Influence of Klebsiella pneumoniae and quinolone treatment on prognosis in patients with pancreatic cancer.

BACKGROUND: An increasing body of evidence suggests that microbiota may promote progression of pancreatic ductal adenocarcinoma (PDAC). It was hypothesized that gammaproteobacteria (such as Klebsiella pneumoniae) influence survival in PDAC, and that quinolone treatment may attenuate this effect. METHODS: This was a retrospective study of patients from the Massachusetts General Hospital (USA) and Ludwig-Maximilians-University (Germany) who underwent preoperative treatment and pancreatoduodenectomy for locally advanced or borderline resectable PDAC between January 2007 and December 2017, and for whom a bile culture was available. Associations between tumour characteristics, survival data, antibiotic use and results of intraoperative bile cultures were investigated. Survival was analysed using Kaplan-Meier curves and Cox regression analysis. RESULTS: Analysis of a total of 211 patients revealed that an increasing number of pathogen species found in intraoperative bile cultures was associated with a decrease in progression-free survival (PFS) (-1·9 (95 per cent c.i. -3·3 to -0·5) months per species; P = 0·009). Adjuvant treatment with gemcitabine improved PFS in patients who were negative for K. pneumoniae (26·2 versus 15·3 months; P = 0·039), but not in those who tested positive (19·5 versus 13·2 months; P = 0·137). Quinolone treatment was associated with improved median overall survival (OS) independent of K. pneumoniae status (48·8 versus 26·2 months; P = 0·006) and among those who tested positive for K. pneumoniae (median not reached versus 18·8 months; P = 0·028). Patients with quinolone-resistant K. pneumoniae had shorter PFS than those with quinolone-sensitive K. pneumoniae (9·1 versus 18·8 months; P = 0·001). CONCLUSION: K. pneumoniae may promote chemoresistance to adjuvant gemcitabine, and quinolone treatment is associated with improved survival.

NX4: a web-based visualization of large multiple sequence alignments.

SUMMARY: Multiple Sequence Alignments (MSAs) are a fundamental operation in genome analysis. However, MSA visualizations such as sequence logos and matrix representations have changed little since the nineties and are not well suited for displaying large-scale alignments. We propose a novel, web-based MSA visualization tool called NX4, which can handle genome alignments comprising thousands of sequences. NX4 calculates the frequency of each nucleotide along the alignment and visually summarizes the results using a color-blind friendly palette that helps identifying regions of high genetic diversity. NX4 also provides the user with additional assistance in finding these regions with a 'focus + context' mechanism that uses a line chart of the Shannon entropy across the alignment. The tool offers geneticists an easy-to-use and scalable analysis for large MSA studies. AVAILABILITY AND IMPLEMENTATION: NX4 is freely available at https://www.nx4.io, and its source code at https://github.com/NX4/nx4. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Risk of malignancy in small pancreatic cysts decreases over time.

BACKGROUND: Pancreatic cysts <15 mm without worrisome features have practically no risk of malignancy at the time of diagnosis but this can change over time. Optimal duration of follow-up is a matter of debate. We evaluated predictors of malignancy and attempted to identify a time to safely discontinue surveillance. METHODS: Bi-centric study utilizing prospectively collected databases of patients with pancreatic cysts measuring <15 mm and without worrisome features who underwent surveillance at the Massachusetts General Hospital (1988-2017) and at the University of Verona Hospital Trust (2000-2016). The risk of malignant transformation was assessed using the Kaplan-Meier method and parametric survival models, and predictors of malignancy were evaluated using Cox regression. RESULTS: 806 patients were identified. Median follow-up was 58 months (6-347). Over time, 58 (7.2%) cysts were resected and of those, 11 had high grade dysplasia (HGD) or invasive cancer. Three additional patients had unresectable cancer for a total rate of malignancy of 1.7%. Predictors of development of malignancy included an increase in size ≥2.5 mm/year (HR = 29.54, 95% CI: 9.39-92.91, P < 0.001) and the development of worrisome features (HR = 9.17, 95% CI: 2.99-28.10, P = 0.001). Comparison of parametric survival models suggested that the risk of malignancy decreased after three years of surveillance and was lower than 0.2% after five years. CONCLUSIONS: Pancreatic cysts <15  mm at the time of diagnosis have a very low risk of malignant transformation. Our findings indicate the risk decreases over time. Size increase of ≥2.5 mm/year is the strongest predictor of malignancy.

An elevated CA 19-9 is associated with invasive cancer and worse survival in IPMN.

BACKGROUND: Current guidelines for IPMN include an elevated serum carbohydrate antigen (CA) 19-9 among the worrisome features. However, the correlation of CA 19-9 with histological malignant features and survival is unclear. Serum CEA is also currently used for preoperative management of IPMN, although its measurement is not evidence-based. Accordingly, we aimed to assess the role of these tumor markers as predictors of malignancy in IPMN. METHODS: IPMN resected between 1998 and 2018 at Massachusetts General Hospital were analyzed. Clinical, pathological and survival data were collected and compared to preoperative levels of CA 19-9 and CEA. Receiver operating characteristic (ROC) and Cox regression analyses were performed considering cut-offs of 37 U/ml (CA 19-9) and 5 µg/l (CEA). RESULTS: Analysis of 594 patients showed that preoperative CA 19-9 levels > 37 U/ml (n = 128) were associated with an increased likelihood of invasive carcinoma when compared to normal levels (45.3% vs. 18.0%, P < 0.001), while there was no difference with respect to high-grade dysplasia (32.9% vs 31.9%, P = 0.88). The proportion of concurrent pancreatic cancer was higher in patients with CA 19-9 > 37 U/ml (17.2% vs 4.9%, P < 0.001). An elevated CA 19-9 was also associated with worse overall and disease-free survival (HR = 1.943, P = 0.007 and HR = 2.484, P < 0.001 respectively). CEA levels did not correlate with malignancy. CONCLUSION: In patients with IPMN, serum CA19-9 > 37 U/ml is associated with invasive IPMN and concurrent pancreatic cancer as well as worse survival, but not with high-grade dysplasia. Serum CEA appears to have minimal utility in the management of these patients.

International consensus guidelines for surgery and the timing of intervention in chronic pancreatitis.

BACKGROUND/OBJECTIVES: Chronic pancreatitis (CP) is a complex inflammatory disease with pain as the predominant symptom. Pain relief can be achieved using invasive interventions such as endoscopy and surgery. This paper is part of the international consensus guidelines on CP and presents the consensus guideline for surgery and timing of intervention in CP. METHODS: An international working group with 15 experts on CP surgery from the major pancreas societies (IAP, APA, JPS, and EPC) evaluated 20 statements generated from evidence on 5 questions deemed to be the most clinically relevant in CP. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the level of evidence available for each statement. To determine the level of agreement, the working group voted on the 20 statements for strength of agreement, using a nine-point Likert scale in order to calculate Cronbach's alpha reliability coefficient. RESULTS: Strong consensus was obtained for the following statements: Surgery in CP is indicated as treatment of intractable pain and local complications of adjacent organs, and in case of suspicion of malignant (cystic) lesion; Early surgery is favored over surgery in a more advanced stage of disease to achieve optimal long-term pain relief; In patients with an enlarged pancreatic head, a combined drainage and resection procedure, such as the Frey, Beger, and Berne procedure, may be the treatment of choice; Pancreaticoduodenectomy is the most suitable surgical option for patients with groove pancreatitis; The risk of pancreatic carcinoma in patients with CP is too low (2% in 10 year) to recommend active screening or prophylactic surgery; Patients with hereditary CP have such a high risk of pancreatic cancer that prophylactic resection can be considered (lifetime risk of 40-55%). Weak agreement for procedure choice in patients with dilated duct and normal size pancreatic head: both the extended lateral pancreaticojejunostomy and Frey procedure seems to provide equivalent pain control in patients. CONCLUSIONS: This international expert consensus guideline provides evidenced-based statements concerning key aspects in surgery and timing of intervention in CP. It is meant to guide clinical practitioners and surgeons in the treatment of patients with CP.

In vitro mechanism of antibacterial action of a citrus essential oil on an enterotoxigenic Escherichia coli and Lactobacillus rhamnosus.

AIM: This study investigated the in vitro mechanism of action of a commercial citrus EO, Brazilian orange terpenes (BOT), on an enterotoxigenic Escherichia coli (ETEC) isolated from pig gut and on Lactobacillus rhamnosus. METHODS AND RESULTS: Firstly, bacteria were exposed sequentially to BOT every 3 h (three times) at sub-minimal inhibitory concentrations and results showed that sequential exposure to BOT provoked a higher reduction of bacteria viability than a single exposure and the reduction of ETEC viability was higher compared to that of L. rhamnosus. Then, evaluation of the BOT effects on the cell membrane permeability and integrity, indicated that BOT increased the membrane permeability and caused disruptive effects on the integrity of bacterial cells as reflected by an increase of the relative electric conductivity and the release of essential cell constituents. Interestingly, BOT effects were more pronounced on the ETEC than on L. rhamnosus. This was ratified by scanning electron microscopy, which showed more noticeable morphological damages and disturbances on ETEC cells than on the L. rhamnosus cells. Limonene was detected as the major compound in BOT by polar/nonpolar GC-MS (78·65%/79·38%). CONCLUSIONS: Results revealed that the probable mechanism of the selective antibacterial action of the citrus EO, BOT, can be described as altering more remarkable the permeability and integrity of the cytoplasmic membrane as well as the external structure of ETEC cells than L. rhamnosus cells. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides information about the mechanism of antibacterial action displayed by a citrus EO, a by-product of the citrus processing industry, as a natural alternative to antibiotics used in pig production sector to combat pathogens such as ETECs.

A Multimodal Intention Detection Sensor Suite for Shared Autonomy of Upper-Limb Robotic Prostheses.

Neurorobotic augmentation (e.g., robotic assist) is now in regular use to support individuals suffering from impaired motor functions. A major unresolved challenge, however, is the excessive cognitive load necessary for the human-machine interface (HMI). Grasp control remains one of the most challenging HMI tasks, demanding simultaneous, agile, and precise control of multiple degrees-of-freedom (DoFs) while following a specific timing pattern in the joint and human-robot task spaces. Most commercially available systems use either an indirect mode-switching configuration or a limited sequential control strategy, limiting activation to one DoF at a time. To address this challenge, we introduce a shared autonomy framework centred around a low-cost multi-modal sensor suite fusing: (a) mechanomyography (MMG) to estimate the intended muscle activation, (b) camera-based visual information for integrated autonomous object recognition, and (c) inertial measurement to enhance intention prediction based on the grasping trajectory. The complete system predicts user intent for grasp based on measured dynamical features during natural motions. A total of 84 motion features were extracted from the sensor suite, and tests were conducted on 10 able-bodied and 1 amputee participants for grasping common household objects with a robotic hand. Real-time grasp classification accuracy using visual and motion features obtained 100%, 82.5%, and 88.9% across all participants for detecting and executing grasping actions for a bottle, lid, and box, respectively. The proposed multimodal sensor suite is a novel approach for predicting different grasp strategies and automating task performance using a commercial upper-limb prosthetic device. The system also shows potential to improve the usability of modern neurorobotic systems due to the intuitive control design.

[Characterization of full term newborns with hypernatremic dehydration]. / Caracterización de recién nacidos a término con deshidratación hipernatrémica.

INTRODUCTION: The hypernatremic neonatal dehydration is a severe condition whose incidence has increased in recent years resulting in complications leading to the hospitalization of the newborn. OBJECTIVE: Describe the clinical and laboratory characteristics of term-newborns with Hypernatremic Dehy dration diagnosis. PATIENTS AND METHOD: Descriptive observational study of hospitalized term- newborns due to hypernatremic dehydration between a period from 2014 to 2016. Term newborns over 37 weeks with clinical signs of dehydration (dry mucous membranes, depressed fontanel, tear less crying, signs of the cutaneous pleat), and/or excessive weight loss greater than 7% and serum sodium greater than 145 mEq/L were included. Sociodemographic and biochemical variables were recorded for analysis. RESULTS: 43 neonates were included. 60.5 percent of their mothers were pri- miparous, 90 percent of neonates received exclusive breastfeeding, mothers reported breastfeeding problems in 76.7 percent. Incoming neonates reported weight loss compared to birth weight at 15.3% on average. 83.3% had public health insurance. 65.1% had dehydration clinical signs at entry and 83.5% transient neurological signs. The average sodium was 155 mEq/L at revenue. The sodium decrease in the first 24 hours of handling was 7.74 mEq/L (0.32mEq/L per hour). The correction of the hypernatremia was 55.8% by oral intake and 4 days hospital stay on average. CONCLUSIONS: The feeding's problems came up in a (76%), primiparous mothers in an (88.4%). 90.6 percent of this population administered exclusive breastfeeding, results that can help to alert the health professional to timely identification, warning signs, and early post-discharge control and preventive measures.

A subgroup of lupus patients with nephritis, innate T cell activation and low vitamin D is identified by the enhancement of circulating MHC class I-related chain A.

The major histocompatibility complex (MHC) class I-related chain A (MICA) is induced upon stress, and labels malfunctioning cells for their recognition by cytotoxic lymphocytes. Alterations in this recognition and also abnormal natural killer (NK) functions have been found in systemic lupus erythematosus (SLE). MICA can be shed from cells, subsequently acting as a soluble decoy receptor (sMICA). Our purpose was to study circulating sMICA levels in relationship with the activation of innate pathways in PBMC in a cohort of lupus patients. NK cells were characterized by flow cytometry. Gene expression of Toll-like receptors (TLR), interferon (IFN)-I sensitive genes and MICA were separately analyzed in monocytes, T cells and B cells. Serum sMICA was measured with enzyme-linked immunosorbent assay (ELISA). In our cohort, NK cell counts dropped in relationship with disease activity. sMICA showed an inverse trend with NK cell counts, as well as a significant association with activity indices, but not with complement decrease. Levels of sMICA associated to proteinuria and active nephritis. A multivariate regression model revealed anti-nuclear antibody (ANA) titres, the up-regulation of TLR-4 in T cells and lower vitamin D as predictors of sMICA enhancement. Interestingly, vitamin D showed an inverse association with proteinuria and a strong correlation with T cell MICA mRNA levels. According to our data, circulating sMICA identifies a subgroup of lupus patients with low vitamin D, innate activation of T cells and nephritis. We propose that lymphocyte shedding could account for the enhancement of sMICA and reflect an immune evasion mechanism driving disease activation in lupus.

Wrinkled titanium nitride nanocomposite for robust bendable electrodes.

Electrical contacts and interconnections are critical components for all electronic devices. Bendable electrodes with enhanced electro-mechanical properties are highly desirable to develop innovative wearable electronic devices. Herein we report on a fabrication method for robust bendable coatings based on titanium nitride (TiN) thin films and silver nanowires (Ag NWs). TiN and TiN-AgNWs nanocomposites were deposited on polyethylene terephthalate (PET) substrates using a plasma enhanced pulsed laser deposition (PLD) technique. The resulting TiN coatings exhibit excellent adhesion to PET and their sheet resistance can be tuned using a dual frequency PLD process and further decreased by incorporating Ag NWs into the TiN layers. Sample sheet resistance was decreased down to values as low as [Formula: see text] corresponding to the formation of TiN-AgNWs nanocomposites. The electro-mechanical robustness of TiN based coatings were evaluated by four-probe resistance measurements in situ under cyclic bending tests. We show that the TiNAgNWs nanocomposites surpass both ITO and Ag NWs coatings in terms of mechanical robustness and electrical conductivity respectively. These nanocomposites withstand high strain fatigue loading up to ϵ = 2.6%, keeping R S below 5 Ω/□. The data demonstrates that the incorporation of Ag NWs in TiN coatings improve the mechanical robustness, limiting the crack growth and propagation, with low optical transmittance decrease (≈11%). These results indicate that Ag NWs based nanocomposites are attractive materials for flexible electronic devices.

Intraoperative Fluid Administration and Surgical Outcomes Following Pancreaticoduodenectomy: External Validation at a Tertiary Referral Center.

BACKGROUND: While intraoperative fluid overload is associated with higher complication rates following surgery, data for pancreaticoduodenectomy are scarce and heterogeneous. We evaluated multiple prior definitions of restrictive and liberal fluid regimens and analyzed whether these affected surgical outcomes at our tertiary referral center. METHODS: Studies evaluating different intraoperative fluid regimens on outcomes after pancreatic resections were retrieved. After application of all prior definitions of restrictive and liberal fluid regimens to our patient cohort, relative risks of each outcome were calculated using all reported infusion regimens. RESULTS: Five hundred and seven pancreaticoduodenectomies were included. Nine different fluid regimens were evaluated. Two regimens utilized absolute volume cutoffs, and the remaining evaluated various infusion rates, ranging from 5 to 15 mL/kg/h. Total volume administration of >5000 mL and >6000 mL was associated with increased complications (RR 1.25 and RR 1.17, respectively) and >6000 mL with increased sepsis (RR 2.14). Conversely, a rate of <5 mL/kg/h was associated with increased risk of postoperative pancreatic fistula (POPF, RR 3.16) and sepsis (RR 3.20), <6.8 mL/kg/h with increased major morbidity (RR 1.64) and sepsis (RR 2.27), and <8.2 mL/kg/h with increased POPF (RR 2.16). No effects were observed on pulmonary complications, surgical site infections, length of stay, or mortality. CONCLUSIONS: In an uncontrolled setting with no standard intraoperative or postoperative care map, the volume of intraoperative fluid administration appears to have limited impact on early postoperative outcomes following pancreaticoduodenectomy, with adverse outcomes only seen at extreme values.

Impact of severe hematological abnormalities in the outcome of hospitalized patients with influenza virus infection.

Although hematological abnormalities have been described among patients with influenza virus infection, little is known about their impact on the outcome of the patients. The aim of this study was to assess the frequency and clinical impact of severe hematological abnormalities in patients with confirmed influenza virus infection. This was an observational retrospective study including all adult patients with diagnosis of influenza virus infection hospitalized from January to May 2016 in our institution. Influenza virus infection was diagnosed by means of rRT-PCR assay performed on respiratory samples. Poor outcome was defined as a composite endpoint in which at least one of the following criteria had to be fulfilled: (a) respiratory failure, (b) SOFA ≥2, or (c) death. Two hundred thirty-nine patients were included. Applying the HLH-04 criteria for the diagnosis of hemophagocytic syndrome, cytopenias (hemoglobin ≤9 g/dl, platelets <100,000/µl or neutrophils <1,000/µl) were present in 51 patients (21%). Patients with hematological abnormalities showed higher SOFA scores, respiratory failure, septic shock and in-hospital mortality than the remaining patients. The composite endpoint was present in 33.3% in the cytopenias group vs. 13.3% in the group without cytopenias (p=0.001). In a multivariate analysis, variables associated with the composite endpoint were: use of steroids prior to present admission (OR: 0.12; 95% CI: 0.015-0.96, p=0.046), presence of any hematological abnormality (OR: 3.54; 95% CI:1.66-7.51, p= 0.001), and LDH>225 U/l (OR:4.45; CI:1-19.71, p=0.049). Hematological abnormalities are not uncommon among hospitalized patients with influenza virus infection, and they are associated with a poorer outcome.

Hydrogen storage in bimetallic Ti-Al sub-nanoclusters supported on graphene.

Recent studies suggest that graphene decorated with light metal atoms is a feasible alternative for the design of the next generation of hydrogen storage systems, that is, materials which require a gravimetric content of at least 7.5 wt%, and an adsorption energy of 0.2-0.6 eV per H2. We present a first principles study of hydrogen adsorption in titanium, and bimetallic Ti5-xAlx (x = 1-3) and Ti7-xAlx (x = 1-4) clusters supported on graphene. Our results for Ti5, Ti4Al, Ti7, and Ti6Al show that doping titanium clusters with small amounts of aluminum does not influence the cluster stability on graphene, but that notably, it enhances its hydrogen gravimetric content up to 3.2-3.6 wt%. A further increment of the aluminum concentration was found to reduce the cluster stability and to favor hydrogen desorption, as shown by our calculations for supported Ti3Al2, Ti2Al3, TiAl4 and Ti5Al2. An analysis of atomic charges and density of states reveals the role of charge transfer and orbital interactions in the stability of hydride and dihydrogen complexes in the studied systems. Our results support the hypothesis that a controlled introduction of small metal clusters to graphene is a feasible way to enhance its hydrogen gravimetric content, and it opens up the possibility of investigating other binary TMx-Ay (TM = transition metal and A = main group) clusters supported on graphene as promising candidates for hydrogen storage.

[Intravenous thrombolysis for acute ischemic stroke. A four years’ experience in a Chilean public hospital]. / Evolución del protocolo de trombolisis endovenosa en ataque cerebrovascular isquémico agudo.

BACKGROUND: Intravenous thrombolysis (IVT) with alteplase (tissue plasminogen activator) is the standard pharmacological treatment in acute ischemic stroke (AIS), reducing disability in patients. AIM: To report the results a thrombolysis protocol during four years in a regional public hospital. MATERIAL AND METHODS: Data from 106 consecutive patients aged 68 ± 13 years (57% men) who were treated with IVT, from May 2012 until April 2016, was analyzed. RESULTS: The median door-to-needle time was 80 minutes (interquartile range = 57-113). The median National Institute of Health Stroke Scale (NIHSS) scores on admission and at discharge were was 11.5 and 5 points respectively. At discharge, 27% of hospitalized patients had a favorable outcome (n = 99), defined as having 0 to 1 points in the modified Rankin scale. Symptomatic intracerebral hemorrhage and mortality rates were 5.7 and 13.1%, respectively. The thrombolysis rate rose from 0.7% in 2012 to 6% in 2016. CONCLUSIONS: The implementation of 24/7 neurology shifts in the Emergency Department allowed us to increase the amount and quality of IVT in our hospital, as measured by the rate of thrombolysis and by process indicators such as door-to-needle time.

Serous cystic neoplasm of the pancreas: a multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas).

OBJECTIVES: Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. DESIGN: Retrospective multinational study including SCN diagnosed between 1990 and 2014. RESULTS: 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16-99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2-200)), 9% had resection beyond 1 year of follow-up (3 years (1-20), size at diagnosis: 25 mm (4-140)) and 39% had no surgery (3.6 years (1-23), 25.5 mm (1-200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1). CONCLUSIONS: After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN. TRIAL REGISTRATION NUMBER: IRB 00006477.

Association of oxidative status and insulin sensitivity in periparturient dairy cattle: an observational study.

Post-parturient insulin resistance (IR) is a common feature in all mammalian animals. However, in dairy cows, it can be exacerbated because of high milk yield, leading to excessive negative energy balance, which is related with increased disease incidence, reduced milk production and worsened reproductive performance. IR has been extensively investigated in humans suffering from diabetes mellitus. In these subjects, it is known that oxidative stress (OS) plays a causative role in the onset of IR. Although OS occurs in transitional dairy cattle, there are yet no studies that investigated the association between IR and OS in dairy cattle. Therefore, the aim of this study was to investigate whether there is a relationship between OS and IR in dairy cattle. Serum samples were taken repeatedly from 22 dairy cows from 2 months prior to the expected calving date to 2 months after calving and were analysed for markers of metabolic and redox balance. Surrogate indices of insulin sensitivity were also calculated. Generalised linear mixed models revealed an effect of the oxidative status on peripheral insulin concentration and on indices of insulin sensitivity. Hence, field trials should investigate the effectiveness of antioxidant therapy on insulin sensitivity in peripheral tissues during the transition period of dairy cattle.

Effects of cytomegalovirus infection in human neural precursor cells depend on their differentiation state.

Cytomegalovirus (CMV) is the most common cause of congenital infection in developed countries and a major cause of neurological disability in children. Although CMV can affect multiple organs, the most important sequelae of intrauterine infection are related to lesions of the central nervous system. However, little is known about the pathogenesis and the cellular events responsible for neuronal damage in infants with congenital infection. Some studies have demonstrated that neural precursor cells (NPCs) show the greatest susceptibility to CMV infection in the developing brain. We sought to establish an in vitro model of CMV infection of the developing brain in order to analyze the cellular events associated with invasion by this virus. To this end, we employed two cell lines as a permanent source of NPC, avoiding the continuous use of human fetal tissue, the human SK-N-MC neuroblastoma cell line, and an immortalized cell line of human fetal neural origin, hNS-1. We also investigated the effect of the differentiation stage in relation to the susceptibility of these cell lines by comparing the neuroblastoma cell line with the multipotent cell line hNS-1. We found that the effects of the virus were more severe in the neuroblastoma cell line. Additionally, we induced hNS-1 to differentiate and evaluated the effect of CMV in these differentiated cells. Like SK-N-MC cells, hNS-1-differentiated cells were also susceptible to infection. Viability of differentiated hNS-1 cells decreased after CMV infection in contrast to undifferentiated cells. In addition, differentiated hNS-1 cells showed an extensive cytopathic effect whereas the effect was scarce in undifferentiated cells. We describe some of the effects of CMV in neural stem cells, and our observations suggest that the degree of differentiation is important in the acquisition of susceptibility.

Lipopolysaccharide-Induced Ionized Hypocalcemia and Acute Kidney Injury in Carotid Chemo/Baro-Denervated Rats.

The acute kidney injury (AKI) observed during sepsis is due to an uncontrolled release of inflammatory mediators. Septic patients develop electrolytic disturbances and one of the most important is ionized hypocalcemia. AKI adversely affects the function of other organs and hypocalcemia is associated with cardiovascular and respiratory dysfunctions. Since carotid body chemoreceptors modulate the systemic inflammatory response during sepsis syndromes, we used pentobarbitone-anesthetized male Sprague-Dawley rats in control condition (SHAM surgery) and after bilateral carotid neurotomy (carotid chemo/baro-denervated, BCN). We evaluate serum creatinine (CRE), serum neutrophil gelatinase-associated lipocaline (NGAL), ionized calcium (iCa) and cardiac Troponin I (cTnI) 90 min after the IP administration of 15 mg/kg lipopolysaccharide (LPS) or saline. In the SHAM group, LPS failed to induce significant changes CRE, NGAL, or iCa, and increased cTnI. Conversely, in the BCN group LPS increased CRE and NGAL, decreased iCa, and enhanced the increase of cTnI. Our results suggest that carotid chemo/baro-receptors might contribute to the regulation of both renal function and calcemia during sepsis. In addition, results imply that the carotid chemo-baroreceptors serve as an immunosensory organ.

A Pilot Study to Compare Oxidative Status between Organically and Conventionally Managed Dairy Cattle During the Transition Period.

The aim of this study was to assess the redox balance of organically managed dairy cattle (OMC; n = 40) during the transition period and to compare this with conventionally managed cattle (CMC; n = 22). Serum samples of dairy cows from two organic and one conventional farm were taken. Markers of oxidants production [reactive oxygen species] and total serum antioxidant capacity were measured in four different production stages: (i) far-off dry (2 to 1 months before calving; 44 samples in CMC and 48 in OMC); (ii) close-up dry (1 month until 3 days before calving; 44 CMC; 54 OMC); (iii) fresh (3 days to +1 month after calving; 44 CMC; 49 OMC); and (iv) peak of lactation (+1 to +3 months; 71 CMC; 78 OMC). Values were compared between production stages and against a metabolic baseline status (4th-5th month of pregnancy; 40 CMC; 30 OMC). Our results indicated that throughout the periparturient period, OMC had lower concentrations of reactive oxygen species, but also a lower antioxidant capacity than CMC. Indeed, when the two components of the redox balance were assessed together through the Oxidative Stress index, the values of this parameter were higher for OMC than for CMC, thereby implying a higher risk of oxidative stress. Therefore, further larger studies are needed to confirm the current observations, as organically reared animals might be exposed to a lack of antioxidants supply.

The importance of the oxidative status of dairy cattle in the periparturient period: revisiting antioxidant supplementation.

Dairy cows are especially vulnerable to health disorders during the transition period, when they shift from late pregnancy to the onset of lactation. Diseases at this stage affect not only the animals' well-being, but also cause a major economic impact in dairy farms, because apart from treatment costs, affected cows will not reach their peak milk-producing capacity. The overproduction of reactive oxygen species (ROS) leads to oxidative stress, which has been identified as an underlying factor of dysfunctional inflammatory responses. Supplementation with vitamins and trace elements attempts to minimize the harmful consequences of excessive ROS production, thereby trying to improve animals' health status and to reduce disease incidence. However, results regarding the effects of supplementing antioxidants on dairy cows' health and performance have been inconsistent, because in most cases, the antioxidant potential of the animals was not assessed beforehand and the nutritional strategy planned accordingly. Therefore, reviewing the physiological and harmful effects of ROS production, along with the different options available for assessing the redox balance in dairy cattle and some of the key findings of different supplementation trials, could bring one step forward the on-farm application of determinations of oxidative status for establishing nutritional strategies early enough in the dry period that could improve transition cow health.