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BACKGROUND Cardiovascular disease (CVD) is an important cause of morbidity in people living with HIV (PLWH). We compared the predictive value of HIV-related and traditional CVD risk factors to assess which factors best predict the presence of subclinical coronary atherosclerosis in PLWH. METHODS Cross-sectional study in PLWH over 50 years of age who performed CT coronary artery calcium (CAC) scoring between 2009-2019 at Chelsea and Westminster Hospital. The following outcomes were analyzed: CAC=0 (no calcification), CAC >0 (any calcification), CAC >100 (moderate calcification) and CAC >400 (severe calcification). Univariate and multivariate logistic regression analyses were performed to assess predictors of coronary calcification. RESULTS A total of 744 patients were included (mean age 56 ± 5.7 years, 94.8% male, 84% white). A CAC >0 was found in 392 (52.7%), CAC >100 in 90 (12.1%) and CAC >400 in 42 (5.6%) subjects. CAC >100 was strongly associated with hypertension [odds ratio OR: 2.91, (95% confidence interval CI: 1.93-4.36), P 6 years) to protease inhibitors [1.67 (1.06-2.61), P =0.05] whereas exposure to tenofovir (> 8 years) was negatively associated with CAC >100 [0.54 (0.30-0.98), P =0.05]. Despite the high prevalence of hypertension (45.4%), only 21.5% were on anti-hypertensives whereas only 29.2% of eligible candidates were receiving lipid lowering drugs for primary prevention of CVD. CONCLUSIONS Traditional cardio-metabolic risk factors remain the strongest predictors of coronary atherosclerosis in PLWH as in the general population. These results underscore the importance of optimizing treatment of hypertension and promoting primary prevention strategies that may be underused in PLWH.

BACKGROUND Several cutaneous manifestations such as urticarial rash, erythematous patches and chilblain-like lesions have been described in young adults with coronavirus disease 2019 (COVID-19) and are present in up to 20% patients, but few reports exist describing histopathological and immunophenotypic characteristics of dermatological lesions in older patients. Our aim was to characterize skin lesions in elderly patients during late stages of COVID-19 from clinical, histological and immunophenotypic perspectives. CASE SUMMARY Three patients, admitted for COVID-19, and who developed cutaneous manifestations underwent skin biopsies. Immunophenotypic analysis for CD20, CD3, CD4 and CD8 was performed on skin biopsies to assess immune cell infiltrates. CD1a was used as a marker of Langerhans cells, and CD31 as a marker of endothelial cells. In the three study patients, cutaneous manifestations were evident in the late-stage of COVID-19 (mean time from the first positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swab to rash onset was 35 d). Skin biopsies showed a similar pattern of T lymphocyte infiltration in all patients. Indeed, a chronic dermatitis with perivascular lymphocytic infiltrate was observed with predominance of CD3+ T-cell (CD3+). CONCLUSION Our study confirms previous reports. Histological and immunophenotypic patterns in our patients confirm results described in the two previous reported experiences. This pattern is similar to what is found in some lympho-proliferative disorders. Therefore, since these findings are non-specific, SARS-CoV-2 infection should be suspected.

The diagnosis of hypogonadism in people living with HIV (PLWH) remains challenging by the lack of a standardised diagnostic algorithm. Since sexual hormone-binding globulin levels are commonly increased in PLWH, guidelines recommend assessing free testosterone (FT) along with total testosterone levels. We compared different online equations available to estimate FT levels and found a good correlation amongst all algorithms. Estimating FT levels increased diagnostic accuracy of hypogonadism and therefore should be encouraged in clinical practice in PLWH with clinical symptoms of hypogonadism, even when total testosterone levels are normal.

Successful management of HIV infection as a chronic condition has resulted in a demographic shift where the proportion of people living with HIV (PLWH) older than 50 years is steadily increasing. A dedicated clinic to PLWH older than 50 years was established at Chelsea and Westminster Hospital in January 2009 and then extended to HIV services across the directorate. We report the results of a service evaluation reviewing 10 years of activities of this clinic between January 2009 and 2019. We aimed to estimate the prevalence of major noninfectious comorbidities, polypharmacy (≥5 medications), and multimorbidity (≥2 non-HIV-related comorbidities) and describe algorithms devised for use in HIV outpatient clinics across the directorate. A cohort of 744 PLWH older than 50 years attending this service were analyzed (93% male; mean age of 56 ± 5.5 years; 84% white ethnicity); 97.7% were on antiretroviral treatment and 95.9% had undetectable HIV-RNA at the time of evaluation. The most common comorbidities diagnosed were dyslipidemia (50.1%), hypertension (21.5%), mental health disorders (depression and/or anxiety disorders, 15.7%), osteoporosis (12.2%), obesity (11.9%), chronic kidney disease (7.5%), and diabetes (5.8%). Low vitamin D levels were found in 62% of patients [43% with vitamin D deficiency (40 mmol/liter) and 57% with vitamin D insufficiency (40-70 mmol/liter)]. The overall prevalence of polypharmacy and multimorbidity was 46.6% and 69.3%, respectively. This study showed significant rates of non-HIV-related comorbidities and polypharmacy in PLWH older than 50 years, leading on to the implementation of clinical care pathways and new joint HIV/specialty clinics (cardiology, nephrology, neurology, metabolic, menopause, and geriatric) to improve prevention, diagnosis, and management of major comorbidities in people aging with HIV.

Changes in body weight in people living with HIV vary by regimen components, timing of therapy introduction (naive, switch) and demographic factors. Our objective was to evaluate weight change and factors associated in an ageing cohort of treated subjects with HIV at Chelsea and Westminster Hospital. We found that the prevalence of obesity was similar to general population and was associated with a number of health conditions, which increase metabolic risk.

OBJECTIVES Treatment with bisphosphonates and discontinuation of tenofovir disoproxil fumarate (TDF) are recommended strategies for managing osteoporosis in people living with HIV (PLHIV). This study aimed to compare the effects on bone mineral density (BMD) of TDF discontinuation with and without bisphosphonate therapy in osteoporotic PLHIV. METHODS The present study is a retrospective cohort analysis of dual-energy X-ray absorptiometry scan results of PLHIV attending Chelsea and Westminster Hospital HIV clinic between 2009 and 2020. Osteoporotic (T-score

BACKGROUND Cardiovascular disease (CVD) risk assessment remains a critical step in guiding decisions to initiate primary prevention interventions in people living with HIV (PLWH). SETTING We investigated whether coronary artery calcium (CAC) scoring allowed a more accurate selection of patients who may benefit from statin therapy, compared with current risk assessment tools alone. METHODS Cross-sectional analysis of PLWH over 50 years old who underwent CAC scoring between 2009 and 2019. Framingham Risk score (FRS), QRISK2 and D:A:D scores were calculated for each participant at the time of CAC scoring and statin eligibility determined based on current European guidelines on the prevention of CVD in PLWH. RESULTS A total of 739 patients were included (mean age 56 ± 5, 92.8% male, 84% white). Among 417 (56.4%) candidates for statin therapy based on FRS ≥10%, 174 (23.5%) had no detectable calcification (CAC = 0). Conversely, 145 (19.6%) patients with detectable calcification (CAC > 0) were identified as low-risk (FRS < 10%). When compared with FRS, CAC scoring reclassified CVD risk in 43.1% of patients, 145 (19.6%) to a higher risk group that could benefit from statin therapy and 174 (23.5%) statin candidates to a lower risk group. QRISK2 and D:A:D scores performed similarly to FRS, underestimating the presence of significant coronary calcification in 21.1% and 24.9% respectively and overestimating risk in 16.9% and 18.8% patients with CAC = 0. CONCLUSIONS Establishing a decision-model based on the combination of conventional risk tools and CAC scoring improves risk assessment and the selection of PLWH who would benefit from statin therapy.

Ageing is associated with re-modelling of the immune system to enable the maintenance of life-long immunity. In the CD8(+) T cell compartment, ageing results in the expansion of highly-differentiated cells that exhibit characteristics of cellular senescence. Here we found that CD27(−)CD28(−)CD8(+) T lost the signalling activity of the T cell antigen receptor (TCR) and expressed a protein complex containing the agonistic NK receptor NKG2D and the NK adaptor molecule DAP12, which promoted cytotoxicity against cells that expressed NKG2D ligands. Immunoprecipitation and imaging cytometry indicated that the NKG2D-DAP12 complex was associated with sestrin 2. The genetic inhibition of sestrin 2 resulted in decreased expression of NKG2D and DAP12 and restored TCR signaling in senescent-like CD27(−)CD28(−)CD8(+) T cells. Therefore, during ageing, sestrins induces the reprogramming of non-proliferative senescent-like CD27(−)CD28(−)CD8(+) T cells to acquire a broad-spectrum, innate-like killing activity.

The introduction of antiretrovirals has resulted in a demographic shift with an increasing proportion of people living with HIV older than 50 years and a change in the spectrum of diseases affecting this population. A specialised clinical service dedicated to older people living with HIV was implemented at Chelsea and Westminster Hospital, London, UK in 2009, following training of health-care providers in HIV, ageing, comorbidity, and polypharmacy management. We report the results of a service evaluation reviewing 10 years of activity of this specialised clinic, including lessons to be applied in routine practice.We estimated the prevalence of multimorbidity and polypharmacy and described algorithms devised for use across our HIV outpatient services following implementation of the specialised clinical pathway. The service evaluation was approved by our local clinical governance system and data relative to the period 2009-19 were collected on a secured trust database.Dedicated time was created for senior and junior doctors, a nurse, and a pharmacy to create clinical appointments for older people living with HIV referred by all service care providers. The team would review different clinical scenarios, book follow-up appointments to review results, refer to different specialists or to complex multidisciplinary teams when necessary. 744 people with HIV aged 50 years and older attended our services (93% [691] male, 7·1% [53] female; mean age 56·5 years [SD 5·5]; 84·2% [622] White, 7·5% [56] Black, 0·9% [7] Asian, 7·5% [56] other race or ethnicity). The prevalence of multimorbidity was 69·3% and of polypharmacy was 46·6%. The most common comorbidities were vitamin D deficiency (428 of 690, 62%), dyslipidaemia (373, 50·1%), hypertension (157, 21·5%), depressive or anxious disorders (117, 15·8%), osteoporosis (91, 12·2%), obesity (98, 13·2%), chronic kidney disease (56, 7·5%), and diabetes (43, 5·7%). Patients with dyslipidaemia, osteoporosis, and metabolic disorders were referred to a live well pathway clinic focusing on targeted lifestyle interventions, including diet and physical exercise, under the supervision of a dietician and a physiotherapist.We have described how our HIV over-50 clinic was organised and implemented, and we reported data showing high rates of comorbidities and polypharmacy, which led to the establishment of a specialised care pathway for all HIV care providers and to the implementation of further joint HIV and specialty clinics (cardiology, metabolic, menopause, nephrology, neurology, and geriatric).None.

As a consequence of ageing, the number of prescribed medications for people living with HIV is increasing. Concomitant use of different drugs and their potential interactions may increase anticholinergic exposure and escalate the risk for side effects. We conducted an analysis in our cohort of people living with HIV over 50 years of age to evaluate the overall anticholinergic risk, as it is useful to identify, prevent, and manage increased side effect risks.

Service of Infectious Diseases, Coimbra University Hospitals, Coimbra, PortugalEtravirine (ETR) is a non-nucleoside analoguereverse transcriptase inhibitor (NNRTI) with ahigh genetic barrier to the development ofresistance and with potential activity againstHuman immunodeficiency virus type 1 (HIV-1)strains resistant to first-generation NNRTIs. Theobjective of this study was to investigate theprevalence of ETR resistance associated muta-tions (RAMs) in HIV-1 strains isolated frominfected individuals failing efavirenz (EFV), aswell as to evaluate possible differences in thedistribution of ETR RAMs between subtype Band non-B genetic variants. Nucleotide sequen-ces of the protease and partial reverse tran-scriptase (RT) coding regions of the pol gene of55 HIV-1 strains isolated from infected individu-als failing EFV on regular follow-up at a refer-ence center in Portugal, were retrospectivelyanalyzed. The most prevalent ETR RAMsobserved were L100I, V90I, and K101E, with aprevalence of 16.4% (n ¼ 9), 9.1% (n ¼ 5), and5.5% (n ¼ 3), respectively. Overall, 47.3%(n ¼ 26) of the nucleotide sequences had atleast one ETR RAM: 38.2% (n ¼ 21) had oneETR RAM, 7.3% (n ¼ 4) had two ETR RAMs and1.8% (n ¼ 1) had three ETR RAMs. No statisti-cally significant differences were found in thedistribution of ETR RAMs between subtype Band non-B genetic variants. The results demon-strate that ETR rescue therapy is a viable optionin treatment-experienced individuals failingEFV and suggests that ETR may be equallyuseful in HIV-1 infections caused by differentgenetic variants. J. Med. Virol. 84:551–554,2012.

Purpose of review Advances in the health system and medical sciences are continuously pushing the barrier of life-expectancy. As a consequence, humans are being increasingly afflicted by age-associated diseases, such as cancer. The challenge now lies in understanding the mechanisms underlying ageing in order to reduce the lifetime risk for cancer. Recent findings In long-lived mammals, telomere length and restriction of telomerase activity are important barriers preventing the uncontrolled cell division. Absence of telomerase dictates the continuous telomere erosion with each cell division, thus restraining the proliferation of incipient tumour cells. However, recent findings have revealed the unintended consequences of telomere control of cell division. Cells with short telomeres accumulate in older individuals increasing the risk of telomere depletion. Loss of telomere protection results in tetraploidization and genomic instability characteristic of epithelial cancers. Additionally, telomere shortening blocks cell proliferation and induces cell senescence. Senescent cells secrete proinflammatory factors and reactive oxygen species that increase the likelihood of cellular transformation and create the perfect soil for cancer development. Summary Telomere shortening thus provides an example of antagonist pleiotropy, in which a beneficial characteristic that acts during the reproductive years of an organism may, later in life, contain the seed to its demise.

Our aim was to determine the frequencies of the angiotensin-converting enzyme (ACE) gene alleles D and I and any associations to cardiovascular risk factors in a population sample from Rio de Janeiro, Brazil. Eighty-four adults were selected consecutively during a 6-month period from a cohort subgroup of a previous large cross-sectional survey in Rio de Janeiro. Anthropometric data and blood pressure measurements, echocardiogram, albuminuria, glycemia, lipid profile, and ACE genotype and serum enzyme activity were determined. The frequency of the ACE*D and I alleles in the population under study, determined by PCR, was 0.59 and 0.41, respectively, and the frequencies of the DD, DI, and II genotypes were 0.33, 0.51, and 0.16, respectively. No association between hypertension and genotype was detected using the Kruskal-Wallis method. Mean plasma ACE activity (U/mL) in the DD (N = 28), DI (N = 45) and II (N = 13) groups was 43 (in males) and 52 (in females), 37 and 39, and 22 and 27, respectively; mean microalbuminuria (mg/dL) was 1.41 and 1.6, 0.85 and 0.9, and 0.6 and 0.63, respectively; mean HDL cholesterol (mg/dL) was 40 and 43, 37 and 45, and 41 and 49, respectively, and mean glucose (mg/dL) was 93 and 108, 107 and 98, and 85 and 124, respectively. A high level of ACE activity and albuminuria, and a low level of HDL cholesterol and glucose, were found to be associated with the DD genotype. Finally, the II genotype was found to be associated with variables related to glucose intolerance.

Dissertação de Mestrado em Educação - Área de Especialização em Supervisão Pedagógica em Ensino das Ciências da Natureza, O ensino das Ciências tem vindo a sofrer mudanças ao longo dos tempos. Muitos são os investigadores que procuram estratégias ou reformulam as existentes de forma a melhorar o ensino das Ciências e a contribuir para a formação de cidadãos activos, críticos e interventivos. O trabalho de campo (TC) é um recurso ao qual cada vez mais é atribuído, por professores e investigadores, um maior valor no ensino e aprendizagem das Ciências. Neste âmbito, a nossa investigação incidiu sobre dois estudos. No primeiro estudo procuramos saber quais as concepções actuais de professores do 2º Ciclo sobre TC e quais as práticas de TC que os professores deste nível de ensino dizem implementar. Para o efeito recorremos a um questionário que foi respondido por 106 professores de Ciências da Natureza deste nível de ensino. Com o objectivo de clarificar alguma da informação recolhida com o questionário, realizamos 5 entrevistas a professores de Ciências da Natureza do referido nível de ensino. Sabendo ainda que o ensino das Ciências e a prática de professores são influenciados pelo manual escolar e que este é um dos recursos mais acessíveis ao aluno, completamos este estudo com um outro estudo sobre a presença das actividades de campo apresentadas nos manuais deste nível de ensino e sobre as características das mesmas. Com isto pretendíamos saber se existia alguma coincidência entre as concepções e práticas dos professores e as propostas de actividades incluídas nos manuais. Os resultados do primeiro estudo indicam que a maioria dos professores entende que o tipo de TC mais adequado para este nível de ensino é o tipo Orientado para a Resolução de Problemas, no entanto a maior parte das descrições de algumas actividades por eles efectuadas revelam que o TC implementado é do tipo Observação Dirigida. Relativamente ao segundo estudo, a análise das sugestões de actividades de campo incluídas nos manuais revelou que na sua maioria as actividades são também do tipo Observação Dirigida. Isto indica que, apesar de entenderem que o tipo de TC mais adequado a este nível seja o tipo Orientado para a Resolução de Problemas, os professores realizam o tipo de TC que é sugerido pelos manuais, Observação Dirigida. Os resultados desta investigação parecem indicar assim, a necessidade de formação prática de professores ao nível da implementação de TC baseada na Resolução de Problemas e a alteração das sugestões de actividades de campo incluídas nos manuais ao nível da tipologia, uma vez que este é o tipo de TC defendido por estes professores e pelas perspectivas actuais de investigadores no âmbito do ensino das Ciências., Science teaching has changed over times. Many science education researchers have been looking for new teaching strategies or reformulating the usual ones in order to trying to improve science learning and to prepare active, critical and participative citizens. Fieldwork is a teaching resource that has been given an increasing pedagogic value by teachers and researchers. This piece of research includes two related research studies. The first one aims at diagnosing Natural Sciences (5th and 6th grades) teachers’ conceptions about fieldwork and their own representations of the teaching practices relative to fieldwork. To attain this objective a questionnaire was developed and answered by 106 Natural Sciences teachers. In order to go further on the information collected, an interview was conducted with 5 Natural Sciences teachers. As the school textbook influences both teachers’ teaching practices and students’ learning, the second study aims at analysing fieldwork activities included in the 5th and 6th grades natural sciences textbooks. Taken together, the two studies may inform about whether or not teachers’ conceptions and practices are consistent with the textbooks fieldwork activities. The results from the first study seem to indicate that according to the teachers that participated in it, the most appropriate type of fieldwork is Oriented to Problem Solving. However, the analysis of teachers’ descriptions of the fieldwork activities they themselves implemented in their classes indicates that those activities tend to be Directed Observation like activities. The results of the second study also indicate that most of the textbook fieldwork activities are Directed Observation activities. Taken together, the results of this piece of research indicate that although teachers state that problem solving activities are the most adequate type of fieldwork activities, they nevertheless tend to use the type of activities suggested by the textbook, that is directed observation activities. Hence, these results suggest that in-service teacher education is needed in order to lead teachers to implement problem-based fieldwork. They also suggest that school textbooks fieldwork activities should be rethought and include more problem-based activities, as this type of activities is the one that both teachers believe being the most adequate to the school level under question and the most consistent with nowadays perspectives for science education.

Background Infectious diseases are a common cause of increased morbidity and mortality in elderly patients. Bacteraemia in the elderly is a difficult diagnosis and a therapeutic challenge due to age-related vicissitudes and to their comorbidities. The main purpose of the study was to assess independent risk factors for in-hospital mortality among the elderly with bacteraemia admitted to an Internal Medicine Ward. Methods Overall, a cohort of 135 patients, 65 years of age and older, with bacteraemia were retrospectively studied. Data related to demographic information, comorbidities, clinical parameters on admission, source and type of infection, microorganism isolated in the blood culture, laboratory data and empirical antibiotic treatment was recorded from each patient. Multivariate logistic regression was performed to identify independent predictors of all-cause in-hospital mortality. Results Of these 135 patients, 45.9% were women. The most common infections in this group of patients were urinary tract infections (46.7%). The main microorganisms isolated in the blood cultures were Escherichia coli (14.9%), Methicillin-resistant Staphylococcus aureus (MRSA) (12.0%), non-MRSA (11.4%), Klebsiella pneumoniae (9.1%) and Enterococcus faecalis (8.0%). The in-hospital mortality was 22.2%. Independent prognostic factors associated with in-hospital mortality were age ≥ 85 years, chronic renal disease, bacteraemia of unknown focus and cognitive impairment at admission (OR, 2.812 [95% CI, 1.039-7.611; p = 0.042]; OR, 6.179 [95% CI, 1.840-20.748; p = 0.003]; OR, 8.673 [95% CI, 1.557-48.311; p = 0.014] and OR, 3.621 [95% CI, 1.226-10.695; p = 0.020], respectively). By multivariate analysis appropriate antibiotic therapy was not associated with lower odds of mortality. Conclusion Bacteraemia in the elderly has a high mortality rate. There are no set of signs or clinical features that can predict bacteraemia in the elderly. However, older age (≥ 85 years), chronic renal disease, bacteraemia of unknown focus and severe cognitive impairment adversely affects the outcome of elderly patients with bacteraemia admitted to an Internal Medicine ward.