Dual antiretroviral therapy with tenofovir (TDF) and darunavir/ritonavir (DRV/RTV) in an HIV-1 positive patient: a case report, review, and meta-analysis of the literature on dual treatment strategies using protease inhibitors in combination with an NRTI.

BACKGROUND: Here, we report the case of an HIV positive patient under a dual antiretroviral drug regimen with tenofovir disoproxil and darunavir/ritonavir with stable clinical, virological, and immunological response over 126 weeks. Dual antiretroviral therapy has the advantage of reduced toxicity and lower health care costs, treatment failure and fostering drug resistance are perceived risks. Optimal drug combinations and indication criteria for dual treatment remain controversial. Nevertheless, first clinical trials indicate non-inferiority for combinations of nucleoside reverse transcriptase inhibitors and protease inhibitors. This case presents the combination of tenofovir disoproxil in combination with a protease inhibitor as a new potential dual treatment regimen. METHOD: We performed a systematic literature search and meta-analysis of trials comparing dual to triple ART. RESULTS: Literature review revealed nine studies in which dual therapy with a protease inhibitor and an NRTI was compared to triple therapy. We performed a meta-analysis of six trials that reported a 48-week follow-up. In treatment-naïve patients as well when ART switch was assessed, there was no difference in the treatment success in patients with dual ART versus triple. CONCLUSION: We conclude that dual therapy with a protease inhibitor and NRTI is safe and effective. The use of tenofovir in dual treatment as described in our case needs to be assessed in future clinical trials.

["Hic gaudet mors succurere vitae", autopsy findings of the Mainz Institute of Pathology 1971-2010. An analysis on the occasion of the 100 year jubilee]. / "Hic gaudet mors succurere vitae", Sektionsbefunde der Mainzer Pathologie 1971-2010. Eine Analyse aus Anlass des 100-jährigen Jubiläums.

In the past numerous analyses have studied several aspects of autopsies in particular with regard to the decline of frequency; however, long-term studies spanning more than one decade have rarely been published, especially in recent years. On the occasion of the 100 year jubilee the archive data of the Institute of Pathology of the University of Mainz were analyzed for autopsies performed between 1971 and 2010. In this cohort, we focused on patients over 14 years old (n = 14,724) who died in the University hospital. We compared the number of autopsies with the total number of deceased patients and, in addition, studied several epidemiological aspects with special relevance for the cause of death (COD). In 1973 the peak autopsy frequency was reached with a value of 73.4 % followed by a decrease to 49.1 % in 1980. In the following decade a relatively steady state was achieved (frequency 53.3 % in 1985, and 43.2 % in 1990), followed by a remarkable decline after the 1990s (1997: 26.4 %, 1998: 15.9 % and 2010: 5.6 %). The mean overall age increased during the observation period (59.1 years in 1971 and 67.5 years in 2008). Among the COD groups cardiovascular diseases were predominantly recorded (between 35 % in the 1970s and 39 % in 1995-2010), followed by infectious diseases (between 20 and 25 %). Malignancies represented the third most common COD group with an increase in frequency from approximately 10.5 % in the 1970s to 17 % observed in the last decade. Among the single specific CODs, pulmonary embolism was most often encountered in the 1970s (about 11.5 %), while in the following decades myocardial infarction predominated (up to 15.8 % between 1995 and 2010). In the overall period, lung cancer was the single most common malignancy of the CODs (between 2.5 and 3.9 %). These data confirmed previous studies showing that in Germany the autopsy frequency began to decline remarkably in the 1990s. Besides general aspects, the specific local causes for these phenomena are discussed.

Lisina digestível em dietas de baixa proteína para frangos de corte tipo caipira de um aos 28 dias / Digestible lysine in diets containing low protein concentrations for broiler type redneck from 1 to 28 days

Avaliou-se a inclusão de diferentes porcentagens de lisina digestível em dietas de baixa proteína para frangos de corte tipo caipira, machos e fêmeas, com idade entre um e 28 dias. Utilizaram-se 792 machos e 792 fêmeas de linhagem comercial, de um dia de idade, distribuídos em delineamento inteiramente ao acaso, em esquema fatorial 2x6 (sexo x porcentagem de lisina digestível: 0,85; 0,90; 0,95; 1,00; 1,05 e 1,10%) com seis repetições de 22 aves. Não foi constatada interação (P>0,05) de sexo versus inclusão de lisina. Observou-se superioridade (P<0,05) dos machos em relação às fêmeas para todas as variáveis avaliadas. O ganho de peso dos frangos diminuiu linearmente (P<0,05) em função do aumento da porcentagem de lisina digestível na dieta e observou-se redução linear (P<0,01) nos consumos de ração e de proteína. O consumo de lisina digestível aumentou linearmente (P<0,01) em função do aumento de sua concentração na dieta. Não houve diferença (P>0,05) para conversão alimentar. Da composição centesimal da carcaça, apenas o percentual de matéria mineral foi influenciada (P<0,05) pela porcentagem de lisina digestível. Conclui-se que 0,85% de lisina para frangos tipo caipira de pescoço pelado atende à exigência nutricional de lisina digestível em dietas com baixa concentração proteica.

The inclusion of different percentages of digestible lysine in low-protein diets was evaluated for male and female free-range broiler chickens, from 1 to 28 days. We used 792 female and 792 male naked neck chickens a day in a completely randomized 2x6 factorial scheme (sex x percentages of digestible lysine: 0.85, 0.90, 0.95, 1.00, 1.05 and1.10%) with six replicates of 22 broilers. No interaction of sex versus lysine was found. Superiority was observed (P<0.05) in males compared to females for all variables.Weight gainof chickens decreased linearly(P<0.05) with increasing levels of digestible lysine in the diet. There was a linear reduction (P<0.01) in feed intake, protein and metabolizable energy. On the other hand, the consumption of digestible lysine increased linearly (P<0.01) with the increase of its concentration in the diet. There was nodifference (P>0.05) in food conversion.In the chemical composition of the carcass, only thepercentage of mineral matter was influenced (P<0.05) bydigestible lysine levels.It was concluded that the level of 0.85% for type redneck broiler meets the nutritional requirement of digestible lysine in diets containing lower protein concentrations.

The influence of Cu addition on precipitation in Fe-Cr-Ni-Al-(Cu) model alloys.

Precipitation in Fe-Cr-Ni-Al-(Cu) model alloys was investigated after ageing for 0.25, 3, 10 and 100h at 798K. Characterization of nanoscale precipitates was performed using three-dimensional atom probe microscopy and transmission electron microscopy. The precipitates are found to be enriched in Ni and Al (Cu) and depleted in Fe and Cr. After 0.25h of ageing the number density of precipitates is approximately 8x10(24)m((-3)), their volume fraction is about 15.5% and they are near-spherical with an average diameter of about 2-3nm. During further ageing the precipitates in the both alloys grow, but the coarsening behaviour is different for both alloys. The precipitates of the Cu-free alloy grow much faster compared with the Cu-containing alloy and their density decreases. Precipitates in Cu-free alloy change to plate shaped even after 10h of ageing, whereas those of Cu-containing alloy remain spherical up to 10h of ageing. The influence of Cu addition on precipitation in these model alloys is discussed with respect to the different coarsening mechanisms.