Multi-drug Resistant and Extended Spectrum ß-lactamase Producing Salmonella Species Isolated from Fresh Chicken Liver Samples.

Background Ductus arteriosus is a vascular structure which connects the roof of main pulmonary artery near the origin of the left branch pulmonary artery to the proximal descending aorta. Patent ductus arteriosus (PDA) closure is indicated for any patient who is symptomatic from left to right shunting. Objective To investigate the hospital outcomes of surgical closure of patent ductus arteriosus over last 19 years starting from the very first case of our center. Method This is a retrospective analysis of all patent ductus arteriosus treated surgically from August 2001 to July 2019. Patients who underwent isolated surgical closure of patent ductus arteriosus were included. Data have been presented in three different eras (Era 1: 2001-2007, Era 2: 2008-2013, and Era 3: 2014-2019) to see the trend of evolution of this surgery. Result A total of 901 patients aged 8.67±8.76 years under went patent ductus arteriosus surgical closure over last 19 years. Patients in the initial era 2001-2007 were significantly older compared with other 2 eras (p=0.000). Males accounted for 35.5% of all cases. Twenty percent had severe pulmonary artery hypertension.Duration of mechanical ventilation was 3.57±9.64 hours with ICU stay of 1.55±1.53 days, and hospital stay of 3.9±2.3 days. Overall in hospital mortality was 0.8%; for isolated patent ductus arteriosus diagnosis, mortality was 0.2%. Chylothorax was noted in 0.4%. Conclusion This is the first report to analyze surgical outcomes of patent ductus arteriosus ligation in our center. We have discussed the evolution of patent ductus arteriosus surgery in our center, and have shown favorable outcomes in terms of morbidity and mortality.

Central melanocortin stimulation increases phosphorylated perilipin A and hormone-sensitive lipase in adipose tissues.

Norepinephrine (NE) released from the sympathetic nerves innervating white adipose tissue (WAT) is the principal initiator of lipolysis in mammals. Central WAT sympathetic outflow neurons express melanocortin 4-receptor (MC4-R) mRNA. Single central injection of melanotan II (MTII; MC3/4-R agonist) nonuniformly increases WAT NE turnover (NETO), increases interscapular brown adipose tissue (IBAT) NETO, and increases the circulating lipolytic products glycerol and free fatty acid. The WAT pads that contributed to this lipolysis were inferred from the increases in NETO. Because phosphorylation of perilipin A (p-perilipin A) and hormone-sensitive lipase are necessary for NE-triggered lipolysis, we tested whether MTII would increase these intracellular markers of lipolysis. Male Siberian hamsters received a single 3rd ventricular injection of MTII or saline. Trunk blood was collected at 0.5, 1.0, and 2.0 h postinjection from excised inguinal, retroperitoneal, and epididymal WAT (IWAT, RWAT, and EWAT, respectively) and IBAT pads. MTII increased circulating glycerol concentrations at 0.5 and 1.0 h, whereas free fatty acid concentrations were increased at 1.0 and 2.0 h. Western blot analysis showed that MTII specifically increased p-perilipin A and hormone-sensitive lipase only in fat pads that previously had MTII-induced increases in NETO. Phosphorylation increased in IWAT at all time points and IBAT at 0.5 h, but not RWAT or EWAT at any time point. These results show for the first time in rodents that p-perilipin A can serve as an in vivo, fat pad-specific indictor of lipolysis and extend our previous findings showing that central melanocortin stimulation increases WAT lipolysis.

CD19-positive antibody-secreting cells provide immune memory.

Long-lived antibody-secreting cells (ASCs) are critical for the maintenance of humoral immunity through the continued production of antibodies specific for previously encountered pathogen or vaccine antigens. Recent reports describing humoral immune memory have suggested the importance of long-lived CD19- bone marrow (BM) ASCs, which secrete antibodies recognizing previously encountered vaccine antigens. However, these reports do not agree upon the unique contribution of the CD19+ BM ASC subset toward humoral immunity. Here, we found both CD19+ and negative ASCs from human BM were similar in functional capacity to react to a number of vaccine antigens via ELISpot assays. The CD19+ cells were the predominant ASC population found in lymphoid tissues, and unlike the CD19- ASCs, which were found only in spleen and BM, the CD19+ ASCs were found in tonsil and blood. CD19+ ASCs from the BM, spleen, and tonsil were capable of recognizing polio vaccine antigens, indicating the CD19+ ASC cells play a novel role in long-lasting immune defense. Comparative gene expression analysis indicated CD19+ and negative BM ASCs differed significantly by only 14 distinct messenger RNAs and exhibited similar gene expression for cell cycle, autophagy, and apoptosis control necessary for long life. In addition, we show identical CDR-H3 sequences found on both BM ASC subsets, indicating a shared developmental path. Together, these results provide novel insight for the distribution, function, genetic regulation, and development of long-lived ASCs and may not only impact improved cell therapies but also enhance strategies for vaccine development.

The diffusing capacity in adult cystic fibrosis.

The value of adjusting the diffusing capacity for the lung volume has been demonstrated in a large number of patients with other lung diseases but has not been validated in patients with cystic fibrosis (CF). Pulmonary function test results on a cohort of 52 adult CF patients were analyzed to determine whether the diffusing capacity of carbon monoxide by single breath method (DLCO(SB)) when adjusted for alveolar volume (V(A)%), correlated with the severity of pulmonary dysfunction. The DLCO(SB) remained within the reference range except in those with severe lung impairment (61.88 +/- 15.48%). DLCO(SB) has a significant (P < 0.05) positive correlation (0.70, 0.67, 048, 0.69 and 0.31, respectively) with measures of airflow limitation (FVC%, FEV1%, FEV1/FVC%, MVV%, and sGaw) and negative correlation (-0.36 and -0.21, respectively) with measures of air trapping (RV% and RV/TLC%). DLCO(SB)/V(A) remained above 100% of predicted despite worsening lung disease and did not correlate with other measures of lung function. On the other hand, the DLCO(SB) and DLCO(SB)/V(A), when adjusted for V(A)%, decreased and were significantly correlated with worsening airflow limitation and, to a lesser extent, air trapping. The relatively preserved adjusted DLCO(SB) and DLCO(SB)/V(A) values in CF patients up until late in its course may be explained the predominant airway involvement, minimal loss of alveolar-capillary units, and enhanced V/Q relationship due to claustration in CF.

PAK1 is a breast cancer oncogene that coordinately activates MAPK and MET signaling.

Activating mutations in the RAS family or BRAF frequently occur in many types of human cancers but are rarely detected in breast tumors. However, activation of the RAS-RAF-MEK-ERK MAPK pathway is commonly observed in human breast cancers, suggesting that other genetic alterations lead to activation of this signaling pathway. To identify breast cancer oncogenes that activate the MAPK pathway, we screened a library of human kinases for their ability to induce anchorage-independent growth in a derivative of immortalized human mammary epithelial cells (HMLE). We identified p21-activated kinase 1 (PAK1) as a kinase that permitted HMLE cells to form anchorage-independent colonies. PAK1 is amplified in several human cancer types, including 30--33% of breast tumor samples and cancer cell lines. The kinase activity of PAK1 is necessary for PAK1-induced transformation. Moreover, we show that PAK1 simultaneously activates MAPK and MET signaling; the latter via inhibition of merlin. Disruption of these activities inhibits PAK1-driven anchorage-independent growth. These observations establish PAK1 amplification as an alternative mechanism for MAPK activation in human breast cancer and credential PAK1 as a breast cancer oncogene that coordinately regulates multiple signaling pathways, the cooperation of which leads to malignant transformation.

Characterization of a novel melanocortin receptor-containing node in the SNS outflow circuitry to brown adipose tissue involved in thermogenesis.

The melanocortins (MC) can affect interscapular brown adipose tissue (IBAT) thermogenesis via its sympathetic nervous system (SNS) innervation. We chose a site of high MC4-receptor (MC4-R) mRNA co-localization with SNS outflow neurons to IBAT, the subzona incerta (subZI) to test whether IBAT thermogenesis could be increased or decreased. We first performed immunohistochemical characterization of the subZI and found neurons and/or fibers in this area positive for melanin concentrating hormone, oxytocin, arginine vasopressin, agouti-related protein and alpha-melanocyte stimulating hormone. Functional characterization of the subZI was tested via site-specific microinjections. The MC3/4-R agonist, melanotan II [MTII (0.025, 0.05 and 0.075nmol)], and specific MC4-R agonist (cyclo [ß-Ala-His-D-Phe-Arg-Trp-Glu]-NH2; 0.024nmol) both significantly increased IBAT temperature (T(IBAT)) and pretreatment with the MC4R antagonist, HS024 (0.072nmol) blocked the MC4-R agonist-induced increased T(IBAT) in conscious, freely-moving Siberian hamsters. Injection of the MC4-R antagonist alone significantly decreased T(IBAT) up to 3h post injection. Collectively, these results highlight the identification of a brain area that possesses high concentrations of MC4-R mRNA and SNS outflow neurons to IBAT that has not been previously reported to be involved in the control of T(IBAT). These results add to previously identified neural nodes that are components of the central circuits controlling thermogenesis.

Sensory and sympathetic nervous system control of white adipose tissue lipolysis.

Circulating factors are typically invoked to explain bidirectional communication between the CNS and white adipose tissue (WAT). Thus, initiation of lipolysis has been relegated primarily to adrenal medullary secreted catecholamines and the inhibition of lipolysis primarily to pancreatic insulin, whereas signals of body fat levels to the brain have been ascribed to adipokines such as leptin. By contrast, evidence is given for bidirectional communication between brain and WAT occurring via the sympathetic nervous system (SNS) and sensory innervation of this tissue. Using retrograde transneuronal viral tract tracers, the SNS outflow from brain to WAT has been defined. Functionally, sympathetic denervation of WAT blocks lipolysis to a variety of lipolytic stimuli. Using anterograde transneuronal viral tract tracers, the sensory input from WAT to brain has been defined. Functionally, these WAT sensory nerves respond electrophysiologically to increases in WAT SNS drive suggesting a possible neural negative feedback loop to regulate lipolysis.