Reduced auditory steady state responses in autism spectrum disorder.

BACKGROUND: Auditory steady state responses (ASSRs) are elicited by clicktrains or amplitude-modulated tones, which entrain auditory cortex at their specific modulation rate. Previous research has reported reductions in ASSRs at 40 Hz for autism spectrum disorder (ASD) participants and first-degree relatives of people diagnosed with ASD (Mol Autism. 2011;2:11, Biol Psychiatry. 2007;62:192-197). METHODS: Using a 1.5 s-long auditory clicktrain stimulus, designed to elicit an ASSR at 40 Hz, this study attempted to replicate and extend these findings. Magnetencephalography (MEG) data were collected from 18 adolescent ASD participants and 18 typically developing controls. RESULTS: The ASSR localised to bilateral primary auditory regions. Regions of interest were thus defined in left and right primary auditory cortex (A1). While the transient gamma-band response (tGBR) from 0-0.1 s following presentation of the clicktrain stimulus was not different between groups, for either left or right A1, the ASD group had reduced oscillatory power at 40 Hz from 0.5 to 1.5 s post-stimulus onset, for both left and right A1. Additionally, the ASD group had reduced inter-trial coherence (phase consistency over trials) at 40 Hz from 0.64-0.82 s for right A1 and 1.04-1.22 s for left A1. LIMITATIONS: In this study, we did not conduct a clinical autism assessment (e.g. the ADOS), and therefore, it remains unclear whether ASSR power and/or ITC are associated with the clinical symptoms of ASD. CONCLUSION: Overall, our results support a specific reduction in ASSR oscillatory power and inter-trial coherence in ASD, rather than a generalised deficit in gamma-band responses. We argue that this could reflect a developmentally relevant reduction in non-linear neural processing.

Correction to: Abaloparatide effect on forearm bone mineral density and wrist fracture risk in postmenopausal women with osteoporosis.

The original version of this article, published on 21 March 2019, unfortunately contains some typos in Figs. 2, 3, 4, and Supplemental Fig. 1. The corrected figures are given below.

Effects of dietary supplementation with vitamin E, selenium yeast or both on egg incubation response, embryonic development, keet quality, and posthatch growth of helmeted guinea fowl breeders.

This study investigated the effects of dietary supplementation with vitamin E (vit. E), selenium yeast (Se yeast), or both on egg incubation response, embryonic development, keet quality, and posthatch growth of helmeted guinea fowls. Two hundred and forty 24-week old helmeted guinea fowl hens (average weight 1.75 + 0.22 kg) and cocks (average weight 2.15 + 0.20 kg) were assigned into 24 pens; each pen housed 10 hens and 2 cocks. There were four dietary treatments consisting of a basal diet (control), basal diet supplemented with vit. E (30 IU/kg), Se yeast (0.3 mg/kg Se), or both. Six pens were assigned to each treatment. Egg incubation response were estimated using 504 settable eggs sampled from each treatment collected during 15 to 17 weeks in lay. A total of 72 fertile eggs sampled from each treatment were used for the estimation of embryonic development. Quality of day-old keets hatched was scored based on physical conditions, while posthatch growth was measured for 21 days. Guinea fowl breeders fed diet supplemented with both vit. E and Se yeast produced the highest (P < 0.05) number of fertile eggs, percentage fertility, number of hatchlings, hatchability of total eggs, and hatchability of fertile eggs. Supplementation with vit. E + Se yeast resulted in the heaviest (P < 0.05) embryo weight, relative embryo weight, least (P < 0.05) yolk sac weight, and relative yolk sac weight on 25 days of incubation. Hatchlings from breeders fed diet supplemented with Se yeast and vit. E + Se yeast showed normal swallowed yolk. Supplementation of maternal diet with vit. E, Se yeast, and vit. E + Se yeast resulted in improved (P < 0.05) feed conversion ratio of subsequent hatchlings during 1 to 7-day posthatch growth. It can be concluded that dietary supplementation of vit. E + Se yeast in guinea fowl breeders resulted in improved egg fertility, hatchability, heavier embryo weights, hatchlings of good quality, and improved posthatch growth during the first 7 days.

Quantifying bi-variate coordination variability during longitudinal motor learning of a complex skill.

Biofeedback (BFb) can enhance the motor learning process by guiding skill exploration. Too much BFb, however, can foster dependency leading to skill retention deficits once removed. A reducing BFb schedule could negate dependency effects, however limited methodologies exist to assess the effectiveness of an intervention during application. This research proposes a new bi-variate method (CI2Area) to quantify coordination variability (CoordVar) as a measure of skill exploration during a motor learning intervention. Thirty-two participants were introduced to a novel explosive-lunge task. A BFb group (n = 16) were provided with visual BFb on rear hip, knee and ankle joint extension magnitudes and timing during a 26-week reducing schedule BFb intervention. CoordVar of hip-knee and knee-ankle angular velocities were quantified by calculating the area encompassed by the 95% confidence intervals of joint coupling angular-velocity bi-variate plots (CI2Area). Linear regressions were fitted to group and individual CoordVar longitudinal data. The BFb was effective in successfully altering whole limb technique within just two sessions, and these changes were retained. The BFb group demonstrated a continual increase of CoordVar throughout the intervention, showing continual skill exploration strategies, while the Control group remained unchanged. Gradually increasing time between sessions, using a longitudinally reducing BFb schedule, successfully negates dependency effects on BFb while also encouraging motor learning. Manipulating time between sessions allows for the provision of a high frequency of 100% BFb without fostering dependency. The CI2Area method was able to detect individual exploration strategies and could be used in the future to direct individual intervention modifications.

Risk factors for blood transfusion after shoulder arthroplasty.

AIMS: Currently, there is little information about the need for peri-operative blood transfusion in patients undergoing shoulder arthroplasty. The purpose of this study was to identify the rate of transfusion and its predisposing factors, and to establish a blood conservation strategy. METHODS: We identified all patients who had undergone shoulder arthroplasty at our hospital between 1 January 2011 and 31 December 2013. The rate of transfusion was determined from the patient's records. While there were exceptions, patients typically underwent transfusion if they had a level of haemoglobin of < 7.5 g/dl if asymptomatic, < 9.0 g/dl if they had a significant cardiac history or symptoms of dizziness or light headedness. Multivariable regression analysis was undertaken to identify predictors of transfusion. High- and low-risk cohorts for transfusion were identified from a receiver operating characteristic (ROC) curve. RESULTS: Of 1174 shoulder arthroplasties performed on 1081 patients, 53 cases (4.5%) required transfusion post-operatively. Predictors of blood transfusion were a lower pre-operative haematocrit (p < 0.001) and shoulder arthroplasty undertaken for post-traumatic arthritis (p < 0.001). ROC analysis identified pre-operative haematocrit of 39.6% as a 90% sensitivity cut-off for transfusion. In total 48 of the 436 (11%) shoulder arthroplasties with a pre-operative haematocrit < 39.6% needed transfusion compared with five of the 738 (0.70%) shoulder arthroplasties with a haematocrit above this level. DISCUSSION: We found that transfusion was needed less frequently than previously described for shoulder arthroplasty. Patients with a pre-operative haematocrit < 39.6% should be advised that there is an increased risk for blood transfusion, while those with a haematocrit above this level are unlikely to require transfusion. TAKE HOME MESSAGE: The rate of transfusion after shoulder arthroplasty is under 5%, and those with a pre-operative haematocrit greater than or equal to 39.6% have a very low likelihood (< 1%) of requiring a transfusion.

Nutritional Programming of Accelerated Puberty in Heifers: Involvement of Pro-Opiomelanocortin Neurones in the Arcuate Nucleus.

The timing of puberty and subsequent fertility in female mammals are dependent on the integration of metabolic signals by the hypothalamus. Pro-opiomelanocortin (POMC) neurones in the arcuate nucleus (ARC) comprise a critical metabolic-sensing pathway controlling the reproductive neuroendocrine axis. α-Melanocyte-stimulating hormone (αMSH), a product of the POMC gene, has excitatory effects on gonadotrophin-releasing hormone (GnRH) neurones and fibres containing αMSH project to GnRH and kisspeptin neurones. Because kisspeptin is a potent stimulator of GnRH release, αMSH may also stimulate GnRH secretion indirectly via kisspeptin neurones. In the present work, we report studies conducted in young female cattle (heifers) aiming to determine whether increased nutrient intake during the juvenile period (4-8 months of age), a strategy previously shown to advance puberty, alters POMC and KISS1 mRNA expression, as well as αMSH close contacts on GnRH and kisspeptin neurones. In Experiment 1, POMC mRNA expression, detected by in situ hybridisation, was greater (P < 0.05) in the ARC in heifers that gained 1 kg/day of body weight (high-gain, HG; n = 6) compared to heifers that gained 0.5 kg/day (low-gain, LG; n = 5). The number of KISS1-expressing cells in the middle ARC was reduced (P < 0.05) in HG compared to LG heifers. In Experiment 2, double-immunofluorescence showed limited αMSH-positive close contacts on GnRH neurones, and the magnitude of these inputs was not influenced by nutritional status. Conversely, a large number of kisspeptin-immunoreactive cells in the ARC were observed in close proximity to αMSH-containing varicosities. Furthermore, HG heifers (n = 5) exhibited a greater (P < 0.05) percentage of kisspeptin neurones in direct apposition to αMSH fibres and an increased (P < 0.05) number of αMSH close contacts per kisspeptin cell compared to LG heifers (n = 6). These results indicate that the POMC-kisspeptin pathway may be important in mediating the nutritional acceleration of puberty in heifers.

Reproduction Symposium: hypothalamic neuropeptides and the nutritional programming of puberty in heifers.

Nutrition during the juvenile period has a major impact on timing reproductive maturity in heifers. Restricted growth delays puberty, whereas elevated BW gain advances the onset of puberty. The initiation of high-frequency episodic release of GnRH and, consequently, LH during the peripubertal period is crucial for maturation of the reproductive axis and establishment of normal estrous cycles. Nutritional signals are perceived by metabolic-sensing cells in the hypothalamus, which interact with estradiol-receptive neurons to regulate the secretory activity of GnRH neurons. The orexigenic peptide, neuropeptide Y (NPY), and the anorexigenic peptide derived from the proopiomelanocortin (POMC) gene, melanocyte-stimulating hormone α (αMSH), are believed to be major afferent pathways that transmit inhibitory (NPY) and excitatory (αMSH) inputs to GnRH neurons. The neuropeptide kisspeptin is considered a major stimulator of GnRH secretion and has been shown to mediate estradiol's effect on GnRH neuronal activity. Kisspeptin may also integrate the neuronal pathways mediating the metabolic and gonadal steroid hormone control of gonadotropin secretion. Recent studies in our laboratories indicate that functional and structural changes in the pathways involving NPY, POMC, and kisspeptin neurons occur in response to high rates of BW gain during the juvenile period in heifers. Changes include regulation of expression in NPY, POMC, and KISS1 and plasticity in the neuronal projections to GnRH neurons and within the neuronal network comprising these cells. Moreover, an intricate pattern of differential gene expression in the arcuate nucleus of the hypothalamus occurs in response to feeding high concentrate diets that promote elevated BW gain. Genes involved include those controlling feeding intake and cell metabolism, neuronal growth and remodeling, and synaptic transmission. Characterizing the cellular pathways and molecular networks involved in the mechanisms that control the timing of pubertal onset will assist in improving existing strategies and facilitate the development of novel approaches to program puberty in heifers. These include the use of diets that elevate BW gain during strategic periods of prepubertal development.

The influence of dietary ß-glucan, PAMP exposure and Aeromonas salmonicida on apoptosis modulation in common carp (Cyprinus carpio).

The association between ß-glucan (MacroGard®) supplemented feed and apoptosis in immune-related organs of common carp (Cyprinus carpio) was studied using fluorescence microscopy and real-time PCR. In addition the effect of Aeromonas salmonicida, LPS and Poly(I:C) injections on this relationship was evaluated. Whilst acridine orange staining revealed that apoptosis levels were independent of MacroGard® and LPS/Poly(I:C) administration or their combination, it was shown that injection with A. salmonicida increased the percentage of apoptotic cells irrespective of the feeding regime. It was apparent that in all the treatments gene expression profiles displayed organ and time dependency. For example no effect was observed at 7 days of MacroGard® administration while 25 days of feeding led to increased iNOS expression and differential up-regulation of anti- or pro-apoptotic genes depending on organ. This may indicate differences in NO sensitivity. MacroGard® also led to an elevation of pro- as well as anti-apoptotic genes in LPS or Poly(I:C) injected fish, while LPS/Poly(I:C) alone had little effect. A. salmonicida caused enhanced iNOS expression and it is possible that the type of apoptosis pathway induced is organ dependent as Caspase 9 is induced in mid-gut but not in pronephros. These results indicate that MacroGard® feeding alone or in combination with other pathogenic factors did not induce significant apoptosis in immune organs.

Reproductive seasonality in the mare: neuroendocrine basis and pharmacologic control.

Reproductive seasonality in the mare is characterized by a marked decline in adenohypophyseal synthesis and secretion of LH beginning near the autumnal equinox. Thus, ovarian cycles have ceased in most mares by the time of the winter solstice. Endogenous reproductive rhythms in seasonal species are entrained or synchronized as a result of periodic environmental cues. In the horse, this cue is primarily day length. Hence, supplemental lighting schemes have been used managerially for decades to modify the annual timing of reproduction in the mare. Although a full characterization of the cellular and molecular bases of seasonal rhythms has not been realized in any species, many of their synaptic and humoral signaling pathways have been defined. In the mare, neuroendocrine-related studies have focused primarily on the roles of GnRH and interneuronal signaling pathways that subserve the GnRH system in the regulatory cascade. Recent studies have considered the role of a newly discovered neuropeptide, RF-related peptide 3 that could function to inhibit GnRH secretion or gonadotrope responsiveness. Although results that used native peptide sequences have been negative in the mare and mixed in all mammalian females, new studies that used an RFRP3 antagonist (RF9) in sheep are encouraging. Importantly, despite continuing deficits in some fundamental areas, the knowledge required to control seasonal anovulation pharmacologically has been available for >20 yr. Specifically, the continuous infusion of native GnRH is both reliable and efficient for accelerating reproductive transition and is uniquely applicable to the horse. However, its practical exploitation continues to await the development of a commercially acceptable delivery vehicle.

Greasing the wheels of managing overweight and obesity with omega-3 fatty acids.

The epidemic of overweight and obesity around the world and in the US is a major public health challenge, with 1.5 billion overweight and obese adults worldwide, and 68% of US adults and 31% of US children and adolescents overweight or obese. Obesity leads to serious health consequences, including an increased risk of type 2 diabetes mellitus and heart disease. Current preventive and medical treatments include lifestyle modification, medication, and bariatric surgery in extreme cases; however, they are either not very efficacious or are very expensive. Obesity is a complex condition involving the dysregulation of several organ systems and molecular pathways, including adipose tissue, the pancreas, the gastrointestinal tract, and the CNS. The role of the CNS in obesity is receiving more attention as obesity rates rise and treatments continue to fail. While the role of the hypothalamus in regulation of appetite and food intake has long been recognized, the roles of the CNS reward systems are beginning to be examined as the role of environmental influences on energy balance are explored. Omega-3 polyunsaturated fatty acids are essential nutrients that play a beneficial role in several disease processes due to their anti-inflammatory effects, modulation of lipids, and effects on the CNS. Omega-3 fatty acids, specifically EPA and DHA, have shown promising preliminary results in animal and human studies in the prevention and treatment of obesity. Given their effects on many of the pathways involved in obesity, and specifically in the endocannabinoid and mesocorticolimbic pathways, we hypothesize that EPA and DHA supplementation in populations can reduce the reward associated with food, thereby reduce appetite and food intake, and ultimately contribute to the prevention or reduction of obesity. If these fatty acids do harbor such potential, their supplementation in many parts of the world may hold great promise in reducing the global burden of obesity.

Developmental changes in hypothalamic Kiss1 expression during activation of the pulsatile release of luteinising hormone in maturing ewe lambs.

Onset of puberty is characterised by a marked increase in the frequency of release of gonadotrophin-releasing hormone (GnRH) and luteinising hormone (LH). The Kiss1 gene plays a critical role in pubertal development, and its product, kisspeptin, stimulates GnRH and LH release. In the present study, we tested the hypothesis that Kiss1 gene expression in the preoptic area (POA) and hypothalamus increases during maturation of the reproductive neuroendocrine axis in association with increased LH pulsatility. Ovariectomised, oestradiol-replaced lambs were euthanised at 25, 30 and 35 weeks of age. Blood samples were collected before euthanasia to characterise the pattern of LH release. Kiss1 mRNA was detected in coronal sections of the POA and hypothalamus and Kiss1-expressing cells were identified on the basis of silver grain density. The mean number of Kiss1-expressing cells in the POA/periventricular (PeV) areas increased from 25 to 30 weeks of age. No further increase at 35 weeks of age was observed, and the changes in Kiss1 expression in the POA/PeV were independent of changes in LH pulse frequency. The mean number of Kiss1-expressing cells in the arcuate (ARC) nucleus did not differ among age groups, although it was greater in the middle ARC of lambs exhibiting increased frequency of LH release. The density of silver grains per cell did not differ among groups in any of the areas studied. The results obtained indicate that the Kiss1 gene is activated in the POA/PeV and ARC of ewe lambs during juvenile development, and that kisspeptin neurones in the middle ARC, in particular, are involved in the acceleration of pulsatile LH release during maturation of the reproductive neuroendocrine axis in ewe lambs.

Extrathyroidal expression of TSH receptor.

The TSH receptor expressed on the cell surface of thyroid follicular cells plays a pivotal role in the regulation of thyroid status and growth of the thyroid gland. In recent years it has become evident that the TSH receptor is also expressed widely in a variety of extrathyroidal tissues including: anterior pituitary; hypothalamus; ovary; testis; skin; kidney; immune system; bone marrow and peripheral blood cells; white and brown adipose tissue; orbital preadipocyte fibroblasts and bone. A large body of evidence is emerging to describe the functional roles of the TSH receptor at these various sites but their physiological importance in many cases remains a subject of controversy and much interest. Current understanding of the actions of the TSH receptor in extrathyroidal tissues and their possible physiological implications is discussed.

Diagnosis of prostate cancer by detection of minichromosome maintenance 5 protein in urine sediments.

BACKGROUND: The accuracy of prostate-specific antigen (PSA) testing in prostate cancer detection is constrained by low sensitivity and specificity. Dysregulated expression of minichromosome maintenance (Mcm) 2-7 proteins is an early event in epithelial multistep carcinogenesis and thus MCM proteins represent powerful cancer diagnostic markers. In this study we investigate Mcm5 as a urinary biomarker for prostate cancer detection. METHODS: Urine was obtained from 88 men with prostate cancer and from two control groups negative for malignancy. A strictly normal cohort included 28 men with complete, normal investigations, no urinary calculi and serum PSA <2 ng ml(-1). An expanded control cohort comprised 331 men with a benign final diagnosis, regardless of PSA level. Urine was collected before and after prostate massage in the cancer patient cohort. An immunofluorometric assay was used to measure Mcm5 levels in urine sediments. RESULTS: The Mcm5 test detected prostate cancer with 82% sensitivity (confidence interval (CI)= 72-89%) and with a specificity ranging from 73 (CI=68-78%) to 93% (CI=76-99%). Prostate massage led to increased Mcm5 signals compared with pre-massage samples (median 3440 (interquartile range (IQR) 2280 to 5220) vs 2360 (IQR <1800 to 4360); P=0.009), and was associated with significantly increased diagnostic sensitivity (82 vs 60%; P=0.012). CONCLUSIONS: Urinary Mcm5 detection seems to be a simple, accurate and noninvasive method for identifying patients with prostate cancer. Large-scale prospective trials are now required to evaluate this test in diagnosis and screening.

Multicenter study to assess potential hazards from exposure to lipid peroxidation products in soya bean oil from Trilucent breast implants.

In response to a Hazard Notice by the Medical Devices Agency of the UK in 2000 regarding the Trilucent breast implant (TBI), an expert panel was convened to implement a research program to determine whether genotoxic compounds were formed in the soybean oil filler (SOF) of TBIs and whether these could be released to produce local or systemic genotoxicity. The panel established a research program involving six laboratories. The program recruited 47 patients who had received TBIs (9 patients had received silicone implants previously). A reference group (REBI) of 34 patients who had exchanged either silicone (17 patients) implants (REBI-E) or patients (17) who were to receive primary implantation augmentation with silicone (REBI-PIA), and who were included as needed to increase either the pre- or post-explantation sample number. Of the 17 REBI-E patients, 5 had silicone implants and 12 had saline implants previously (prior to the last exchange). Investigation was undertaken before and after replacement surgery in the TBI patients and before and after replacement or augmentation surgery in the REBI patients. The pre- to post-operative sample interval was 8-12 weeks. Pre-operative samples were collected within 7 days prior to the operation. Information on a variety of demographic and behavioral features was collected. Biochemical and biological endpoints relating to genotoxic lipid peroxidation (LPO) products potentially formed in the SOF, and released locally or distributed systemically, were measured. The SOF of explanted TBIs was found to have substantial levels of LPO products, particularly malondialdehyde (MDA), and low levels of trans-4-hydroxy-2-nonenal (HNE) not found in unused implants. Mutagenicity of the SOF was related to the levels of MDA. Capsules that formed around TBIs were microscopically similar to those of reference implants, but MDA-DNA adducts were observed in capsular macrophages and fibroblasts of only TBI capsules. These cell types are not progenitors of breast carcinoma (BCa) and the location of the implants precludes LPO products reaching the mammary epithelial cells which are progenitors of BCa. Blood levels of LPO products were not increased in TBI patients compared to REBI patients and did not change with explantation. In TBI patients, white blood cells did not show evidence of increased levels of LPO-related aldehyde DNA adducts. In conclusion, based on a number of measured parameters, there was no evident effect that would contribute to breast or systemic cancer risk in the TBI patients, and the recommended treatment of TBI patients involving explantation was judged appropriate.

Voxel-based morphometry in the R6/2 transgenic mouse reveals differences between genotypes not seen with manual 2D morphometry.

The R6/2 mouse is the most common mouse model used for Huntington's disease (HD), a fatal, inherited neurodegenerative CAG disorder characterized by marked brain atrophy. We scanned 47 R6/2 transgenic and 42 wildtype (WT) ex vivo mouse brains at 18 weeks of age using high resolution, three-dimensional magnetic resonance imaging (MRI) for automated voxel-based morphometry (VBM) analysis. We found differences between genotypes in specific brain structures. Many of these changes were bilateral and were found in regions known to be involved in the behavioral deficits present in both R6/2 mice and HD patients. In particular, changes were evident in the basal ganglia, hippocampus, cortex and hypothalamus. In the striatum, changes were heterogenous and reminiscent of striosomal distribution. Changes were also seen in the cerebellum, as might be expected in a mouse carrying a repeat length typical of juvenile onset HD. Many of these changes were not detected by manual 2D morphometry from the same MR images. These data indicate that VBM will be a valuable technique for in vivo measurement of developing pathology in HD transgenic mice, and may be particularly useful for correlating histologically undetectable changes with behavioral deficits.

Seasonal effects of central leptin infusion on secretion of melatonin and prolactin and on SOCS-3 gene expression in ewes.

Recent studies have demonstrated photoperiodic changes in leptin sensitivity of seasonal mammals. Herein, we examined the interaction of season (long days (LD) versus short days (SD)) and recombinant ovine leptin (roleptin) on secretion of melatonin and prolactin (PRL) and on mRNA expression of suppressor of cytokine signaling-3 (SOCS-3) in the medial basal hypothalamus (MBH) in sheep. Twenty-four Polish Longwool ewes, surgically fitted with third ventricle (IIIV) cannulas, were utilized in a replicated switchback design involving 12 ewes per season. Within-season and replicate ewes were assigned randomly to one of three treatments (four ewes/treatment) and infused centrally three times at 0, 1 and 2 h beginning at sunset. Treatments were 1) control, Ringer-Locke buffer; 2) L1, roleptin, 0.5 microg/kg BW; and 3) L2, roleptin, 1.0 microg/kg BW. Jugular blood samples were collected at 15-min intervals beginning immediately before the start of infusions and continued for 6 h. At the end of blood sampling, a washout period of at least 3 days elapsed before ewes were re-randomized and treated with one of the treatments described above (four ewes/treatment). Ewes were then killed and brains were collected for MBH processing. Leptin treatments increased (P<0.001) circulating leptin concentrations compared with controls during both seasons in a dose-dependent manner. Overall, mean plasma concentrations of melatonin were greater (P<0.001) during LD than SD. However, leptin treatments increased melatonin concentrations during SD in a dose-dependent manner and decreased it during LD. Similarly, plasma concentrations of PRL were greater (P<0.001) during LD than SD. However, unlike changes in melatonin, circulating PRL decreased (P<0.001) in response to leptin during LD. Semi-quantitative PCR revealed that leptin increased (P<0.001) SOCS-3 expression in the MBH region during LD in a dose-dependent manner. Data provide evidence that secretion of photoperiodic hormones such as melatonin and PRL are inversely regulated by leptin during SD and LD. However, the increase in expression of SOCS-3 in the MBH during LD compared with SD fails to fully explain these effects.

The development of a new three-step protocol to determine the efficacy of disinfectant wipes on surfaces contaminated with Staphylococcus aureus.

We developed a three-step protocol to quantify the efficacy of disinfectant wipes, their ability to remove and prevent microbial transfer from surfaces and their overall antimicrobial activity. Meticillin-resistant (MRSA) or -susceptible (MSSA) Staphylococcus aureus (6-7 log(10)cfu) were inoculated onto stainless steel discs with or without organic load and dried. Grapefruit extract-containing test wipes and unmedicated control wipes were used. In step 1, wipes were mechanically rotated against surfaces for 10s at 60rpm, exerting a weight of 100+/-5g. Bacterial removal was assessed by transferring the steel discs to neutraliser, resuspending and counting remaining bacteria. In step 2, bacterial transfer from wipes was assessed by eight consecutive mechanical adpression transfers to agar/neutraliser plates. Step 3 was the measurement of antimicrobial activity by direct inoculation of the wipes for 10s followed by neutralisation and enumeration. Test wipes achieved a significantly higher bacterial cell removal than control wipes on all surfaces (P<0.05). The low bactericidal activity of the wipes (<1 log(10) reduction when directly inoculated) and the subsequent survival of bacteria on the wipes, however, led to repeated microbial transfer when initially high contamination levels were present. There were no differences between MRSA and MSSA in removal, transfer or antimicrobial activity. The three-step method is a useful tool for developing future guidelines to assess the ability of wipes to disinfect surfaces.

Aspartame: a safety evaluation based on current use levels, regulations, and toxicological and epidemiological studies.

Aspartame is a methyl ester of a dipeptide used as a synthetic nonnutritive sweetener in over 90 countries worldwide in over 6000 products. The purpose of this investigation was to review the scientific literature on the absorption and metabolism, the current consumption levels worldwide, the toxicology, and recent epidemiological studies on aspartame. Current use levels of aspartame, even by high users in special subgroups, remains well below the U.S. Food and Drug Administration and European Food Safety Authority established acceptable daily intake levels of 50 and 40 mg/kg bw/day, respectively. Consumption of large doses of aspartame in a single bolus dose will have an effect on some biochemical parameters, including plasma amino acid levels and brain neurotransmitter levels. The rise in plasma levels of phenylalanine and aspartic acid following administration of aspartame at doses less than or equal to 50 mg/kg bw do not exceed those observed postprandially. Acute, subacute and chronic toxicity studies with aspartame, and its decomposition products, conducted in mice, rats, hamsters and dogs have consistently found no adverse effect of aspartame with doses up to at least 4000 mg/kg bw/day. Critical review of all carcinogenicity studies conducted on aspartame found no credible evidence that aspartame is carcinogenic. The data from the extensive investigations into the possibility of neurotoxic effects of aspartame, in general, do not support the hypothesis that aspartame in the human diet will affect nervous system function, learning or behavior. Epidemiological studies on aspartame include several case-control studies and one well-conducted prospective epidemiological study with a large cohort, in which the consumption of aspartame was measured. The studies provide no evidence to support an association between aspartame and cancer in any tissue. The weight of existing evidence is that aspartame is safe at current levels of consumption as a nonnutritive sweetener.

The Addis Ababa fistula hospital: an holistic approach to the management of patients with vesicovaginal fistulae.

Ethiopia is amongst the world's poorest countries. It is estimated that approximately 30,000 women have an untreated vesicovaginal fistula, the overwhelming proportion of which are complications of neglected, prolonged or obstructed labour. When unrelieved, the presenting foetal part is impacted against the soft tissues of the pelvis, resulting in a widespread ischaemic injury. This 'field injury' often results in multiple other injuries, in addition to a vesicovaginal fistula. Focusing simply on the 'hole' between the bladder and vagina will ignore many of the other injuries these women have sustained. These include both physical and social problems, stress and urge urinary incontinence, hydronephrosis, renal failure, rectovaginal fistulae, third degree tears, amenorrhea, secondary infertility, vaginal scarring and foot drop. Over 50% will be divorced by their husband and excluded from religious activities, their home, public transport and hospitals. The Fistula Hospital in Addis Ababa in Ethiopia, founded in 1975 and run entirely by charitable donation, is dedicated exclusively to the care of women with obstetric fistulae, and the treatment of other physical and social injuries they have sustained.

Plasma fibrinogen in ulcerative colitis: the effect of disease activity and nicotine therapy in a randomised controlled trial.

BACKGROUND: Smoking increases plasma fibrinogen and cardiovascular risk whereas transdermal nicotine may not. Fibrinogen is an acute phase protein and may reflect disease activity in ulcerative colitis. AIMS: To examine the effect of topical nicotine on plasma fibrinogen and any relationship between fibrinogen and ulcerative colitis disease activity. PATIENTS: Forty-eight non-smokers with moderately active ulcerative colitis. METHODS: Patients were randomised to 6 mg nicotine enema or placebo for 6 weeks, followed by open nicotine therapy for 4 weeks. Plasma fibrinogen was measured at baseline and after 6 and 10 weeks; at each assessment sigmoidoscopy with a rectal biopsy was performed. RESULTS.: At 6 weeks median plasma fibrinogen was 3.30 g/l on nicotine compared to 3.05 g/l on placebo, P = 0.90 when adjusted for baseline values. There was a correlation between fibrinogen and the UC disease activity index (UCDAI) at weeks 0 and 10, P = 0.036 and 0.033, respectively, and between fibrinogen and sigmoidoscopic grade at each assessment, P = 0.014, 0.021 and 0.034. Changes in fibrinogen did not correlate with changes in disease severity. CONCLUSIONS: There was no significant effect of nicotine enemas, in either direction, on plasma fibrinogen-this was raised in moderately active UC and correlated with the sigmoidoscopic grade of colitis and the UCDAI; however, fibrinogen was not sufficiently sensitive to be of practical clinical value.