Evaluating the performance of temporal and spatial early warning statistics of algal blooms.

Regime shifts have large consequences for ecosystems and the services they provide. However, understanding the potential for, causes of, proximity to, and thresholds for regime shifts in nearly all settings is difficult. Generic statistical indicators of resilience have been proposed and studied in a wide range of ecosystems as a method to detect when regime shifts are becoming more likely without direct knowledge of underlying system dynamics or thresholds. These early warning statistics (EWS) have been studied separately but there have been few examples that directly compare temporal and spatial EWS in ecosystem-scale empirical data. To test these methods, we collected high-frequency time series and high-resolution spatial data during a whole-lake fertilization experiment while also monitoring an adjacent reference lake. We calculated two common EWS, standard deviation and autocorrelation, in both time series and spatial data to evaluate their performance prior to the resulting algal bloom. We also applied the quickest detection method to generate binary alarms of resilience change from temporal EWS. One temporal EWS, rolling window standard deviation, provided advanced warning in most variables prior to the bloom, showing trends and between-lake patterns consistent with theory. In contrast, temporal autocorrelation and both measures of spatial EWS (spatial SD, Moran's I) provided little or no warning. By compiling time series data from this and past experiments with and without nutrient additions, we were able to evaluate temporal EWS performance for both constant and changing resilience conditions. True positive alarm rates were 2.5-8.3 times higher for rolling window standard deviation when a lake was being pushed towards a bloom than the rate of false positives when it was not. For rolling window autocorrelation, alarm rates were much lower and no variable had a higher true positive than false positive alarm rate. Our findings suggest temporal EWS provide advanced warning of algal blooms and that this approach could help managers prepare for and/or minimize negative bloom impacts.

Minimalist style boot improves running but not walking economy in trained men.

This study examined movement economy under load with 1000 g minimalist (MIN) vs. 1600 g traditional (TRD) style boots. Fourteen trained, male participants completed a VO2peak test (46.6 ± 7.3 ml/kg/min) while wearing a 16 kg external load. Treadmill speeds for the running economy (RE) trials were determined by the slowest pace in which participants completed a full stage with a running gait pattern during the VO2peak test. Walking economy (WE) pace was 1.6 km/h slower than RE pace. During the second session, participants completed 5-min exercise bouts at WE and RE pace under load wearing MIN and TRD. There were no differences for any measured variables during WE trials. In contrast, RE (MIN = 2.95 ± 0.28 vs. TRD = 3.04 ± 0.30 L/min; p = .003: Cohen's d = 0.32), respiratory exchange ratio (p < .001), and perceptual measures (p < .05) were all improved while wearing MIN. Practitioner summary: In trained men, 1000 g/pair minimalist style boots (MIN) resulted in improvements of approximately 3% and 5% for running economy and respiratory exchange ratio versus 1600 g/pair traditional boots while wearing a 16 kg kit. Perceptual responses, including comfort, also favoured MIN. These effects were not found at walking pace. Abbreviations: MIN: minimalist style boots; TRD: traditional style boots; RE: running economy; WE: walking economy; ES: effect size; RER: respiratory exchange ratio; HR: heart rate.

The impact of immunoglobulin in acute HIV infection on the HIV reservoir: a randomized controlled trial.

OBJECTIVES: Antiretroviral therapy (ART) during acute HIV infection (AHI) restricts the HIV reservoir, but additional interventions are necessary to induce a cure. Intravenous immunoglobulin (IVIG) is not HIV-specific but is safe and temporarily reduces the HIV reservoir in chronic HIV infection. We present a randomized controlled trial to investigate whether IVIG plus ART in AHI reduces the HIV reservoir and immune activation compared with ART alone. METHODS: Ten men with AHI (Fiebig II-IV) initiated ART (tenofovir, entricitabine, ritonavir boosted darunavir and raltegravir) at HIV-1 diagnosis and were randomized to ART alone or ART plus 5 days of IVIG, once virally suppressed (week 19). Blood samples were evaluated for viral reservoir, immune activation, immune exhaustion and microbial translocation. Flexible sigmoidoscopy was performed at weeks 19, 24 and 48, and gut proviral DNA and cell numbers determined. RESULTS: IVIG was well tolerated and no viral blips (> 50 HIV-1 RNA copies/mL) occurred during IVIG therapy. From baseline to week 48, total HIV DNA in peripheral blood mononuclear cells (PBMCs) (cases: -3.7 log10 copies/106 CD4 cells; controls: -3.87 log10 copies/106 CD4 cells) declined with no differences observed between the groups (P = 0.49). Declines were observed in both groups from week 19 to week 48 in total HIV DNA in PBMCs (P = 0.38), serum low copy RNA (P = 0.57) and gut total HIV DNA (P = 0.55), but again there were no significant differences between arms. Biomarkers of immune activation, immune exhaustion and microbial translocation and the CD4:CD8 ratio were similar between arms for all comparisons. CONCLUSIONS: Although safe, IVIG in AHI did not impact total HIV DNA, immune function or microbial translocation in peripheral blood or gut tissue.

Is intrathecal bupivacaine plus dexmedetomidine superior to bupivacaine in spinal anesthesia for a cesarean section? A systematic review and meta-analysis.

OBJECTIVE: This study aimed to investigate whether the administration of intrathecal dexmedetomidine as a bupivacaine adjuvant for caesarean section can prolong the duration of analgesia compared with bupivacaine alone. Secondary outcomes included postoperative pain, the time interval to the first analgesic request, the level of sedation, the incidence of adverse effects, and the fetal outcomes. MATERIALS AND METHODS: A systematic review and meta-analysis were conducted. The study compared the intrathecal administration of bupivacaine plus dexmedetomidine (group BD) to the intrathecal administration of bupivacaine alone (group B) for cesarean sections. RESULTS: Fourteen publications were included. Among patients who underwent spinal anesthesia for a cesarean section, 514 patients received intrathecal bupivacaine alone, and 533 patients received intrathecal bupivacaine plus dexmedetomidine. The onset of sensory and motor block was essentially the same in both groups; the time for sensory and motor block regression was significantly longer in the BD group. Postoperative Visual Analogue Scale (VAS) values were similar in group BD when compared to group B. Postoperative VAS scores remained consistently low in Group BD compared to Group B, starting from 1 hour after surgery. The level of sedation measured at the end of the cesarean section in both groups was almost similar. No difference in terms of safety, adverse events, and neonatal outcomes was found between the two groups. CONCLUSIONS: Use of intrathecal dexmedetomidine for spinal anesthesia in cesarean section significantly prolongs sensory and motor block compared to using bupivacaine alone as an adjuvant. It also improves analgesia after 1 hour with no difference in the incidence of maternal and neonatal adverse effects compared to bupivacaine alone. The optimal dose of dexmedetomidine to use remains to be ingested.

The effects of prolonged cathodal direct current stimulation on the excitatory and inhibitory circuits of the ipsilateral and contralateral motor cortex.

Weak cathodal transcranial direct current stimulation (tDCS) of the human hand area modulates corticospinal excitability with a suppression of motor-evoked potentials (MEPs) evoked by transcranial magnetic stimulation (TMS). The changes in excitability persist beyond the time of stimulation if tDCS is given for several minutes and can remain stable for an hour or more. The aim of present study was to evaluate whether a long-lasting suppression of cortical excitability could be induced by prolonged cathodal tDCS (20 min of stimulation). We also explored the impact of brain-derived neurotrophic factor (BDNF) gene polymorphisms, on tDCS after-effects. Cortical excitability to single and paired-pulse TMS was evaluated both for the stimulated and contralateral hemisphere, before and up to 24 h after 20 min of cathodal tDCS. We evaluated threshold and amplitude of MEPs, short interval intracortical inhibition (SICI), and intracortical facilitation (ICF). tDCS produced a pronounced suppression of MEP amplitude that was still significant at 3 h after the end of stimulation. The BDNF genotype had not influence on tDCS after-effects. Thresholds for MEPs, SICI and ICF were not affected. No significant effect was observed in the contralateral hemisphere. Twenty minutes of cathodal tDCS is capable of inducing a long-lasting suppression of the excitability of the human motor cortex.

Lidocaine 700 mg medicated plaster for post-herpetic neuralgia: focus on Quality of Life, effectiveness and safety - a retrospective observational study.

OBJECTIVE: Postherpetic neuralgia (PHN) is a neuropathic pain syndrome following herpes zoster (HZ) infection, characterized by pain that persists for months to years after the resolution of the HZ rash. Therapeutic management remains challenging for every clinician. We report the follow-up of patients diagnosed with PHN and treated with lidocaine 700 mg medicated plaster (LMP), focusing on effectiveness, safety, and Quality of Life (QoL). MATERIALS AND METHODS: This study is a retrospective observational investigation of patients with PHN treated with LMP. Patients were regularly followed for pain intensity, co-analgesic consumption, adverse effects, QoL using the EQ-5D, and patient satisfaction for 8 weeks. RESULTS: A total of 31 patients were evaluated. At enrollment, 18 patients (58.1%) were treated with at least one PHN concomitant medication, for which the number and dosing remained constant during the study. Patients had a mean average pain intensity of 6.5±1.0 at baseline, which decreased to 3.6±1.1 at week 4 and 2.8±0.9 at week 8. Four patients reported erythema, and one complained of vesicles eruption associated with pruritus. EQ-5D at weeks 4 and 8 of treatment showed persisting improvements in all domains except for the "anxiety/depression" domain. At week 8, <80% of patients reported to be satisfied or very satisfied. CONCLUSIONS: This study adds further weight to the growing body of clinical and research evidence that LMP treatment is effective and well-tolerated in patients with PHN.

Expression of type I interferon-associated genes at antiretroviral therapy interruption predicts HIV virological rebound.

Although certain individuals with HIV infection can stop antiretroviral therapy (ART) without viral load rebound, the mechanisms under-pinning 'post-treatment control' remain unclear. Using RNA-Seq we explored CD4 T cell gene expression to identify evidence of a mechanism that might underpin virological rebound and lead to discovery of associated biomarkers. Fourteen female participants who received 12 months of ART starting from primary HIV infection were sampled at the time of stopping therapy. Two analysis methods (Differential Gene Expression with Gene Set Enrichment Analysis, and Weighted Gene Co-expression Network Analysis) were employed to interrogate CD4+ T cell gene expression data and study pathways enriched in post-treatment controllers versus early rebounders. Using independent analysis tools, expression of genes associated with type I interferon responses were associated with a delayed time to viral rebound following treatment interruption (TI). Expression of four genes identified by Cox-Lasso (ISG15, XAF1, TRIM25 and USP18) was converted to a Risk Score, which associated with rebound (p < 0.01). These data link transcriptomic signatures associated with innate immunity with control following stopping ART. The results from this small sample need to be confirmed in larger trials, but could help define strategies for new therapies and identify new biomarkers for remission.

CD1A and CD1E gene polymorphisms are associated with susceptibility to multiple sclerosis.

Multiple sclerosis (MS) is thought to be an autoimmune T-cell-mediated disease directed at myelin antigens of the central nervous system. Besides myelin proteins, lipid components of CNS are supposed to play a role as antigens for T cells in MS. CD1 is a family of MHC-like glycoproteins specialized in capturing and presenting a variety of microbial and self lipids and glycolipids to antigen-specific T cells. CD1-restricted T cells specific for gangliosides and sulfatide have been isolated from subjects with MS and in mice with experimental allergic encephalopathy. We genotyped exon 2 of CD1A and CD1E in 205 MS patients and 223 unrelated healthy controls and determined their association with the presence of anti-ganglioside and anti-sulfatide antibodies. CD1E 01-01 is associated with a reduced risk of MS (OR 0.54, p=0.001); CD1A 02-02 (OR 1.99, p=0.012) or CD1E 02-02 (OR 2.45, p=0.000) with an increased risk. The combination of the genotypes CD1A 02-02 and CD1E 02-02 is present in 90.7% of patients but in only 9.4% controls (OR 94.16, p= 0.000). CD1A and CD1E polymorphisms contribute to the polygenic susceptibility to MS. The functional effects of CD1 polymorphisms are unknown, however changes in CD1 alleles may affect numerous immunological functions.

Control of SHIV-89.6P-infection of cynomolgus monkeys by HIV-1 Tat protein vaccine.

Vaccine strategies aimed at blocking virus entry have so far failed to induce protection against heterologous viruses. Thus, the control of viral infection and the block of disease onset may represent a more achievable goal of human immunodeficiency virus (HIV) vaccine strategies. Here we show that vaccination of cynomolgus monkeys with a biologically active HIV-1 Tat protein is safe, elicits a broad (humoral and cellular) specific immune response and reduces infection with the highly pathogenic simian-human immunodeficiency virus (SHIV)-89.6P to undetectable levels, preventing the CD4+ T-cell decrease. These results may provide new opportunities for the development of a vaccine against AIDS.

Analgesia with paracetamol/tramadol vs. paracetamol/codeine in one day-surgery: a randomized open study.

OBJECTIVES: The analgesic efficacy of two fixed combinations of tramadol/paracetamol (TP 37.5/325 mg) and codeine/paracetamol (CP 30/500 mg) was compared in 122 patients undergoing one-day surgical procedures (hallux valgus, haemorrhoidectomy, varicectomy and inguinal hernia repair), randomly treated with TP 37.5/325 mg or CP 30/500 mg one tablet after surgery ended, followed by one tablet four times daily for 48 hours. METHODS: Pain was assessed by a Verbal Rating Scale (VRS). Whenever the VRS score was > or = 3, the patient was given a "rescue medication" (tramadol 50 mg s.c.). The quality of life (time to return to normal daily activities, nightly rest, appetite, mood, deambulation, and self-care) was assessed in the postoperative period. Patients were asked to give their judgment on the surgical procedure and postoperative outcome. RESULTS: The results indicate that TP 37.5/325 mg was superior to CP 30/500 mg in terms of higher analgesic efficacy (VSR at 24 hours: CP 30/500, 2.52 +/- 0.86 vs. TP 37.5/325, 1.40 +/- 0.76; p < 0.001), less patients reporting adverse events (CP 30/500: 62% vs. TP 37.5/325: 36%; p < 0.01), less patients requiring rescue medications (CP 30/500: 18.2% vs. TP 37.5/325: 5.5%; p < 0.01), and more favorable judgment (scored "excellent" by 16% and 54.5% of CP 30/500 or TP 37.5/325-treated patients, respectively; p < 0.001). CONCLUSIONS: We conclude that a fixed association of tramadol/paracetamol is a valuable and safe tool for pain management in day hospital surgery, especially whenever any effort is done to reduce the time for hospitalization.

Septic shock due to Escherichia coli meningoencephalitis treated with immunoglobulin-M-enriched immunoglobulin preparation as adjuvant therapy: a case report.

BACKGROUND: Gram-negative bacteria are an uncommon etiology of spontaneous community-acquired adult meningitis and meningoencephalitis. Escherichia coli is a Gram-negative bacterium that is normally present in the intestinal microbial pool. Some Escherichia coli strains can cause diseases in humans and animals, with both intestinal and extraintestinal manifestations (extraintestinal pathogenic Escherichia coli) such as urinary tract infections, bacteremia with sepsis, and, more rarely, meningitis. Meningitis continues to be an important cause of mortality throughout the world, despite progress in antimicrobial chemotherapy and supportive therapy. The mortality rate fluctuates between 15% and 40%, and about 50% of the survivors report neurological sequelae. The majority of Escherichia coli meningitis cases develop as a result of hematogenous spread, with higher degrees of bacteremia also being related to worse prognosis. Cases presenting with impaired consciousness (that is, coma) are also reported to have poorer outcomes. CASE PRESENTATION: We describe the case of a 48-year-old caucasian woman with meningoencephalitis, with a marked alteration of consciousness on admission, and septic shock secondary to pyelonephritis caused by Escherichia coli, treated with targeted antimicrobial therapy and immunoglobulin-M-enriched immunoglobulin (Pentaglobin) preparation as adjuvant therapy. CONCLUSION: Despite the dramatic presentation of the patient on admission, the conflicting data on the use of immunoglobulins in septic shock, and the lack of evidence regarding their use in adult Escherichia coli meningoencephalitis, we obtained a remarkable improvement of her clinical condition, accompanied by partial resolution of her neurological deficits.

Spontaneous metastatic angiosarcoma of the tongue in a Wistar rat: morphological and immunohistochemical characterization.

A primary angiosarcoma was found in the tongue of a six-week-old female Wistar rat, sacrificed for humane reasons during the course of a four-week toxicology study. At necropsy, a nodule protruding from the dorsal part of the tongue was found. The nodule displayed microscopically, irregularly shaped vascular spaces separated by collagenous stroma. The spindle-shaped endothelial cells showed pleomorphism, hyperchromatism, and low mitotic activity; large nuclei with one or more nucleoli were present. Multiple metastases were found in the lungs, and the morphology of the cells resembled that of the primary tumor. Immunohistochemically, the primary tumor and the lung metastases were positive for von Willebrand factor and vimentin. The diagnosis of tongue angiosarcoma metastasizing to the lungs was made on the basis of microscopic and immunohistochemical findings.

The effect of an antimicrobial stewardship programme in two intensive care units of a teaching hospital: an interrupted time series analysis.

OBJECTIVES: To evaluate the effect of an antimicrobial stewardship programme in two intensive care units (ICUs) of a teaching hospital. METHODS: Between January 2017 and June 2018 we conducted a prospective, interventional, interrupted time-series study, based on Prospective Audit and Feedback in two ICUs of an acute-care teaching hospital. The primary outcomes were the difference in the antibiotic consumption, and the incidence of bloodstream infections (BSI) caused by multidrug-resistant (MDR) organisms. The secondary outcomes included the hospital mortality rate, the mean length of stay and the antibiotic expense. RESULTS: During the study, 231 audits were performed, evaluating 693 antibiotic prescriptions. The programme led to a global reduction in antibiotic consumption, with a change in level (CL) of -324.8 defined daily doses (DDD)/100 patient-days (PD), p 0.04, and particularly in the use of fluoroquinolone: (CL: -63.48 DDD/100 PD, p < 0.001). A non-significant reduction was obtained for the consumption of carbapenems (CL: -34.7 DDD/100 PD, p 0.25) and third- and fourth-generation cephalosporins (CL: -27.3 DDD/100 PD, p 0.102). Furthermore, we registered a significant decrease in all BSI (CL: -5.8 events/100 PD, p 0.026) and in BSI due to MDR Gram-negative organisms (CL: -2.96 events/100 PD, p 0.043). No difference was observed in the hospital mortality and length of stay. CONCLUSIONS: Our study demonstrated that implementation of an antimicrobial stewardship programme in two ICUs of a teaching hospital induced a significant reduction in antibiotic consumption and in the incidence of BSI due to MDR Gram-negative organisms, without any impact on the mortality rate.

Continuous intravenous low-dose diclofenac sodium to control a central fever after ischemic stroke in the intensive care unit: a case report and review of the literature.

INTRODUCTION: Elevation in body temperature within the first 24 hours of ischemic stroke is fairly common and known to be associated with worse outcomes. Only after thoroughly ruling out infection and the noninfectious etiologies and in the appropriate clinical setting should the diagnosis of central fever be made. Acetaminophen and nonsteroidal anti-inflammatory drugs are typical therapeutic options. External cooling is frequently used when pharmacologic interventions are inadequate. However, reports have suggested that neurogenic fevers are somewhat resistant to traditional pharmacologic therapies. CASE PRESENTATION: We describe a case of a Caucasian patient with central fever after ischemic stroke not responsive to acetaminophen administration and external cooling. After an initial bolus of diclofenac sodium (0.2 mg/kg in 100 ml of saline solution for 30 minutes), a continuous infusion (75 mg in 50 ml of saline solution) was started. After 5 days of treatment, the patient's body temperature was below 37.5 °C, and the diclofenac sodium infusion was stopped. CONCLUSIONS: We observed that a low-dose diclofenac sodium infusion was effective in treating fever without systemic side effects. This treatment may be suggested as an alternative to conventional antipyretic drugs, but additional clinical trials are required.

Leading indicators of trophic cascades.

Regime shifts are large, long-lasting changes in ecosystems. They are often hard to predict but may have leading indicators which are detectable in advance. Potential leading indicators include wider swings in dynamics of key ecosystem variables, slower return rates after perturbation and shift of variance towards lower frequencies. We evaluated these indicators using a food web model calibrated to long-term whole-lake experiments. We investigated whether impending regime shifts driven by gradual increase in exploitation of the top predator can create signals that cascade through food webs and be discerned in phytoplankton. Substantial changes in standard deviations, return rates and spectra occurred near the switch point, even two trophic levels removed from the regime shift in fishes. Signals of regime shift can be detected well in advance, if the driver of the regime shift changes much more slowly than the dynamics of key ecosystem variables which can be sampled frequently enough to measure the indicators. However, the regime shift may occur long after the driver has passed the critical point, because of very slow transient dynamics near the critical point. Thus, the ecosystem can be poised for regime shift by the time the signal is discernible. Field tests are needed to evaluate these indicators.

Comprehensive laparoscopic approach to pediatric varicocele based on preoperative color Doppler ultrasound assessment.

BACKGROUND: This study aimed to assess whether laparoscopic treatment for any kind of varicocele is possible after preoperative identification of refluxing veins by color Doppler ultrasound (CDUS). METHODS: At the authors' institution, 98 patients with a median age of 11.3 years (range, 7.1-16 years) were evaluated for a left varicocele. Preoperatively, all the patients underwent ultrasound scan assessment of testicular volume and CDUS to rule out reflux into the internal spermatic vein (ISV), deferential vein, or cremasteric vein. In all the patients, laparoscopic division of the spermatic artery and veins was performed as close as possible to the internal inguinal ring. The other vessels were coagulated and divided if shown to be refluxing on CDUS. RESULTS: Color Doppler ultrasound showed reflux only in the ISV in 87 cases (88.7%), but in both the ISV and the deferential in the remaining 11 cases (11.2%). During a median follow-up period of 18 months (range, 6-49 months), none of the authors' patients experienced varicocele recurrence either clinically or according to CDUS scanning. The median left testicular volume increased significantly postoperatively. CONCLUSION: The proposed technique based on laparoscopic interruption of the ISV and testicular artery very close to the internal inguinal ring, meticulous CDUS assessment to rule out reflux in the deferential vein, and coagulation of refluxing deferential veins allows successful laparoscopic treatment of most varicoceles.

Antibiotic effects on SO4(2-) uptake in human erythrocytes.

The erythrocyte is a cell highly exposed to oxygen pressure that, in turn, provokes oxidative stress involving loss of SH-groups, cell shrinkage by activation of K(+)-Cl(-) cotransport (KCC) and membrane destabilization which plays an important role in the premature haemolysis of red blood cells (RBCs). Oxidative stress provoked by chemicals frequently occurs in human erythrocytes. The aim of this study was to test whether the antibiotics alter the redox state and investigate their influences on band 3 protein that is involved in the facilitated electro neutral exchange of Cl(-) for HCO(3)(-) across the membrane of mammalian erythrocytes. Normal erythrocytes were treated with some antibiotics and thiol oxidizing agent N-ethylmaleimide (NEM) and tested for sulphate uptake, K(+) efflux and for glutathione (GSH) concentration as an index of oxidative stress. The rate constant of SO(4)(=) uptake measured in erythrocytes treated with antibiotics as well as NEM was decreased with respect to control cells as a result of band 3 SH-groups oxidation or the stress-induced K(+)-Cl(-) symport-mediated cell shrinkage. In fact, this hypothesis was verified by increased K(+) efflux and decreased GSH values measured in treated erythrocytes compared to controls.

Characteristics and surgical outcomes for medial temporal post-traumatic epilepsy.

A common post-traumatic location of epileptogenesis is the medial temporal lobe despite evidence of associated diffuse or remote cerebral injury. We undertook a review of post-traumatic medial temporal lobe epilepsy (MTLE) patients as part of an overall post-traumatic epilepsy population to assess the extent of cerebral injury sustained by this subpopulation and to establish whether surgical outcome differed from that of a non-traumatically-induced epilepsy population. A retrospective review of 57 patients operated for post-traumatic epilepsy (PTE) over a 10-year period (1993-2003) was undertaken with particular attention to those undergoing medial temporal resection. Preoperative magnetic resonance imaging (MRI) was assessed for the type and location of abnormalities. Postoperative outcomes were compared with those of patients with MTLE of non-traumatic origin operated by the same surgeon. Of the 57 patients operated, 30 cases underwent medial temporal lobe resection. The most common mechanism of injury was blunt trauma attributable to motor vehicle accidents with imaging abnormalities characterized by medial temporal sclerosis (MTS; 16 cases), T2/FLAIR hyperintensities (nine cases), periventricular gliosis (seven cases), diffuse cerebral atrophy (five cases) and focal encephalomalacia (three cases). Six patients had normal MRI studies. No significant differences in postoperative outcomes were found between post- and non-traumatic MTLE epilepsy groups. The presence of histopathological change in the medial temporal lobe varied greatly and provided no indication of a favourable postoperative outcome. Patients with post-traumatic medial temporal lobe epilepsy respond favourably to surgical treatment. In the case of medial temporal sclerosis, there is substantial variation of histopathological findings which correlate poorly with current imaging applications. The favourable outcomes obtained following surgery in this group attest to a commonality with other risk factors in the genesis of epilepsy in this location.

The hairy elbows syndrome: clinical and neuroradiological findings.

The hairy elbows syndrome (HES) is a rare congenital phenotype characterized by an abnormal increase in long hairs localized on the upper limbs extensor surfaces. This feature is often associated with short stature, facial asymmetry, dysmorphisms, intrauterine growth retardation (IUGR), and mental and speech delay. We report a case with hypertricosis cubiti associated with infantile spasms, behaviour disorders and cerebral hemisphere asymmetry. Although these findings have not been previously described we are uncertain whether they are unusual or underestimated. However, it is likely that these neurological findings are strongly interrelated leading to a more severe phenotype of the syndrome.

Estrogen upregulates cyclooxygenase-1 gene expression in ovine fetal pulmonary artery endothelium.

Prostacyclin (PGI2) is a key mediator of pulmonary vasodilation in the perinatal period and its synthesis in the pulmonary vasculature increases markedly during late gestation due to enhanced expression of the rate-limiting enzyme cyclooxygenase-1 (COX-1). The hormone estrogen may play a role in COX-1 upregulation since fetal estrogen levels rise dramatically during late gestation and estrogen enhances PGI2 synthesis in nonpulmonary vascular cells. We therefore studied the direct effects of estrogen on COX-1 expression in ovine fetal pulmonary artery endothelial cells (PAEC). Exposure to estradiol-17beta (E2beta, 10(-)10 to 10(-)6 M) caused a dose-related increase in COX-1 mRNA expression that was evident after 48 h and maximal at 10(-)8 M (fourfold increase). COX-1 mRNA stability was unchanged, suggesting that the upregulation is mediated at the level of transcription. E2beta treatment (10(-)8 M for 48 h) also caused a threefold increase in COX-1 protein expression and a threefold increase in PGI2 synthesis stimulated by bradykinin, the calcium ionophore A23187, or arachidonic acid. The estrogen receptor (ER) antagonist ICI 182,780 fully reversed the effects of the hormone on COX-1 protein expression and on arachidonic acid-stimulated PGI2 synthesis, and ER expression was evident in the PAEC by immunoblot analysis. These findings indicate that physiologic levels of estrogen cause upregulation of COX-1 expression and PGI2 synthesis in fetal PAEC via activation of PAEC ER. This process may play a critical role in optimizing the capacity for PGI2-mediated pulmonary vasodilation at birth, and it may also be involved in estrogen responsiveness in other vascular beds.