Trends of changes in the specific contribution of selected risk factors for shoulder dystocia over a period of more than two decades.

Objectives Shoulder dystocia (SD) is an obstetrical emergency with well-recognized risk factors. We aimed to identify trends of changes in the specific contribution of risk factors for SD over time. Methods A nested case control study comparing all singleton deliveries with and without SD was undertaken. A multivariable logistic regression model was used in order to identify independent risk factors for SD and a comparison of the prevalence and the specific contribution (odds ratio (OR)) of the chosen risk factors in three consecutive eight-year intervals from 1988 to 2014 was performed. Results During the study period, there were 295,946 deliveries. Of them 514 (0.174%) were complicated with SD. Between 1988 and 2014 the incidence of SD has decreased from 0.3% in 1988 to 0.1% in 2014. Using a logistic regression model grandmultiparity, diabetes mellitus (DM), fetal weight, and large for gestational age (LGA) were found to be independent risk factors for SD (OR 1.25 95% CI 1.04-1.51, p=0.02; OR 1.53 95% CI 1.19-1.97, p=0.001; OR 1.002 95% CI 1.001-1.002, p < 0.001; OR 3.88 95% CI 3.09-4.87, p < 0.001; respectively). While the OR for grandmultiparity, fetal weight, and LGA has significantly changed during the study period with a mixed trend, the OR of DM has demonstrated a significant linear increase over time. Conclusions The individual contribution of selected risk factors for the occurrence of SD has significantly changed throughout the years. The contribution of DM has demonstrated a linear increase over time, emphasizing the great impact of DM on SD.

Retrograde renal cooling to minimize ischemia.

OBJECTIVE: During partial nephrectomy, renal hypothermia has been shown to decrease ischemia induced renal damage which occurs from renal hilar clamping. In this study we investigate the infusion rate required to safely cool the entire renal unit in a porcine model using retrograde irrigation of iced saline via dual-lumen ureteral catheter. MATERIALS AND METHODS: Renal cortical, renal medullary, bowel and rectal temperatures during retrograde cooling in a laparoscopic porcine model were monitored in six renal units. Iced normal saline was infused at 300 cc/hour, 600 cc/hour, 1000 cc/hour and gravity (800 cc/hour) for 600 seconds with and without hilar clamping. RESULTS: Retrograde cooling with hilar clamping provided rapid medullary renal cooling and significant hypothermia of the medulla and cortex at infusion rates ≥ 600 cc/hour. With hilar clamping, cortical temperatures decreased at -0.90 C/min. reaching a threshold temperature of 26.90 C, and medullary temperatures decreased at -0.90 C/min. reaching a temperature of 26.10 C over 600 seconds on average for combined data at infusion rates = 600 cc/hour. The lowest renal temperatures were achieved with gravity infusion. Without renal hilum clamping, retrograde cooling was minimal at all infusion rates. CONCLUSIONS: Significant renal cooling by gravity infusion of iced cold saline via a duel lumen catheter with a clamped renal hilum was achieved in a porcine model. Continuous retrograde irrigation with iced saline via a two way ureteral catheter may be an effective method to induce renal hypothermia in patients undergoing robotic assisted and/or laparoscopic partial nephrectomy.

The anticonvulsant levetiracetam potentiates alcohol consumption in non-treatment seeking alcohol abusers.

BACKGROUND: Levetiracetam (Keppra) is a commonly prescribed anticonvulsant that has been shown to attenuate alcohol consumption in an open-label study of treatment-seeking, alcohol-dependent subjects. METHODS: Here we performed a 42-day placebo-controlled, double-blind, randomized crossover trial to evaluate the effects of levetiracetam on moderate to heavy drinkers receiving either a low (500-1000 g/d) or a moderate (1000-2000 g/d) dose. Electronic diaries were used to monitor daily ethanol intake. RESULTS: Across the entire group, there was no effect of levetiracetam on drinking irrespective of dose, treatment order, family history, ethnicity, sex, or adverse effects. However, a median split of the data based on the number of drinks consumed while taking placebo revealed that levetiracetam significantly increased drinking in the lower drinking subjects (n = 23, P = 0.05, t = 2.07) while having no effect on drinking in the higher half (n = 23, P = 0.75, t = 0.32). Preliminary stratification based on common polymorphisms associated with alcoholism and impulsivity indicated that subjects with alcoholism-associated alleles may drink even more while taking levetiracetam. CONCLUSIONS: Our data suggest that levetiracetam is not an appropriate treatment for non-treatment seeking alcohol abusers and can, in fact, increase their consumption of alcohol.

Serotonergic modulation of appetitive and ingestive behavior in crayfish.

Serotonin is an important modulator of feeding behavior across animal species. In invertebrates, much is known about the regulation of feeding in several model organisms, but comparative data are limited. We examined the modulation of feeding behavior in crayfish by administering serotonin and two serotonin receptor ligands, mianserin and 5-carboxamidotryptamine. We found that, compared to control injections, exogenous serotonin significantly reduced appetitive behaviors in response to a chemical food stimulant and reduced consumption when food was present. The two ligands also significantly reduced the amount of food consumed. However, they had no significant effects on appetitive feeding movements, suggesting that appetitive and consummatory feeding phases may be regulated by different serotonergic mechanisms. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Memantine Usage for Management of Korsakoff Syndrome in the Setting of Chronic Alcohol Use and Unspecified Eating Disorder.

Korsakoff syndrome is a neuropsychiatric condition frequently seen as a progression of Wernicke's encephalopathy and is often associated with long-term alcohol abuse. It is characterized by further cognitive impairments, such as indiscriminate anterograde and retrograde amnesia, in addition to executive function deficits. As the syndrome is a result of severe thiamine deficiency, its management primarily focuses on nutritional replenishment and electrolyte maintenance. In recent years, a few published reports have detailed the off-label use of Food and Drug Administration (FDA) approved drugs for Alzheimer's in an attempt to treat neurocognitive deficits associated with Korsakoff patients. In this particular case, we note subjective improvement in cognition after initiating memantine, an N-Methyl-d-aspartate (NMDA) receptor antagonist.

Anxiogenic-like effects of chronic nicotine exposure in zebrafish.

Nicotine is one of the most widely used and abused legal drugs. Although its pharmacological profile has been extensively investigated in humans and rodents, nicotine CNS action remains poorly understood. The importance of finding evolutionarily conserved signaling pathways, and the need to apply high-throughput in vivo screens for CNS drug discovery, necessitate novel efficient experimental models for nicotine research. Zebrafish (Danio rerio) are rapidly emerging as an excellent organism for studying drug abuse, neuropharmacology and toxicology and have recently been applied to testing nicotine. Anxiolytic, rewarding and memory-modulating effects of acute nicotine treatment in zebrafish are consistently reported in the literature. However, while nicotine abuse is more relevant to long-term exposure models, little is known about chronic effects of nicotine on zebrafish behavior. In the present study, chronic 4-day exposure to 1-2mg/L nicotine mildly increased adult zebrafish shoaling but did not alter baseline cortisol levels. We also found that chronic exposure to nicotine evokes robust anxiogenic behavioral responses in zebrafish tested in the novel tank test paradigm. Generally paralleling clinical and rodent data on anxiogenic effects of chronic nicotine, our study supports the developing utility of zebrafish for nicotine research.

Aquatic toxicology of fluoxetine: understanding the knowns and the unknowns.

Fluoxetine is one of the most prescribed psychotropic medications, and is an agent of increasing interest for environmental toxicology. Fish and other aquatic organisms are excellent models to study neuroactive small molecules like fluoxetine. However, prone to variance due to experimental factors, data obtained in these models need to be interpreted with caution, using proper experimental protocols, study designs, validated endpoints as well as well-established models and tests. Choosing the treatment protocol and dose range for fluoxetine and other serotonergic drugs is critical for obtaining valid test results and correct data interpretation. Here we discuss the value of aquatic models to study fluoxetine effects, based on prior high-quality research, and outline the directions of future translational studies in the field. We review fluoxetine-evoked phenotypes in acute vs. chronic protocols, discussing them in the contact of complex role of serotonin in behavioral regulation. We conclude that zebrafish and other aquatic models represent a useful in-vivo tool for fluoxetine pharmacology and (eco)toxicology research.

Protective effects of reducing renal ischemia-reperfusion injury during renal hilar clamping: use of allopurinol as a nephroprotective agent.

OBJECTIVE: To investigate the relationship between renal ischemia injury and concentrations of 8-isoprostane in a rat kidney model during renal hilar clamping and their correlation with the administration of allopurinol before clamping. MATERIALS AND METHODS: Reperfusion injury occurs after the reintroduction of blood flow after a prolonged period of ischemia. Thought to be due to oxygen free radicals released by the endothelial, mitochondrial, and parenchymal cells, this process leads to a cascade of events whereby infiltrative leukocytes generate cytokines and reactive oxygen species. The present study was performed in 2 parts. Our primary objective was to first develop a method of quantitating the renal damage using a prostaglandin compound formed in vivo, specifically isoprostane. After the development of this animal model of quantitating renal injury, our second objective was to apply this model and investigate allopurinol's nephroprotective abilities. A microdialysis probe was inserted into the renal parenchyma of rats to allow continuous dialysis and collection of the effluent for isoprostane levels. After clamping of the renal vessels to induce ischemia, the interstitial effluent from the probe was collected and subsequently analyzed for 8-isoprostane levels with and without allopurinol pretreatment. RESULTS: Clamping of the renal hilum in this rat model significantly increased 8-isoprostane levels. After 60 minutes of clamp time, the largest absolute increase in 8-isoprostane levels resulted, representing a 3.2-fold increase from baseline. However, the rats that had been pretreated with allopurinol demonstrated significantly less isoprostane levels, to baseline levels. CONCLUSION: Allopurinol has demonstrated significant benefits by reducing reperfusion injury in rat kidneys, as demonstrated by the use of 8-isoprostane as a tool for the real-time measurement of ischemic injury.

Underutilization of partial nephrectomy for stage T1 renal cell carcinoma in the United States, trends from 2000 to 2008. A long way to go.

INTRODUCTION: Recent American Urologic Association Guidelines for small renal masses recommend partial nephrectomy for surgical treatment of T1 renal masses to preserve renal function and minimize cardiovascular comorbidities. This procedure is performed more often than in the past, after the technical issues of hemorrhage, fistula, and technique evolved. We reviewed the trends, practice patterns, and application of partial nephrectomy for T1 renal cell carcinoma in the United States from 2000 to 2008, before the American Urologic Association Guidelines. The objective is to investigate whether economic or societal factors favor the use of partial over radical nephrectomy surgery. METHODS: Data on 142,194 cases from 1267 hospitals diagnosed with kidney and renal pelvis cancer in the National Cancer DataBase from 2000 to 2008 were the basis of the study. RESULTS: Partial nephrectomy rates for stage T1 kidney and renal pelvis cancer have increased from 17% in 2000 to 31% in 2008. Differences in partial nephrectomy rates that arise from sex or race were not large. However, there was a disproportionate increase based on income and education. Also, there were differences based on insurance status; patients with managed care, in the military and veterans had higher partial nephrectomy rates. Partial nephrectomy rates were higher in teaching and research hospitals and in veterans hospitals. Geographically, the procedure was performed at higher rates in the eastern and midwestern parts of the country. CONCLUSIONS: Partial nephrectomy rates for stage T1 renal cell carcinoma increased from 17% in 2000 to 31% in 2008. The procedure has been used preferentially with patients who are more educated and have high incomes.

Isoprostane: quantitation of renal ischemia and reperfusion injury after renal artery clamping in an animal model.

BACKGROUND AND PURPOSE: Laparoscopic and robotic partial nephrectomy involves temporary clamping of the renal artery, making the kidney susceptible to ischemic damage. Isoprostane represents one potential marker of oxidative injury. The objective was to determine if renal interstitial isoprostane levels can quantitate renal damage secondary to warm ischemia. A second goal is to investigate allopurinol for renoprotective abilities using this model. We chose to investigate potential renoprotection of allopurinol because previous studies have demonstrated transplant kidneys pretreated with allopurinol to have less damage from ischemia. MATERIALS AND METHODS: A microdialysis probe was inserted into the renal parenchyma of rats to allow continuous dialysis and collection of the effluent for isoprostane levels. After clamping of the renal vessels for predefined intervals of ischemia, the interstitial effluent from the probe was collected and subsequently analyzed for isoprostane levels with and without allopurinol pretreatment. RESULTS: Clamping of the renal artery and vein produced increases in isoprostane levels during the ischemic period and larger increases during reperfusion. There was a trend for increased postclamp isoprostane levels as clamp times increased. When comparing isoprostane levels in rats that did not receive allopurinol, there were significant differences between the clamp and postclamp levels of isoprostane, with allopurinol offering protection to the kidney from ischemic changes caused by clamping the renal hilum. CONCLUSIONS: Our data have demonstrated that isoprostane levels are a potential real-time marker of renal ischemia and reperfusion injury. We also found allopurinol administration demonstrated a trend toward renoprotective abilities in the hilar occluded kidney.

Behavioral and physiological effects of RDX on adult zebrafish.

1,3,5-Trinitroperhydro-1,3,5-triazine (RDX) is a nitroamine explosive, with common toxic effects including seizures. Here, we explore the behavioral effects of acute RDX exposure in adult zebrafish Danio rerio, a rapidly developing model in neuroscience and neurotoxicology research. Overall, a 30-min exposure to RDX low dose of 0.1 mM evoked behavioral activation in zebrafish, while a higher dose of 1 mM markedly reduced exploration, increased freezing and evoked seizure-like responses (i.e., bouts of hyperactivity, spasms, and corkscrew swimming). Likewise, whole-body cortisol levels were also significantly elevated in fish exposed to 1 mM (but not 0.1 mM) RDX. In line with clinical and animal data, our study demonstrates the dose-dependent behavioral activation and pro-convulsant effects of RDX in zebrafish-based models.

Effects of piracetam on behavior and memory in adult zebrafish.

Piracetam, a derivative of γ-aminobutyric acid, exerts memory-enhancing and mild anxiolytic effects in human and rodent studies. To examine the drug's behavioral profile further, we assessed its effects on behavioral and endocrine (cortisol) responses of adult zebrafish (Danio rerio)--a novel model species rapidly gaining popularity in neurobehavioral research. Overall, acute piracetam did not affect zebrafish novel tank and light-dark box behavior at mild doses (25-400mg/L), but produced nonspecific behavioral inhibition at 700mg/L. No effects on cortisol levels or inter-/intra-session habituation in the novel tank test were observed for acute or chronic mild non-sedative dose of 200mg/L. In contrast, fish exposed to chronic piracetam at this dose performed significantly better in the cued learning plus-maze test. This observation parallels clinical and rodent literature on the behavioral profile of piracetam, supporting the utility of zebrafish paradigms for testing nootropic agents.

Modeling seizure-related behavioral and endocrine phenotypes in adult zebrafish.

Larval zebrafish (Danio rerio) have recently been suggested as a high-throughput experimental model of epilepsy-related pathogenetic states. Here we use adult zebrafish to study behavioral symptoms associated with drug-evoked seizures. Experimental epilepsy-like states were evoked in zebrafish by exposure for 20min to three chemoconvulsant drugs: caffeine (250mg/L; 1.3mM), pentylenetetrazole (1.5g/L; 11.0mM) and picrotoxin (100mg/L; 0.17mM). Fish behavior was analyzed using manual and video-tracking methods (Noldus Ethovision XT7). Compared to their respective controls, all three drug-treated groups showed robust seizure-like responses (hyperactivity bouts, spasms, circular and corkscrew swimming) accompanied by elevated whole-body cortisol levels (assessed by ELISA). In contrast, control fish did not display seizure-like behaviors and had significantly lower cortisol levels. Paralleling behavioral and endocrine phenotypes observed in clinical and rodent studies, our data implicates adult zebrafish as an emerging experimental model for epilepsy research.

Characterization of behavioral and endocrine effects of LSD on zebrafish.

Lysergic acid diethylamide (LSD) is a potent hallucinogenic drug that strongly affects animal and human behavior. Although adult zebrafish (Danio rerio) are emerging as a promising neurobehavioral model, the effects of LSD on zebrafish have not been investigated previously. Several behavioral paradigms (the novel tank, observation cylinder, light-dark box, open field, T-maze, social preference and shoaling tests), as well as modern video-tracking tools and whole-body cortisol assay were used to characterize the effects of acute LSD in zebrafish. While lower doses (5-100 microg/L) did not affect zebrafish behavior, 250 microg/L LSD increased top dwelling and reduced freezing in the novel tank and observation cylinder tests, also affecting spatiotemporal patterns of activity (as assessed by 3D reconstruction of zebrafish traces and ethograms). LSD evoked mild thigmotaxis in the open field test, increased light behavior in the light-dark test, reduced the number of arm entries and freezing in the T-maze and social preference test, without affecting social preference. In contrast, LSD affected zebrafish shoaling (increasing the inter-fish distance in a group), and elevated whole-body cortisol levels. Overall, our findings show sensitivity of zebrafish to LSD action, and support the use of zebrafish models to study hallucinogenic drugs of abuse.

Measuring behavioral and endocrine responses to novelty stress in adult zebrafish.

Several behavioral assays are currently used for high-throughput neurophenotyping and screening of genetic mutations and psychotropic drugs in zebrafish (Danio rerio). In this protocol, we describe a battery of two assays to characterize anxiety-related behavioral and endocrine phenotypes in adult zebrafish. Here, we detail how to use the 'novel tank' test to assess behavioral indices of anxiety (including reduced exploration, increased freezing behavior and erratic movement), which are quantifiable using manual registration and computer-aided video-tracking analyses. In addition, we describe how to analyze whole-body zebrafish cortisol concentrations that correspond to their behavior in the novel tank test. This protocol is an easy, inexpensive and effective alternative to other methods of measuring stress responses in zebrafish, thus enabling the rapid acquisition and analysis of large amounts of data. As will be shown here, fish anxiety-like behavior can be either attenuated or exaggerated depending on stress or drug exposure, with cortisol levels generally expected to parallel anxiety behaviors. This protocol can be completed over the course of 2 d, with a variable testing duration depending on the number of fish used.

Retrograde Renal Cooling to Minimize Ischemia

Objective: During partial nephrectomy, renal hypothermia has been shown to decrease ischemia induced renal damage which occurs from renal hilar clamping. In this study we investigate the infusion rate required to safely cool the entire renal unit in a porcine model using retrograde irrigation of iced saline via dual-lumen ureteral catheter. Materials and Methods: Renal cortical, renal medullary, bowel and rectal temperatures during retrograde cooling in a laparoscopic porcine model were monitored in six renal units. Iced normal saline was infused at 300 cc/hour, 600 cc/hour, 1000 cc/hour and gravity (800 cc/hour) for 600 seconds with and without hilar clamping. Results: Retrograde cooling with hilar clamping provided rapid medullary renal cooling and significant hypothermia of the medulla and cortex at infusion rates ≥ 600 cc/hour. With hilar clamping, cortical temperatures decreased at -0.9° C/min. reaching a threshold temperature of 26.9° C, and medullary temperatures decreased at -0.90 C/min. reaching a temperature of 26.1° C over 600 seconds on average for combined data at infusion rates ≥ 600 cc/hour. The lowest renal temperatures were achieved with gravity infusion. Without renal hilum clamping, retrograde cooling was minimal at all infusion rates. Conclusions: Significant renal cooling by gravity infusion of iced cold saline via a duel lumen catheter with a clamped renal hilum was achieved in a porcine model. Continuous retrograde irrigation with iced saline via a two way ureteral catheter may be an effective method to induce renal hypothermia in patients undergoing robotic assisted and/or laparoscopic partial nephrectomy. .