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Antipsychotics may prolong or retain telomere length, affect mitochondrial function, and then affect the metabolism of nerve cells. To validate the hypothesis that antipsychotics can prolong telomere length after oxidative stress injury, leukocytes from healthy volunteers were extracted using Ficoll-Histopaque density gradient. The mononuclear cells layer was resuspended in cell culture medium. Oxidative stress was induced with hydrogen peroxide in cultured leukocytes. Four days later, leukocytes were treated with aripiprazole, haloperidol or clozapine for 7 days. Real-time PCR revealed that treatments with aripiprazole and haloperidol increased the telomere length by 23% and 20% in peripheral blood mononuclear cells after acute oxidative stress injury. These results suggest that haloperidol and aripiprazole can reduce the damage to telomeres induced by oxidative stress. The experiment procedure was approved by the Ethics Committee of Faculty of Medicine of the University of São Paulo (FMUSP/CAAE approval No. 52622616.8.0000.0065).

The hyperphosphorylation of tau is a central mechanism in the pathogenesis of Alzheimer’s disease (AD). Lithium is a potent inhibitor of glycogen synthase kinase-3beta (GSK3β), the most important tau kinase in neurons, and may also affect tau phosphorylation by modifying the expression and/or activity of other kinases, such as protein kinase A (PKA), Akt (PKB), and calcium calmodulin kinase-II (CaMKII). The aim of the present study is to determine the effect of chronic lithium treatment on the protein expression of tau and its major kinases in cortical and hippocampal neurons, at distinct working concentrations. Primary cultures of cortical and hippocampal neurons were treated with sub-therapeutic (0.02 mM and 0.2 mM) and therapeutic (2 mM) concentrations of lithium for 7 days. Protein expression of tau and tau-kinases was determined by immunoblotting. An indirect estimate of GSK3β activity was determined by the GSK3β ratio (rGSKβ). Statistically significant increments in the protein expression of tau and CaMKII were observed both in cortical and hippocampal neurons treated with subtherapeutic doses of lithium. GSK3β activity was increased in cortical, but decreased in hippocampal neurons. Distinct patterns of changes in the expression of the remaining tau tau-kinases were observed: in cortical neurons, lithium treatment was associated with consistent decrements in Akt and PKA, whereas hippocampal neurons displayed increased protein expression of Akt and decreased PKA. Our results suggest that chronic lithium treatment may yield distinct biological effects depending on the concentration range, with regional specificity. We further suggest that hippocampal neurons may be more sensitive to the effect of lithium, presenting with changes in the expression of tau-related proteins at subtherapeutic doses, which may not be mirrored by the effects observed in cortical neurons.

This study aimed to prepare an inventory of the main active ingredients of pesticides and estimate the risk of pollution of groundwater and surface water resources in a Brazilian semiarid basin. The inventory was prepared using data from government agency databases. The contamination risk estimate was obtained using the GOSS index, Groundwater Ubiquity Score (GUS), Groundwater Screening Index (GSI), Leachability Index (LIX), US Environmental Protection Agency (USEPA) criteria, Leaching Index (LEACH), and Relative Leaching Potential Index (RLPI). The inventory identified 57 active ingredients commercialized under a well-defined chemical class. Most of these (51.5%) belong to the very dangerous class, while 43.6% belong to the moderately toxic class. The GOSS model showed that 23.7% of the active ingredients have a low potential, 50.85% have a moderate potential, and 13.56% have a high potential for surface water contamination, with its transport being associated with the sediment. The GUS index indicates a low potential for groundwater contamination. However, the GSI points to a high potential for water contamination, the USEPA criteria for a possible contamination of groundwater, and, according to the LIX, most of the pollutants do so by leaching. The information provided contributes to the management of xenobiotic compounds in arid and semiarid basins, adding to the water security effort by providing tools for the assessment of potential pesticide pollution. Integr Environ Assess Manag 2022;00:1-13. © 2022 SETAC.

Background Treatment persistence, as well as time to dose optimisation, can be a proxy for a drug’s real-world therapeutic benefit. We sought to describe treatment persistence of biologics or small molecules in inflammatory bowel disease (IBD) patients and need for optimisation in patients with IBD in Argentina and their potential predictors. Methods A retrospective cohort study involving 13 hospitals from Argentina was undertaken. Adult patients with a diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) who received therapy with a biologic or a small molecule were included. Initiation date was registered for every therapy each patient received; in addition, treatment finalization as well as need for optimisation were registered. Treatment persistence was defined as the time between treatment initiation and treatment finalization, or as time between treatment initiation and last follow-up if patient continued with the treatment. Time to optimisation was defined as the time between treatment initiation and treatment dose optimisation. In patients that received more than one type of advanced therapy, treatment persistence and need for optimisation was analyzed separately for each treatment received. Kaplan-Meier analysis as well as Cox regression model were used to determine predictors of treatment persistence and need for optimisation. Results A total of 403 patients were included; 55.28% had a diagnosis of UC, mean age was 44.57±16 and 47.71% were male. Median time of follow-up was 80 months [IQR 41-152]. Adalimumab was the most frequently used biologic as a first-line treatment for CD and UC (59.78% and 51.39%, respectively), whereas ustekinumab and vedolizumab were the most frequently used agents for CD and UC patients previously exposed to biologics, respectively (41.42% and 36.73%). Median treatment persistence duration was 68 months [IQR 22-146]. History of steroid-dependency [HR 2.87 (1.02-8.12)], CD [0.42 (0.22-0.78]), prior biologic exposure [HR 2.25 (1-5.06)], dose optimisation [HR 2.93 (1.36-6.33)] and need for systemic steroids 6 months from treatment initiation [HR 4.98 (1.57-15.75)] were significant predictors of shorter treatment persistence. Median time to optimisation was 34 months [IQR 9-132]. CD [0.81 (0.55-0.94)], moderate-to-severe endoscopic activity [HR 1.91 (1-3.95)], prior biologic exposure [HR 2.29 (1.27-4.14)] and biologic initiation after 2017 [2.06 (1.09-3.55)] were significant predictors of need for dose optimisation. Conclusion A considerable proportion of IBD patients required dose optimisation or treatment finalization. Lower treatment persistence and time for dose optimisation were observed in UC patients and other factors were identified.

Lithium activates Wnt/β-catenin signaling leading to stabilization of free cytosolic β-catenin. The aim of the present study is to evaluate the in vivo effect of acute and chronic lithium treatment on the expression of β-catenin target genes, addressing its transcripts HIG2, Bcl-xL, Cyclin D1, c-myc, in cortical and hippocampal tissue from adult mice. Lithium doses were established to yield therapeutic working concentrations. In acute treatment, mice received a 300µL of a 350 mg/kg solution of LiCl by gavage, and were euthanized after 2 h, 6 h and 12 h. To determine the effect of chronic treatment, animals were continuously fed either with chow supplemented with 2 g/kg Li2CO3, or regular chow (controls), being euthanized after 30 days. All animals had access to drinking water and 0.9% saline ad libitum. After acute and chronic treatments samples of peripheral blood were obtained from the tail vein for each animal, and serum concentrations of lithium were determined. All transcripts were up-regulated in cortical and hippocampal tissues of lithium-treated mice, both under acute and chronic treatments. There was a positive correlation between serum lithium concentrations and the increment in the expression of all transcripts. This effect was observed in all time points of the acute treatment (i.e., 2, 6 and 12 hours) and also after 30 days. We conclude that Wnt/β-catenin transcriptional response (HIG2, Bcl-xL, Cyclin D1 and c-myc) is up-regulated in the mouse brain in response to acute and chronic lithium treatment at therapeutic concentrations.

The hyperphosphorylation of tau is a central mechanism in the pathogenesis of Alzheimer's disease (AD). Lithium is a potent inhibitor of glycogen synthase kinase-3beta (GSK3β), the most important tau kinase in neurons, and may also affect tau phosphorylation by modifying the expression and/or activity of other kinases, such as protein kinase A (PKA), Akt (PKB), and calcium calmodulin kinase-II (CaMKII). The aim of the present study is to determine the effect of chronic lithium treatment on the protein expression of tau and its major kinases in cortical and hippocampal neurons, at distinct working concentrations. Primary cultures of cortical and hippocampal neurons were treated with sub-therapeutic (0.02 mM and 0.2 mM) and therapeutic (2 mM) concentrations of lithium for 7 days. Protein expression of tau and tau-kinases was determined by immunoblotting. An indirect estimate of GSK3β activity was determined by the GSK3β ratio (rGSKβ). Statistically significant increments in the protein expression of tau and CaMKII were observed both in cortical and hippocampal neurons treated with subtherapeutic doses of lithium. GSK3β activity was increased in cortical, but decreased in hippocampal neurons. Distinct patterns of changes in the expression of the remaining tau tau-kinases were observed: in cortical neurons, lithium treatment was associated with consistent decrements in Akt and PKA, whereas hippocampal neurons displayed increased protein expression of Akt and decreased PKA. Our results suggest that chronic lithium treatment may yield distinct biological effects depending on the concentration range, with regional specificity. We further suggest that hippocampal neurons may be more sensitive to the effect of lithium, presenting with changes in the expression of tau-related proteins at subtherapeutic doses, which may not be mirrored by the effects observed in cortical neurons.

Approximately 95% of the symbiotic microbes in human body are located in the gut. This microbioma is involved in important homeostatic processes, not only related to gastrointestinal function but also to several complex modulatory processes, such as glucose and bone metabolism, inflammation and immune response, peripheral (enteric) and central neurotransmission. For that reason, recent studies proposed that abnormalities in gut microbiota may play a role in systemic and central nervous system (CNS) conditions. Therefore, the integrity of gut microbiota be relevant to the pathophysiology and control of important medical diseases like diabetes mellitus, inflammatory and autoimmune diseases, and even neuropsychiatric disorders such as depression, autism spectrum disorder, Parkinson's and Alzheimer disease. Gut microbiota may affect brain function and behaviour through the microbiota-gut-brain axis, in bidirectional interplay with top-down and bottom-up regulations. Through metabolic activity of non- pathogenical microorganisms and secretion of functional by-products that increase the permeability of the intestinal mucosa, the gut microbiota influences both the production and absorption of neurotransmitters (e.g., serotonin and GABA), increasing their bioavailability to the CNS. It has been further shown some components of the gut microbiota - predominantly bacteria - synthesize and release amyloid peptides and lipopolysaccharides, which in turn activate inflammatory signalling through the release of cytokines, with potential effects on the pathophysiological cascade of Alzheimer disease.

Telomere length (TL) is a biomarker of cell aging, and its shortening has been linked to several age-related diseases. In Alzheimer's disease (AD), telomere shortening has been associated with neuroinflammation and oxidative stress. The majority of studies on TL in AD were based on leucocyte DNA, with little information about its status in the central nervous system. In addition to other neuroprotective effects, lithium has been implicated in the maintenance of TL. The present study aims to determine the effect of chronic lithium treatment on TL in different regions of the mouse brain, using a triple-transgenic mouse model (3xTg-AD). Eighteen transgenic and 22 wild-type (Wt) male mice were treated for eight months with chow containing 1.0 g (Li1) or 2.0 g (Li2) of lithium carbonate/kg, or standard chow (Li0). DNA was extracted from parietal cortex, hippocampus and olfactory epithelium and TL was quantified by real-time PCR. Chronic lithium treatment was associated with longer telomeres in the hippocampus (Li2, p = 0.0159) and in the parietal cortex (Li1, p = 0.0375) of 3xTg-AD compared to Wt. Our findings suggest that chronic lithium treatment does affect telomere maintenance, but the magnitude and nature of this effect depend on the working concentrations of lithium and characteristics of the tissue. This effect was observed when comparing 3xTg-AD with Wt mice, suggesting that the presence of AD pathology was required for the lithium modulation of TL.

Lithium activates Wnt/β-catenin signaling leading to stabilization of free cytosolic β-catenin. The aim of the present study is to evaluate the in vivo effect of acute and chronic lithium treatment on the expression of β-catenin target genes, addressing its transcripts HIG2, Bcl-xL, Cyclin D1, c-myc, in cortical and hippocampal tissue from adult mice. Lithium doses were established to yield therapeutic working concentrations. In acute treatment, mice received a 300µL of a 350 mg/kg solution of LiCl by gavage, and were euthanized after 2 h, 6 h and 12 h. To determine the effect of chronic treatment, animals were continuously fed either with chow supplemented with 2 g/kg Li2CO3, or regular chow (controls), being euthanized after 30 days. All animals had access to drinking water and 0.9% saline ad libitum. After acute and chronic treatments samples of peripheral blood were obtained from the tail vein for each animal, and serum concentrations of lithium were determined. All transcripts were up-regulated in cortical and hippocampal tissues of lithium-treated mice, both under acute and chronic treatments. There was a positive correlation between serum lithium concentrations and the increment in the expression of all transcripts. This effect was observed in all time points of the acute treatment (i.e., 2, 6 and 12 hours) and also after 30 days. We conclude that Wnt/β-catenin transcriptional response (HIG2, Bcl-xL, Cyclin D1 and c-myc) is up-regulated in the mouse brain in response to acute and chronic lithium treatment at therapeutic concentrations.

The incidence and prevalence of inflammatory bowel disease (IBD) has increased in recent years in several Latin American countries. There is a need to raise awareness in gastroenterologists and the population in general, so that early diagnosis and treatment of ulcerative colitis (UC) and Crohn's Disease (CD) can be carried out. It is important for all physicians to have homogeneous criteria regarding the diagnosis and treatment of IBD in Latin America. The Pan American Crohn's and Colitis Organisation (PANCCO) is an organization that aims to include all the countries of the Americas, but it specifically concentrates on Latin America. The present Consensus was divided into two parts for publication: 1) Diagnosis and treatment and 2) Special situations. This is the first Latin American Consensus whose purpose is to promote a perspective adapted to our Latin American countries for the diagnosis, treatment, and monitoring of patients with UC and CD.

Objectives The putative neuroprotective effects of lithium treatment rely on the fact that it modulates several homeostatic mechanisms involved in the neurotrophic response, autophagy, oxidative stress, inflammation, and mitochondrial function. Lithium is a well-established therapeutic option for the acute and long-term management of bipolar disorder and major depression. The aim of this study was to evaluate the effects of subtherapeutic and therapeutic concentrations of chronic lithium treatment on brain-derived neurotrophic factor (BDNF) synthesis and secretion. Methods Primary cultures of cortical and hippocampal neurons were treated with different subtherapeutic (0.02 and 0.2 mM) and therapeutic (2 mM) concentrations of chronic lithium treatment in cortical and hippocampal cell culture. Results Lithium treatment increased the intracellular protein expression of cortical neurons (10% at 0.02 mM) and hippocampal neurons (28% and 14% at 0.02 mM and 0.2 mM, respectively). Extracellular BDNF of cortical neurons increased 30% and 428% at 0.02 and 0.2 mM, respectively and in hippocampal neurons increased 44% at 0.02 mM. Conclusion The present study indicates that chronic, low-dose lithium treatment up-regulates BDNF production in primary neuronal cell culture.

Lithium is associated with various effects on immune functions, some of which are still poorly understood. The roles of many cytokines have been characterized in a variety of neurodevelopmental processes including neurogenesis, neuronal and glial cell migration, proliferation, differentiation, synaptic maturation and synaptic pruning. This work aims to evaluate the effects of different doses of lithium (0.02; 0.2 and 2mM) on the secretion of cytokines in co-cultures of cortical and hippocampal neurons with glial cells. Our results indicate that chronic treatment with lithium chloride at subtherapeutic concentrations are able to modify the secretion of pro- and anti-inflammatory interleukins in co-cultures of cortical and hippocampal neurons with glial cells.

Background: Experimental evidence supports the neuroprotective properties of lithium, with implications for the treatment and prevention of dementia and other neurodegenerative disorders. Lithium modulates critical intracellular pathways related to neurotrophic support, inflammatory response, autophagy and apoptosis. There is additional evidence indicating that lithium may also affect membrane homeostasis. Objective: To investigate the effect of lithium on cytosolic phospholipase A2 (PLA2) activity, a key player on membrane phospholipid turnover which has been found to be reduced in blood and brain tissue of patients with Alzheimer’s disease (AD). Methods: Primary cultures of cortical and hippocampal neurons were treated for 7 days with different concentrations of lithium chloride (0.02 mM, 0.2 mM and 2 mM). A radio-enzymatic assay was used to determine the total activity of PLA2 and two PLA2 subtypes: cytosolic calcium-dependent (cPLA2), and calcium-independent (iPLA2). Results: cPLA2 activity increased by 82% (0.02 mM, p = 0.05) and 26% (0.2 mM, p = 0.04) in cortical neurons and by 61% (0.2 mM, p = 0.03) and 57% (2 mM, p = 0.04) in hippocampal neurons. iPLA2 activity was increased by 7% (0.2 mM, p = 0.04) and 13% (2 mM, p = 0.05) in cortical neurons and by 141% (0.02 mM, p = 0.0198) in hippocampal neurons. Conclusion: long-term lithium treatment increases membrane phospholipid metabolism in neurons through the activation of total, c- and iPLA2. This effect is more prominent at sub-therapeutic concentrations of lithium, and the activation of distinct cytosolic PLA2 subtypes is tissue specific, i.e., iPLA2 in hippocampal neurons, and cPLA2 in cortical neurons. Because PLA2 activities are reported to be reduced in Alzheimer’s disease (AD) and bipolar disorder (BD), the present findings provide a possible mechanism by which long-term lithium treatment may be useful in the prevention of the disease.

A new species of Anchietea (Violaceae) is described and illustrated. Anchietea ferrucciae is characterized by its 4-carpellate ovary, small flowers and mostly, by its obovate seeds, cuneate at the base, and with a narrow, toothed wing. The new species is narrowly endemic to a very restricted area of the dry Caatinga in Bahia state (Brazil). An identification key to the species of Anchietea is provided.

La incidencia y la prevalencia de la enfermedad inflamatoria intestinal (EII) se han incrementado en los últimos años en varios países de Latinoamérica. Existe una necesidad de concientizar a gastroenterólogos y a la población en general para poder tener un diagnóstico y tratamiento oportunos en la colitis ulcerosa crónica idiopática (CUCI) y enfermedad de Crohn (EC). Es importante que todos los médicos tengan un criterio homogéneo acerca del diagnóstico y el tratamiento de la EII en América Latina. La Pan American Crohn's and Colitis Organisation (PANCCO) es un organismo con el propósito de incluir a todos los países del continente americano pero se enfoca de manera específica a los países latinos. Este Consenso está dividido en 2 partes para su publicación: 1) diagnóstico y tratamiento, y 2) situaciones especiales. Este es el primer Consenso latinoamericano cuyo objetivo es promover una perspectiva adaptada a nuestros países latinos para el diagnóstico, el tratamiento y la monitorización de pacientes con CUCI y EC.

Switched-mode dc-dc converters are used to regulate dc voltages or currents at a certain desired level. Due to inherent switching action, currents and voltages in the circuit tend to oscillate around a given average value, as the output values present some ripple in steady-state condition. The low-frequency output current ripple (OCR) is a key parameter for design considerations when a light-emitting diode (LED) string load is considered. In order to compare their ripple magnitudes under distinct conditions regarding a buck-based LED driver operating in continuous conduction mode (CCM), this paper analyzes the conventional voltage mode control as well as the peak-current mode control in order to compare its OCR responses by the classical control theory. The methods are implemented considering the same control bandwidth so that a proper comparison can be established.

The incidence and prevalence of inflammatory bowel disease (IBD) has increased in recent years in several Latin American countries. There is a need to raise awareness in gastroenterologists and the population in general, so that early diagnosis and treatment of ulcerative colitis (UC) and Crohn's Disease (CD) can be carried out. It is important for all physicians to have homogeneous criteria regarding the diagnosis and treatment of IBD in Latin America. The Pan American Crohn's and Colitis Organisation (PANCCO) is an organization that aims to include all the countries of the Americas, but it specifically concentrates on Latin America. The present Consensus was divided into two parts for publication: 1) Diagnosis and treatment and 2) Special situations. This is the first Latin American Consensus whose purpose is to promote a perspective adapted to our Latin American countries for the diagnosis, treatment, and monitoring of patients with UC and CD.

The aging process may impair exercise tolerance in the heat. It is not clear whether this impairment is partly due to a reduction in aerobic capacity. To compare the exercise performance and thermoregulatory responses of middle-aged and young adults with similar aerobic capacities and training statuses, 7 middle-aged (54±2 years; 58±4 ml·kg - 1·min - 1) and 7 young (28±1 years; 61±5 ml·kg - 1·min - 1) male competitive endurance runners underwent 2 10-km self-paced and 2 fixed-workload (90% of race speed) runs until fatigue on a treadmill in hot (40°C) and moderate (20°C) environments on separate days. The runners' total time, average speed, rectal temperature, heat storage rate, physiological strain index, sweat rate, sweat sensitivity, number of heat-activated sweat glands and sweat rate per sweat gland were measured or calculated. Body fat, body surface area, body surface area per body mass, training volume and VO2max were similar between the 2 groups. No differences were observed in total time (59±3; 49±3; 27±2; 54±5 min in the middle-aged and 60±2; 49±3; 27±2; 51±4 min in the young group), average speed, rectal temperature, heat storage rate, physiological strain index, sweat rate (17±7; 15±3; 23±7; 13±2 g.m - 2.min - 1 in the middle-aged and 20±5; 14±4; 22±5; 15±4 g.m - 2.min - 1 in the young group) or sweat sensitivity between age groups (p>0.05) in any trial. The number of heat-activated sweat glands (88±14; 80±18; 90±16; 66±14 cm - 2 in the middle-aged and 43±10; 32±10; 37±11; 31±11 cm - 2 in the young group) was higher, and the sweat rate per sweat gland was smaller, in the middle-aged than the young group (p

Background Lithium salts have a well-established role in the treatment of psychiatric disorders as major affective disorders and more recently Alzheimer disease. Experimental and clinical studies have provided evidence that lithium may exert neuroprotective effects at therapeutically and sub therapeutically doses. In animal model and cell culture models, lithium has been shown to increase neuronal viability through a combination of mechanisms that includes the inhibition of apoptosis, regulation of autophagy, increased mitochondrial function, and synthesis of neurotrophic factors. Objective: The Objective of the study is to compare biological process and pathways enriched in hippocampal neurons treated with different doses of lithium (0.02 mM, 0.2 mM and 2 mM) integrating genes and proteins differentially expressed. Methods Primary cultures of hippocampal neurons; Assessment of cell viability; Experimental design considerations, Microarray; LC-MS analyses; Data Analysis; Neural stem cell differentiation in Random differentiation; String Database and Functional enrichment analysis. Results The results showed that growing gene networks using differentially expressed genes and proteins as seeds alterations in mitochondria, ribosome and proteasome were observed in all lithium treatment doses. But also more specific biological process such as mitochondria respiratory chain, energy production (glucose and ATP) and apoptosis biological functions were enriched in each dose treatment. Discussion Given all the analyzes we can see that there is a dissociation dose effect of the treatment with lithium, the dose of 0.02Mm modified genes of degradation pathway proteins. The dose of 0.2Mm altered pathways of energy metabolism and the dose of 2Mm change related to nuclear and nuclear membrane. we can understand the specific function of each dose of the treatment.

Avaliaram-se os efeitos do níquel e da concentração protéica da dieta sobre o consumo e a digestibilidade aparente da matéria seca (MS), proteína bruta (PB) e energia, e balanço de nitrogênio do feno de Brachiaria brizantha cv. Marandu, oferecido a ovinos. As dietas testadas foram: A- feno; B- feno + níquel; C- feno + mistura protéica; D- feno + níquel + mistura protéica. As dietas continham, respectivamente 0,2, 5,2, 0,5 e 5,5ppm de níquel e 3,1, 3,1, 8,2 e 8,2% de PB. Nos níveis com menor concentração protéica (A e B; 3,1% PB), não foi observado efeito do níquel sobre o consumo e a digestibilidade aparente de matéria seca, energia e proteína, assim como os balanços protéico e energético. Nos com maior concentração protéica (C e D; 8,2% PB), o uso do níquel resultou em menor consumo de MS digestível, energia digestível e energia metabolizável. A maior concentração protéica teve efeito positivo sobre as características avaliadas, independentemente da suplementação ou não com níquel, com exceção da digestibilidade aparente da energia bruta, semelhantes entre as dietas B e D. This study was carried out to evaluate the effect of nickel supplementation and protein concentration of the diet on dry matter intake and apparent digestibilities of dry matter, crude protein (CP) and energy, and nitrogen balance of male sheep fed on Brachiaria brizantha cv. marandu hay. The experimental diets were: A- hay; B- hay + nickel; C- hay + protein; D- hay + nickel + protein. The diets contained 0.2, 5.2, 0.5 e 5.5ppm of nickel and 3.1, 3.1, 8.2 and 8.2% of crude protein, respectively. No effect of nickel supplementation on the apparent digestibility of dry matter, energy and protein, as well as the balance of protein and energy were observed for lower protein concentration diets (A and B; 3.1% CP). The nickel supplementation reduced the digestible dry matter, digestible energy and metabolizible energy consumption of higher protein concentration diets (C and D; 8.2% CP). The protein concentration of diets increased all the studied parameters, independently of nickel supplementation, except the apparent digestibility of crude energy, which were similar for B and D diets.

Schizophrenia has been suggested as a syndrome of accelerated aging. Telomere length (TL) decrease is considered one biological marker associated with age and can be accelerated by pathological characteristics present in schizophrenia. Several studies evaluated TL in schizophrenia, but the results are still controversial. The aim of this study was to conduct a meta-analysis of the existing results of TL in leukocytes of individuals with schizophrenia compared to healthy controls. A search was performed in PubMed, using the keywords 'telomere schizophrenia' and 'telomere psychosis'. We included data from original articles that measured TL in leukocytes of human patients with schizophrenia and healthy control subjects. 45 articles were found, but only 7 met our criteria. Telomere length of controls was not statistically different from that of patients with schizophrenia (p=0.07). Crossvalidation with the leave-one-out method resulted in a significant model (p=0.03) in which TL of individuals with schizophrenia is smaller than control (SMD=0.38; 95% CI=[0.05, 0.72]). We also propose a biological pathway through which schizophrenia could promote telomere erosion and how antipsychotics might compensate this loss. There are few studies made on this subject with diverse methodology and heterogeneous sample. Some articles did not consider other possible influences on TL. Overall our results suggest that TL is decreased in schizophrenia. Although this is consistent with the idea of accelerated aging, schizophrenia is a complex disease and there are several factors that influence TL that should be controlled in future studies.

A multiplex, single-step PCR protocol for the detection of human cytomegalovirus (HCMV) DNA is described. The protocol amplifies regions of the viral LA and IE genes and employs elevated temperatures for both reagent mixing and primer annealing together with product detection by silver staining on polyacrylamide gels. This assay detects one to five HCMV genomes in clinical samples containing up to 100 ng of human DNA, a level of sensitivity equivalent to that of more complex assays involving either nested PCR or postamplification hybridization. As well as being of importance in clinical situations where high-sensitivity qualitative diagnosis is required, this assay is also applicable to the monitoring of HCMV infection in renal transplant recipients. Due to its multiplex format the assay provides quantitative information, in that samples from which a single target is amplified contain on average sevenfold fewer viral genomes per 10(6) leukocytes than those from which both targets are amplified. When weekly blood leukocyte DNA preparations from renal transplant patients were assayed, findings of three consecutive tests in which both HCMV targets were amplified were highly indicative of patients who had developed very high loads of HCMV (100% sensitivity, 88% specificity). We thus show that the same simple PCR assay which permits highly sensitive HCMV diagnosis can also be used for the efficient identification of transplant recipients at risk of clinically significant infection.

To determine the presence of tricuspid regurgitation (TR) in patients affected by acute lung injury (ALI) and the adult respiratory distress syndrome (ARDS) during mechanical ventilation with positive end-expiratory pressure (PEEP). Design: A prospective clinical study. Setting: 10-bed general intensive care unit in a University Hospital. Patients: 7 consecutive patients an age 44.7 ± 8.6 years with a diagnosis of ALI or ARDS were studied. All were on mechanical ventilation with PEEP. Interventions: PEEP was increased in steps of 5 cm H2O until the appearance of TR or up to a limit of 20 cm H2O. Measurements and results: Right atrial pressure, pulmonary artery pressure, and wedge pressure were measured and cardiac output was determined by thermodilution. TR was graded from 0 to 3. Standard 2D echocardiographic and pulsed-wave images were obtained at each level of PEEP. PEEP was increased from 4 ± 3 to 17 ± 2 cm H2O. Mean PAP increased from 27.7 ± 2.9 to 36.7 ± 3.5 mm Hg (p < 0.02) when PEEP was increased. Five patients had competent valves and two had mild TR at baseline. In six out of the seven, TR either developed or increased when PEEP was increased. Conclusions: Our study demonstrated the development of TR after the use of PEEP in patients with ALI and ARDS as a consequence of pulmonary hypertension and right ventricular overloading. Since TR may randomly affect cardiac output values and derived parameters, the assessment of cardiac performance by some techniques such as thermodilution should be used with caution.