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PURPOSE: Anterior cruciate ligament (ACL) rupture is increasingly common in paediatric and adolescent populations, typically requiring surgical ACL reconstruction (ACLR) to restore knee stability. However, ACLR substantially alters knee biomechanics (e.g., motion and tissue mechanics) placing the patient at elevated risk of early-onset knee osteoarthritis. METHODS: This study employed a linked neuromusculoskeletal (NMSK)-finite element (FE) model to determine effects of four critical ACLR surgical parameters (graft type, size, location and pre-tension) on tibial articular cartilage stresses in three paediatric knees of different sizes during walking. Optimal surgical combinations were defined by minimal kinematic and tibial cartilage stress deviations in comparison to a corresponding intact healthy knee, with substantial deviations defined by normalized root mean square error (nRMSE) > 10%. RESULTS: Results showed unique trends of principal stress deviations across knee sizes with small knee showing least deviation from intact knee, followed by large- and medium-sized knees. The nRMSE values for cartilage stresses displayed notable variability across different knees. Surgical combination yielding the highest nRMSE in comparison to the one with lowest nRMSE resulted in an increase of maximum principal stress on the medial tibial cartilage by 18.0%, 6.0% and 1.2% for small, medium and large knees, respectively. Similarly, there was an increase of maximum principal stress on lateral tibial cartilage by 11.2%, 4.1% and 12.7% for small, medium and large knees, respectively. Knee phenotype and NMSK factors contributed to deviations in knee kinematics and tibial cartilage stresses. Although optimal surgical configurations were found for each knee size, no generalizable trends emerged emphasizing the subject-specific nature of the knee and neuromuscular system. CONCLUSION: Study findings underscore subject-specific complexities in ACLR biomechanics, necessitating personalized surgical planning for effective restoration of native motion and tissue mechanics. Future research should expand investigations to include a broader spectrum of subject-specific factors to advance personalized surgical planning. LEVEL OF EVIDENCE: Level III.
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Coronary artery disease (CAD) is the leading cause of death in India. Many genetic polymorphisms play a role in regulating oxidative stress, blood pressure and lipid metabolism, contributing to the pathophysiology of CAD. This study examined the association between ten polymorphisms and CAD in the Jat Sikh population from Northern India, also considering polygenic risk scores. This study included 177 CAD cases and 175 healthy controls. The genetic information of GSTM1 (rs366631), GSTT1 (rs17856199), ACE (rs4646994), AGT M235T (rs699), AGT T174M (rs4762), AGTR1 A1166C (rs5186), APOA5 (rs3135506), APOC3 (rs5128), APOE (rs7412) and APOE (rs429358) and clinical information was collated. Statistical analyses were performed using SPSS version 27.0 and SNPstats. Significant independent associations were found for GST*M1, GST*T1, ACE, AGT M235T, AGT T174M, AGTR1 A1166C and APOA5 polymorphisms and CAD risk (all p < 0.05). The AGT CT haplotype was significantly associated with a higher CAD risk, even after controlling for covariates (adjusted OR = 3.93, 95% CI [2.39-6.48], p < 0.0001). The APOA5/C3 CC haplotype was also significantly associated with CAD (adjusted OR = 1.86, 95% CI [1.14-3.03], p < 0.05). A higher polygenic risk score was associated with increased CAD risk (adjusted OR = 1.98, 95% CI [1.68-2.34], p < 0.001). Seven polymorphisms were independently associated with an increase in the risk of CAD in this North Indian population. A considerable risk association of AGT, APOA5/C3 haplotypes and higher genetic risk scores is documented, which may have implications for clinical and public health applications.
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Angiotensinógeno , Apolipoproteína A-V , Apolipoproteínas E , Enfermedad de la Arteria Coronaria , Puntuación de Riesgo Genético , Glutatión Transferasa , Polimorfismo de Nucleótido Simple , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Angiotensinógeno/genética , Apolipoproteína A-V/genética , Apolipoproteína C-III , Apolipoproteínas E/genética , Estudios de Casos y Controles , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/epidemiología , Frecuencia de los Genes , Estudios de Asociación Genética , Glutatión Transferasa/genética , Haplotipos , India/epidemiología , Peptidil-Dipeptidasa A/genética , Receptor de Angiotensina Tipo 1/genética , Factores de RiesgoRESUMEN
Bluetongue virus (BTV, Sedoreoviridae: Orbivirus) causes an economically important disease, namely, bluetongue (BT), in domestic and wild ruminants worldwide. BTV is endemic to South India and has occurred with varying severity every year since the virus was first reported in 1963. BT can cause high morbidity and mortality to sheep flocks in this region, resulting in serious economic losses to subsistence farmers, with impacts on food security. The epidemiology of BTV in South India is complex, characterized by an unusually wide diversity of susceptible ruminant hosts, multiple vector species biting midges (Culicoides spp., Diptera: Ceratopogonidae), which have been implicated in the transmission of BTV and numerous co-circulating virus serotypes and strains. BT presence data (1997-2011) for South India were obtained from multiple sources to develop a presence/absence model for the disease. A non-linear discriminant analysis (NLDA) was carried out using temporal Fourier transformed variables that were remotely sensed as potential predictors of BT distribution. Predictive performance was then characterized using a range of different accuracy statistics (sensitivity, specificity, and Kappa). The top ten variables selected to explain BT distribution were primarily thermal metrics (land surface temperature, i.e., LST, and middle infrared, i.e., MIR) and a measure of plant photosynthetic activity (the Normalized Difference Vegetation Index, i.e., NDVI). A model that used pseudo-absence points, with three presence and absence clusters each, outperformed the model that used only the recorded absence points and showed high correspondence with past BTV outbreaks. The resulting risk maps may be suitable for informing disease managers concerned with vaccination, prevention, and control of BT in high-risk areas and for planning future state-wide vector and virus surveillance activities.
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Germanium-on-Silicon (Ge-on-Si) avalanche photodiodes (APDs) are of considerable interest as low intensity light detectors for emerging applications. The Ge absorption layer detects light at wavelengths up to ≈ 1600â nm with the Si acting as an avalanche medium, providing high gain with low excess avalanche noise. Such APDs are typically used in waveguide configurations as growing a sufficiently thick Ge absorbing layer is challenging. Here, we report on a new vertically illuminated pseudo-planar Ge-on-Si APD design utilizing a 2 µm thick Ge absorber and a 1.4 µm thick Si multiplication region. At a wavelength of 1550â nm, 50 µm diameter devices show a responsivity of 0.41 A/W at unity gain, a maximum avalanche gain of 101 and an excess noise factor of 3.1 at a gain of 20. This excess noise factor represents a record low noise for all configurations of Ge-on-Si APDs. These APDs can be inexpensively manufactured and have potential integration in silicon photonic platforms allowing use in a variety of applications requiring high-sensitivity detectors at wavelengths around 1550â nm.
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OBJECTIVE: Following a mild traumatic brain injury (mTBI), the most prevalent and profoundly debilitating occurrence is the emergence of an acute and persistent post-traumatic headache (PTH), for which there are presently no approved treatments. A crucial gap in knowledge exists regarding the consequences of an mTBI, which could serve as a foundation for the development of therapeutic approaches. The activation of trigeminal sensory nerve terminals that innervate the calvarial periosteum (CP)-a densely innervated tissue layer covering the calvarial skull-has been implicated in both migraines and PTHs. We have previously shown that trigeminal oxytocin receptors (OTRs) may provide a therapeutic target for PTHs. This study examined the expression of oxytocin receptors on trigeminal nerves innervating the periosteum and whether these receptors might serve as a therapeutic target for PTHs using a direct application of oxytocin to the periosteum in a rodent model of PTH. METHODS: We used retrograde tracing and immunohistochemistry to determine if trigeminal ganglion (TG) neurons innervating the periosteum expressed OTRs and/or CGRPs. To model the impact of local inflammation that occurs following an mTBI, we applied chemical inflammatory mediators directly to the CP and assessed for changes in immediate-early gene expression as an indication of neuronal activation. We also determined whether mTBI would lead to expression changes to OTR levels. To determine whether these OTRs could be a viable therapeutic target, we assessed the impact of oxytocin injections into the CP in a mouse model of PTH-induced periorbital allodynia. RESULTS: The results of these experiments demonstrate the following: (1) the cell bodies of CP afferents reside in the TG and express both OTRs and CGRPs; (2) inflammatory chemical stimulation of the periosteum leads to rapid activation of TG neurons (phospho-ERK (p-ERK) expression), (3) mTBI-induced inflammation increased OTR expression compared to the sham group; and (4) administration of oxytocin into the periosteum on day 2 and day 40 blocked cutaneous allodynia for up to one hour post-administration for both acute and persistence phases in the PTH model-an effect that was preventable by the administration of an OTR antagonist. CONCLUSION: Taken together, our observations suggest that periosteal trigeminal afferents contribute to post-TBI craniofacial pain, and that periosteum tissue can be used as a potential local target for therapeutics such as oxytocin.
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BACKGROUND: The number of asylum seekers awaiting decisions on their claims in the UK has more than tripled since 2014. How we meet international obligations to provide appropriate healthcare to asylum seekers and refugees (ASRs) is therefore an increasingly important issue. The views of frontline healthcare workers are vital to ensure the development of sustainable and effective health policy when it comes to caring for this group. METHOD: A single-centre qualitative study in the form of semistructured interviews was conducted at the Queen Elizabeth University Hospital ED in Glasgow, Scotland, between January and March 2023. Volunteering ED care providers (EDCPs)-doctors and nurses-working in the ED were interviewed and the data analysed and presented through a thematic analytical framework. RESULTS: 12 semistructured interviews were conducted-6 doctors and 6 nurses. Analysis revealed four themes: (1) 'staff attitudes' highlighted in particular the positive views of the participants in providing care for ASRs; (2) 'presentation patterns' revealed significant variations in opinion, with one-third of participants, for example, believing there was no difference in presentations compared with the general population; (3) 'challenges to optimal care' outlines multiple subthemes which impact care including the unique challenge of the ED triage system; and (4) 'transition in care' discusses participant concerns regarding arranging safe and appropriate follow-up for ASR patients. Ethical dilemmas in providing care, as highlighted in previous studies, did not feature heavily in discussions in this study. CONCLUSION: This study provides an insight into the views of EDCPs in providing care to ASRs in the ED. Study findings can potentially contribute to the development of ED-specific guidelines as well as inform wider health policy and provide a focus and direction for further research.
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Background: Acute leukemia is a cancer of the white blood cells which progresses rapidly and aggressively. There are two types: acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). The latter has a rare subtype: acute promyelocytic leukemia (APL). For some patients, following first-line treatment, remission is not achieved ("refractory disease"), and for others the leukemia returns after achieving remission ("relapse"). For these individuals, outcomes are typically poor. It is, therefore, important to understand patients' treatment priorities in this context. Methods: Building upon formative qualitative research, an online survey containing a discrete choice experiment (DCE) was designed to explore patients' treatment preferences in the relapsed/refractory setting. The DCE attributes were mode of administration; quality of life during treatment; chance of response; duration of response; and quality of life during response. Each respondent completed twelve scenarios containing two hypothetical treatments. Participants were eligible if they lived in the United Kingdom and had a diagnosis of acute leukemia. The data were analysed using a latent class model. Results: A total of 95 patients completed the survey. The latent class analysis identified two classes. For both, chance of response was the most important attribute. For class 1, every attribute was important, whereas for class 2, the only important attributes were quality of life (during treatment and response) and chance of response. A greater proportion of respondents would fall into class 1 overall, and those with ALL or APL and those more recently diagnosed were more likely to be in class 2. Conclusion: Our results indicate that patients are strongly concerned about the chance of response, as well as quality of life (to a lesser extent), when faced with different treatment options in the relapsed/refractory setting. However, there is significant preference heterogeneity within the patient population, and other treatment characteristics also matter to many.
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BACKGROUND: A standard of care and optimal duration of therapy have not been established for patients with multiply relapsed or refractory follicular lymphoma. The aim of this study was to evaluate epcoritamab, a novel CD3â×âCD20 bispecific antibody, in the third-line and later setting of follicular lymphoma. METHODS: EPCORE NHL-1 is a multicohort, single-arm, phase 1-2 trial conducted at 88 sites across 15 countries. Here, we report the primary analysis of patients with relapsed or refractory follicular lymphoma in the phase 2 part of the trial, which included the pivotal (dose expansion) cohort and the cycle 1 optimisation cohort. Eligible patients were aged 18 years or older, had relapsed or refractory CD20+ follicular lymphoma (grade 1-3A), an Eastern Cooperative Oncology Group performance status of up to 2, and had received at least two previous lines of therapy (including an anti-CD20 monoclonal antibody and an alkylating agent or lenalidomide). Patients were treated with subcutaneous epcoritamab 48 mg in 28-day cycles: weekly in cycles 1-3, biweekly in cycles 4-9, and every 4 weeks until disease progression or unacceptable toxicity. To mitigate the risk and severity of cytokine release syndrome, in the pivotal cohort, cycle 1 consisted of a step-up dosing regimen of a 0·16-mg priming dose on day 1 and a 0·80-mg intermediate dose on day 8, followed by subsequent 48-mg full doses and prophylactic prednisolone 100 mg; in the cycle 1 optimisation cohort, a second intermediate dose of 3 mg on day 15, adequate hydration, and prophylactic dexamethasone 15 mg were evaluated during cycle 1 to further reduce risk and severity of cytokine release syndrome. Primary endpoints were independently reviewed overall response rate for the pivotal cohort and the proportion of patients with grade 2 or worse and any-grade cytokine release syndrome for the cycle 1 optimisation cohort. Analyses were done in all enrolled patients who had received at least one dose of epcoritamab. This study is registered with ClinicalTrials.gov, NCT03625037, and is ongoing. FINDINGS: Between June 19, 2020, and April 21, 2023, 128 patients (median age 65 years [IQR 55-72]; 49 [38%] female and 79 [62%] male) were enrolled and treated in the pivotal cohort (median follow-up 17·4 months [IQR 9·1-20·9]). The overall response rate was 82·0% (105 of 128 patients; 95% CI 74·3-88·3), with a complete response rate of 62·5% (80 of 128; 95% CI 53·5-70·9). The most common grade 3-4 treatment-emergent adverse event was neutropenia in 32 (25%) of 128 patients. Grade 1-2 cytokine release syndrome was reported in 83 (65%) of 128 patients; grade 3 cytokine release syndrome was reported in two (2%). Immune effector cell-associated neurotoxicity syndrome was reported in eight (6%) of 128 patients (five [4%] grade 1; three [2%] grade 2). Between Oct 25, 2022, and Jan 8, 2024, 86 patients (median age 64 years [55-71]; 37 [43%] female and 49 [57%] male) were enrolled and treated in the cycle 1 optimisation cohort. The incidence of cytokine release syndrome was 49% (42 of 86 patients; eight [9%] grade 2; none of grade 3 or worse), with no reported immune effector cell-associated neurotoxicity syndrome. INTERPRETATION: Epcoritamab monotherapy showed clinically meaningful activity in patients with multiply relapsed or refractory follicular lymphoma, and had a manageable safety profile. FUNDING: Genmab and AbbVie.
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Anticuerpos Biespecíficos , Linfoma Folicular , Humanos , Linfoma Folicular/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Anticuerpos Biespecíficos/uso terapéutico , Anticuerpos Biespecíficos/efectos adversos , AdultoRESUMEN
PURPOSE: Interhospital transfer of critically injured patients to a major trauma service reduces preventable death in major trauma. Yet some of those transferred die without intervention. These 'futile' interhospital trauma transfers (IHTs), and other potentially avoidable IHTs place enormous stress on families of trauma victims, can delay care, and incur great cost to public health resources. This study sought to characterise these IHTs using current state guidelines for interhospital transfer. METHODS: A retrospective cohort study was conducted using our institution's trauma registry from January 2016-December 2020. All adult patients transferred to our major trauma service were analysed. Futile IHTs were defined as death or transfer to hospice care without surgical, endoscopic, or radiological intervention, and without ICU admission, within 72 h of admission. Potentially avoidable IHTs were defined as all patients discharged alive without intervention or ICU care, and secondary over-triage patients are a subset of these patients who were discharged within 72 h of admission. Patient demographics, injuries, and treatments were categorised from electronic records and analysed. RESULTS: Of 2,837 IHTs, seven (0.2 %) met criteria for futility. The majority were female, median age of 80 (IQR 85-75) and had a median Injury Severity Score (ISS) of 16 (IQR 25.5-11.5). By contrast, 1391 patients (49 %) were classified as potentially avoidable and 513 (18 %) were considered secondary over-triage. The majority were male, median age of 43 (IQR 62-28), and had a median ISS of 9 (IQR 13-4). Of these potentially avoidable IHTs, 984 (70.7 %) were discharged directly home. CONCLUSION: Futile IHTs were infrequent, however over half of all trauma patients transferred from other hospitals were discharged without tertiary-level intervention. Trauma services should consider developing systems such as telehealth to support regional general and orthopaedic surgeons to co-manage lower risk trauma, particularly minor head and minor spinal trauma patients. This could be an integral part of safely reducing potentially avoidable IHTs and their associated costs while maintaining a low rate of preventable mortality in trauma.
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Puntaje de Gravedad del Traumatismo , Inutilidad Médica , Transferencia de Pacientes , Centros Traumatológicos , Humanos , Transferencia de Pacientes/estadística & datos numéricos , Femenino , Masculino , Estudios Retrospectivos , Anciano , Anciano de 80 o más Años , Sistema de Registros , Heridas y Lesiones/terapia , Heridas y Lesiones/epidemiología , Triaje , Mortalidad Hospitalaria , Persona de Mediana Edad , Unidades de Cuidados Intensivos , Adulto , Alta del Paciente/estadística & datos numéricosRESUMEN
The effect of deprivation on total bone health status has not been well defined. We examined the relationship between socioeconomic deprivation and poor bone health and falls and we found a significant association. The finding could be beneficial for current public health strategies to minimise disparities in bone health. PURPOSE: Socioeconomic deprivation is associated with many illnesses including increased fracture incidence in older people. However, the effect of deprivation on total bone health status has not been well defined. To examine the relationship between socioeconomic deprivation and poor bone health and falls, we conducted a cross-sectional study using baseline measures from the United Kingdom (UK) Biobank cohort comprising 502,682 participants aged 40-69 years at recruitment during 2006-2010. METHOD: We examined four outcomes: 1) low bone mineral density/osteopenia, 2) fall in last year, 3) fracture in the last five years, and 4) fracture from a simple fall in the last five years. To measure socioeconomic deprivation, we used the Townsend index of the participant's residential postcode. RESULTS: At baseline, 29% of participants had low bone density (T-score of heel < -1 standard deviation), 20% reported a fall in the previous year, and 10% reported a fracture in the previous five years. Among participants experiencing a fracture, 60% reported the cause as a simple fall. In the multivariable logistic regression model after controlling for other covariates, the odds of a fall, fracture in the last five years, fractures from simple fall, and osteopenia were respectively 1.46 times (95% confidence interval [CI] 1.42-1.49), 1.26 times (95% CI 1.22-1.30), 1.31 times (95% CI 1.26-1.36) and 1.16 times (95% CI 1.13-1.19) higher for the most deprived compared with the least deprived quantile. CONCLUSION: Socioeconomic deprivation was significantly associated with poor bone health and falls. This research could be beneficial to minimise social disparities in bone health.
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Accidentes por Caídas , Densidad Ósea , Enfermedades Óseas Metabólicas , Fracturas Osteoporóticas , Factores Socioeconómicos , Humanos , Persona de Mediana Edad , Masculino , Femenino , Reino Unido/epidemiología , Anciano , Estudios Transversales , Accidentes por Caídas/estadística & datos numéricos , Densidad Ósea/fisiología , Adulto , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/fisiopatología , Fracturas Osteoporóticas/etiología , Fracturas Osteoporóticas/prevención & control , Enfermedades Óseas Metabólicas/epidemiología , Enfermedades Óseas Metabólicas/fisiopatología , Disparidades en el Estado de Salud , Osteoporosis/epidemiología , Osteoporosis/fisiopatología , Estudios de Cohortes , Biobanco del Reino UnidoRESUMEN
Background. Advocates argue that end-of-life (EOL) care is systematically disadvantaged by the quality-adjusted life-year (QALY) framework. By definition, EOL care is short duration and not primarily intended to extend survival; therefore, it may be inappropriate to value a time element. The QALY also neglects nonhealth dimensions such as dignity, control, and family relations, which may be more important at EOL. Together, these suggest the QALY may be a flawed measure of the value of EOL care. To test these arguments, we administered a stated preference survey in a UK-representative public sample. Methods. We designed a discrete choice experiment (DCE) to understand public preferences over different EOL scenarios, focusing on the relative importance of survival, conventional health dimensions (especially physical symptoms and anxiety), and nonhealth dimensions such as family relations, dignity, and sense of control. We used latent class analysis to understand preference heterogeneity. Results. A 4-class latent class multinomial logit model had the best fit and illustrated important heterogeneity. A small class of respondents strongly prioritized survival, whereas most respondents gave relatively little weight to survival and, generally speaking, prioritized nonhealth aspects. Conclusions. This DCE illustrates important heterogeneity in preferences within UK respondents. Despite some preferences for core elements of the QALY, we suggest that most respondents favored what has been called "a good death" over maximizing survival and find that respondents tended to prioritize nonhealth over conventional health aspects of quality. Together, this appears to support arguments that the QALY is a poor measure of the value of EOL care. We recommend moving away from health-related quality of life and toward a more holistic perspective on well-being in assessing EOL and other interventions. Highlights: Advocates argue that some interventions, including but not limited to end-of-life (EOL) care, are valued by patients and the public but are systematically disadvantaged by the quality-adjusted life-year (QALY) framework, leading to an unfair and inefficient allocation of health care resources.Using a discrete choice experiment, we find some support for this argument. Only a small proportion of public respondents prioritized survival in EOL scenarios, and most prioritized nonhealth aspects such as dignity and family relations.Together, these results suggest that the QALY may be a poor measure of the value of EOL care, as it neglects nonhealth aspects of quality and well-being that appear to be important to people in hypothetical EOL scenarios.
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Astrocytes throughout the central nervous system are heterogeneous in both structure and function. This diversity leads to tissue-specific specialization where morphology is adapted to the surrounding neuronal circuitry, as seen in Bergman glia of the cerebellum and Müller glia of the retina. Because morphology can be a differentiating factor for cellular classification, we recently developed a mouse where glial-fibrillary acidic protein (GFAP)-expressing cells stochastically label for full membranous morphology. Here we utilize this tool to investigate whether morphological and electrophysiological features separate types of mouse retinal astrocytes. In this work, we report on a novel glial population found in the inner plexiform layer and ganglion cell layer which expresses the canonical astrocyte markers GFAP, S100ß, connexin-43, Sox2 and Sox9. Apart from their retinal layer localization, these cells are unique in their radial distribution. They are notably absent from the mid-retina but are heavily concentrated near the optic nerve head, and to a lesser degree the peripheral retina. Additionally, their morphology is distinct from both nerve fiber layer astrocytes and Müller glia, appearing more similar to amacrine cells. Despite this structural similarity, these cells lack protein expression of common neuronal markers. Additionally, they do not exhibit action potentials, but rather resemble astrocytes and Müller glia in their small amplitude, graded depolarization to both light onset and offset. Their structure, protein expression, physiology, and intercellular connections suggest that these cells are astrocytic, displaced from their counterparts in the nerve fiber layer. As such, we refer to these cells as displaced retinal astrocytes.
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Astrocitos , Ratones Transgénicos , Retina , Animales , Astrocitos/metabolismo , Astrocitos/fisiología , Retina/citología , Retina/metabolismo , Retina/fisiología , Ratones , Proteína Ácida Fibrilar de la Glía/metabolismo , Ratones Endogámicos C57BL , Potenciales de Acción/fisiologíaRESUMEN
BACKGROUND: Health is a matter of human rights, and dental caries is the most common noncommunicable disease globally. Consequently, dental caries is a matter of human rights and its control, particularly prevention, must be a priority. Although largely preventable, this is too often neglected, both in the literature of human rights and health law, and in dental research. The right to oral health has recently been acknowledged by the World Health Organization (WHO), but it is insufficiently clear what this right entails. SUMMARY: This article introduces a right to health-based narrative in the context of dental caries. The right to health is stipulated in human rights treaties, including the International Covenant on Economic, Social and Cultural Rights (ICESCR) and the Convention on the Rights of the Child (CRC). States that are parties to these treaties, which are virtually all States globally, are mandated to ensure the enjoyment of individuals' right to the highest attainable standard of health, including oral health. KEY MESSAGES: Dental caries is a matter of human rights. States have binding obligations to address dental caries: they require the regulation of the healthcare system, i.e., the traditional focus on operative care, but also put the regulation of other risk factors on an equal footing, such as the regulation of the living environment and access to fluoride. A right to health-based approach to dental caries thus offers a comprehensive approach to dental caries control, particularly prevention.
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Caries Dental , Salud Bucal , Derecho a la Salud , Humanos , Caries Dental/prevención & control , Salud Global , Organización Mundial de la Salud , Accesibilidad a los Servicios de SaludRESUMEN
OBJECTIVE: Extending on previous findings that computerized Memory Specificity Training (c-MeST) improves memory specificity and depressive symptoms in Major Depressive Disorder (MDD) in adults, this study aimed to assess the effects of c-MeST in youth with MDD on memory specificity and depression in addition to other treatment. METHODS: Participants aged 15-25 (N = 359, 76 % female; M age = 19.2, SD = 3.1), receiving predominantly psychological therapy or counseling (85 %) and/or antidepressants (52 %) were randomized to usual care and c-MeST or usual care. Cognitive and clinical outcomes were assessed at baseline and at one, three, and six-month follow-ups. RESULTS: The usual care and c-MeST group reported higher memory specificity at one-month (d = 0.42, p = .022), but not at three or six months (d's < 0.15, p's > 0.05). The rate of MDE was numerically lower in the c-MeST group at each follow-up time-point, but group was not a statistically significant predictor at one month (64 % usual care and c-MeST vs. 68 % usual care, OR = 0.81, p = .606), three months (67 % usual care and c-MeST vs. 72 % usual care, OR = 0.64, p = .327) or six months (55 % usual care and c-MeST vs. 68 % usual care, OR = 0.56, p = .266). The usual care and c-MeST group did report lower depressive symptoms at one month (d = 0.42, p = .023) and six-months (d = 0.84, p = .001), but not three-months (d = 0.13, p > .05). CONCLUSIONS: c-MeST may reduce symptoms in youth with MDD when provided alongside other treatments. However, there are significant limitations to this inference, including high attrition in the study and a need for more data on the acceptability of the intervention.
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Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/terapia , Femenino , Masculino , Adolescente , Adulto Joven , Adulto , Antidepresivos/uso terapéutico , Terapia Cognitivo-Conductual/métodos , Resultado del Tratamiento , Memoria , Terapia Asistida por Computador/métodos , Consejo/métodosRESUMEN
The health risks and harm associated with regular alcohol consumption are well documented. In a recent WHO statement published in The Lancet Public Health alcohol consumption has been estimated to contribute worldwide to 3 million deaths in 2016 while also being responsible for 5·1% of the global burden of disease and injury. The total elimination of alcohol consumption, which has been long imbedded in human culture and society, is not practical and prohibition policies have proved historically ineffective. However, valuable strategies to reduce alcohol harms are already available and improved alternative approaches are currently being developed. Here, we will review and discuss recent advances on two main types of approaches, that is nutritional interventions and functional alcohol alternatives.
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Consumo de Bebidas Alcohólicas , Humanos , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/prevención & controlRESUMEN
BACKGROUND AND OBJECTIVE: Incidence of paediatric anterior cruciate ligament (ACL) rupture has increased substantially over recent decades. Following ACL rupture, ACL reconstruction (ACLR) surgery is typically performed to restore passive knee stability. This surgery involves replacing the failed ACL with a graft, however, surgeons must select from range of surgical parameters (e.g., type, size, insertion, and pre-tension) with no robust evidence guiding these decisions. This study presents a systemmatic computational approach to study effects of surgical parameter variation on kinematics of paediatric knees. METHODS: This study used sequentially-linked neuromusculoskeletal (NMSK) finite element (FE) models of three paediatric knees to estimate the: (i) sensitivity of post-operative knee kinematics to four surgical parameters (type, size, insertion, and pre-tension) through multi-input multi-output sensitivity analysis; (ii) influence of motion and loading conditions throughout stance phase of walking gait on sensitivity indices; and (iii) influence of subject-specific anatomy (i.e., knee size) on sensitivivty indices. A previously validated FE model of the intact knee for each subject served as a reference against which ACLR knee kinematics were compared. RESULTS: Sensitivity analyses revealed significant influences of surgical parameters on ACLR knee kinematics, albeit without discernible trend favouring any one parameter. Graft size and pre-tension were primary drivers of variation in knee translations and rotations, however, their effects fluctuated across stance indicating motion and loading conditions affect system sensitivity to surgical parameters. Importantly, the sensitivity of knee kinematics to surgical parameter varied across subjects, indicating geometry (i.e., knee size) influenced system sensitivity. Notably, alterations in graft parameters yielded substantial effects on kinematics (normalized root-mean-square-error > 10 %) compared to intact knee models, indicating surgical parameters vary post-operative knee kinematics. CONCLUSIONS: Overall, this initial study highlights the importance of surgical parameter selection on post-operative kinematics in the paediatric ACLR knee, and provides evidence of the need for personalized surgical planning to ultimately enhance patient outcomes.
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Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Humanos , Niño , Análisis de Elementos Finitos , Fenómenos Biomecánicos , Rango del Movimiento Articular , Articulación de la Rodilla/cirugía , Lesiones del Ligamento Cruzado Anterior/cirugíaRESUMEN
BACKGROUND: Component-resolved diagnosis allows detection of IgE sensitization having the advantage of reproducibility and standardization compared to crude extracts. The main disadvantage of the traditional allergen identification methods, 1- or 2-dimensional western blotting and screening of expression cDNA libraries with patients' IgEs, is that the native structure of the protein is not necessarily maintained. METHODS: We used a novel immunoprecipitation technique in combination with mass spectrometry to identify new allergens of Aspergillus fumigatus. Magnetic Dynabeads coupled with anti-human IgE antibodies were used to purify human serum IgE and subsequently allergens from A. fumigatus protein extract. RESULTS: Of the 184 proteins detected by subsequent mass peptide fingerprinting, a subset of 13 were recombinantly expressed and purified. In a panel of 52 A. fumigatus-sensitized people with asthma, 23 non-fungal-sensitized asthmatics and 18 healthy individuals, only the former showed an IgE reaction by immunoblotting and/or ELISA. We discovered 11 proteins not yet described as A. fumigatus allergens, with fructose-bisphosphate aldolase class II (FBA2) (33%), NAD-dependent malate dehydrogenase (31%) and Cu/Zn superoxide dismutase (27%) being the most prevalent. With respect to these three allergens, native versus denatured protein assays indicated a better recognition of the native proteins. Seven of 11 allergens fulfilled the WHO/IUIS criteria and were accepted as new A. fumigatus allergens. CONCLUSION: In conclusion, we introduce a straightforward method of allergen identification from complex allergenic sources such as A. fumigatus by immunoprecipitation combined with mass spectrometry, which has the advantage over traditional methods of identifying allergens by maintaining the structure of the proteins.
Asunto(s)
Alérgenos , Antígenos Fúngicos , Aspergillus fumigatus , Asma , Inmunoglobulina E , Humanos , Aspergillus fumigatus/inmunología , Asma/inmunología , Asma/diagnóstico , Alérgenos/inmunología , Inmunoglobulina E/inmunología , Inmunoglobulina E/sangre , Masculino , Femenino , Antígenos Fúngicos/inmunología , Adulto , Persona de Mediana Edad , Inmunoprecipitación , Proteínas Fúngicas/inmunología , Espectrometría de Masas , Anciano , Adulto JovenRESUMEN
Patient Support Programmes (PSPs) are used by the pharmaceutical industry to provide education and support to consumers to overcome the challenges they face managing their condition and treatment. Whilst there is an increasing number of PSPs, limited information is available on whether these programmes contribute to safety signals. PSPs do not have a scientific hypothesis, nor are they governed by a protocol. However, by their nature, PSPs inevitably generate adverse event (AE) reports. The main goal of the research was to gather all Novartis-initiated PSPs for sacubitril/valsartan, followed by research in the company safety database to identify all AE reports emanating from these PSPs. Core data sheets (CDS) were reviewed to assess if these PSPs contributed to any new, regulatory-authority approved, validated signals. Overall, AEs entered into the safety database from PSPs confirmed no contribution to CDS updates. Detailed review of real-world data revealed tablet splitting or taking one higher dose tablet a day instead of twice daily. This research, and subsequent analyses, revealed that PSPs did not impact safety label changes for sacubitril/valsartan. It revealed an important finding concerning drug utilisation i.e. splitting of sacubitril/valsartan tablets to reduce cost. This finding suggests that PSPs may contribute important real-world data on patterns of medication usage. There remains a paucity of literature available on this topic, hence further research is required to assess if it would be worth designing PSPs for collecting data on drug utilisation and (lack of) efficacy. Such information from PSPs could be important for all stakeholders.
Asunto(s)
Aminobutiratos , Insuficiencia Cardíaca , Humanos , Valsartán/uso terapéutico , Aminobutiratos/uso terapéutico , Compuestos de Bifenilo/uso terapéutico , Utilización de Medicamentos , Combinación de Medicamentos , Comprimidos/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Tetrazoles/uso terapéutico , Volumen Sistólico , Antagonistas de Receptores de Angiotensina/uso terapéuticoRESUMEN
A styrene-butadiene-styrene co-polymer matrix nanocomposite filled with graphene nanoplatelets was studied to prepare chemiresistive volatile organic compounds (VOCs) room temperature sensors with considerable response and selectivity. Nanofiller concentration was estimated from the electrical conductivity percolation behaviour of the nanocomposite. Fabricated sensors provided selective relative responses to representative VOCs differing by orders of magnitude. Maximum observed average relative responses upon exposure to saturated vapours of the tested VOCs were ca. 23% for ethanol, 1600% for acetone, and the giant values were 9 × 106% for n-heptane and 10 × 106% for toluene. The insensitivity of the sensor to the direct saturated water vapour exposure was verified. Although high humidity decreases the sensor's response, it paradoxically enhances the resolution between hydrocarbons and polar organics. The non-trivial sensing mechanism is explained using the Hansen solubility parameters (HSP), enabling a rational design of new sensors; thus, the HSP-based class of sensors is outlined.