A scale for assessing nursing students' emotional competence: A validation study.

BACKGROUND: The wellbeing of nursing professionals can be affected by emotionally challenging situations. Emotional intelligence (EI) is a recognised ability to manage stress, reduce work overload, and improve clinical relationships and decision making. Therefore, these emotional skills should be identified and developed throughout nursing education. OBJECTIVES: The aim of this study is to create an observer-based emotional measurement tool to assess the level of emotional skills in university students. DESIGN: This is a cross-sectional study. SETTING: Complutense University in Madrid, Spain. PARTICIPANTS: A total of 415 first- and fourth-year nursing students participated. METHODS: The Situational Emotional Response Scale (ERES) is a questionnaire for observing emotional competence in nursing practice. It underwent content validation using the Delphi method with 6 experts, resulting in a final version of 34 items. Focus group sessions were conducted with nursing students to ensure readability and appropriateness. Participants completed the ERES after viewing two clinical interaction videos, resulting in two sets of responses. Half of the responses were used for exploratory factor analysis (EFA) and half for confirmatory factor analysis (CFA). RESULTS: A total of 415 nursing students participated in the study. Four factors were extracted, explaining 55.1 % of the variance. The CFA was conducted with 208 students, yielding a total of 4 factors and a variance of 55.1 %. The internal consistency of the scale was high, with Cronbach's α and McDonald's ω coefficients of 0.947 and 0.949, respectively. Test-retest reliability showed a moderate intra-class correlation coefficient of 0.604 (95 % CI: 0.503-0.688) over a 15-day interval. CONCLUSIONS: The ERES questionnaire is well grounded in the theoretical framework of emotional competence as manifested in clinical practice. The empirical evidence provided by this study suggests that the ERES is a reliable, valid, useful, and innovative instrument for measuring emotional competence in university students.

Basal procalcitonin, C-reactive protein, interleukin-6, and presepsin for prediction of mortality in critically ill septic patients: a systematic review and meta-analysis.

BACKGROUND: Numerous biomarkers have been proposed for diagnosis, therapeutic, and prognosis in sepsis. Previous evaluations of the value of biomarkers for predicting mortality due to this life-threatening condition fail to address the complexity of this condition and the risk of bias associated with prognostic studies. We evaluate the predictive performance of four of these biomarkers in the prognosis of mortality through a methodologically sound evaluation. METHODS: We conducted a systematic review a systematic review and meta-analysis to determine, in critically ill adults with sepsis, whether procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), and presepsin (sCD14) are independent prognostic factors for mortality. We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials up to March 2023. Only Phase-2 confirmatory prognostic factor studies among critically ill septic adults were included. Random effects meta-analyses pooled the prognostic association estimates. RESULTS: We included 60 studies (15,681 patients) with 99 biomarker assessments. Quality of the statistical analysis and reporting domains using the QUIPS tool showed high risk of bias in > 60% assessments. The biomarker measurement as a continuous variable in models adjusted by key covariates (age and severity score) for predicting mortality at 28-30 days showed a null or near to null association for basal PCT (pooled OR = 0.99, 95% CI = 0.99-1.003), CRP (OR = 1.01, 95% CI = 0.87 to 1.17), and IL-6 (OR = 1.02, 95% CI = 1.01-1.03) and sCD14 (pooled HR = 1.003, 95% CI = 1.000 to 1.006). Additional meta-analyses accounting for other prognostic covariates had similarly null findings. CONCLUSION: Baseline, isolated measurement of PCT, CRP, IL-6, and sCD14 has not been shown to help predict mortality in critically ill patients with sepsis. The role of these biomarkers should be evaluated in new studies where the patient selection would be standardized and the measurement of biomarker results. TRIAL REGISTRATION: PROSPERO (CRD42019128790).

Pressure release technique versus placebo applied to cervical and masticatory muscles in patients with chronic painful myofascial temporomandibular disorder: A randomised clinical trial.

BACKGROUND: The therapeutic approach to myofascial TMD should focus on pain relief and rehabilitation of function. OBJECTIVE: This study investigated whether pressure release technique (PRT) is effective for reducing pain in people with chronic myofascial temporomandibular disorders (TMD). METHODS: A single-blinded randomised parallel-group trial, with 3 months follow-up was conducted. A total of 72 patients were randomly allocated to receive PRT or sham PRT. Primary outcome was pain assessed with a visual analogue scale (VAS). Secondary outcomes included pressure pain thresholds (PPTs), range of opening of the mouth (ROM), Neck Disability Index (NDI), Pain Catastrophizing Scale (PCS), Tampa Scale for Kinesiophobia (TSK-11), State-Trait Anxiety Index (STAI) and State-Trait Depression Index (ST-DEP). All parameters were assessed at baseline, at the end of the treatment and at 3 months follow-up. Statistical analysis was performed by ANOVA. RESULTS: There were significant main effects of time, group and interaction between time and group (F ≥ 21.92; p < .001) on VAS pain. Post hoc tests showed a significant reduction in VAS pain scores in the PRT group (≥31.9%; p < .001). Effect sizes were moderate in the PRT group at all follow-up periods (≥1.25 Cohen's d). Also, there were significant effects of time in secondary outcomes (F ≥ 9.65; p < .001), and there were also interactions between time and group (F ≥ 3.82; p < .002) with better effects in the PRT group. CONCLUSIONS: The inclusion of PRT to conventional management with occlusal splints and self-care management appears to be effective to improve self-reported levels of pain in patients with chronic myofascial TMD pain. Retrospectively registered (ClinicalTrials.gov: NCT03619889).

Evaluation of Pressure Pain Sensitivity in the Forefoot of Healthy Individuals.

BACKGROUND: The evaluation of musculoskeletal pain in podiatric medical practice is mainly based on anamnesis and manual examination. However, when manual palpation is performed, the digital pressure necessary to adequately explore the different structures of the foot is unknown. We evaluated the pressure pain threshold in forefoot structures to determine the intensity and duration of the stimulus as clinically relevant and representative. METHODS: In a transversal analytical study of 15 healthy individuals, 16 forefoot points were explored with a handheld pressure palpometer calibrated to exert maximum pressing force of 1.0 or 2.0 kilogram-force (kgf) applied during 5 or 10 sec. The combinations of the different pressures and intervals were selected randomly. Participants had to self-rate the pressure pain sensitivity of each stimuli on a 100-mm horizontal line (0-100 numeric rating scale), setting the pain threshold to 50 (100 being pain as bad as it could be). Likewise, aftersensation and referred pain patterns were recorded. RESULTS: All participants indicated painful stimuli at some of the 16 forefoot points studied in the experimental protocol when pressure was applied with the 2.0-kgf palpometer; 53.3% showed evidence of pain at any forefoot point when the 1.0-kgf palpometer was used. The odds of evoking a painful sensation are 9.8 times higher when using a 2.0-kgf palpometer versus a 1.0-kgf palpometer. In addition, referred sensations were observed with a significantly higher frequency when applying the 2.0-kgf palpometer. CONCLUSIONS: Bone and soft structures show differences in pressure sensitivity, increasing significantly when applying higher pressure force. Soft structures, specifically intermetatarsal spaces, showed the lowest pain pressure thresholds. More research is needed to better understand pressure pain response.

Análisis multivariante del uso de espacios virtualizados por estudiantes pregraduados en Ciencias de la Salud / Multivariate analysis of the use of virtualized spaces by Health Sciences undergraduate students

Introducción: Los entornos virtuales de aprendizaje permiten crear espacios dinámicos y facilitadores del aprendizaje. Investigar el uso dado por los estudiantes puede identificar patrones de comportamiento y detectar tempranamente alumnos en riesgo de abandono, y se han descrito correlaciones entre su uso y el rendimiento académico. Materiales y métodos: Se estudiaron siete espacios virtualizados correspondientes a cuatro asignaturas de tres grados de Ciencias de la Salud impartidas en los cursos 2017/2018 y 2018/2019, con un total de 517 estudiantes. Previamente se extrajeron, depuraron y anonimizaron los registros de cada espacio. Las variables analizadas fueron: número de visitas al campus virtual, de accesos a recursos y a URL, y uso del foro. Se aplicó un análisis de correspondencias múltiples, seguido de un análisis de conglomerados jerárquico. Resultados: Se obtuvieron cuatro clústeres, con tamaños de entre el 20,9 y el 29,4% de los estudiantes, caracterizados por comportamientos diferenciales en cuanto al uso del campus virtual, y se establecieron relaciones con las calificaciones finales, las notas teóricas y las prácticas de las asignaturas. Se observa que, a menor interacción en el campus virtual, menor rendimiento académico, mientras que, a mayor actividad registrada, mejores calificaciones. Conclusiones: Nuestro estudio revela grupos de estudiantes con comportamientos homogéneos según su uso del campus virtual y establece relaciones con el rendimiento académico.(AU)

Introduction: Virtual learning environments enable users to create dynamics and learning facilitator spaces. To investigate the students’ use can identify patterns and help to an early detection of students at high risk of dropping out since correlations between its use and the academic performance have been described. Materials and methods: Seven virtualized spaces corresponding to four courses from three Health Sciences degrees taught in 2017/18 and 2018/19, with a total of 517 students were studied. Previously, logs had been extracted from every space, debugged and anonymized. Number of logins, of access to resources and to URL as well as the forums use were considered. A multiple correspondence analysis was applied followed by a hierarchical clustering analysis. Results: 4 clusters, with sizes between 20.9% and 29.4% of the students, were obtained and characterized by differential behaviors of the virtual campus use. Relationships can be established with final grades as well as theory’ and practical’ grades. Results pointed out that the lower interaction in virtual campus, the lower the grades, while the higher interaction, the higher the marks. Conclusions: Our study pinpoints different student clusters with homogeneous virtual campus behavior and establishes relationships with the academic performance.(AU)

Factors associated with falls in hemodialysis patients: a case-control study.

OBJECTIVE: to identify possible associations between a higher probability of falls among hemodialysis patients and laboratory values, comorbidities, pharmacological treatment, hemodynamic changes, dialysis results and stabilometric alterations. METHOD: this was a retrospective case-control study with hemodialysis patients. Patients in a hemodialysis unit who had suffered one or more falls were included in the case group. Patients from the same unit who had not suffered falls were the controls. Data were gathered from the patients' clinical history and also from the results of a balance test conducted six months before the study. RESULTS: thirty-one patients were included (10 cases and 21 controls). Intradialytic body weight change was significantly greater among cases (p <0.05). Patients in the case group also presented greater lateral instability after dialysis (p <0.05). Other factors such as high blood pressure, antihypertensives, beta-blockers, and lower heart rates were also associated with falls. CONCLUSION: a greater intradialytic weight change was associated with an increase in risk of falls. Nursing staff can control these factors to prevent the incidence of falls in dialysis patients.

Neumonía bilateral por SARS-CoV2: evolución radiográfica / SARS-CoV2 bilateral pneumonia: chest X-ray evolution

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Factors associated with falls in hemodialysis patients: a case-control study / Factores asociados a caídas en pacientes hemodializados: un estudio de caso-control / Fatores associados às quedas em pacientes de hemodiálise: um estudo caso-controle

Objective: to identify possible associations between a higher probability of falls among hemodialysis patients and laboratory values, comorbidities, pharmacological treatment, hemodynamic changes, dialysis results and stabilometric alterations. Method: this was a retrospective case-control study with hemodialysis patients. Patients in a hemodialysis unit who had suffered one or more falls were included in the case group. Patients from the same unit who had not suffered falls were the controls. Data were gathered from the patients' clinical history and also from the results of a balance test conducted six months before the study. Results: thirty-one patients were included (10 cases and 21 controls). Intradialytic body weight change was significantly greater among cases (p <0.05). Patients in the case group also presented greater lateral instability after dialysis (p <0.05). Other factors such as high blood pressure, antihypertensives, beta-blockers, and lower heart rates were also associated with falls. Conclusion: a greater intradialytic weight change was associated with an increase in risk of falls. Nursing staff can control these factors to prevent the incidence of falls in dialysis patients.

Objetivo: identificar la posible asociación entre los valores analíticos, comorbilidades, tratamiento farmacológico, cambios hemodinámicos, resultado de la diálisis y alteraciones estabilométricas con una mayor probabilidad de caídas en pacientes en hemodiálisis. Método: estudio retrospectivo de casos y controles en pacientes en hemodiálisis. Se consideraron como casos pacientes de una unidad de hemodiálisis que habían sufrido una o varias caídas. Los controles fueron pacientes de la misma unidad que no sufrieron caídas. Se obtuvieron los datos de la historia clínica de los pacientes y, también, se valoró una prueba de equilibrio realizada 6 meses antes a dichos pacientes. Resultados: se incluyeron 31 pacientes (10 casos y 21 controles). El cambio de peso durante la diálisis fue significativamente mayor en el grupo de personas que sufrieron una caída (p <0,05). Los pacientes que sufrieron una caída presentaron mayor inestabilidad lateral después de la diálisis (p <0.05). Otros factores como la hipertensión arterial, los antihipertensivos, los betabloqueantes y las frecuencias cardiacas más bajas también se relacionaron con las caídas. Conclusión: un mayor cambio de peso intradiálisis se relaciona con mayor riesgo de caídas. El control de estos factores por parte del personal de enfermería podría prevenir la incidencia de caídas en pacientes dializados.

Objetivo: identificar a possível associação entre valores laboratoriais, comorbidades, tratamento farmacológico, alterações hemodinâmicas, resultado da diálise e alterações estabilométricas com uma maior probabilidade de quedas em pacientes de hemodiálise. Método: estudo caso-controle retrospectivo em pacientes de hemodiálise. Foram analisados os casos de pacientes de uma unidade de hemodiálise que sofreram uma ou mais quedas. Os controles foram pacientes da mesma unidade que não sofreram quedas. Os dados foram obtidos a partir do histórico clínico dos pacientes e, também, de um teste de equilíbrio realizado seis meses antes nesses pacientes. Resultados: 31 pacientes foram avaliados (10 casos e 21 controles). A alteração de peso durante a diálise foi significativamente maior no grupo de pessoas que sofreu uma queda (p <0,05). Pacientes que sofreram queda apresentaram maior instabilidade lateral após a diálise (p <0,05). Outros fatores, como hipertensão, anti-hipertensivos, betabloqueadores e frequência cardíaca mais baixa, também foram associados às quedas. Conclusão: uma maior alteração do peso intradialítico está relacionada a um maior risco de quedas. O controle desses fatores pela equipe de enfermagem poderia prevenir a incidência de quedas em pacientes em diálise.

Los pacientes en hemodiálisis presentan peor equilibrio postural, que se relaciona con el riesgo de caídas / Haemodialysis patients have worse postural balance with an associated risk of falls

INTRODUCCIÓN: El equilibrio postural es el resultado de una compleja interacción de aferencias sensoriales que nos mantiene erguidos. Los pacientes en hemodiálisis presentan alteraciones que pueden generar inestabilidad postural y riesgo de caídas. Nuestro objetivo es analizar, mediante una plataforma de fuerzas, la estabilidad postural en pacientes hemodializados y su relación con el riesgo de caídas. MATERIAL Y MÉTODOS: Se realizó un estudio prospectivo transversal. El balanceo postural se registró mediante una plataforma de fuerzas en los pacientes prevalentes en hemodiálisis. Se recogen datos epidemiológicos, de diálisis, analíticos y de tratamiento. La incidencia de caídas fue registrada durante los 6 meses siguientes a las pruebas. El análisis de la estabilidad postural se realizó con una plataforma portátil de galgas extensiométricas (AMTI AccuGait®) y una unidad de software específico para estabilometría (programa Balance Trainer®). Se determinan 31 parámetros de equilibrio; las variables de equilibrio utilizadas son: Area 95, AreaEffect, VyMax, Xrange y Yrange. Los estudios de estabilometría se realizan en 3 situaciones: con los ojos abiertos, con los ojos cerrados y mientras el paciente realiza una tarea simultánea. Se realiza un estudio al iniciar la sesión de diálisis y el segundo, al terminar. La estabilometría en condiciones semejantes se mide en un grupo control. RESULTADOS: Se estudian 32 pacientes, con una edad media de 68 años; 20 hombres y 12 mujeres. Su peso medio es de 74 kg y el IMC, de 27,6 kg/m2. En los controles no hay diferencias significativas en la estabilometría entre las 3 situaciones estudiadas. Los pacientes con los ojos cerrados, pre y poshemodiálisis, presentan más desequilibrio, con diferencias significativas con el resto de las situaciones y los controles. Después de la sesión de hemodiálisis se observa un aumento significativo de la inestabilidad. Se observa mayor inestabilidad en los 13 pacientes diabéticos (p < 0,05). Los 4 pacientes con hiponatremia (Na < 136 mmol/L) presentaban peor equilibrio en la situación de tarea simultánea (p= 0,038). Varios fármacos, como la insulina (p = 0,022), los antiagregantes (p = 0,036) y los betabloqueantes (p = 0,029), se relacionaban con el desequilibrio. Los 10 pacientes que sufrieron caídas presentaban mayor desequilibrio, Yrange, Xrange, Area 95 y AreaEffect, pre y poshemodiálisis (p < 0,05) que los que no tuvieron caídas. CONCLUSIONES: Los pacientes en hemodiálisis presentan alteraciones que pueden generar inestabilidad postural y riesgo de caídas. Programas de prevención que incluyan ejercicios específicos para mejorar el equilibrio podrían ser beneficiosos, reduciendo el riesgo de caídas en esta población

INTRODUCTION: Postural balance is the result of a complex interaction of sensory input which keeps us upright. Haemodialysis patients have alterations which can lead to postural instability and a risk of falls. Our objective was to analyse postural stability and its relationship with the risk of falls in haemodialysis patients using a force platform. MATERIAL AND METHODS: This was a prospective cross-sectional study. Postural balance was recorded using a force platform in prevalent haemodialysis patients. We collected epidemiological, dialysis, analytical and treatment data. The incidence of falls was recorded over the 6 months following the tests. The postural stability analysis was performed with a portable strain gauge platform (AMTI AccuGait®) and a specific software unit for stabilometry (Balance Trainer® program). We measured 31 balance parameters; the balance variables used were: Area95; AreaEffect; VyMax; Xrange and Yrange. The stabilometry studies were performed in 3 situations: with eyes open; with eyes closed; and with the patient performing a simultaneous task. We performed one study at the start of the dialysis session, and a second study at the end. Stabilometry was measured in a control group under similar conditions. RESULTS: We studied 32 patients with a mean age of 68 years old; of this group, 20 subjects were male and 12 were female. Their mean weight was 74kg, with a mean BMI of 27.6kg/m2. In the controls, there were no significant differences in the stabilometry between the 3 situations studied. Both pre- and post-haemodialysis, patients with closed eyes showed greater imbalance, and there were significant differences with the other situations and controls. We found a significant increase in instability after the haemodialysis session, and greater instability in the 13 patients with diabetes (P < .05). The 4 patients with hyponatraemia (Na < 136 mmol/l) had worse balance in the simultaneous task situation (P = .038). Various drugs, such as insulin (P = .022), antiplatelet agents (P =.036) and beta-blockers (P = .029), were associated with imbalance. The 10 patients who suffered falls had greater imbalance, Yrange, Xrange, Area 95 and AreaEffect, both pre- and post-haemodialysis (P < .05) than those without falls. CONCLUSIONS: Haemodialysis patients have alterations which can lead to postural instability and a risk of falls. Prevention programmes which include specific exercises to improve balance could be beneficial in reducing the risk of falls in this population

Haemodialysis patients have worse postural balance with an associated risk of falls. / Los pacientes en hemodiálisis presentan peor equilibrio postural, que se relaciona con el riesgo de caídas.

INTRODUCTION: Postural balance is the result of a complex interaction of sensory input which keeps us upright. Haemodialysis patients have alterations which can lead to postural instability and a risk of falls. Our objective was to analyse postural stability and its relationship with the risk of falls in haemodialysis patients using a force platform. MATERIAL AND METHODS: This was a prospective cross-sectional study. Postural balance was recorded using a force platform in prevalent haemodialysis patients. We collected epidemiological, dialysis, analytical and treatment data. The incidence of falls was recorded over the 6 months following the tests. The postural stability analysis was performed with a portable strain gauge platform (AMTI AccuGait®) and a specific software unit for stabilometry (Balance Trainer® program). We measured 31 balance parameters; the balance variables used were: Area95; AreaEffect; VyMax; Xrange and Yrange. The stabilometry studies were performed in 3 situations: with eyes open; with eyes closed; and with the patient performing a simultaneous task. We performed one study at the start of the dialysis session, and a second study at the end. Stabilometry was measured in a control group under similar conditions. RESULTS: We studied 32 patients with a mean age of 68 years old; of this group, 20 subjects were male and 12 were female. Their mean weight was 74kg, with a mean BMI of 27.6kg/m2. In the controls, there were no significant differences in the stabilometry between the 3 situations studied. Both pre- and post-haemodialysis, patients with closed eyes showed greater imbalance, and there were significant differences with the other situations and controls. We found a significant increase in instability after the haemodialysis session, and greater instability in the 13 patients with diabetes (P<.05). The 4 patients with hyponatraemia (Na<136mmol/l) had worse balance in the simultaneous task situation (P=.038). Various drugs, such as insulin (P=.022), antiplatelet agents (P=.036) and beta-blockers (P=.029), were associated with imbalance. The 10 patients who suffered falls had greater imbalance, Yrange, Xrange, Area95 and AreaEffect, both pre- and post-haemodialysis (P<.05) than those without falls. CONCLUSIONS: Haemodialysis patients have alterations which can lead to postural instability and a risk of falls. Prevention programmes which include specific exercises to improve balance could be beneficial in reducing the risk of falls in this population.

Carcinoembryonic Antigen (CEA)-Specific 4-1BB-Costimulation Induced by CEA-Targeted 4-1BB-Agonistic Trimerbodies.

4-1BB (CD137) is an inducible costimulatory receptor that promotes expansion and survival of activated T cells; and IgG-based 4-1BB-agonistic monoclonal antibodies exhibited potent antitumor activity in clinical trials. However, the clinical development of those antibodies is restricted by major off-tumor toxicities associated with FcγR interactions. We have recently generated an EGFR-targeted 4-1BB-agonistic trimerbody that demonstrated strong antitumor activity and did not induce systemic inflammatory cytokine secretion and hepatotoxicity associated with first-generation 4-1BB agonists. Here, we generate a bispecific 4-1BB-agonistic trimerbody targeting the carcinoembryonic antigen (CEA) that is highly expressed in cancers of diverse origins. The CEA-targeted anti-4-1BB-agonistic trimerbody consists of three 4-1BB-specific single-chain fragment variable antibodies and three anti-CEA single-domain antibodies positioned around a murine collagen XVIII-derived homotrimerization domain. The trimerbody was produced as a homogenous, non-aggregating, soluble protein purifiable by standard affinity chromatographic methods. The purified trimerbody was found to be trimeric in solution, very efficient at recognizing 4-1BB and CEA, and potently costimulating T cells in vitro in the presence of CEA. Therefore, trimerbody-based tumor-targeted 4-1BB costimulation is a broadly applicable and clinically feasible approach to enhance the costimulatory environment of disseminated tumor lesions.

Behavioural changes as the first manifestation of a silent frontal lobe stroke.

A 67-year-old man was admitted to our hospital after his relatives found him to have severe personality and behavioural changes. His behaviour was inappropriate and uninhibited. The patient reported no symptoms and he showed poor insight into his own behaviour. Neuroimaging showed an orbitofrontal lesion, due to an infarction of the anterior cerebral artery. The patient was diagnosed with frontal lobe syndrome.

Importance of Standardized Palpation of the Human Temporomandibular Joint.

AIMS: To test whether standardized palpation around the lateral pole of the condyle can influence mechanical sensitivity and unpleasantness and evoke referred sensations/pain in healthy individuals. METHODS: Palpometers (0.5, 1.0, and 2.0 kg) with spherical extensions were applied around the lateral pole of the condyle in relaxed and protruded positions of the mandible for 2, 5, and 10 seconds in 30 healthy participants. Mechanical sensitivity, unpleasantness, and referred sensations/pain were assessed using a 0 to 100 numeric rating scale (NRS) for each palpation. The NRS scores were compared using analysis of variance and McNemar test. RESULTS: Participants reported significantly higher mechanical sensitivity and unpleasantness scores for the 2.0-kg stimulus compared to the 0.5- and 1.0-kg stimuli for 2, 5, and 10 seconds (mean NRS > 50; P < .001). Application of a 1.0-kg stimulus was significantly different from the 0.5- and 2.0-kg stimuli applied for 5 seconds (mean NRS < 50; P < .001). One-third of participants reported referred sensations/pain. CONCLUSION: Application of a 2.0-kg stimulus around the lateral pole of the condyle is painful and unpleasant regardless of time of palpation. Application of a 1.0-kg stimulus for 5 seconds was found to be nonpainful and not unpleasant in healthy participants. Thus, this study supports the Diagnostic Criteria for TMD recommendation for standardized examination of the TMJ and indicates that referred sensation/pain is a common finding in healthy individuals.

Bispecific light T-cell engagers for gene-based immunotherapy of epidermal growth factor receptor (EGFR)-positive malignancies.

The recruitment of T-cells by bispecific antibodies secreted from adoptively transferred, gene-modified autologous cells has shown satisfactory results in preclinical cancer models. Even so, the approach's translation into the clinic will require incremental improvements to its efficacy and reduction of its toxicity. Here, we characterized a tandem T-cell recruiting bispecific antibody intended to benefit gene-based immunotherapy approaches, which we call the light T-cell engager (LiTE), consisting of an EGFR-specific single-domain VHH antibody fused to a CD3-specific scFv. We generated two LiTEs with the anti-EGFR VHH and the anti-CD3 scFv arranged in both possible orders. Both constructs were well expressed in mammalian cells as highly homogenous monomers in solution with molecular weights of 43 and 41 kDa, respectively. In situ secreted LiTEs bound the cognate antigens of both parental antibodies and triggered the specific cytolysis of EGFR-expressing cancer cells without inducing T-cell activation and cytotoxicity spontaneously or against EGFR-negative cells. Light T-cell engagers are, therefore, suitable for future applications in gene-based immunotherapy approaches.

Systematic Mapping of Pressure Pain Thresholds of the Masseter and Temporalis Muscles and Assessment of Their Diversity Through the Novel Application of Entropy.

AIMS: To assess the diversity of pressure pain thresholds (PPTs) within the masseter and temporalis muscles by using the novel concept of entropy and to assess the differences in PPT scores between different sites of the masseter and temporalis muscles. METHODS: In this randomized, single-blinded study, the left and right masseter and temporalis muscles of 14 healthy volunteers were divided into 15 sites each, and the PPT was assessed for each of these sites. PPT assessments were performed in two different sessions. Entropy and center of gravity (COG) values were calculated for the PPTs of each muscle. Repeated measures analysis of variance was used to assess differences between muscles, sides, and sites for PPT, entropy, and COG scores. RESULTS: The main findings were: (1) PPT scores varied significantly between the masseter and temporalis muscles and within each of these muscles; (2) entropy values of PPT scores were not different between the masseter and temporalis muscles; and (3) COG values of PPT scores varied statistically, but these changes do not seem to be clinically relevant. CONCLUSION: The results of this study suggest that the anatomical layout of the masseter and temporalis muscles has implications for mechanical pain sensitivity and that areas have different sensitivities within these muscles. Furthermore, reference values for the entropy of PPTs in healthy individuals have been estimated, and comparing these values with those of patients with muscle-related pain conditions can provide quantitative information about the spatial heterogeneity of mechanical pain sensitivity, which may be a valuable clinical outcome measure.

Efficacy and toxicity management of CAR-T-cell immunotherapy: a matter of responsiveness control or tumour-specificity?

Chimaeric antigen receptor (CAR)-expressing T-cells have demonstrated potent clinical efficacy in patients with haematological malignancies. However, the use of CAR-T-cells targeting solid tumour-associated antigens (TAAs) has been limited by organ toxicities related to activation of T-cell effector functions through the CAR. Most existing CARs recognize TAAs, which are also found in normal tissues. CAR-T-cell-mediated destruction of normal tissues constitutes a major roadblock to CAR-T-cell therapy, and must be avoided or mitigated. There is a broad range of strategies for modulating antigen responsiveness of CAR-T-cells, with varying degrees of complexity. Some of them might ameliorate the acute and chronic toxicities associated with current CAR constructs. However, further embellishments to CAR therapy may complicate clinical implementation and possibly create new immunogenicity issues. In contrast, the development of CARs targeting truly tumour-specific antigens might circumvent on-target/off-tumour toxicities without adding additional complexity to CAR-T-cell therapies, but these antigens have been elusive and may require novel selection strategies for their discovery.

The coming of age of engineered multivalent antibodies.

The development of monoclonal antibody (mAb) technology has had a profound impact on medicine. The therapeutic use of first-generation mAb achieved considerable success in the treatment of major diseases, including cancer, inflammation, autoimmune, cardiovascular, and infectious diseases. Next-generation antibodies have been engineered to further increase potency, improve the safety profile and acquire non-natural properties, and constitute a thriving area of mAb research and development. Currently, a variety of alternative antibody formats with modified architectures have been generated and are moving fast into the clinic. In fact, the bispecific antibody blinatumomab was the first in its class to be approved by the US Food and Drug Administration (FDA) as recently as December 2014. Here, we outline the fundamental strategies used for designing the next generation of therapeutic antibodies, as well as the most relevant results obtained in preclinical studies and clinical trials.

Basement membrane-rich organoids with functional human blood vessels are permissive niches for human breast cancer metastasis.

Metastatic breast cancer is the leading cause of death by malignancy in women worldwide. Tumor metastasis is a multistep process encompassing local invasion of cancer cells at primary tumor site, intravasation into the blood vessel, survival in systemic circulation, and extravasation across the endothelium to metastasize at a secondary site. However, only a small percentage of circulating cancer cells initiate metastatic colonies. This fact, together with the inaccessibility and structural complexity of target tissues has hampered the study of the later steps in cancer metastasis. In addition, most data are derived from in vivo models where critical steps such as intravasation/extravasation of human cancer cells are mediated by murine endothelial cells. Here, we developed a new mouse model to study the molecular and cellular mechanisms underlying late steps of the metastatic cascade. We have shown that a network of functional human blood vessels can be formed by co-implantation of human endothelial cells and mesenchymal cells, embedded within a reconstituted basement membrane-like matrix and inoculated subcutaneously into immunodeficient mice. The ability of circulating cancer cells to colonize these human vascularized organoids was next assessed in an orthotopic model of human breast cancer by bioluminescent imaging, molecular techniques and immunohistological analysis. We demonstrate that disseminated human breast cancer cells efficiently colonize organoids containing a functional microvessel network composed of human endothelial cells, connected to the mouse circulatory system. Human breast cancer cells could be clearly detected at different stages of the metastatic process: initial arrest in the human microvasculature, extravasation, and growth into avascular micrometastases. This new mouse model may help us to map the extravasation process with unprecedented detail, opening the way for the identification of relevant targets for therapeutic intervention.