Pain in alcohol use disorder: Evaluating effects of childhood trauma, perceived stress, and psychological comorbidity.

The relationship between pain and alcohol use disorder (AUD) is complex and bidirectional. The current study examines risk factors for pain in a large comprehensively phenotyped sample including individuals from across the spectrum of alcohol use and misuse. Participants (n = 1101) were drawn from the National Institute on Alcohol Abuse and Alcoholism Natural History Protocol and included treatment-seeking AUD inpatients (AUD+Tx, n = 369), individuals with AUD not seeking treatment (AUD+, n = 161), and individuals without AUD (AUD-, n = 571). General linear models were utilized to test the effects of AUD status, history of childhood trauma exposure, perceived stress, and psychological comorbidity on daily percent time in pain, as well as change in daily percent time in pain across the inpatient stay in AUD+Tx individuals. Overall, 60.2% individuals reported any pain, with a significantly higher prevalence in the AUD+Tx group (82.1%) compared to the AUD+ (56.5%) and AUD- (47.1%) groups. Daily percent time in pain was also highest in the AUD+Tx group (30.2%) and was further increased in those with a history of childhood abuse and comorbid posttraumatic stress disorder (PTSD). Years of heavy drinking and craving were also associated with increased percent time in pain in the AUD+Tx group. Percent time in pain decreased following acute withdrawal in the AUD+Tx group but plateaued around 25% just prior to discharge. Individuals seeking inpatient treatment for AUD, especially those with a history of childhood trauma and/or comorbid PTSD, report greater percent time in pain compared to those not seeking treatment and those without AUD. The prolonged experience of pain in abstinent AUD inpatients after the resolution of acute withdrawal may signal the early stages of protracted withdrawal. Integrative treatments targeting pain and other symptoms of protracted withdrawal may be effective in improving overall function in people with severe AUD.

Elevated stearoyl-CoA desaturase 1 activity is associated with alcohol-associated liver disease.

Chronic binge drinking induces hepatic lipid accumulation, but only certain individuals develop alcohol-associated liver disease (ALD). Specific patterns of lipid accumulation are thought to be associated with ALD, but this has not been comprehensively investigated to date. We analyzed plasma fatty acid levels, quantified by gas chromatography-mass spectrometry, in a sample of patients with alcohol use disorder (AUD). Given that elevation in serum alanine transaminase (ALT) levels are strongly associated with ALD, patients were stratified into two groups based on ALT levels: an ALD group (ALT >40 IU/L) and a non-ALD group (ALT ≤40 IU/L). There was a shift toward greater concentrations of monounsaturated fatty acids in the ALD group compared to the non-ALD group. Stearoyl-CoA desaturase (SCD1) activity in the ALD group was then estimated as the ratio of palmitoleic acid (16:1) to palmitic acid (16:0). SCD1 activity was greater in the ALD than the non-ALD group. A series of linear regression models demonstrated that SCD1 activity mediated the association between binge drinking and ALD. These findings provide initial evidence that SCD1 activity may be associated with ALD. If validated prospectively, elevated SCD1 activity could potentially be used as a biomarker to identify individuals at high risk for developing ALD.

Concentrations of oxidized linoleic acid derived lipid mediators in the amygdala and periaqueductal grey are reduced in a mouse model of chronic inflammatory pain.

Chronic pain is both a global public health concern and a serious source of personal suffering for which current treatments have limited efficacy. Recently, oxylipins derived from linoleic acid (LA), the most abundantly consumed polyunsaturated fatty acid in the modern diet, have been implicated as mediators of pain in the periphery and spinal cord. However, oxidized linoleic acid derived mediators (OXLAMs) remain understudied in the brain, particularly during pain states. In this study, we employed a mouse model of chronic inflammatory pain followed by a targeted lipidomic analysis of the animals' amygdala and periaqueductal grey (PAG) using LC-MS/MS to investigate the effect of chronic inflammatory pain on oxylipin concentrations in these two brain nuclei known to participate in pain sensation and perception. From punch biopsies of these brain nuclei, we detected twelve OXLAMs in both the PAG and amygdala and one arachidonic acid derived mediator, 15-HETE, in the amygdala only. In the amygdala, we observed an overall decrease in the concentration of the majority of OXLAMs detected, while in the PAG the concentrations of only the epoxide LA derived mediators, 9,10-EpOME and 12,13-EpOME, and one trihydroxy LA derived mediator, 9,10,11-TriHOME, were reduced. This data provides the first evidence that OXLAM concentrations in the brain are affected by chronic pain, suggesting that OXLAMs may be relevant to pain signaling and adaptation to chronic pain in pain circuits in the brain and that the current view of OXLAMs in nociception derived from studies in the periphery is incomplete.

The effect of modifying dietary LA and ALA intakes on omega-3 long chain polyunsaturated fatty acid (n-3 LCPUFA) status in human adults: a systematic review and commentary.

This paper presents a systematic review of human studies investigating the effect of altering dietary omega-3 polyunsaturated fatty acid (n-3 PUFA) alpha-linolenic acid (ALA) and omega-6 polyunsaturated fatty acid (n-6 PUFA) linoleic acid (LA) intakes on n-3 long-chain polyunsaturated fatty acid (LCPUFA) status in adult humans. The results suggest that it is possible to increase n-3 LCPUFA status by reducing LA and/or increasing ALA intake in humans, although decreasing LA intake to below 2.5%E may be required to specifically increase levels of the n-3 LCPUFA docosahexaenoic acid (DHA). The majority of studies in this area to date have been relatively poor in quality, which limits the ability to draw robust conclusions, and we present a series of recommendations to improve the quality of future studies in fatty acid nutrition in humans.

A low omega-6 polyunsaturated fatty acid (n-6 PUFA) diet increases omega-3 (n-3) long chain PUFA status in plasma phospholipids in humans.

This study aimed to determine the effect of reducing the dietary linoleic acid (LA) intake from ~5% to <2.5% energy (%E) on n-3 long chain PUFA (LCPUFA) status in humans. Thirty-six participants followed a <2.5%E LA diet for 4 weeks. Nutrient intakes were estimated from diet diaries and blood samples were collected for assessment of fatty acid composition in plasma and erythrocyte phospholipids. LA intakes were reduced from 4.6%E to 2%E during the low LA intervention (P<0.001) while n-3 LCPUFA intakes were unchanged. LA and total n-6 PUFA content of plasma and erythrocyte phospholipids were significantly reduced after the low LA diet phase (P<0.001). The n-3 LCPUFA content of plasma phospholipids was significantly increased after the low LA diet compared to baseline (6.22% vs. 5.53%, P<0.001). These data demonstrate that reducing LA intake for 4 weeks increases n-3 LCPUFA status in humans in the absence of increased n-3 LCPUFA intake.

Sub-lethal effects of titanium dioxide nanoparticles on the physiology and reproduction of zebrafish.

There are limited data on the sub-lethal physiological effects of titanium dioxide nanoparticles (TiO(2) NPs) in adult fishes, and the consequences of TiO(2) NP exposure on reproductive success are also unclear. This study aimed to examine the sub-lethal effects of a 14-d aqueous TiO(2) (TiO(2) NP, 0.1 or 1.0 mg l(-1); TiO(2) bulk, 1.0 mg l(-1)) exposure on the physiology and reproductive health of zebrafish. After the 14-d exposure, fish were examined for haematology, whole body electrolyte and trace metal profiles, biochemistry, and histopathology. Then, during a 21-d post exposure recovery period, effects of the TiO(2) exposure on reproductive success were evaluated. Whole body Ti concentrations increased significantly in fish exposed to both the 1.0 mg l(-1) TiO(2) NP and bulk TiO(2) compared to controls, but concentrations returned to control levels by the end of the recovery period. No change in erythrocyte counts were observed, but there was a two-fold decline in leukocyte counts in all TiO(2) treatment groups relative to time-matched controls. Whole body electrolyte and trace metal profiles were not affected by exposure to TiO(2), and there were no changes in Na(+)K(+)-ATPase activity in brain, gill or liver tissues. Total glutathione (GSH) levels in brain, gill and liver tissues were higher in fish exposed to TiO(2) NP (both 0.1 and 1.0 mg l(-1)) compared to bulk TiO(2) and control fish. Histological examination of gill, liver, brain and gonad tissues showed little evidence of treatment-related morphological change. At the end of the 14-d exposure adult zebrafish were able to reproduce; however, the cumulative number of viable embryos produced was lower in fish exposed to 1.0 mg l(-1) TiO(2) (both NP and bulk) by the end of the 21-d recovery period. Overall, this study showed limited toxicity of bulk or nano scale TiO(2) during the exposure; however reproduction was affected in both bulk and NP 1.0 mg l(-1) groups.

Indomethacin impairs coronary perfusion in infants with hemodynamically significant ductus arteriosus.

BACKGROUND: A haemodynamically significant ductus arteriosus (HSDA) is commonly associated with morbidity in preterm infants. AIM: To study the effect of the first dose of indomethacin on coronary blood flow in preterm neonates diagnosed with an HSDA. METHOD: A prospective observational echocardiographic study was performed on preterm infants. A single study dose of intravenous indomethacin (0.1 mg/kg) was administered over 1 h. Serial echocardiography was performed before and after indomethacin treatment to study the effect on coronary artery perfusion and cardiovascular performance. RESULTS: Eighteen infants born at a median gestation of 25.8 (24.2, 28.1) weeks and a birth weight of 773 g (704, 1,002) were evaluated. The median age at indomethacin administration was 7.5 days (4, 17). There was no significant change in arterial pressure or ventilatory indices. Left anterior descending artery diastolic velocity and time integral declined from 0.3 ± 0.1 and 3.19 ± 1.2 m/s to 0.22 ± 0.08 and 2.01 ± 0.9 m/s, respectively, within 10 min of completion of infusion. These indices showed partial recovery when reassessed after 60 min. There were no changes in left ventricular output or transductal flow. CONCLUSIONS: Intravenous indomethacin was followed by a decline in coronary arterial diastolic blood flow.

Effects of manufactured nanomaterials on fishes: a target organ and body systems physiology approach.

Manufactured nanomaterials (NM) are already used in consumer products and exposure modelling predicts releases of ng to low µg l(-1) levels of NMs into surface waters. The exposure of aquatic ecosystems, and therefore fishes, to manufactured NMs is inevitable. This review uses a physiological approach to describe the known effects of NMs on the body systems of fishes and to identify the internal target organs, as well as outline aspects of colloid chemistry relevant to fish biology. The acute toxicity data, suggest that the lethal concentration for many NMs is in the mg l(-1) range, and a number of sublethal effects have been reported at concentrations from c. 100 µg to 1 mg l(-1). Exposure to NMs in the water column can cause respiratory toxicity involving altered ventilation, mucus secretion and gill pathology. This may not lead, however, to overt haematological disturbances in the short term. The internal target organs include the liver, spleen and haematopoietic system, kidney, gut and brain; with toxic effects involving oxidative stress, ionoregulatory disturbances and organ pathologies. Some pathology appears to be novel for NMs, such as vascular injury in the brain of rainbow trout Oncorhynchus mykiss with carbon nanotubes. A lack of analytical methods, however, has prevented the reporting of NM concentrations in fish tissues, and the precise uptake mechanisms across the gill or gut are yet to be elucidated. The few dietary exposure studies conducted show no effects on growth or food intake at 10-100 mg kg(-1) inclusions of NMs in the diet of O. mykiss, but there are biochemical disturbances. Early life stages are sensitive to NMs with reports of lethal toxicity and developmental defects. There are many data gaps, however, including how water quality alters physiological responses, effects on immunity and chronic exposure data at environmentally relevant concentrations. Overall, the data so far suggest that the manufactured NMs are not as toxic as some traditional chemicals (e.g. some dissolved metals) and the innovative, responsible, development of nanotechnology should continue, with potential benefits for aquaculture, fisheries and fish health diagnostics.

An outbreak of necrotizing enterocolitis associated with norovirus genotype GII.3.

BACKGROUND: Necrotizing enterocolitis (NEC) is an acute abdominal emergency of unknown etiology predominantly affecting preterm infants. We describe a cluster of NEC in a level III NICU involving 15 infants over a6-month period. Cohorting and stringent infection control measures were associated with termination of the cluster. A case-control study was used to investigate potential risk factors associated with development of NEC. METHODS: Stool samples were collected from 55 infants (10 of 15 NEC and 45 non-NEC controls). Enteric pathogens were identified by culture and/or molecular diagnostic techniques. For the case-control study, controls were selected from admitted neonates during the same time and in the preceding 6-month period, matched for gestation and birthweight. RESULTS: Forty percent (4/10) of NEC infants had norovirus RNA detected compared with 9% (4/45) of non-NEC infants (OR: 6.83, 95% CI: 1.3-34.9,P = 0.021). A lower rate of prolonged rupture of membranes and a higher rate of maternal smoking was also observed in NEC infants than in controls. No significant differences in incidences of chorioamnionitis, intrapartum antibiotics,volume of feedings, time of first formula feeding, and rates of patent ductus arteriosus or intrauterine growth retardation were detected. CONCLUSIONS: Infants who developed NEC had an increased incidence of norovirus detection in their stool following diagnosis. This further strengthens the case for an etiologic role of norovirus in the pathogenesis of NEC.

Congenital tuberculosis after in-vitro fertilisation.

A 6-week old infant who had been conceived through in-vitro fertilisation (IVF) presented with a skin lesion and enlarged lymph nodes, and developed severe respiratory distress. Mycobacterium tuberculosis was identified; his mother was the only potential source identified. To our knowledge, this is the first case of congenital tuberculosis after IVF reported in Australia and the second worldwide. It highlights the importance of adequate screening during investigation of infertility and the difficulties in diagnosing congenital tuberculosis.

[Post-traumatic cyclodialysis cleft treated with transscleral diode laser]. / Ciclodiálisis postraumática tratada con láser diodo transescleral.

CASE REPORT: A 28-year-old man who received a blunt trauma in his left eye, presented with persistent ocular hypotony (intraocular pressure: 4 mmHg) as well as loss of visual acuity (0.4), optic disc edema and chorioretinal folds in the macula. The foveal thickness, measured by optic coherence tomography, was 326 microns. Using ultrasound biomicroscopy, a desinsertion of the nasal iris and a 360 degrees choroidal detachment was observed. The hypotony did not respond to conservative treatment and 10 months after the trauma he underwent a transscleral cyclopexy with contact diode laser. One year after the laser treatment the visual acuity was 1.0, the intraocular pressure 14 mmHg and the foveal thickness 240 microns. DISCUSSION: Transscleral cyclopexy with diode laser may be an effective alternative treatment to resolve post-traumatic cyclodialysis that does not respond to medical treatment.

Dopaquinone redox exchange with dihydroxyindole and dihydroxyindole carboxylic acid.

A pulse radiolytic investigation has been conducted to establish whether a redox reaction takes place between dopaquinone and 5,6-dihydroxyindole (DHI) and its 2-carboxylic acid (DHICA) and to measure the rate constants of the interactions. To obviate possible confounding reactions, such as nucleophilic addition, the method employed to generate dopaquinone used the dibromide radical anion acting on dopa to form the semiquinone which rapidly disproportionates to dopaquinone. In the presence of DHI the corresponding indole-5,6-quinone (and/or tautomers) was also formed directly but, by judicious selection of suitable relative concentrations of initial reactants, we were able to detect the formation of additional indolequinone from the redox exchange reaction of DHI with dopaquinone which exhibited a linear dependency on the concentration of DHI. Computer simulation of the experimental time profiles of the absorption changes showed that, under the conditions chosen, redox exchange does proceed but not quite to completion, a forward rate constant of 1.4 x 10(6)/M/s being obtained. This is in the same range as the rate constants previously established for reactions of dopaquinone with cyclodopa and cysteinyldopa. In similar experiments carried out with DHICA, the reaction more obviously does not go to completion and is much slower, k (forward) =1.6 x 10(5)/M/s. We conclude that, in the eumelanogenic pathway, DHI oxidation may take place by redox exchange with dopaquinone, although such a reaction is likely to be less efficient for DHICA.

Velocity and attenuation of sound in the isolated fetal lung as it is expanded with air.

We measured the velocity and attenuation of audible sound in the isolated lung of the near-term fetal sheep to test the hypothesis that the acoustic properties of the lung provide a measure of the volume of gas it contains. We introduced pseudorandom noise (bandwidth 70 Hz-7 kHz) to one side of the lung and recorded the noise transmitted to the surface immediately opposite, starting with the lung containing only fetal lung liquid and making measurements after stepwise inflation with air until a leak developed. The velocity of sound in the lung fell rapidly from 187 +/- 28.2 to 87 +/- 3.7 m/s as lung density fell from 0.93 +/- 0.01 to 0.75 +/- 0.01 g/ml (lung density = lung weight/gas volume plus lung tissue volume). For technical reasons, no estimate of velocity could be made before the first air injection. Thereafter, as lung density fell to 0.35 +/- 0.01 g/ml, there was a further decline in velocity to 69.6 +/- 4.6 m/s. High-frequency sound was attenuated as lung density decreased from 1.0 to 0.5 g/ml, with little change thereafter down to a density of 0.35 +/- 0.01 g/ml. We conclude that both the velocity of audible sound through the lung and the degree to which high-frequency sound is attenuated in the lung provide information on the degree of inflation of the isolated fetal lung, particularly at high lung densities. If studies of sound transmission through the lung in the intact organism were to confirm these findings, the acoustic properties of the lung could provide a means for monitoring lung aeration during mechanical ventilation of newborn infants.

[Frequency doubling perimetry in terminal visual field defects]. / Perimetría de duplicación de frecuencias en defectos campimétricos terminales.

PURPOSE: To evaluate the Frequency Doubling Technology (FDT) in end-stage glaucomatous visual field defects. METHODS: FDT (C-20 threshold test) was performed in 22 consecutive patients presenting an end-stage visual field defect with 24-2 SITA (0 dB in more than 75% and less than 100% of the visual field). Comparisons of the percentage of non-abolished points, topographic correlation, test duration and global indexes were performed between C-20 and 24-2 SITA test. RESULTS: FDT sensitivity was 100%. C-20 test showed 13.7% more points with sensitivity greater than 0 dB compared to 24-2 test (P = 0.002). Two and a half less minutes were required for C-20 test performing (P<0.001). The mean value of Mean Defect was 11.48 dB better in FDT (P = 0,000). The mean value of the Pattern Standard Deviation was 5.37 dB (SD: 1.92) and 6.35 dB (SD: 3.61) for 24-2 and C-20 test respectively (P = 0.258). The inferotemporal quadrant was the best conserved in both perimetric strategies (Kappa agreement test value = 0.911; P<0.001). CONCLUSIONS: FDT showed greater ability than 24-2 test for end-stage visual field defects evaluation, with the advantage of being less time-consuming. Very good topographic correlation between both strategies was found. Further studies evaluating FDT reproducibility in severe glaucomatous visual field damage are necessary.

[Frequency-doubling perimetry in retrochiasmatic disorders]. / Perimetría de duplicación de frecuencias en lesiones retroquiasmáticas.

OBJECTIVE: To determine the ability of frequency doubling technology (FDT) to evaluate retrochiasmatic lesions. METHODS: 21 patients with characteristic retrochiasmatic visual field defects in automated perimetry (Humphrey field analyzer, 24-2 SITA) underwent FDT using C-20 screening and threshold tests. Two independent observers described the visual field defects, the degree of congruence and macular sparing of the three explorations. RESULTS: The visual field defect found in the 24-2 test was inferred in 63.2% and 70% of the eyes from the C-20 screening and C-20 threshold test respectively. The retrochiasmatic lesions were congruent in 45% of the cases in automated perimetry, 5.6% in C-20 screening and 15% in C-20 threshold test. Macular sparing was present in 45% of cases with automated perimetry, 89% with C-20 screening and 82% with C-20 threshold test. CONCLUSIONS: The FDT allows us to suspect retrochiasmatic lesions in more than one-half of patients, but it tends to underestimate the defects. It is not useful for detecting macular sparing or the evaluation of visual field congruence. Both FDT strategies offer similar results, so the C-20 screening test could be more advisable because of its speed (mean: 70 seconds). However, in retrochiasmatic lesions the FDT accuracy is considerably lower than the 24-2 SITA strategy.

A realistic view of domestic violence screening in an emergency department.

Sutherland Hospital is a district hospital serving The Sutherland Shire, a metropolitan area of Sydney. It has a population of approximately 220,000 which is predominantly Anglo-Saxon in ethnic origin. The Emergency Department provides emergency services for 30,000 new patients per annum. New South Wales Department of Health obtained Commonwealth funding from Partnerships Against Domestic Violence to pilot routine screening for domestic violence within 2 Area Health Services. One of the participating sites was the Emergency Department in South East Sydney Area Health Service. The aim was for nursing and medical staff to screen, for three months, all women sixteen years old and over. Information cards on state-wide domestic violence resources and referral flow charts were developed for the pilot. Staff undertook training and issues were addressed prior to the screening. In this article we will discuss the findings, including the rate of screening by the staff, disclosure rate of domestic violence, and action taken on disclosure. We will then proceed to explain the difficulties in undertaking screening within an Emergency Department, and make recommendations for those Emergency Departments interested in commencing screening.