Clinical profile and microbiological aetiology diagnosis in adult patients hospitalized with community-acquired pneumonia.

Early introduction of appropriate antibiotherapy is one of the major prognostic-modifying factors in community acquired pneumonia (CAP). Despite established guidelines for empirical therapy, several factors may influence etiology and, consequently, antibiotic choices. The aims of this study were to analyze the etiology of CAP in adults admitted to a northern Portugal University Hospital and evaluate the yield of the different methods used to reach an etiological diagnosis, as well as analyze of the impact of patient demographic and clinical features on CAP etiology. We retrospectively analyzed 1901 cases of CAP with hospitalization. The diagnostic performance increased significantly when blood and sputum cultures were combined with urinary antigen tests. The most frequent etiological agent was Streptococcus pneumoniae (45.7%), except in August, when it was overtaken by gram-negative bacilli (GNB) and Legionella pneumophila infections. Viral infections were almost exclusive to winter and spring. A negative microbiological result was associated with increasing age, non-smoking and lack of both blood/sputum cultures. Younger age was a predictor for S. pneumoniae, Influenza and L. pneumophila infections. Active smoking without any previously known respiratory disease was a risk factor for legionellosis. COPD was associated with Haemophilus influenzae cases, while dementia was typical in GNB and S. aureus patients. Diabetes mellitus (DM) and heart disease were negative predictors of S. pneumoniae and H. influenzae, respectively. P. aeruginosa was an independent risk factor for mortality (OR 13.02, 95% CI 2.94-57.7). This study highlights the importance of a comprehensive microbiological diagnostic workup and provides clues to predicting the most probable CAP causative agents, based on a patient's clinical profile. These may be taken into account when establishing first line antibiotherapy.

Inheritance of Rootstock Effects in Avocado (Persea americana Mill.) cv. Hass.

Grafting is typically utilized to merge adapted seedling rootstocks with highly productive clonal scions. This process implies the interaction of multiple genomes to produce a unique tree phenotype. However, the interconnection of both genotypes obscures individual contributions to phenotypic variation (rootstock-mediated heritability), hampering tree breeding. Therefore, our goal was to quantify the inheritance of seedling rootstock effects on scion traits using avocado (Persea americana Mill.) cv. Hass as a model fruit tree. We characterized 240 diverse rootstocks from 8 avocado cv. Hass orchards with similar management in three regions of the province of Antioquia, northwest Andes of Colombia, using 13 microsatellite markers simple sequence repeats (SSRs). Parallel to this, we recorded 20 phenotypic traits (including morphological, biomass/reproductive, and fruit yield and quality traits) in the scions for 3 years (2015-2017). Relatedness among rootstocks was inferred through the genetic markers and inputted in a "genetic prediction" model to calculate narrow-sense heritabilities (h 2) on scion traits. We used three different randomization tests to highlight traits with consistently significant heritability estimates. This strategy allowed us to capture five traits with significant heritability values that ranged from 0.33 to 0.45 and model fits (r) that oscillated between 0.58 and 0.73 across orchards. The results showed significance in the rootstock effects for four complex harvest and quality traits (i.e., total number of fruits, number of fruits with exportation quality, and number of fruits discarded because of low weight or thrips damage), whereas the only morphological trait that had a significant heritability value was overall trunk height (an emergent property of the rootstock-scion interaction). These findings suggest the inheritance of rootstock effects, beyond root phenotype, on a surprisingly wide spectrum of scion traits in "Hass" avocado. They also reinforce the utility of polymorphic SSRs for relatedness reconstruction and genetic prediction of complex traits. This research is, up to date, the most cohesive evidence of narrow-sense inheritance of rootstock effects in a tropical fruit tree crop. Ultimately, our work highlights the importance of considering the rootstock-scion interaction to broaden the genetic basis of fruit tree breeding programs while enhancing our understanding of the consequences of grafting.

African histoplasmosis in a Guinea Bissau patient with HIV-2: Case report and review.

African histoplasmosis is the relatively unknown infection by Histoplasma capsulatum var. duboisii. It is endemic to Central and West Africa, generally involving the skin with potential for systemic dissemination, and has been described mainly in immunocompetent hosts. We present the case of a 30-year-old Bissau-Guinean man with HIV-2 infection known for 16 years, irregularly treated, admitted with two weeks of fever, diarrhoea and cutaneous lesions. Examination revealed multiple subcutaneous nodes, Molluscum contagiosum-like lesions, generalized lymphadenopathy and painful palpation of the left iliac fossa. Laboratory tests showed severe nonhaemolytic anaemia and CD4+ count of 9/mm3, with normal creatinine and hepatic enzymes. Chest roentgenogram was unremarkable and a research for Mycobacterium tuberculosis by GeneXpert® was negative. Nonetheless, given the lack of further diagnostic tools, a presumptive diagnosis of disseminated tuberculosis was made, and the patient was started on tuberculostatic and antiretroviral drugs. Despite initial improvement, a national shortage of antiretrovirals precluded further treatment, with worsening of the clinical picture, namely an increase in the number and dimensions of the skin lesions. An excisional biopsy of a subcutaneous nodule revealed Histoplasma capsulatum var. duboisii. Unfortunately, due to the unavailability of antifungals, the patient died one week later. To our best knowledge, this is the first confirmed case of an HIV infected patient with African histoplasmosis in Guinea-Bissau.

Daily supplementation with 5 mg of folic acid in Brazilian patients with hereditary spherocytosis.

Patients with hereditary spherocytosis (HS) have increased rates of erythropoiesis and higher folate requirements. In a case-control study of patients with HS, we evaluated the associations between the use of 5 mg folic acid (FA) daily and serum concentrations of folate, unmetabolized folic acid (UMFA), interleukin (IL)-6, IL-8, IL-10, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α); and mRNA expression of dihydrofolate reductase (DHFR), methylene tetrahydrofolate reductase (MTHFR), IL8, IFNG and TNFA genes. Total serum folate and folate forms were measured in 27 patients with HS (21 users [HS-U] and 6 non-users [HS-NU] of supplemental FA) and 54 healthy controls not consuming 5 mg/day supplemental FA. Each patient was matched to two controls based on age, sex and body mass index. The mononuclear leucocyte mRNA expression of relevant genes and their products were determined. Serum folate, UMFA, 5-methyl-tetrahydrofolate (5-methyl-THF) and tetrahydrofolate (THF) concentrations were significantly higher in HS-U compared with matched healthy controls (p<0.001, n=42). HS-NU had lower serum folate concentrations than matched healthy controls (p=0.044, n=12). HS-U and HS-NU presented similar hematological and biochemical markers profiles. No differences were found between HS-U and HS-NU for cytokine serum concentrations and mRNA expression genes. DHFR mRNA expression was higher in HS-U than in HS-NU. The use of high daily doses of FA for treatment of patients with HS may be excessive and is associated with elevated serum UMFA and elevated DHFR mRNA expression. It is not known whether long-term high-dose FA use by patients with HS might have adverse health effects.

Tandem Recruitment and Foraging in the Ponerine Ant Pachycondyla harpax (Fabricius).

Tandem running is a common recruitment strategy in ant species with small colony sizes. During a tandem run, an informed leader guides a usually naïve nestmate to a food source or a nest site. Some species perform tandem runs only during house hunting, suggesting that tandem running does not always improve foraging success in species known to use tandem running as a recruitment strategy, but more natural history information on tandem running under natural conditions is needed to better understand the adaptive significance of tandem recruitment in foraging. Studying wild colonies in Brazil, we for the first time describe tandem running in the ponerine ant Pachycondyla harpax (Fabricius). We asked if foragers perform tandem runs to carbohydrate- (honey) and protein-rich (cheese) food items. Furthermore, we tested whether the speed and success rate of tandem runs depend on the foraging distance. Foragers performed tandem runs to both carbohydrate food sources and protein-rich food items that exceed a certain size. The probability to perform a tandem run and the travelling speed increase with increasing foraging distances, which could help colonies monopolize more distant food sources in a competitive environment. Guiding a recruit to a food source is costly for leaders as ants are ~66% faster when travelling alone. If tandem runs break up (~23% of all tandem runs), followers do not usually discover the food source on their own but return to the nest. Our results show that tandem running to food sources is common in P. harpax, but that foragers modify their behaviour according to the type of food and its distance from the nest. Competition with other ants was intense and we discuss how tandem running in P. harpax might help colonies to build-up a critical number of ants at large food items that can then defend the food source against competitors.

Temporal changes in hematologic markers after splenectomy, splenic embolization, and observation for trauma.

INTRODUCTION: The spleen is one of the most commonly injured abdominal solid organs during blunt trauma. Modern management of splenic trauma has evolved to include non-operative therapies, including observation and angioembolization to preclude splenectomy in most cases of blunt splenic injury. Despite the shift in management strategies, relatively little is known about the hematologic changes associated with these various modalities. The aim of this study was to determine if there are significant differences in hematologic characteristics over time based on the treatment modality employed following splenic trauma. We hypothesized that alterations seen in hematologic parameters would vary between observation (OBS), embolization (EMB), and splenectomy (SPL) in the setting of splenic injury. METHODS: An institutional review board-approved, retrospective study of routine hematologic indices examined data between March 2000 and December 2014 at three academic trauma centers. A convenience sample of patients with splenic trauma and admission lengths of stay >96 h was selected for inclusion, resulting in a representative sample of each sub-group (OBS, EMB, and SPL). Basic demographics and injury severity data (ISS) were abstracted. Platelet count, red blood cell (RBC) count and RBC indices, and white blood cell (WBC) count with differential were analyzed between the time of admission and a maximum of 1080 h (45 days) post-injury. Comparisons between OBS, EMB, and SPL groups were then performed using non-parametric statistical testing, with statistical significance set at p < 0.05. RESULTS: Data from 130 patients (40 SPL, 40 EMB, and 50 OBS) were analyzed. The median age was 40 years, with 67 % males. Median ISS was 21.5 (21 for SPL, 19 for EMB, and 22 for OBS, p = n/s) and median Glasgow Coma Scale (GCS) was 15. Median splenic injury grade varied by interventional modality (grade 4 for SPL, 3 for EMB, and 2 for OBS, p < 0.05). Inter-group comparisons demonstrated no significant differences in RBC counts. However, mean corpuscular volume (MCV) and RBC distribution width (RDW) were elevated in the SPL and EMB groups (p < 0.01). Similarly, EMB and SPL groups had higher platelet counts than the OBS group (p < 0.01). In aggregate, WBC counts were highest following SPL, followed by EMB and OBS (p < 0.01). Similar trends were noted in neutrophil and monocyte counts (p < 0.01), but not in lymphocyte counts (p = n/s). CONCLUSION: This study describes important trends and patterns among fundamental hematologic parameters following traumatic splenic injuries managed with SPL, EMB, or OBS. As expected, observed WBC counts were highest following SPL, then EMB, and finally OBS. No differences were noted in RBC count between the three groups, but RDW was significantly greater following SPL compared to EMB and OBS. We also found that MCV was highest following OBS, when compared to EMB or SPL. Finally, our data indicate that platelet counts are similarly elevated for both SPL and EMB, when compared to the OBS group. These results provide an important foundation for further research in this still relatively unexplored area.

Functional lateralization of the medial prefrontal cortex in the modulation of anxiety in mice: Left or right?

It has been suggested that the left medial prefrontal cortex (LmPFC) has an inhibitory role in controlling the right mPFC (RmPFC), thereby reducing the deleterious effects of stressors on emotional states. Here, we investigated the effects on anxiety of bilateral or unilateral injections of NOC-9 [a nitric oxide (NO) donor] and cobalt chloride (CoCl2; a synaptic inhibitor) into the mPFC of mice exposed to the elevated plus-maze (Experiments 1 and 2). The effects of restraint or social defeat on anxiety in undrugged mice were recorded at 5 min or 24 h after exposure to the stress (Experiment 3). Experiment 4 investigated the effects of LmPFC injection of CoCl2 combined with restraint or social defeat on anxiety, which was recorded 24 h later. Although intra-RmPFC NOC-9 produced anxiogenesis, its injection into the LmPFC, or bilaterally, did not change anxiety. Intra-RmPFC or -LmPFC injection of CoCl2 produced anxiolytic- and anxiogenic-like effects, respectively. Both restraint and social defeat produced anxiogenesis at 5 min, but defeated mice did not display anxiety 24 h after the stress. Although intra-LmPFC CoCl2 did not change anxiety, which was recorded 24 h later in non-stressed mice, this synaptic inhibitor produced a clear, anxiogenic-like effect in defeated (but not restrained) mice. These results suggest that (i) nitrergic activation of the RmPFC increases anxiety, which in turn is inhibited by NO production within the LmPFC; (ii) neuronal inhibition of the RmPFC or LmPFC elicits anxiolysis and anxiogenesis, respectively; and (iii) inactivation of the LmPFC results in recrudescence of anxiety induced by social defeat stress.

Incidentally discovered hepatocellular carcinoma in explanted liver: clinical, histopathologic features and outcome.

BACKGROUND: Incidental hepatocellular carcinomas (iHCCs) are tumors discovered on the explanted liver that were not present on imaging before transplantation. The natural history, histopathologic characteristics, and prognosis are not clearly defined. METHODS: We compared the characteristics of iHCC and previously known hepatocellular carcinoma (pkHCC) in patients who underwent liver transplantation from 1998 to 2012 in a retrospective study. RESULTS: During this period a total of 675 patients were transplanted; 56 patients (9%) had pkHCC and 12 (2%) had iHCC. The sex and age distributions were similar. The median Model for End-Stage Liver Disease score in iHCC patients was 17.0 versus 13.0 in patients with pkHCC (P = .001). Thirty-three percent of iHCC patients had multiple tumors, and 25% had bilobar involvement. The median cumulative tumor size in iHCC was 1.8 cm, and 5.5 cm in pkHCC (P = .005). Incidence of microvascular invasion was not different (16.7% vs 38.9%; P = .191). American Joint Committee on Cancer T1 stage was found in 58.3% of patients with iHCC and in 22.2% of pkHCC patients. Patients with iHCC had 1-, 3-, and 5-year survivals, respectively, of 100%, 83% and 64%, compared with 80%, 66%, and 38% for patients with pkHCC (P = .138). None of the patients with iHCC had recurrence of HCC, whereas incidence of recurrence in pkHCC patients was 12.5%. CONCLUSIONS: iHCC occurred in patients with more advanced liver disease. The cumulative tumor size of iHCC was smaller but one-third were multifocal. Survival was similar to patients with pkHCC, and recurrence was not noted in patients with iHCC.

In vitro interactions of blood, platelet, and fibroblast with biodegradable magnesium-zinc-strontium alloys.

Magnesium (Mg) alloy is an attractive class of metallic biomaterial for cardiovascular applications due to its biodegradability and mechanical properties. In this study, we investigated the degradation in blood, thrombogenicity, and cytocompatibility of Magnesium-Zinc-Strontium (Mg-Zn-Sr) alloys, specifically four Mg-4 wt % Zn-xSr (x = 0.15, 0.5, 1, and 1.5 wt %) alloys, together with pure Mg control and relevant reference materials for cardiovascular applications. Human whole blood and platelet rich plasma (PRP) were used as the incubation media to investigate the degradation behavior of the Mg-Zn-Sr alloys. The results showed that the PRP had a greater pH increase and greater concentration of Mg(2+) ions when compared with whole blood after 2 h of incubation with the same respective Mg alloys, suggesting that the Mg alloys degraded faster in PRP than in whole blood. The Mg alloy with 4 wt % Zn and 0.15 wt % Sr (named as ZSr41A) was identified as the most promising alloy for cardiovascular stent applications, because it showed slower degradation and less thrombogenicity, as indicated by the lower concentrations of Mg(2+) ions released and less deposition of platelets. Additionally, ZSr41 alloys were cytocompatible with fibroblasts in direct exposure culture in which the cells adhered and proliferated around the samples, with no statistical difference in cell adhesion density compared with the blank reference. Future studies on the ZSr41 alloys are necessary to investigate their direct interactions with other important cells in cardiovascular system, such as vascular endothelial cells and smooth muscle cells.

Effect of maternal deprivation on acetylcholinesterase activity and behavioral changes on the ketamine-induced animal model of schizophrenia.

Maternal deprivation has been associated with physiological and developmental changes that may be related to an increased risk for childhood and adult neuropsychiatric diseases. A growing number of studies demonstrated the importance of childhood experiences in the development of psychosis and schizophrenia in adulthood. Therefore, the present study investigated different behavior responses in rats following maternal deprivation and/or ketamine treatment in adulthood. Male rats were subjected to maternal deprivation for 180 min from postnatal day-01 to postnatal day-10. We evaluated locomotor activity, avoidance task and social interaction of adult male rats deprived or not deprived that were administered with saline or acute subanesthetic doses of ketamine (5, 15 and 25 mg/kg, i.p.). Our results show that only ketamine (25 mg/kg, i.p.) treatment in the adult rats lead to hyperlocomotion but not ketamine (5 and 15 mg/kg) and maternal deprivation alone. However, maternally deprived rats treated with ketamine (5 mg/kg) induced hyperlocomotion. Additionally, ketamine (25 mg/kg) and maternal deprivation alone induced cognitive deficit in the avoidance task. Rats deprived of and treated with ketamine (5, 15 and 25 mg/kg) also lead to memory deficit. Moreover, ketamine (25 mg/kg) and maternal deprivation alone increased latency to start social behavior. However, ketamine (5 mg/kg) and maternal deprivation lead to an increase of latency to start social behavior. Biochemistry data showed that all doses of ketamine and ketamine plus maternal deprivation increased the acetylcholinesterase (AChE) activity in the prefrontal cortex, hippocampus and striatum. The major doses of ketamine associated with maternal deprivation induced a major increase of AChE activity. Together, our results suggest that animals subjected to maternal deprivation had an increased risk for schizophrenia-like behavior and cholinergic alteration.

Circulating concentrations, cerebral output of the CINC-1 and blood­brain barrier disruption in Wistar rats after pneumococcal meningitis induction.

Pneumococcal meningitis is a severe infectious illness of the central nervous system (CNS), with high rates of lethality and morbidity, being that the microorganism and the host's inflammatory response are responsible for cerebral complications. Moreover, the blood­brain barrier (BBB) itself secretes cytokines and, because of the bipolar nature of the BBB, these substances can be secreted into either the CNS compartment or in the blood, so patients with acute bacterial meningitis frequently develop sepsis. Therefore, the aim of this study was to evaluate the cytokine/chemokine levels in different vessels and the BBB integrity after pneumococcal meningitis induction. Wistar rats were infected with Streptococcus pneumoniae, and the BBB integrity was investigated using Evan's blue dye. Also, blood from the carotid artery and jugular vein was collected in order to perform tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), interleukin-6 (IL-60 and cytokine-induced neutrophil chemoattractant-1 (CINC-1) analyses by enzyme-linked immunosorbent assay (ELISA). CINC-1 levels were increased at 6 h in the arterial plasma and at 3 and 6 h in the jugular plasma. We observed BBB breakdown between 12 and 24 h in the hippocampus and at 12 and 18 h in the cortex after pneumococcal meningitis induction. The increase of CINC-1 occurred prior to the BBB breakdown. CINC-1 is a neutrophil chemoattractant and it may be related to early events in the pneumococcal meningitis pathophysiology.

Metformin and atorvastatin combination further protect the liver in type 2 diabetes with hyperlipidaemia.

BACKGROUND: non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes are associated with dyslipidaemia, inflammation and oxidative stress. However, the pathophysiology of NAFLD in type 2 diabetes with hyperlipidaemia is not fully known, as well as the utility of the commonly prescribed anti-diabetic and lipid-lowering drugs in ameliorating liver injury markers. METHODS: hepatic complications of type 2 diabetes with hyperlipidaemia and the effects of atorvastatin and metformin, isolated and in association, in systemic and hepatic inflammatory and oxidative stress markers were tested using genetic type 2 diabetic Goto-Kakizaki rats fed with a high-fat diet. RESULTS: the high-fat diet aggravated the overall metabolic state and the hepatic markers of injury. All treatments decreased fasting glycaemia, insulin resistance and free fatty acid levels. Combined treatment further decreased C-reactive protein (CRP), adiponectin, liver tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6), systemic and hepatic oxidative stress and portal inflammation. CONCLUSIONS: our data provides evidence of a greater benefit with a combination of atorvastatin and metformin in improving liver injury in type 2 diabetes with hyperlipidaemia.

A role for atorvastatin and insulin combination in protecting from liver injury in a model of type 2 diabetes with hyperlipidemia.

Non-alcoholic fatty liver disease (NAFLD) is a major complication linked with the metabolic syndrome associated with dyslipidemia, inflammation, and oxidative stress. Impact of type 2 diabetes with hyperlipidemia in NAFLD has to be established, as well as the utility of commonly prescribed anti-diabetic and lipid-lowering agents in improving liver injury markers. Genetic type 2 diabetic Goto-Kakizaki rats were fed with a high-fat diet to test hepatic effects of type 2 diabetes with hyperlipidemia and the effect of atorvastatin and insulin, individually and in combination, in systemic and hepatic inflammatory and oxidative stress markers. High-fat diet aggravated fasting glycemia, systemic and liver lipids, and inflammatory and oxidative stress markers. Individual treatments improved glycemic and lipid profiles, but failed to improve inflammatory markers, whereas insulin was able to reduce liver oxidative stress parameters. Combination of insulin and atorvastatin further improved glycemic and lipid profiles and decreased circulating C-reactive protein levels and liver inflammatory and oxidative stress markers. Insulin and atorvastatin combination leads to better glycaemic and lipid profiles and to better protection against liver inflammation and oxidative stress, giving a superior level of liver protection in type 2 diabetic with hyperlipidemia.

Fosinopril-induced prolonged cholestatic jaundice and pruritus: first case report.

We report a case of fosinopril-induced prolonged cholestatic jaundice and pruritus in a 61-year-old man, with no previous hepatobiliary disease, who presented with asthenia, jaundice and itching 3 weeks after starting fosinopril therapy. Other drugs taken by the patient were not considered probable causes. The diagnostic evaluation showed no biliary obstruction and other possible causes of intra-hepatic cholestasis were excluded. Liver biopsy showed cholestasis without bile duct damage. The disease ran a severe course during the 2 months of hospitalization, with prolonged itching for 6 months, eventually controlled with oral naltrexone. Jaundice subsided after 4 months, with anicteric cholestasis persisting for more than 18 months. Similar occurrences have been reported with other inhibitors of angiotensin-converting enzyme (mostly captopril), but this is the first case of an important adverse reaction to fosinopril.

Ticlopidine-induced prolonged cholestasis: a case report.

We report a case of ticlopidine-induced prolonged cholestasis in a 60-year-old man with no previous hepatobiliary disease who presented with sudden right upper abdominal pain, jaundice and pruritus three months after starting ticlopidine therapy. Other drugs taken by the patient were not considered probable causes. The diagnostic evaluation showed no biliary obstruction and other possible causes of intra-hepatic cholestasis were excluded. The liver biopsy showed a cholestatic hepatitis with bile duct damage. The disease ran a severe and protracted course, but symptoms and jaundice eventually subsided five months after drug withdrawal. More than a year later, relevant abnormalities of liver function tests consistent with anicteric cholestasis still persist, fulfilling criteria for a minor form of drug-induced prolonged cholestasis. This syndrome has been reported infrequently in relation to several drugs, mainly chlorpromazine, and only once with ticlopidine.

A model of internal control may improve the response time of an automatic arterial pressure controller.

A simplified model for the arterial pressure control system was implemented on a personal computer using Matlab Simulink. Model responses to variations of systemic vascular resistance were comparable to those predicted by physiology. Computer simulation suggested that including this model of the internal pressure control system within the design of an external controller would achieve better arterial pressure control and faster response than previous systems.

Estimation of cardiac function from computer analysis of the arterial pressure waveform.

This paper presents a method for estimating parameters of a cardiovascular model, including the left-ventricular function, using the sequential quadratic programming (SQP) and the least minimum square (LMS) algorithms. In a first stage, a radial arterial-pressure waveform with corresponding cardiac output are used to automatically seek the set of parameters of the diastolic model. Computer simulation of the model using these parameters generate a pressure waveform and a cardiac output very close to those used for the estimation. In a second stage, the estimated arterial load parameters are used to select the best left-ventricular model function, from four different possibilities, and to estimate its optimum parameter values. The method has been tested numerically and applied to real cases, using data obtained from cardiovascular patients. It has also been subjected to preliminary validation using data obtained from laboratory dogs, in which cardiovascular function was artificially altered.