty-five medical records were reviewed. The adequacy of the treatments showed that antibiotic indication, time of administration of the first dose, and monitoring of efficacy and adverse effects were the items with the greatest agreement between the three departments. This was not the case with the choice of antibiotic, de-escalation/sequential therapy, duration of treatment, and registration in the medical record, which have been widely discussed. The choice of antibiotic was optimal in 63.64% and might have been better in 25.45%. De-escalation/oral sequencing might have been better in 50.91%. The treatment duration was optimal in 45.45% of the patients and excessive in 45.45%., Discussion: The team agreed to disseminate these data among the hospital professionals and to propose audits and feedback through an antibiotic stewardship program. Besides this, implementing the local guideline and defining stability criteria to apply sequential therapy/de-escalation was considered essential.

A pyogenic hepatic abscess is an uncommon complication after laparoscopic sleeve gastrectomy (LSG) that can develop secondary to an infected hematoma or a staple line leak due to bacterial seeding. Appropriate screening for and management of a pyogenic hepatic abscess are essential in patients with clinical suspicion for complications after LSG. Early diagnosis is essential as pyogenic hepatic abscess can be fatal if not treated early. Only five cases have been reported in the literature so far. We present a case of pyogenic hepatic abscess that occurred two weeks after LSG in a 46-year-old female without immunosuppressive conditions or early postoperative leak. The abscess was diagnosed by computed tomography (CT) and was successfully treated with antibiotics and CT-guided drainage., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The COVID-19 pandemic has impacted the economic market and labor contexts worldwide. Brazil has suffered one of the worst social and governmental managements of the COVID-19 crisis, forcing workers and organizations to develop coping strategies. This environment can affect both well-being and performance at work. Sustainable well-being at work refers to different patterns of relationships between performance and well-being. It may include eudaimonic (e.g., Meaning of Work-MOW) or hedonic (e.g., emotions) forms of well-being. This study tests the moderating role of recovery from work stress in the relationship between flexibility i-deals and patterns of sustainable well-being at work in Brazilian teleworkers. We relied on two studies to achieve this objective. In Study 1, conducted during the pandemic's first outbreak in Brazil ( N = 386), recovery experiences moderated the relationship between i-deals and clusters formed by performance and MOW (eudaimonic happiness). In Study 2, conducted during the second outbreak ( N = 281), we identified relationships between clusters of emotions (hedonic happiness) and MOW (eudaimonic) with performance. The results supported the idea that recovery experiences moderated the relationship between i-deals and patterns of sustainable well-being at work differently. Our findings have implications for Human Resource Management and teleworkers, especially for employee behaviors to deal with stress.

Unicellular eukaryotic predators play a crucial role in the functioning of the ocean ecosystem by recycling nutrients and energy that are channeled to upper trophic levels. Traditionally, these evolutionarily diverse organisms have been combined into a single functional group (heterotrophic flagellates), overlooking their organismal differences. Here, we investigated four evolutionarily related species belonging to one cosmopolitan group of uncultured marine picoeukaryotic predators: marine stramenopiles (MAST)-4 (species A, B, C, and E). Co-occurrence and distribution analyses in the global surface ocean indicated contrasting patterns in MAST-4A and C, suggesting adaptation to different temperatures. We then investigated whether these spatial distribution patterns were mirrored by MAST-4 genomic content using single-cell genomics. Analyses of 69 single cells recovered 66 to 83% of the MAST-4A/B/C/E genomes, which displayed substantial interspecies divergence. MAST-4 genomes were similar in terms of broad gene functional categories, but they differed in enzymes of ecological relevance, such as glycoside hydrolases (GHs), which are part of the food degradation machinery in MAST-4. Interestingly, MAST-4 species featuring a similar GH composition (A and C) coexcluded each other in the surface global ocean, while species with a different set of GHs (B and C) appeared to be able to coexist, suggesting further niche diversification associated with prey digestion. We propose that differential niche adaptation to temperature and prey type has promoted adaptive evolutionary diversification in MAST-4. We show that minute ocean predators from the same phylogenetic group may have different biogeography and genomic content, which needs to be accounted for to better comprehend marine food webs., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Heterotrophic lineages of stramenopiles exhibit enormous diversity in morphology, lifestyle, and habitat. Among them, the marine stramenopiles (MASTs) represent numerous independent lineages that are only known from environmental sequences retrieved from marine samples. The core energy metabolism characterizing these unicellular eukaryotes is poorly understood. Here, we used single-cell genomics to retrieve, annotate, and compare the genomes of 15 MAST species, obtained by coassembling sequences from 140 individual cells sampled from the marine surface plankton. Functional annotations from their gene repertoires are compatible with all of them being phagocytotic. The unique presence of rhodopsin genes in MAST species, together with their widespread expression in oceanic waters, supports the idea that MASTs may be capable of using sunlight to thrive in the photic ocean. Additional subsets of genes used in phagocytosis, such as proton pumps for vacuole acidification and peptidases for prey digestion, did not reveal particular trends in MAST genomes as compared with nonphagocytotic stramenopiles, except a larger presence and diversity of V-PPase genes. Our analysis reflects the complexity of phagocytosis machinery in microbial eukaryotes, which contrasts with the well-defined set of genes for photosynthesis. These new genomic data provide the essential framework to study ecophysiology of uncultured species and to gain better understanding of the function of rhodopsins and related carotenoids in stramenopiles.

Background: Miniscrews are effective devices for performing upper incisor intrusion. Different mechanics can be applied depending on the treatment objectives. This study aimed to evaluate the efficacy of one or two anterior miniscrews for upper incisor correction in cases of overbite and angulation in adult patients., Methods: Forty-four adults with deep overbite were divided into two groups: group 1 was treated with one miniscrew between upper central incisors and group 2 with two miniscrews between upper lateral incisors and canines. Incisor intrusion and length were measured from lateral cephalograms before treatment, after treatment and at least 12 months into retention (T0, T1 and T2). Forces were applied (90 g) from the miniscrews to the archwire using elastomeric chains. ANOVA analysis was used to determine whether differences between evaluation times were statistically significant., Results: Mean root resorption was 2.15 ± 0.85 mm, which ceased after active treatment. Overbite mean correction was - 3.23 ± 1.73 mm with no statistically significant relapse. Overbite correction and incisor intrusion were significantly greater in group 2 (- 3.80 ± 1.43 versus - 2.75 ± 1.63 for OB and 8.19 ± 3.66 versus 5.69 ± 2.66 for intrusion). Resorption and overbite correction were positively related. No counterclockwise rotation of the mandibular plane was observed., Conclusions: Overbite correction can be performed by means of upper incisor intrusion without rotation of the mandibular plane. Correction of upper incisor intrusion and overbite is greater in patients treated with two miniscrews. The increase in upper incisor buccal angulation is greater with one miniscrew. Root resorption is positively related to the extent of intrusion. Stability is satisfactory regardless of whether one or two miniscrews are used.

In the construction sector, there is a high risk for accidents, injuries, and fatalities, particularly for migrant workers who comprise a large proportion of the workforce. This article presents a systematic literature review of current safety training provision for migrant construction workers. In the interests of rigor, we draw on the learning, training transfer, and training effectiveness literatures, exploring not only the extent to which training brings about the intended outcomes, in terms of enhanced safety behaviors, and reduced accidents and injuries, but also the factors that influence learning and transfer of training back to the working environment. The literature search revealed only 18 peer-reviewed articles have been published since 2000, which is particularly surprising, given the disproportionate accident and fatality rates for migrant workers. Consequently, we propose a research agenda to enhance safety training for low skilled, migrant and native construction workers, drawing on cognitive and social constructivist instructional design models, which view training as a dynamic process involving active participation of trainees. We advocate the importance of attending to the situational context in which workers are embedded, including labor market conditions, social relations, and cultural differences. Finally, we propose the need for further longitudinal, multidimensional research to evaluate the impact of safety training on learning, transfer of training, and individual- and organizational-level outcomes, such as behavior change, and accident and fatality rates. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Purpose: To summarize literature specific to therapeutic interchange (TI) focusing on methodological approaches in order to develop a list of steps that healthcare facilities can consult when developing pharmacotherapeutic interchange guidelines (PTIGs) in hospitals and primary care centers., Methods: A search was conducted in PreMEDLINE, Medline, EMBASE, PsycINFO, and the Cochrane Library up to and including December 2015. PRISMA guidelines were used. The inclusion criteria were articles published on TI: methodology, implementation, guidelines, and position statements of scientific societies. Two authors independently reviewed all articles for eligibility and extracted the data., Results: A total of 102 articles were selected for full-text review; we included three guidelines on how to effect TI, nine position papers of various scientific societies with regard to TI, two articles dealt exclusively about methodology, three articles consisted of recommendations and perspectives on TI, three articles dealt with legal aspects, four articles examined general implementation procedures, two articles were a post-discharge follow-up of patients who had TI, six were surveys referring to TI, and three were articles on the use of TI in ambulatory care The remaining 67 articles focused on therapeutic groups. Study quality was generally low., Conclusions: This review identified articles on TI as published guidelines, recommendations, and studies on TI carried out in hospital settings. As a result, eight fundamental steps were established for obtaining adequate results in the development of TI programs.

Background: Worth syndrome or autosomal dominant endosteal hyperostosis (ADEH) is an extremely rare genetic disease involving increased bone density. To the author's knowledge, this is the second case report of a family with neurologic involvement associated with this condition along with its surgical treatment. The most effective treatment for clinically significant neurologic symptoms in this scenario is currently unknown, and there is sparse experience on surgical treatment for this condition reported in the literature. Therefore we aim to make a contribution to the identification of a standard and consistently successful surgical management., Case Description: Two patients, mother (Patient 1) and daughter (Patient 2), were diagnosed with Worth syndrome. Both presented with the typical facial characteristics described for ADEH. Interestingly, Patient 1 presented the novel mutation in the LRP5 gene that is associated with different conditions involving increased bone density. Although neurologic symptoms are infrequent in ADEH, both referred chronic headache, nausea, and vomiting. Neuroimaging showed an increased cranial bone density and Chiari I malformation. The patients underwent a midline suboccipital craniectomy with excision of the posterior arch of C1 and duroplasty. However, due to a symptomatic recurrence 5 years after surgery, Patient 1 was reoperated on. We extended the craniectomy and also carried out a C2 laminectomy., Conclusion: After surgical interventions, patients' neurologic symptoms were successfully resolved. This report shows that posterior fossa decompression including duroplasty may be a valid treatment option in case of neurologic involvement., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Several publications have related functional decline to the appearance of symptoms, especially psychiatric or psychological ones, such as anxiety and depression. Moreover, an initial depressive disorder or prior to functional decline usually worsens it. It was decided to investigate the relationship between the presence of functional decline, measured by a decrease in the Barthel index (BI), and the presence of symptoms., Material and Methods: A prospective analytical study conducted on patients referred to a Home Care Support Team (HCST)., Results: The study included 638 cases, of which 53.9% (N=344) were male, 56% (N=357) with cancer and 44% (N=281) geriatric. The mean age was 79.64 years+- 10.8. Significant differences (P<.001) were found in functional decline measured by mean decline in the BI between cancer (34.4) and non-cancer patients (12.12). Significant differences (P<.001) were also found in all recorded symptoms (pain, dyspnoea, anorexia, nausea, anxiety, depression, and insomnia), more frequently in cancer patients, except psychomotor agitation. A higher presence of symptoms was detected in patients with greater functional decline, with decreases in BI above 20 points. There were no differences in previous treatments, except in certain analgesics. Differences were found in the different treatments prescribed by HCST., Conclusions: The presence of functional decline and its level may be related to the appearance of symptoms, especially in cancer patients., (Copyright © 2016 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Recently, it has been shown that it is possible to identify tumor profiles of sensitivity for potentially useful drugs, both conventional and experimental, based on whole oligonucleotide microarray gene expression studies in heavily pretreated patients with metastatic solid tumors., Methods: Fresh-frozen tumor biopsies for molecular profiling (MP) were obtained from patients with advanced and refractory cancer. Total tumor and control tissue RNA was hybridized to a whole human genome oligonucleotide microarray. Differentially expressed genes interacting with potential therapeutic targets were identified. Results were complemented with DNA sequencing of selected driver genes and with immunohistochemistry and fluorescent "in situ" hybridization. The results were used to guide experimental treatment., Results: MP assays led to a potentially active available drug in 91.2% of the patients. The median number of available active drugs per tumor was 5 (range, 1 to 9). Nine treated patients were not evaluable for response. Partial response was observed in 18 patients (33%), stable disease in 22 patients (40%) (clinical benefit rate of 73%), and progression in 15 (27%). Overall median progression-free survival and overall survival were 8 and 13 months, respectively., Conclusion: MP-guided therapy is feasible and seems to improve the clinical outcome of extensively pretreated patients but prospective and confirmatory trials are needed.

Pico-sized eukaryotes play key roles in the functioning of marine ecosystems, but we still have a limited knowledge on their ecology and evolution. The MAST-4 lineage is of particular interest, since it is widespread in surface oceans, presents ecotypic differentiation and has defied culturing efforts so far. Single cell genomics (SCG) are promising tools to retrieve genomic information from these uncultured organisms. However, SCG are based on whole genome amplification, which normally introduces amplification biases that limit the amount of genomic data retrieved from a single cell. Here, we increase the recovery of genomic information from two MAST-4 lineages by co-assembling short reads from multiple Single Amplified Genomes (SAGs) belonging to evolutionary closely related cells. We found that complementary genomic information is retrieved from different SAGs, generating co-assembly that features >74% of genome recovery, against about 20% when assembled individually. Even though this approach is not aimed at generating high-quality draft genomes, it allows accessing to the genomic information of microbes that would otherwise remain unreachable. Since most of the picoeukaryotes still remain uncultured, our work serves as a proof-of-concept that can be applied to other taxa in order to extract genomic data and address new ecological and evolutionary questions., Competing Interests: The authors declare no competing financial interests.

Objective: To (1) evaluate the efficacy of build-ups in the correction of anterior open bite in adults, (2) evaluate their efficacy in producing molar intrusion, (3) analyze skeletal and dental changes, and (4) assess the long-term stability., Materials and Methods: The sample consisted of 93 lateral cephalograms from 31 patients with skeletal and dental anterior open bite. The patients had received orthodontic treatment consisting of bonded resin blocks on the maxillary molars combined with Tip-Edge Plus bracket appliances. Cephalometric measurements were performed on radiographs taken before treatment (T1), after treatment (T2), and after a retention period (T3), which were analyzed and compared., Results: Significant dental and skeletal changes were observed after treatment. Molar intrusion averaging 1 mm; 1.44 and 1.57 mm extrusion of mandibular and maxillary incisors, respectively; and a mean of 3.98 mm overbite increase were observed. The mandibular plane angle showed a mean closure of 1.19°, and there was a mean decrease in anterior facial height of 0.7 mm. A mild relapse tendency was observed, but long-term stability was acceptable., Conclusions: Build-ups are an effective treatment alternative for anterior open bite in adults. Outcomes remain significantly stable during the retention period.

Experimental evidence of extremely high spatial resolution of tip-enhanced Raman scattering (TERS) has been recently demonstrated. Here, we present a full quantum chemical description (at the density functional level of theory) of the non-resonant chemical effects on the Raman spectrum of an adenine molecule mapped by a tip, modeled as a single silver atom or a small silver cluster. We show pronounced changes in the Raman pattern and its intensities depending on the conformation of the nanoparticle-substrate system, concluding that the spatial resolution of the chemical contribution of TERS can be in the sub-nm range.

Abstract- This article uses political economy analysis to identify the factors that contributed to the adoption of policies to expand social protection in health (SPH) in Mexico in the early years of the 21st century. It focuses on the adoption stage of these policies to answer two questions: (1) Which contextual factors created the window of opportunity where SPH reforms could be adopted in Mexico? (2) What political strategies did the main actors driving the reform use to promote its adoption? Two types of analysis were developed: an analysis of the context and a stakeholder analysis. The analysis of the context was used to identify the "enabling factors" (epidemiological, political, and economic) that created the window of opportunity to place the problem of limited health care coverage in Mexico on the national policy agenda. The stakeholder analysis was used to (1) construct a map of actors, positions, and power during the deliberation of these policies in the Mexican Congress; (2) evaluate the behavior, intentions, interrelations, agendas, and interests of key actors; and (3) assess the influence and resources that actors brought to the debate and the strategies used by proponents to pursue and achieve adoption of the policies. This article shows that actors with high political power can take advantage of a propitious context (a window of opportunity for major change) through effective political strategies to design, promote, and successfully negotiate SPH policies, even in the absence of beneficiary mobilization. This was the case in the adoption of Mexico's health reform in 2003.

In this theoretical work, we present a spectroscopic analysis of the cis/trans-isomers of a molecular switch, penta-2,4-dienoic acid, attached to gold clusters of different size (1, 2 and 20 gold atoms). We have simulated 4 different spectroscopic techniques: Infrared spectroscopy, normal Raman scattering, absorption spectra and resonance Raman scattering. We discuss how the position and the conformation of the molecule determine the electronic structure and hence, the spectra. The calculations have been performed using density functional theory for the properties of the ground state and time-dependent density functional theory for the excited-state properties. Special emphasis is put on the resonance Raman spectra for the study of the isomers. In the present case, resonance Raman scattering is best suited to discriminate between the isomers on the gold clusters.