A New Mutation Causing Progressive Familiar Intrahepatic Cholestasis Type 3 in Association with Autoimmune Hepatitis

Background: Some patients exhibit features of both autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC). Similarly, patients with progressive familial intrahepatic cholestasis type 3 (PFIC3) may share histological features with PSC. Case report: We report the case of a 22-year-old man who, since he was 5 years of age, has presented with pruritus, an approximately ninefold elevation of aminotransferases, and γ-glutamyl transferase levels ~10 times the upper limit. Initially he was diagnosed with an overlap syndrome of small duct PSC plus AIH. However, fluctuations in liver enzymes were observed over the following years. Analysis of the ABCB4 gene indicated the diagnosis of PFIC3, revealing a mutation not previously reported. Conclusion: With this case report we aim to describe a new mutation, raise awareness of this rare pathology and highlight the importance of genetic testing of the ABCB4 gene in patients with autoimmune liver disease (mainly small duct PSC) with incomplete response to immunosuppressive treatmen

Analysis of EGFR Overexpression, EGFR gene amplification and the EGFRvIII Mutation in portuguese high-grade gliomas

Background: Patients with malignant gliomas do not respond to any current therapy. Epidermal growth factor receptor (EGFR) controls several oncogenic processes, being frequently up-regulated in gliomas due to overexpression, gene amplification and gene mutation. EGFR inhibitors are being tried in gliomas, yet the molecular determinants of therapeutic response are unclear. Materials and Methods: EGFR overexpression, EGFRvIII mutation and EGFR amplification were determined by immunohistochemistry and chromogenic in situ hybridization (CISH) in 27 primary glioblastomas (GBM), 24 anaplastic oligodendrogliomas (AO) and four anaplastic oligoastrocytomas (AOA). Results: EGFR overexpression was associated with EGFR amplification, being found in 48% and 53% GBM, 33% and 40% AO and 75% and 67% AOA, respectively. EGFRvIII was found in 22% GBM, 8% AO and was absent in AOA. No association was observed between EGFR alterations and patient survival. Conclusion: We characterized, for the first time, EGFR molecular alterations in Portuguese patients with malignant glioma and identified a subpopulation of patients presenting putative biomarkers for EGFR-based therapies

Are lead-free relaxor ferroelectric materials the most promising candidates for energy storage capacitors?

Dielectric capacitors offer high-power density and ultrafast discharging times as compared to electrochemical capacitors and batteries, making them potential candidates for pulsed power technologies (PPT). However, low energy density in different dielectric materials such as linear dielectrics (LDs), ferroelectrics (FEs), and anti-ferroelectric (AFEs) owing to their low polarization, large hysteresis loss and low breakdown strength, respectively, limits their real time applications. Thus, achieving a material with high dielectric constant, large dielectric breakdown strength and slim hysteresis is imperative to obtain superior energy performance. In this context, relaxor ferroelectrics (RFEs) emerged as the most promising solution for energy storage capacitors. This review starts with a brief introduction of different energy storage devices and current advances of dielectric capacitors in PPT. The latest developments on lead-free RFEs including bismuth alkali titanate based, barium titanate based, alkaline niobite based perovskites both in ceramics and thin films are comprehensively discussed. Further, we highlight the different strategies used to enhance their energy storage performance to meet the requirements of the energy storage world. We also provide future guidelines in this field and therefore, this article opens a window for the current advancement in the energy storage properties of RFEs in a systematic way.This study has been partially supported by (i) DST-SERB, Govt. of India through Grant ECR/2017/000068 (KCS), (ii) UGC through grant nos. F.4-5(59-FRP)/ 2014(BSR) and (iii) Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding UIDB/FIS/04650/2020 (JPBS). The author A. R. Jayakrishnan acknowledges the Central University of Tamil Nadu, India for his Ph. D fellowship. The authors acknowledge the CERIC-ERIC Consortium for access to experimental facilities and financial support under proposal 20192055

Large ferro–pyro–phototronic effect in 0.5Ba(Zr0.2Ti0.8)O3–0.5(Ba0.7Ca0.3)TiO3 thin films integrated on silicon for photodetection

Coupling together the ferroelectric, pyroelectric, and photovoltaic characteristics within a single material is a novel way to improve the performance of photodetectors. In this work, we take advantage of the triple multifunctionality shown by 0.5Ba(Zr0.2Ti0.8)O3–0.5(Ba0.7Ca0.3)TiO3 (BCZT), as demonstrated in an Al/Si/SiOx/BCZT/ITO thin-film device. The Si/SiOx acts as an n-type layer to form a metal–ferroelectric–insulator–semiconductor heterostructure with the BCZT, and with Al and ITO as electrodes. The photo-response of the device, with excitation from a violet laser (405 nm wavelength), is carefully investigated, and it is shown that the photodetector performance is invariant with the chopper frequency owing to the pyro-phototronic effect, which corresponds to the coupling together of the pyroelectric and photovoltaic responses. However, the photodetector performance was significantly better than that of the devices operating based only on the pyro-phototronic effect by a factor of 4, due to the presence of ferroelectricity in the system. Thus, after a poling voltage of −15 V, for a laser power density of 230 mW/cm2 and at a chopper frequency of 400 Hz, optimized responsivity, detectivity, and sensitivity values of 13.1 mA/W, 1.7 × 1010 Jones, and 26.9, respectively, are achieved. Furthermore, ultrafast rise and fall times of 2.4 and 1.5 µs, respectively, are obtained, which are 35,000 and 36,000 times faster rise and fall responses, respectively, than previous reports of devices with the ferro–pyro–phototronic effect. This is understood based on the much faster ferroelectric switching in ferroelectric thin films owing to the predominant 180° domains in a single direction out of plane.This work was supported by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding Contracts UIDB/04650/2020. This project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 958174 (M-ERA-NET3/0003/2021—NanOx4EStor). The authors would also like to thank engineer José Santos for technical support at the Thin Film Laboratory. J. L. M.-D. and R. L. Z. H. are grateful for EPSRC CAM-IES grant EP/P007767/. R. L. Z. H. also acknowledges support from the Royal Academy of Engineering under the Research Fellowships scheme (No.: RF\201718\1701). J. L. M.-D. acknowledges support from the Royal Academy of Engineering Chair in Emerging Technologies scheme (No.: CIET1819_24) and the ERC grant EROS, EU-H2020-ERC-ADG # 882929

Recommended age groups and frequency of mammography screening : a systematic review

Esta revisão teve por objetivo avaliar a força de evidência do atual indicador de desempenho português relativo ao rastreio do Câncer da Mama através da mamografia, de modo a determinar o grupo etário e a periodicidade recomendadas. Foram pesquisados artigos nas principais bases de dados internacionais de literatura médica. Incluímos artigos publicados entre Janeiro de 2006 e Janeiro de 2012 que correspondiam aos objetivos da revisão. Foi utilizada a taxonomia SORT para a classificação dos resultados. Dos 253 artigos encontrados foram selecionados cinco que cumpriam os critérios de inclusão. Estes incluem três revisões sistemáticas (RS), uma meta-análise (MA) e uma norma de orientação clínica (NOC) baseada numa RS. Os artigos selecionados avaliaram a redução da mortalidade por câncer da mama através do rastreio com mamografia. A realização do rastreio mamográfico entre os 50 e os 69 anos é recomendado em todos os artigos que avaliam esta faixa etária. A NOC recomenda o rastreio bienal. Em suma, a mamografia deverá ser realizada entre os 50 e os 69 anos com uma periodicidade bienal. Estes resultados vão ao encontro do atual indicador de desempenho do rastreio do câncer da mama em Portugal.The scope of this review was to assess the strength of evidence for the current Portuguese performance indicator on breast cancer screening with mammography in order to determine the recommended age group and periodicity for screening. A search for articles was conducted in the main international databases of medical literature. Articles published between January 2006 and January 2012 addressing the objectives of this review were included. The SORT taxonomy was used to classify the results. Of the 253 articles, five articles met the inclusion criteria and were selected for review. These included three systematic reviews, one meta-analysis and one clinical guideline based on a systematic review. A reduction in breast cancer mortality with mamography screening was the outcome in all articles selected. Mammography screening between 50 and 69 years was recommended in all articles that assess this age group. The clinical guidelines recommended screening every two years. In conclusion, the current literature recommends mammography for women every two years between the ages of 50 and 69 years. This is consistent with the current performance indicator for breast cancer screening in Portugal

Performance indicators for clinical practice management in primary care in Portugal : consensus from a Delphi study

Early OnlineBackground: Performance indicators assessing the quality of medical care and linked to pay for performance may cause disagreement. Portuguese indicators included in recent health care reform are controversial. Objectives: To obtain consensus from opinion leaders in family medicine regarding the performance indicators for practice management used in the evaluation of Family Health Units in Portugal. Methods: Eighty-nine specialists in primary care were invited to answer the following question in an online Delphi study: 'Which performance indicators should be assessed regarding the organization and management of clinical practice in primary care in Portugal?' A Likert scale was used to evaluate validity, reliability, feasibility and sensitivity to change. Twenty-seven experts participated in the second round and achieved a high degree of consensus. Eight categories were created for analysis. Results: The experts suggested the use of existing indicators as well as new indicators. Thirty-nine indicators suggested by the experts are currently in use in Portugal. The assessment of the number of clinical acts performed, the number of administrative acts, and evaluation of the clinical demographic profile achieved a high degree of consensus. The expert panel suggested fifty new indicators. Five categories of these new indicators had a high degree of consensus, and three categories had a low degree of consensus. Conclusion: The expert panel recommended that performance indicators of practice management should first assess the quantity of clinical and administrative activities undertaken. These indicators must take into account the human and financial resources available to the clinic and its demographic context

Evaluation of potential of gamma radiation as a conservation treatment for blackberry fruits

BACKGROUND: Blackberries consumption has been associated with health benefits. However, these fruits present a short shelf-life. Thus, food irradiation is a potential alternative technology for conservation of these fruits without use of chemicals. OBJECTIVE: Analyse the potentiality of gamma radiation as a decontamination method for blackberry fruits. METHODS: Fresh packed blackberries were irradiated in a Co-60 source at two doses (1.0 and 1.5 kGy). Bioburden, physical and rheological, sensorial and total soluble content parameters were assessed before irradiation, immediately after and at two days storage time at 4°C. RESULTS: The characterization of blackberries microbiota point out to an average bioburden value of 104 CFU/g and to a microbial population predominantly composed by filamentous fungi. The inactivation studies on the blackberries mesophilic population indicated a limited microbial inactivation (<1 log decimal reduction) for the applied radiation doses, being the surviving population mainly constituted by filamentous fungi and yeast. No effect of irradiation on colour of blackberries was observed. Concerning texture parameters, no significant differences were observed in both fracturability and firmness between non-irradiated and irradiated blackberries immediately after irradiation. In blackberries stored for two days, both parameters were slightly lower in irradiated blackberries, compared to non-irradiated blackberries. The performed sensorial analysis indicated a similar acceptability among irradiated and non-irradiated fruits. CONCLUSION: This work reveals gamma irradiation treatment potential since no major impact was detected on blackberries physical, rheological and sensory attributes. Further studies with longer periods of storage are needed to elucidate the advantages of irradiation as a conservation treatment.© 2013 - IOS Press and the authors. All rights reserved

Cervical cancer screening: target age bracket, screening frequency and screening method: review of recent evidence and comparison with the Portuguese performance indicator

Esta revisão teve por objetivo avaliar a força de evidência do indicador de desempenho português relativo ao rastreio do Câncer do Colo do Útero (CCU): (1) limites etários das mulheres da população geral que o devem realizar, a (2) periodicidade com que deve ser realizado e (3) qual o melhor exame de rastreio. Foram pesquisados os seguintes termos MeSH: vaginal smears, age groups, periodicity, methods, uterine cervical cancer. Foram excluídos os artigos que não abordavam o objetivo da investigação ou que não fossem redigidos em Inglês, Português ou Espanhol. Para interpretar os artigos selecionados foi utilizada a classificação SORT. Foram encontrados 197 artigos, dos quais seleccionados 9: 1 revisão sistemática (RS), 1 estudo clínico controlado aleatorizado, 2 estudos observacionais retrospectivos e 5 normas de orientação clínica (NOC). Os autores optaram por incluir nesta revisão mais 4 NOCs e 2 RSs por considerarem ser relevantes para a população Portuguesa, apesar de não resultarem da pesquisa efectuada. Os estudos sugerem realização do rastreio entre os 21 e 25 até aos 65 anos, com uma periodicidade trienal usando a citologia convencional. Existe ainda controvérsia no que toca aos 3 objetivos deste artigo (limites etários, frequência e método).The scope of this review was to assess the strength of evidence of Portuguese performance indicators on Cervical Cancer screening: (1) age group of the women that should be screened for cervical cancer; (2) frequency of screening; and (3) the best method for screening. The following MeSH terms were searched: vaginal smears, age groups, periodicity, methods, uterine cervical cancer. Articles not reflecting the study objectives or not available in English, Portuguese or Spanish were excluded. The SORT classification was used to rate the articles selected.Of the 197 articles found, 9 that met all study criteria were selected for inclusion in this review. These included 1 systematic review, 1 randomized controlled clinical trial, 2 retrospective studies and 5 clinical guidelines. The authors also chose to include 4 clinical guidelines and two systematic reviews relevant to the Portuguese population even though they did not appear in the initial search of the literature. The studies suggest screening women between the ages of 21 to 25 years and 65 years of age, once every three years using conventional cytology. There is still controversy regarding the three objectives of this study (target age bracket, screening frequency and screening method)

At a glance:the largest Niemann-Pick type C1 cohort with 602 patients diagnosed over 15 years

Niemann-Pick type C1 disease (NPC1 [OMIM 257220]) is a rare and severe autosomal recessive disorder, characterized by a multitude of neurovisceral clinical manifestations and a fatal outcome with no effective treatment to date. Aiming to gain insights into the genetic aspects of the disease, clinical, genetic, and biomarker PPCS data from 602 patients referred from 47 countries and diagnosed with NPC1 in our laboratory were analyzed. Patients’ clinical data were dissected using Human Phenotype Ontology (HPO) terms, and genotype–phenotype analysis was performed. The median age at diagnosis was 10.6 years (range 0–64.5 years), with 287 unique pathogenic/likely pathogenic (P/LP) variants identified, expanding NPC1 allelic heterogeneity. Importantly, 73 P/LP variants were previously unpublished. The most frequent variants detected were: c.3019C &gt; G, p.(P1007A), c.3104C &gt; T, p.(A1035V), and c.2861C &gt; T, p.(S954L). Loss of function (LoF) variants were significantly associated with earlier age at diagnosis, highly increased biomarker levels, and a visceral phenotype (abnormal abdomen and liver morphology). On the other hand, the variants p.(P1007A) and p.(S954L) were significantly associated with later age at diagnosis (p &lt; 0.001) and mildly elevated biomarker levels (p ≤ 0.002), consistent with the juvenile/adult form of NPC1. In addition, p.(I1061T), p.(S954L), and p.(A1035V) were associated with abnormality of eye movements (vertical supranuclear gaze palsy, p ≤ 0.05). We describe the largest and most heterogenous cohort of NPC1 patients published to date. Our results suggest that besides its utility in variant classification, the biomarker PPCS might serve to indicate disease severity/progression. In addition, we establish new genotype–phenotype relationships for “frequent” NPC1 variants.</p

Dyadic adjustment, family coping, body image, quality of life and psychological morbidity in patients with psoriasis and their partners

Background Psoriasis is an incurable and chronic disease that includes unpredictable periods of remission and relapse requiring long-term therapy. Purpose This paper focuses on the relationship among family coping, psychological morbidity, body image, dyadic adjustment and quality of life in psoriatic patients and their partners. Method One hundred and one patients with psoriasis and 78 partners comprised the sample. They were regular users of the Dermatology Service of a Central Northern hospital in Portugal and a private dermatology clinic. Patients with psoriasis were assessed on anxiety, depression, body image, quality of life, dyadic adjustment and family coping. Partners were assessed on the same measures except body image and quality of life. Results A positive relationship among dyadic adjustment, psychological morbidity and family coping in patients and their partners was found. Also, patients with lower levels of quality of life had partners with higher levels of depressive and anxious symptoms. Better dyadic adjustment predicted family coping in the psoriatic patient. High levels of dyadic adjustment in patients and low partners’ trait anxiety predicted better dyadic adjustment in partners. Conclusion The results highlight the importance of incorporating family variables in psychological interventions in psoriasis’ care, particularly family coping and dyadic adjustment as well as the need for psychological intervention to focus both on patients and partners