Chronic ethanol induces a pro-inflammatory switch in interleukin-1ß regulation of GABAergic signaling in the medial prefrontal cortex of male mice.

Neuroimmune pathways regulate brain function to influence complex behavior and play a role in several neuropsychiatric diseases, including alcohol use disorder (AUD). In particular, the interleukin-1 (IL-1) system has emerged as a key regulator of the brain's response to ethanol (alcohol). Here we investigated the mechanisms underlying ethanol-induced neuroadaptation of IL-1ß signaling at GABAergic synapses in the prelimbic region of the medial prefrontal cortex (mPFC), an area responsible for integrating contextual information to mediate conflicting motivational drives. We exposed C57BL/6J male mice to the chronic intermittent ethanol vapor-2 bottle choice paradigm (CIE-2BC) to induce ethanol dependence, and conducted ex vivo electrophysiology and molecular analyses. We found that the IL-1 system regulates basal mPFC function through its actions at inhibitory synapses on prelimbic layer 2/3 pyramidal neurons. IL-1ß can selectively recruit either neuroprotective (PI3K/Akt) or pro-inflammatory (MyD88/p38 MAPK) mechanisms to produce opposing synaptic effects. In ethanol naïve conditions, there was a strong PI3K/Akt bias leading to a disinhibition of pyramidal neurons. Ethanol dependence produced opposite IL-1 effects - enhanced local inhibition via a switch in IL-1ß signaling to the canonical pro-inflammatory MyD88 pathway. Ethanol dependence also increased cellular IL-1ß in the mPFC, while decreasing expression of downstream effectors (Akt, p38 MAPK). Thus, IL-1ß may represent a key neural substrate in ethanol-induced cortical dysfunction. As the IL-1 receptor antagonist (kineret) is already FDA-approved for other diseases, this work underscores the high therapeutic potential of IL-1 signaling/neuroimmune-based treatments for AUD.

Robotic excision and ureteroureterostomy of blind-ending ureteral 'Duplication'.

INTRODUCTION: Duplicated ureteral anatomy can be a reconstructive challenge. Blind-ending ureteral duplication has been reported with recommendations for surgical excision. OBJECTIVE: This video reviews the importance of exposure of anatomic landmarks in surgical excision of a blind-ending ureteral duplication. MATERIALS AND METHODS: This is a retrospective case report of a patient who presented with a blind-ending ureteral duplication. DISCUSSION: A 13-year-old female presented with a right-sided abdominal mass. Abdominal and pelvic imaging revealed a tubular structure adjacent to and below the right kidney, possibly connecting to the right lower pole. While initially observed, the patient re-presented with urosepsis. A retrograde pyelogram showed no connection between the right ureter and this structure. The patient underwent robotic-assisted excision of this structure. Intra-operatively, it was connected to the right lower pole calyces. A ureteroureterostomy to the orthotopic ureter was performed. Although the structure was adjacent to the bladder dome, there was no communication distally. Postoperatively, the patient did well; follow-up imaging showed a non-dilated lower pole. The pathology of this structure was benign urothelium. CONCLUSIONS: Surgical management of aberrant ureteral duplications should focus on identifying known landmarks and should be considered to prevent symptomatic infections and renal scarring.

Implementation of the accelerated care of torsion pathway: a quality improvement initiative for testicular torsion.

BACKGROUND: Timely diagnosis and management of testicular torsion is of paramount importance. Furthermore, time to surgical intervention is a benchmark for the quality of care provided by pediatric urologists included in US News and World Report (USNWR) methodology. OBJECTIVE: We sought to optimize management of acute testicular torsion at a single institution by decreasing time from presentation to definitive management through the creation and implementation of a clinical care pathway (accelerated care of torsion or ACT) for acute testicular torsion in a 2-year period. STUDY DESIGN: Multidisciplinary process mapping involving the emergency department (ED), radiology, anesthesiology, peri-operative services, and operating room (OR) teams resulted in development of the ACT pathway with the goal of achieving surgical intervention within 4 h of arrival at our institution. The accelerated care of torsion pathway was implemented in April 2016. Thirty-eight consecutive acute torsion cases were then prospectively evaluated from April 2016 to April 2018. For process measures, we recorded triage to OR times and mode of presentation. For outcome measures, we examined orchiectomy rates. We retrospectively reviewed 97 cases of acute torsion from 2004 to 2016 as a control. RESULTS: Time from ED triage to OR start decreased from a median 196 min (interquartile range [IQR] 137-249 min) to 127 min (IQR 100-148 min; P < 0.0001) for all cases of acute torsion. In the control group, 72% of cases met the USNWR criteria for acute treatment of torsion. After ACT implementation, 100% of cases reached the OR within the 240 min time frame. Orchiectomy rates were performed in 24% of control cases vs 30% after ACT implementation (P = NS). Survival curve analysis demonstrated no significant difference in probability of testis salvage before or after implementation of the ACT pathway. DISCUSSION: In agreement with similar studies, despite a significant reduction in triage to OR times, the orchiectomy rate approached 30%. This outcome did not significantly improve after implementation of the ACT pathway. Overall ischemia time was a more important determinant of testis salvage. Study limitations include limited patient follow-up to assess testis atrophy. CONCLUSIONS: The multidisciplinary creation and implementation of a clinical pathway for the care of acute testis torsion has significantly decreased the time from ED to OR in our institution. However, overall orchiectomy rate was not significantly affected.

Reoperative robotic pyeloplasty in children.

INTRODUCTION: Reoperative pyeloplasty for recurrent ureteropelvic junction obstruction (UPJO) can be technically challenging and is associated with greater morbidity and lower success rates than an initial repair. Robotic-assisted laparoscopic pyeloplasty (RALP) previously has been demonstrated to be a safe and effective approach for management of recurrent UPJO; however, the length of follow-up has been limited. The objective of this study was to confirm the safety and efficacy of RALP for UPJO in children following failed previous pyeloplasty and provide clinical benchmarks for intermediate length follow-up in this patient population. METHODS: An IRB approved retrospective chart review was performed for all patients undergoing reoperative RALP from June 2006 to December 2014. All cases were performed by surgeons from two institutions for persistent UPJO following failed initial pyeloplasty. Information including demographic information, radiographic studies, and operative interventions performed between the initial repair and reoperative surgery, reoperative RALP intraoperative data, postoperative clinical course and imaging studies, and subsequent interventions following reoperative RALP were extracted. RESULTS: Twenty-three children underwent reoperative RALP. Eleven patients had right- and 12 left-sided repairs. Median age at reoperative RALP was 4.0 years and median interval between surgeries was 1.3 years. Indications for repeat repair included pain, infection, and/or radiographic evidence of worsening obstruction and/or deteriorating renal function. Mean operative time was 198 min from incision to port closure. Mean length of stay was 2.3 days. Six complications occurred in five patients within 30 days postoperatively, including ileus, pneumonia, and urinary tract infection. Median length of follow-up was 26 months (range 4-45 months) for all patients and 31 months (range 16-45 months) in 18 patients with >12 months of follow-up. More than 80% of patients presenting with flank pain prior to reoperative RALP had resolution of this symptom. To date, 78% of patients with >12 months of follow-up have not required further operative intervention. Excellent results have been achieved in 14 of 18 patients (78%) with sufficient postoperative follow-up in terms of length of follow-up (>12 months), symptom resolution, and/or improved imaging results. CONCLUSIONS: RALP following previous pyeloplasty is technically feasible with acceptable operative times, lengths of stay, and complication rates. Reoperative RALP is our preferred modality for repair of recurrent UPJO with the vast majority of patients having successful outcomes based on imaging, resolution of symptoms, and the rare need for further intervention across an intermediate length follow-up period.

Alternaria alternata Causing Flower Stem Blight of Lupinus havardii.

Lupinus havardii Wats., commonly known as Big Bend or Chisos bluebonnet, is a showy winter annual that can reach 1.0 to 1.5 m in height and produces blue, fragrant inflorescence (racemes). L. havardii is native to a narrow geographic range along the Mexican border in southwest Texas. The inflorescence of L. havardii has considerable potential in the cut flower industry where there is a need for high-quality, durable flowers with a blue color (1). Several crops have been produced in the greenhouse to determine production and post-harvest characteristics of the cut inflorescence. Under greenhouse growing conditions during March through June 1999, numerous plants of L. havardii cv. Texas Sapphire grown in raised beds and in containers in both Dallas and El Paso, TX, were observed with blighted flower racemes with light brown to gray lesions ranging from 1 to 5 cm in length. The racemes were attacked at varying ages and eventually assumed a hooked appearance where the terminal 15 cm of the raceme was bent downward. Isolations from symptomatic lesions removed from L. havardii flower stalks consistently yielded cultures of an Alternaria sp. on potato-dextrose agar. Typical conidia measured 27 µm length and 11 µm width with 3 to 5 transverse septa. The fungus was identified as A. alternata (Fries) Keissler consistent with the description in Ellis (2). Pathogenicity tests were conducted in the laboratory by inoculating cut inflorescences with agar disks containing the fungus. Inoculations produced light brown lesions on the racemes that were typical of disease symptoms observed on greenhouse crops. In addition to the blue-flowered Texas Sapphire cultivar, we also observed the disease symptoms on pink and white flowered breeding lines of L. havardii. This disease is important as a flower stem blighting pathogen and could severely restrict production of cut flowers during the growing season. This is the first report of Alternaria sp. attacking L. havardii. References: (1) T. D. Davis. HortScience 29:1110, 1994. (2) M. B. Ellis. 1971. Dematiaceous Hyphomycetes. Commonwealth Mycological Institute Kew, England.

Diurnal and seasonal patterns of net photosynthesis by irrigated Chrysothamnus nauseosus under field conditions.

Chrysothamnus nauseosus ssp. albicaulis (white rubber rabbitbrush) is a common deciduous C3 desert shrub which is a potential source of natural rubber and which exhibits high rates of net photosynthesis (Pn) for a woody species. When maintained under irrigated conditions in the field, rates of Pn on cloudless days were generally found to be highest during the cool morning hours (peak rates observed between about 0900 and 1000 hrs). Pn declined during mid-day hours and was approximately 75% of that observed in the early morning for the remainder of the light period. This decline in Pn was accompanied by about 26 µmol CO2.m(-2).s(-1) in mid-May (approximately 30 days after bud break) to about 48 µmol CO2.m(-2).s(-1) in early August. Thereafter, Pn declined gradually until leaf fall in November. These data indicate that rabbitbrush is capable of relatively high rates of Pn throughout a substantial portion of the growing season when maintained under irrigated conditions. This may, at least in part, account for the relatively high rates of growth observed under conditions of ample soil moisture.

In vitro production of flowering shoots in 'German Red' carnation: effect of uniconazole and gibberellic acid.

Callus regenerated near the base of senescing petals of flower bud explants of 'German Red' carnation (Dianthus caryophyllus L.) produced adventitious flowering microshoots on MS-medium containing benzylaminopurine (8.9 µM) and naphthaleneacetic acid (2.7 µM). When these microshoots were subcultured with some callus, additional adventitious flowering microshoots were produced from the callus. The production of adventitious flowering shoots continued for many subcultures spanning a period of more than two years. Uniconazole (6.9 µM) increased the number of adventitious shoots formed by as much as two-fold but decreased shoot length by about 50%. In contrast, GA3 (2.9 µM) decreased adventitious shoot formation and increased shoot length. Regardless of the growth regulator treatment, virtually all of the adventitious shoots produced flower buds. Thus, the growth regulators influenced flowering only indirectly by altering the number of adventitious shoots produced in vitro. These results demonstrate that the flowering habit of the adventitious shoots of 'German Red' carnation is highly persistent and the flowering stimulus continues to be transmitted to the newly formed microshoots through the callus.

Effect of gibberellin biosynthesis inhibitors on shoot regeneration from hypocotyl explants of Albizzia julibrissin.

Hypocotyl explants of Albizzia julibrissin were placed on Gamborg's B5 medium supplemented with various levels of paclobutrazol, uniconazole, prohexadione calcium, or GA3. Callus formation was evident within one week after placement of the explants on the culture media. Green nodule-like structures protruded from the distal end of the explants within 10 days and developed into shoots within a month. These shoots readily formed adventitious roots when placed on fresh culture medium. All three of the gibberellin biosynthesis inhibitors increased shoot formation compared to the control. The number of shoots per explants was increased 107, 79, and 168% by 0.3-0.4 µM paclobutrazol, uniconazole, and prohexadione calcium, respectively. In contrast to the gibberellin biosynthesis inhibitors, GA3 decreased shoot formation. These results indicate that modification of gibberellin status can have a strong impact on the number of shoots formed.

Promotion ofin vitro shoot formation from excised roots of silktree (Albizzia julibrissin) by an oxime ether derivative and other ethylene inhibitors.

This report describes the regeneration response of excised seedling roots of silktree (Albizzia julibrissin) to added ethylene precursors/generators (1-amino-cyclopropane-1-carboxylic acid [ACC], 2-chloroethylphosphonic acid [CEPA]), biosynthesis inhibitors (aminoethoxyvinylglycine [AVG], an oxime ether derivative [OED={[(ispropylidene)-amino]oxy}-acetic acid-2-(methoxy)-2-oxoethyl ester], CoCl(2) [Co(++)]), and an ethylene action inhibitor (AgNO3 [Ag(+)]). When placed on B5 medium, about 50% of the control explants formed shoot buds within 15 days. Addition of ACC or CEPA (1-10 µM) to the culture medium decreased both the percentage of cultures forming shoots and the number of shoots formed per culture. In contrast, AVG and OED (1-10 µM) increased shoot formation to almost 100% and increased the number of shoots formed per culture. Likewise, both Co(++) and Ag(+) (1-10 µM) increased shoot regeneration, but the number of shoots produced after 30 days was less than with AVG or OED. The inhibitors of ethylene biosynthesis were partially effective in counteracting the inhibitory effect of ACC on shoot formation. These results suggest that modulation of ethylene biosynthesis and/or action can strongly influence the formation of adventitious shoots from excised roots of silktree.

Influence of 2-(3,4 dichlorophenoxy)-triethylamine on photosynthesis of Phaseolus vulgaris L.

The effect of foliar sprays of the growth regulator 2-(3,4 dichlorophenoxy)-triethylamine (DCPTA) on net photosynthesis (Pn) by intact bean plants depended upon concentration and the stage of development of the leaves. A single foliar spray of 2.0 mM DCPTA reduced Pn when applied to young expanding leaves but had little effect on fully expanded leaves. Lower DCPTA concentrations (0.2 to 0.8 mM) had no effect on Pn, unless applied more than once which resulted in reduced Pn. The DCPTA-induced inhibition of Pn was associated with chlorosis and aberrations in chloroplast ultrastructure. DCPTA did not affect stomatal resistance. When applied to detached leaf disks in the dark, DCPTA retarded the normal loss of chlorophyll suggesting that DCPTA may have anti-seneseent properties.

Infective endocarditis due to Neisseria sicca and associated with intravenous drug abuse.

Intravenous drug abusers are subject to infective endocarditis from unusual pathogens, including the saprophytic species of Neisseria, sometimes transmitted by needles contaminated with oral secretions. We have recently encountered such a case, in which a 37-year-old man with vegetations on the anterior leaflet of the tricuspid valve had blood cultures positive for N sicca. A history of intravenous drug abuse using needles contaminated with oral secretions should alert clinicians to the possibility of infective endocarditis due to saprophytic Neisseria species.

Influence of growth regulators on somatic embryogenesis, plantlet regeneration, and post-transplant survival of Echinochloa frumentacea.

After placement on Murashige and Skoog's basal medium supplemented with 3-5 mg/l 2,4-D, immature inflorescence expiants of Echinochloa frumentacea gave rise to three distinct types of callus: a) loosely arranged and soft; b) compact and translucent; c) compact, sticky and mucilaginous. Somatic embryo formation occurred in type 'b' callus in about 18-24 d. Callus types 'a' and 'c' did not produce somatic embryos. The highest percentage of cultures exhibiting somatic embryogenesis occurred on the medium containing 5 mg/l 2,4-D and 0.5 mg/l kinetin. Somatic embryos also formed directly on the inflorescence (without intervening callus formation) in about 15% of the expiants placed on this medium. The addition of paclobutrazol or uniconazole (0.25 or 1 mg/l) to the medium had no influence on the percentage of cultures exhibiting direct somatic embryogenesis, but paclobutrazol slightly increased the mean number of somatic embryos per culture. Many of the callus-derived somatic embryos germinated when subcultured on basal MS medium supplemented with kinetin. Addition of paclobutrazol or uniconazole to the culture medium at 0.25 or 1 mg/l decreased somatic embryo germination and shoot elongation but increased root length and leaf width. Both paclobutrazol and uniconazole increased survival of the plantlets following transplanting to soil. Increased post-transplant survival was accompanied by reduced water loss from plantlets produced on culture media containing triazoles.

Cost comparison of searching the Iowa Drug Information Service index manually and by computer.

A cost comparison of searching the Iowa Drug Information Service index manually and by computer is presented. Identical searches were performed on a computer system and by hand. The searches were timed and the results compared. Costs of start-up, maintenance, and operation were calculated for the manual and computer systems. Both systems yielded a similar number of relevant references. Start-up and maintenance costs were found more expensive for the computer system, but operational costs were less expensive (p less than 0.05). Operational costs varied according to the number of uses per year. Operational costs were found to increase faster for the manual system than the computer system. At 980 uses per year, the overall cost of the computer system was less than the manual system. A dedicated microcomputer system to search the Iowa Drug Information Service index was found less costly than, and as effective as, the common manual system.

Accelerated fluid bed drying using NIR monitoring and phenomenological modeling.

A "fast-drying" method to accelerate the fluid bed drying process is presented. It relies on concepts of heat and mass transfer with real-time near-infrared (NIR) monitoring of moisture. Triplicate trials show that fast drying can reduce granulation drying time by half over single-temperature cycles. The product is equivalent in every way tested to material made using a conventional cycle even though the inlet temperature throughout the constant-rate stage was higher than the melting point of the compound. Tablets made from the fast-dried granulation exhibit equivalent physical characteristics to tablets made from granulations dried at a single, lower temperature.

Adverse drug reaction reporting in a multicenter surveillance study.

OBJECTIVE: To evaluate the performance of a multicenter, prospective surveillance program in identifying adverse events, and to seek explanations for misclassification bias. DESIGN: The design was a prospective observational study of patients with documented or suspected bacterial pneumonia. SETTING: Data were collected in 74 acute care hospitals across the US. PATIENTS: This evaluation was based on a consecutive sample of 1822 adult patients (> 18 years of age) with documented or suspected bacterial pneumonia who were being treated with a cephalosporin, a penicillin, or an aminoglycoside over a 3-month period. Patients were followed for the duration of antibiotic therapy and were excluded if antibiotic therapy was < 3 days or if the pneumonia was judged to be nonbacterial. INTERVENTIONS: Clinical pharmacists documented patient demographics, concurrent illnesses and medications, antibiotic administration, relevant laboratory data, and the occurrence of nephrotoxicity and neutropenia. MAIN OUTCOME MEASURES: Validity of investigators' identification of neutropenia and nephrotoxicity as compared with objective laboratory data was assessed by using sensitivity, specificity, and positive and negative predictive value measures. RESULTS: Among the 1502 patients with sufficient data to evaluate neutropenia, there was agreement in 1270 patients (84.6%); likewise, among 1291 patients with sufficient data to evaluate nephrotoxicity there was agreement in 1186 patients (91.9%). Sensitivity of the researchers' assessments was 50.9% and 71.0% for neutropenia and nephrotoxicity, respectively. The negative predictive value was > 95% for both events. CONCLUSIONS: Overall, this evaluation demonstrated that the Drug Surveillance Network can successfully identify targeted adverse events. Moreover, this study highlights the importance of validation for all types of outcomes-oriented research studies.

Constitutive expression of functional GABA(B) receptors in mIL-tsA58 cells requires both GABA(B(1)) and GABA(B(2)) genes.

Studies of gamma-aminobutyric acid (GABA)(B) receptor function in heterologous cell systems have suggested that expression of two distinct seven transmembrane G-protein coupled receptor subunits is necessary for receptor activation and signal transduction. Some results suggest that both receptor proteins must be inserted into the plasma membrane to create heterodimers; however, it is possible that subunit monomers or homodimers are functional in cells which constitutively express GABA(B) receptors. A new pituitary intermediate lobe melanotrope cell clone (mIL tsA58) has been isolated which constitutively expresses GABA(B), D(2) and corticotrophin releasing factor receptors. Here, we report on characterization of the GABA(B) receptors. Solution hybridization-nuclease protection assays reveal the presence of GABA(B(1)) and GABA(B(2)) transcripts. Western blots show GABA(B(1a)) and one of two GABA(B(2)) proteins. Addition of the GABA(B) agonist baclofen to cultured mIL-tsA58 (mIL) cells inhibits high voltage activated Ca(2+) channels, as measured by agonist-induced inhibition of the K(+)-depolarization-stimulated increase in Ca(2+) influx. CGP55845, a GABA(B) antagonist, blocks the response to baclofen. Knockdown of either GABA(B(1)) or GABA(B(2)) subunits with selective antisense oligodeoxynucleotides reduced GABA(B) protein levels and completely abolished the GABA(B) receptor response in the mIL cells. Taken together, these results indicate that functionally active GABA(B) receptors in mIL cells require the constitutive expression of both GABA(B) genes. This is a physiologic validation of results from recombinant overexpression in naive cells and shows that the mIL cell line is a useful model for studying GABA(B) receptor expression, regulation and function.