Modelling Pancreatic Neuroendocrine Cancer: From Bench Side to Clinic

Pancreatic neuroendocrine tumours (pNETs) are a heterogeneous group of epithelial tumours with neuroendocrine differentiation. Although rare (incidence of <1 in 100,000), they are the second most common group of pancreatic neoplasms after pancreatic ductal adenocarcinoma (PDAC). pNET incidence is however on the rise and patient outcomes, although variable, have been linked with 5-year survival rates as low as 40%. Improvement of diagnostic and treatment modalities strongly relies on disease models that reconstruct the disease ex vivo. A key constraint in pNET research, however, is the absence of human pNET models that accurately capture the original tumour phenotype. In attempts to more closely mimic the disease in its native environment, three-dimensional culture models as well as in vivo models, such as genetically engineered mouse models (GEMMs), have been developed. Despite adding significant contributions to our understanding of more complex biological processes associated with the development and progression of pNETs, factors such as ethical considerations and low rates of clinical translatability limit their use. Furthermore, a role for the site-specific extracellular matrix (ECM) in disease development and progression has become clear. Advances in tissue engineering have enabled the use of tissue constructs that are designed to establish disease ex vivo within a close to native ECM that can recapitulate tumour-associated tissue remodelling. Yet, such advanced models for studying pNETs remain underdeveloped. This review summarises the most clinically relevant disease models of pNETs currently used, as well as future directions for improved modelling of the disease

MS Prevalence and Patients' Characteristics in the District of Braga, Portugal

Multiple Sclerosis (MS) is a chronic autoimmune disease of the Central Nervous System causing inflammation and neurodegeneration. There are only 3 epidemiological studies in Portugal, 2 in the Centre and 1 in the North, and there is the need to further study MS epidemiology in this country. The objective of this work is to contribute to the MS epidemiological knowledge in Portugal, describing the patients' epidemiological, demographic, and clinical characteristics in the Braga district of Portugal. This is a cross-sectional study of 345 patients followed in two hospitals of Braga district. These hospitals cover a resident population of 866,012 inhabitants. The data was collected from the clinical records, and 31/12/2009 was established as the prevalence day. For all MS patients, demographic characteristics and clinical outcomes are reported. We have found an incidence of 2.74/100,000 and a prevalence of 39.82/100,000 inhabitants. Most patients have an EDSS of 3 or lower and a mean age of 42 years. The diagnosis was done at mean age of 35, with RRMS being the disease type in more than 80% of patients. In this cohort, we found a female : male ratio of 1.79. More than 50% of patients are treated with Interferon β-1b IM or IFNβ-1a SC 22 μg

Patient-Specific Prosthetic Fingers by Remote Collaboration - A Case Study

The concealment of amputation through prosthesis usage can shield an amputee from social stigma and help improve the emotional healing process especially at the early stages of hand or finger loss. However, the traditional techniques in prosthesis fabrication defy this as the patients need numerous visits to the clinics for measurements, fitting and follow-ups. This paper presents a method for constructing a prosthetic finger through online collaboration with the designer. The main input from the amputee comes from the Computer Tomography (CT) data in the region of the affected and the non-affected fingers. These data are sent over the internet and the prosthesis is constructed using visualization, computer-aided design and manufacturing tools. The finished product is then shipped to the patient. A case study with a single patient having an amputated ring finger at the proximal interphalangeal joint shows that the proposed method has a potential to address the patient's psychosocial concerns and minimize the exposure of the finger loss to the public.Comment: Open Access articl

Are SADI-S and BPD/DS bariatric procedures identical twins or distant relatives?-A case report

Given the common anatomical features and similar short-term weight loss outcomes, Biliopancreatic Diversion with Duodenal Switch (BPD/DS) and Single-Anastomosis Duodenoileal bypass with Sleeve gastrectomy (SADI-S) are considered identical bariatric procedures, apart from technical complexity being lower for SADI-S. In the absence of prospective randomized trials or long-term comparative studies the rationale for choosing between procedures is hampered. Post-bariatric hormonal profiles could contribute to understand the underlying mechanisms and potentially be used as a decision aid when choosing between procedures. The main aim of this study was to compare the outcomes of BPD/DS and SADI-S, in genetically identical individuals exposed to similar environmental factors. Two identical twin (T) female patients, one submitted to BPD/DS (T_BPD/DS) and another to SADIS-S (T_SADI-S) were followed up to one year after surgery. Before surgery and at 3, 6 and 12 months after surgery, both patients underwent mixed meal tolerance tests (MMTT) to evaluate postprandial glucose, glucagon and GLP-1 response. In addition, 3 months after surgery, glucose dynamics were assessed using a Flash Glucose Monitoring (FGM) system for 14 days. The percentage of total weight loss (%TWL) was higher for T_BPD/DS compared to T_SADI-S (34.03 vs 29.03 %). During MMTT, T_BPD/DS presented lower glucose, glucagon, insulin and C-peptide excursions at all timepoints when compared to SADI-S; along with a greater percentage of time within the low glucose range (55.97 vs 39.93 %) and numerically lower glucose variability indexes on FGM (MAG change:0.51 vs 0.63 mmol/lxh- 1). In patients with the same genetic background, BPD/DS was shown to result in greater weight loss than SADI-S. The differences in glucose and enteropancreatic hormone profiles observed after BPD/DS and SADI-S suggest that different mechanisms underlie weight loss

Genetic mapping of a new heart rate QTL on chromosome 8 of spontaneously hypertensive rats

BACKGROUND: Tachycardia is commonly observed in hypertensive patients, predominantly mediated by regulatory mechanisms integrated within the autonomic nervous system. The genetic loci and genes associated with increased heart rate in hypertension, however, have not yet been identified. METHODS: An F2 intercross of Spontaneously Hypertensive Rats (SHR) × Brown Norway (BN) linkage analysis of quantitative trait loci mapping was utilized to identify candidate genes associated with an increased heart rate in arterial hypertension. RESULTS: Basal heart rate in SHR was higher compared to that of normotensive BN rats (365 ± 3 vs. 314 ± 6 bpm, p < 0.05 for SHR and BN, respectively). A total genome scan identified one quantitative trait locus in a 6.78 cM interval on rat chromosome 8 (8q22–q24) that was responsible for elevated heart rate. This interval contained 241 genes, of which 65 are known genes. CONCLUSION: Our data suggest that an influential genetic region located on the rat chromosome 8 contributes to the regulation of heart rate. Candidate genes that have previously been associated with tachycardia and/or hypertension were found within this QTL, strengthening our hypothesis that these genes are, potentially, associated with the increase in heart rate in a hypertension rat model

Mode I fracture characterization of human bone using the DCB test

Purpose – Fracture characterization of human cortical bone under pure mode I loading was performed in this work. The purpose of this paper is to validate the proposed test and procedure concerning fracture characterization of human cortical bone under pure mode I loading. Design/methodology/approach – A miniaturized version of the double cantilever beam (DCB) test was used for the experimental tests. A data reduction scheme based on crack equivalent concept and Timoshenko beam theory is proposed to overcome difficulties inherent to crack length monitoring during the test. The application of the method propitiates an easy determination of the Resistance-curves (R-curves) that allow to define the fracture energy under mode I loading from the plateau region. The average value of fracture energy was subsequently used in a numerical analysis with element method involving cohesive zone modelling. Findings – The excellent agreement obtained reveals that the proposed test and associated methodology is quite effective concerning fracture characterization of human cortical bone under pure mode I loading. Originality/value – A miniaturized version of traditional DCB test was proposed for cortical human bone fracture characterization under mode I loading owing to size restrictions imposed by human femur. In fact, DCB specimen propitiates a longer length for self-similar crack propagation without undertaking spurious effects. As a consequence, a R-curve was obtained allowing an adequate characterization of cortical bone fracture under mode I loading

Flood vulnerability and risk assessment of urban traditional buildings in a heritage district of Kuala Lumpur, Malaysia

Flood hazard is increasing in frequency and magnitude in major South East Asian metropolitan areas due to fast urban development and changes in climate, threatening people's property and life. Typically, flood management actions are mostly focused on large-scale defences, such as river embankments or discharge channels or tunnels. However, these are difficult to implement in town centres without affecting the value of their heritage districts and might not provide sufficient mitigation. Therefore, urban heritage buildings may become vulnerable to flood events, even when they were originally designed and built with intrinsic resilient measures, based on the local knowledge of the natural environment and its threats at the time. Their aesthetic and cultural and economic values mean that they can represent a proportionally high contribution to losses in any event. Hence it is worth investigating more localized, tailored mitigation measures. Vulnerability assessment studies are essential to inform the feasibility and development of such strategies. In this study we propose a multilevel methodology to assess the flood vulnerability and risk of residential buildings in an area of Kuala Lumpur, Malaysia, characterized by traditional timber housing. The multiscale flood vulnerability model is based on a wide range of parameters, covering building-specific parameters, neighbourhood conditions and catchment area conditions. The obtained vulnerability index shows the ability to reflect different exposure by different building types and their relative locations. The vulnerability model is combined with high-resolution fluvial and pluvial flood maps providing scenario events with 0.1 % annual exceedance probability (AEP). A damage function of generic applicability is developed to compute the economic losses at individual building and sample levels. The study provides evidence that results obtained for a small district can be scaled up to the city level, to inform both generic and specific protection strategies

Flood Vulnerability Assessment of Urban Traditional Buildings in Kuala Lumpur, Malaysia

Flood hazard is increasing in frequency and magnitude in Southeast Asia major metropolitan areas due to the effects of fast urban development and changes in climate, threatening people's properties and life. Typically, flood management actions are mostly focused on large scale defenses, such as river embankments or discharge channels or tunnels. However, these are difficult to implement in historic centres without disturbing their heritage value, and might not provide sufficient mitigation in these areas. Therefore urban heritage buildings may be particularly exposed to flood events, even when they were originally designed and built with intrinsic resilient measures, based on the local knowledge of the natural environment and its threats at the time. Their attractiveness, cultural and economic values, means that they can represent a proportionally high contribution to losses of any event. Hence it is worth to pursue more localised, tailored, mitigation measures. Vulnerability assessment studies are essential to inform the feasibility and development of such strategies. In the present paper we propose a multi-level methodology to assess the flood vulnerability of residential buildings in an area of Kuala Lumpur Malaysia characterised by traditional timber housing. The multi-scale flood vulnerability model is based on a wide range of parameters, covering building specific parameters, neighbourhood conditions and catchment area condition. Parameters for 163 buildings were measured in detail by a field surveys integrated with Google Street View. The vulnerability model is combined with high resolution fluvial and pluvial flood maps providing likely water depths for a range of different flood return periods. The obtained vulnerability index shows ability to reflect different exposure by different building types and their relative locations. The study provides evidence that results obtained for a small district can be scaled up at city level, to inform both generic and specific protection strategies. The paper discusses these in relation to a scenario event of 0.1 % Annual Exceedance Probability (AEP), based on hydrological and hydraulic models developed for the Disaster Resilient Cities Project

The diseases we cause: Iatrogenic illness in a department of internal medicine

BACKGROUND: The aim of this study was to estimate the incidence, main causes, and risk factors of iatrogenic disease occurring in a department of internal medicine. METHODS: Over a 1-year period, physicians systematically filled out a 2-page questionnaire for all patients admitted to the ward. A database was created and the data were statistically analyzed. Patients undergoing immunosuppressive, chemo-, or radiation therapy were excluded. Missing data were completed by reviewing the patients' charts. The patients were then divided into two groups: those with and those without iatrogenic disease. The groups were compared using several parameters including gender, age, social features, days of hospitalization, associated illness, functional status, medical impression, prognosis, associated renal or liver function impairment, drugs taken daily, and outcome. In the group with iatrogenic disease, the type, severity, and predictability were also analyzed. RESULTS: Of the 879 patients admitted to the ward, 445 completed questionnaires and were included in the study. A total of 102 patients (22.9%) developed 121 iatrogenic events. Forty-four patients (43.1%) were admitted for iatrogenic illness, 10 (9.8%) developed life-threatening events, and in 3 (6.8%) it was the cause of death. Fifty-eight patients (56.8%) registered 77 episodes of iatrogenic disease during their hospital stay, 20 (19.6%) developed life-threatening events, and 9 (11.7%) died, 4 (5.2%) of an iatrogenic cause (nosocomial infections). Significant differences were found in 20 out of 26 parameters studied (p<0.005 for all cases; 95% confidence interval). Eighteen percent of all iatrogenic disease was severe, 61.9% predictable, 54.5% avoidable, and 59% drug-related, 80% of which was due to side effects or adverse reactions. Infection and metabolic and electrolyte disorders were the most frequent effects. CONCLUSIONS: It is possible to identify risk factors for iatrogenic events. Chronically ill elderly inpatients are the main target of iatrogenic events

Impact of malocclusion, tooth loss and oral hygiene habits on quality of life in orthodontic patients: A cross-sectional study

We aimed to assess the impact of malocclusion on oral health-related quality of life (OHRQoL) in a sample composed of adolescents, younger adults and adults seeking orthodontic treatment. Participants were consecutively enrolled from January 2019 to March 2020. The oral health impact profile (OHIP-14) was used to measure the OHRQoL. The index of complexity, outcome and need (ICON) was used to assess malocclusion. Sociodemographic, medical, and clinical questionnaires were recorded. Statistical analyses were performed according as a function of sex and age range (15–30 or >30 years old). Linear and logistic regression models were applied to assess the association between OHIP-14 total score, malocclusion, and other relevant confounding variables. In a final sample of 93 participants (60 females and 33 males, aged 15 to 60 years), men reported significantly better OHRQoL (p = 0.005). Participants aged 30 years or older reported significantly worse OHRQoL (p = 0.042). OHIP-14 was significantly correlated with age (¿ = 0.259, p < 0.05) and the number of missing teeth (¿ = 0.369, p < 0.001). Multivariable regression showed OHIP-14 being associated with the number of missing teeth (B = 1.48, SE = 0.57, p < 0.05) and the presence of missing teeth (B = 1.38, SE = 0.65, p < 0.05). Malocclusion showed no association with OHRQoL. Age and the number of missing teeth may be key factors on self-perceived OHRQoL in adult patients seeking orthodontic treatment