Phosphonoamidate prodrugs of C5-substituted pyrimidine acyclic nucleosides for antiviral therapy

Acyclic nucleoside phosphonates (ANPs) are nowadays one of the key drugs in the treatment of DNA virus and retrovirus infections. In this work, we report the synthesis and antiviral evaluation of phosphonoamidate and diamidates prodrugs of C5-pyrimidine acyclic nucleosides derivatives functionalized with but-2-enyl- chain. In the phosphonoamidate series, the most active compound 15, showed sub-micromolar activity against varicella zoster virus (VZV) (EC50 =0.09-0.5 μM) and μM activity against human cytomegalovirus (HCMV) and herpes simplex virus (HSV). Separation of single diastereoisomers for compound 14, showed that 14b had better anti-herpesvirus activity and no cytotoxicity compared to the diastereoisomeric mixture 14. Very interestingly, phosphonodiamidate 21 showed anti-herpesvirus activity with excellent activity against wild type and thymidine kinase-deficient (TK-) VZV strains (EC50 = 0.47 and 0.2 μM, respectively) and HCMV (EC50 = 3.5-7.2 μM) without any cytotoxicity (CC50 >100)

Total antioxidant capacity of the diet is inversely and independently related to plasma concentration of high-sensitivity C-reactive protein in adult Italian subjects

Inflammation, a risk factor for cardiovascular disease, is associated with low plasma levels of antioxidant vitamins. In addition to vitamins, other antioxidants modulate the synthesis of inflammatory markers in vitro and contribute to the total antioxidant capacity (TAC) of a diet. However, the relationship between dietary TAC and markers of inflammation has never been evaluated in vivo. We investigated the relationship between dietary TAC and markers of systemic (high-sensitivity C-reactive protein (hs-CRP), leucocytes) and vascular (soluble intercellular cell adhesion molecule-1) inflammation in 243 non-diabetic subjects. General Linear Model (GLM) analysis showed a significant (P=0·005) inverse relationship between hs-CRP and quartiles of energy-adjusted dietary TAC, even when recognized modulating factors of inflammation, namely alcohol, fibre, vitamin C, α-tocopherol, β-carotene, BMI, waist circumference, HDL-cholesterol, hypertension, insulin sensitivity and plasma β-carotene, were included in the model as covariates (P=0·004). The relationship was stronger for subjects with hypertension (P=0·013 v. P=0·109 for normotensive individuals). Among dietary factors, TAC was significantly higher (5·3 (sd 3·0) v. 4·9 (sd 2·7) mmol Trolox/d; P=0·026) in subjects with low plasma hs-CRP (range: 0·0–4·1 mg/l) than in subjects with high plasma hs-CRP (range: 4·2–27·8 mg/l). We conclude that dietary TAC is inversely and independently correlated with plasma concentrations of hs-CRP and this could be one of the mechanisms explaining the protective effects against CVD of antioxidant-rich foods such as fruits, whole cereals and red wine. This could be of particular significance for subjects with high blood pressure

Use Of PRP In Severe Bone Defects

Aim of the study is to demonstrate the influence of using growth factors in bone regeneration in advanced implantology cases, such as severe bone defects that involve maxillary sinus. The preliminary study of complex cases through CT scan and computerized implant software, it’s crucial for an accurate preoperative evaluation of the anatomic limitations and facilitates preoperative planning of therapeutic strategy. This two case reports present clinical and radiographic results obtained using PRP in combination with bone grafting materials which lead to a faster and predictable bone healing, allowing a time and cost effectiveness implant-prosthetic rehabilitation

Evaluation of an interprofessional education intervention in partnership with patient educators

Background and aim of the work: Patient involvement in interprofessional education is a novel approach to building collaborative and empathic skills in students. However, this area of teaching is lacking in rigorous studies. The project aimed to evaluate whether an interprofessional education intervention in partnership with patient educators (IPE-PE) would increase readiness for interprofessional learning and empathy in health sciences students. Methods: This is the report of a didactic innovation project. Participants included 310 undergraduate health sciences students who took part in an IPE-PE intervention. Data were collected before and after the training, using the Readiness for Interprofessional Learning Scale (RIPLS) and the Jefferson Scale of Empathy-Health Professions Student version ( JSE-HPS). Only at the end of the intervention, a data collection form was administered to explore the value of the patient educator in the training and to investigate the socio-demographic variables. Results: The mean age of participants was 21±3.2 SD years and 76% were female. The Wilcoxon signed-rank test showed significant changes from before to after the IPE-PE in the RIPLS total score (m=42.7±5.8 SD vs 44.62±5.9 SD, z=-4.168, P<0.001) and in the JSE-HPS total score (m=112.7±12.5 SD vs 116.03±12.8 SD, z=-4.052, P<0.001). Conclusions: Our students reported that IPE-PE had helped them to become more effective healthcare team members, to think positively about other professionals, and to gain an empathic understanding of the perspective of the person being cared for. The results of the project confirm that the intervention promoted the development of empathy, fostering a better understanding of the patient-centred perspective

Ultra-Low-Dose Whole-Body Computed Tomography Protocol Optimization for Patients With Plasma Cell Disorders: Diagnostic Accuracy and Effective Dose Analysis From a Reference Center

BACKGROUND: The whole-body low-dose CT (WBLDCT) is the first-choice imaging technique in patients with suspected plasma cell disorder to assess the presence of osteolytic lesions. We investigated the performances of an optimized protocol, evaluating diagnostic accuracy and effective patient dose reduction using a latest generation scanner. METHODS AND MATERIALS: Retrospective study on 212 patients with plasma cell disorders performed on a 256-row CT scanner. First, WBLDCT examinations were performed using a reference protocol with acquisition parameters obtained from literature. A phantom study was performed for protocol optimization for subsequent exams to minimize dose while maintaining optimal diagnostic accuracy. Images were analyzed by three readers to evaluate image quality and to detect lesions. Effective doses (E) were evaluated for each patient considering the patient dimensions and the tube current modulation. RESULTS: A similar, very good image quality was observed for both protocols by all readers with a good agreement at repeated measures ANOVA test (p>0.05). An excellent inter-rater agreement for lesion detection was achieved obtaining high values of Fleiss’ kappa for all the districts considered (p<0.001). The optimized protocol resulted in a 56% reduction of median DLP (151) mGycm, interquartile range (IQR) 128–188 mGycm vs. 345 mGycm, IQR 302–408 mGycm), of 60% of CTDIvol (2.2 mGy, IQR 1.9–2.7 mGy vs. 0.9 mGy, IQR 0.8–1.2 mGy). The median E value was about 2.6 mSv (IQR 1.7–3.5 mSv) for standard protocol and about 1.5 mSv (IQR 1.4–1.7 mSv) for the optimized one. Dose reduction was statistically significant with p<0.001. CONCLUSIONS: Protocol optimization makes ultra-low-dose WBLDCT feasible on latest generation CT scanners for patients with plasma cell disorders with effective doses inferior to conventional skeletal survey while maintaining excellent image quality and diagnostic accuracy. Dose reduction is crucial in such patients, as they are likely to undergo multiple whole-body CT scans during follow-up

Effectiveness of patients’ involvement in a medical and nursing pain education programme: a protocol for an open-label randomised controlled trial including qualitative data

Introduction Pain is a multidimensional experience that varies among individuals and has a significant impact on their health. A biopsychosocial approach is recommended for effective pain management; however, health professionals’ education is weak on this issue. Patient involvement is a promising didactic methodology in developing a more holistic perspective, however there is a lack of reliable evidence on this topic. The aim of the present study is to evaluate the effectiveness of patient involvement in pain education in undergraduate medicine and nursing students. Methods and analysis An open-label randomised controlled trial including qualitative data will be conducted. After an introductory lesson, each student will be randomly assigned to the intervention group, which includes an educational session conducted by a patient–partner along with an educator, or to the control group in which the session is exclusively conducted by an educator. Both sessions will be carried out according to the Case-Based Learning approach. Primary outcomes will be students’ knowledge, attitudes, opinions and beliefs about pain management, whereas the secondary outcome will be students’ satisfaction. The Pain Knowledge and Attitudes (PAK) and Chronic Pain Myth Scale (CPMS) will be administered preintervention and postintervention to measure primary outcomes. Students’ satisfaction will be measured by a questionnaire at the end of the session. Two focus groups will be conducted to evaluate non-quantifiable aspects of learning. Ethics and dissemination The protocol of this study was approved by the independent Area Vasta Emilia Nord ethics committee

Encefalite de Rasmussen: avaliação de resultados depois da cirurgia

BACKGROUND AND PURPOSE: Rasmussen Encephalitis (RE) is characterized by intractable epilepsy, progressive hemiparesis and unilateral hemispheric atrophy. The progression of the symptoms usually occurs within months to few years. Antiepileptic drugs are usually not effective to control disease progression and epilepsy surgery in the form of hemispheric disconnection has been considered the treatment of choice. This work describes the clinical and electrographic analyses, as well as the post-operative evolution of patients with RE. PATIENTS AND METHODS: This work includes all the patients with RE evaluated from January 1995 to January 2008 by the Ribeirão Preto Epilepsy Surgery Program (CIREP) considering demographic data, interictal and ictal electroencephalographic (EEG) findings; anatomo-pathological findings and clinical outcome. RESULTS: Twenty-five patients were evaluated, thirteen were female. Mean age of epilepsy onset was 4.4±2.0 years. There were no differences between patients with slow and fast evolution with respect to age of epilepsy onset (p=0.79), age at surgery (p=0.24), duration of epilepsy (0.06), and follow-up (p=0.40). There were no correlations between the presence of bilateral EEG abnormalities or the absence of spikes and post-operative seizure outcome (p=0.06). Twenty-three patients underwent surgery. The mean follow-up was 75.3 months. Eleven patients had total seizure control. Twelve individuals persisted with seizures consisting of mild facial jerks (6 patients), occasional hemigeneralized tonic-clonic seizures (3 patients), and frequent tonic-clonic seizures (3 patients). Mental and language impairment was observed in 15 and 12 patients, after surgery, respectively. CONCLUSIONS: This retrospective study reported the clinical and electrographic analysis, as well as the evolution of 23 patients with RE. Fourteen patients achieved satisfactory seizure control, three patients had partial response to surgery, and five patients had maintenance of the pre-operative condition. All patients with left side involvement presented with some language and cognitive disturbance.INTRODUÇÃO E OBJETIVOS: A Encefalite de Rasmussen (ER) é caracterizada por epilepsia intratável, hemiparesia progressiva e atrofia hemisférica unilateral. A progressão dos sintomas geralmente ocorre em meses ou poucos anos. As drogas antiepilépticas são usualmente ineficazes no controle da progressão da doença e o tratamento cirúrgico, com desconexão hemisférica tem sido considerado o tratamento de escolha. Neste trabalho descreveremos os achados clínicos e eletrográficos, assim como a evolução pós-operatória de pacientes com ER. PACIENTES E MÉTODOS: foram incluídos todos os pacientes com ER avaliados no período de janeiro de 1995 a janeiro de 2008, no Centro de Cirurgia de Epilepsia de Ribeirão Preto (CIREP), sendo considerados os dados demográficos, os achados do eletrencefalograma (EEG) interictal e ictal, resultado anatomo-patológico e o seguimento clínico. RESULTADOS: Vinte e cinco pacientes foram avaliados, 13 eram do sexo feminino. A idade média de início da epilepsia foi de 4.4±2.0 anos. Não houve diferenças significativas entre os pacientes com evolução lenta ou rápida considerando-se a idade de início da epilepsia (p=0,79), idade da cirurgia (p=0,24), duração da epilepsia (p=0,06) e tempo de seguimento (p=0,40). Não houve correlação entre a presença de alterações bilaterais ou ausência de descargas ao EEG e o seguimento pós-operatório (p=0,06). Vinte e três pacientes foram submetidos à cirurgia. O tempo médio de seguimento foi de 75,3 meses. Onze pacientes evoluíram com controle total das crises. Doze pacientes permaneceram com crises que consistiram de clonias faciais sutis (6 pacientes), crises tônico-clônicas hemigeneralizadas ocasionais (3 pacientes) ou crises tônico-clônicas frequentes (3 pacientes). Alterações cognitivas e de linguagem foram observadas em 15 e 12 pacientes após a cirurgia, respectivamente. CONCLUSÕES: este estudo retrospectivo relatou os achados clínicos, eletrográficos e a evolução de 23 pacientes. Controle satisfatório das crises foi obtido em 14 pacientes. Três pacientes tiveram resposta parcial com a cirurgia e cinco pacientes mantiveram o quadro pré-operatório. Todos os pacientes com envolvimento do hemisfério cerebral esquerdo evoluíram com distúrbio de linguagem e cognitivo.(FAEPA) USP - Hospital das Clínicas da Faculdade de Medicina de Ribeirão PretoCNPqFAEP

Primary care indicators for disease burden, monitoring and surveillance of COVID-19 in 31 European countries: Eurodata Study

BACKGROUND During the COVID-19 pandemic, the majority of patients received ambulatory treatment, highlighting the importance of primary health care (PHC). However, there is limited knowledge regarding PHC workload in Europe during this period. The utilization of COVID-19 PHC indicators could facilitate the efficient monitoring and coordination of the pandemic response. The objective of this study is to describe PHC indicators for disease surveillance and monitoring of COVID-19's impact in Europe. METHODS Descriptive, cross-sectional study employing data obtained through a semi-structured ad hoc questionnaire, which was collectively agreed upon by all participants. The study encompasses PHC settings in 31 European countries from March 2020 to August 2021. Key-informants from each country answered the questionnaire. Main outcome: the identification of any indicator used to describe PHC COVID-19 activity. RESULTS Out of the 31 countries surveyed, data on PHC information were obtained from 14. The principal indicators were: total number of cases within PHC (Belarus, Cyprus, Italy, Romania and Spain), number of follow-up cases (Croatia, Cyprus, Finland, Spain and Turkey), GP's COVID-19 tests referrals (Poland), proportion of COVID-19 cases among respiratory illnesses consultations (Norway and France), sick leaves issued by GPs (Romania and Spain) and examination and complementary tests (Cyprus). All COVID-19 cases were attended in PHC in Belarus and Italy. CONCLUSIONS The COVID-19 pandemic exposes a crucial deficiency in preparedness for infectious diseases in European health systems highlighting the inconsistent recording of indicators within PHC organizations. PHC standardized indicators and public data accessibility are urgently needed, conforming the foundation for an effective European-level health services response framework against future pandemics