Spontaneous firing patterns in the medial geniculate nucleus in a guinea pig model of tinnitus.

The mechanism of tinnitus, the perception of sound in the absence of acoustic stimulation, remains as yet unknown. It has been proposed that tinnitus is caused by altered spontaneous activity in the auditory pathway following cochlear damage in combination with inadequate gating at the level of the auditory thalamus, the medial geniculate nucleus (MGN). To investigate this further we made electrophysiological recordings in MGN of guinea pigs (n = 9) with and without tinnitus after acoustic trauma (continuous loud tone at 10 kHz, 124 dB SPL for 2 h). Parameters of interest were spontaneous tonic and burst firing. After acoustic trauma, 5 out of 9 guinea pigs developed signs of tinnitus as determined by the gap prepulse inhibition of acoustic startle. Spontaneous firing rates were significantly increased in the tinnitus animals as compared to the non-tinnitus animals and this change was specific to pure-tone responsive MGN neurons. However, burst firing parameters, including number of bursts per minute, burst duration, number of spikes in each burst, and percentage of spikes occurring in a burst, were not different between tinnitus and non-tinnitus animals. In addition, our data showed a strong dependence of spontaneous firing rates with heart rate, which implies that monitoring physiological status in animals is pertinent to obtaining reliable data when recording at higher levels of the auditory pathway. Our results suggest that increases in the tonic spontaneous fining rate of pure-tone responsive MGN neurons but not changes in burst firing parameters, are a robust neural signature of tinnitus in anaesthetised animals.

The impact of COVID-19 on emergency general surgery admissions and operative volumes: A single centre experience.

INTRODUCTION: The COVID-19 pandemic has placed a significant strain on healthcare resources and utilisation globally. The appearance of the disease in the Republic of Ireland resulted in a broad postponement of scheduled and routine surgical care. The influence of the novel coronavirus, and the associated imposition of public health measures such as school closures and social distancing, on the burden of emergency surgical disease is less clear. AIM: The aim of this study was to examine the impact of COVID-19 on the number of patients presenting to our institution with emergent surgical illnesses or requiring emergency general surgical procedures. METHODS: All patients attending our service between March 1st 2020 and April 30th 2020 were identified retrospectively by examining electronic handover and electronic discharge summaries, and data were collected relating to demographics, presenting illness, critical care utilisation, length of stay, operative or endoscopic procedure performed, and in-hospital mortality. Similar data were collected March 1st to April 30th 2019, 2018, and 2017 respectively to allow direct comparison. RESULTS: 151 patients were admitted during the study period, compared to a total of 788 during the proceeding three years (mean 2.49 admissions per night versus 4.35 per night, 42.8% reduction, p < 0.001). Median age of admitted patients was 51.8 years, compared to 50.3 years formerly (p = 0.35). 53 emergency procedures were performed, compared to a median of 70 over the same period in the previous years (mean 0.87 per day versus 1.16 per day, 25.4% reduction, p = 0.05). CONCLUSION: A significant overall reduction in the number of patients being admitted to our unit and requiring emergency surgical procedures during March and April 2020 was seen, in line with patterns reported internationally.

Prophylactic negative wound therapy in laparotomy wounds (PROPEL trial): randomized controlled trial.

BACKGROUND: Superficial surgical site infections are a common post-operative complication. They also place a considerable financial burden on healthcare. The use of prophylactic negative pressure wound therapy has been advocated to reduce wound infection rates. However, there is debate around its routine use. The purpose of this trial is to determine if prophylactic negative pressure wound therapy reduces post-operative wound complications in patients undergoing laparotomy. METHODS/DESIGN: This multi-centre randomised controlled trial will compare standard surgical dressings (control) to two competing negative pressure wound therapy dressings (Prevena™ and PICO™). All patients will be over 18 years, who are undergoing an emergency or elective laparotomy. It is intended to enrol a total of 271 patients for the trial. DISCUSSION: The PROPEL trial is a multi-centre randomised controlled trial of patients undergoing laparotomy. The comparison of standard treatment to two commercially available NPWT will help provide consensus on the routine management of laparotomy wounds. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov (NCT number NCT03871023).

Changes in auditory thalamus neural firing patterns after acoustic trauma in rats.

Tinnitus is an abnormal phantom perception associated with cochlear trauma, and is thought to cause changes in the rates and patterns of firing neurons in the central auditory pathway. Recent studies have suggested a key role for the auditory thalamus, the medial geniculate nucleus (MGN), in the generation of tinnitus as it may serve a gating function for information en route to cortex. Dysfunctional gating would lead to abnormal activity reaching cortex and hence inappropriate perception, tinnitus, would occur. In this study we compared spontaneous MGN firing rates and burst firing parameters in Wistar rats with and without behavioural evidence of tinnitus following an acoustic trauma. Data were also compared with animals subjected to sham surgery and at an early time-point (2 weeks) after acoustic trauma. Acoustic trauma resulted in a temporary but not a permanent threshold loss and no differences were found in spontaneous firing rate between any of the groups. However, acoustic trauma, whether resulting in tinnitus or not, was accompanied by a significant decrease in the percentage of neurons showing burst firing. In bursting neurons, the number of spikes occurring in a burst and the number of burst per minutes was also significantly reduced compared to the sham group. Our results show that in our rat model without permanent threshold loss, elevated spontaneous firing rates are not associated with acoustic trauma and/or tinnitus and that burst firing parameters are associated with acoustic trauma but are not a neural signature for tinnitus.

Medial geniculate neurons show diverse effects in response to electrical stimulation of prefrontal cortex.

Phantom perceptions have been proposed to arise due to dysfunctional sensory gating at the level of the thalamus. Recently, it has been suggested that tinnitus, a phantom perception of sound, may arise from altered cortico-limbic circuitry and its connection with the auditory thalamus, the medial geniculate nucleus (MGN). Indeed, some elements of this cortico-limbic circuitry, such as the prefrontal cortex (PFC), as well as elements of the auditory pathway, have been shown to be altered in humans with tinnitus. However, the functional connectivity between PFC and MGN has not yet been explored. We therefore investigated the effects of activation of the PFC on neuronal activity in MGN in normal anaesthetized Wistar rats. Bipolar electrical stimulation was delivered to the PFC while recording single neuron activity in the MGN. The majority (81%) of MGN neurons sampled showed a change in their spontaneous firing rate in response to electrical stimulation of the PFC. The effects observed varied greatly between neurons and included combinations of inhibitory and excitatory effects with a wide range of latencies. The effects were not dependent on acoustic response type or MGN subdivision. These data demonstrate that PFC activation can modulate MGN neuronal activity and this connection could potentially play a role in sensory gating of auditory signals.

A study of selected factors affecting efficacy of compost tea against several fungal pathogens of potato.

AIM: To investigate selected factors of two nonaerated compost teas (NCT) and mechanisms that influence the restriction of several fungal potato pathogens. METHODS AND RESULTS: Two NCTs, made from either commercial compost, (CCT) or vineyard compost (VCT), were tested for their ability to suppress potato pathogens. The VCT was more suppressive than CCT to mycelial growth of Alternaria solani and Rhizoctonia solani isolate 299, but not for R. solani isolate 422. Metagenomic studies of microbial diversity revealed that the CCT had higher fungal and bacterial diversity and richness than the VCT. Use of CCT significantly reduced lesion area of Alternaria alternata on detached leaves, however, a gum adjuvant did not lead to significantly greater control. Scanning microscopy showed that the spatial distribution of microbes from the CCT was altered with gum addition, to resemble what may have been a microbial biofilm. CONCLUSION: We confirmed that each NCT could suppress the mycelial growth of selected potato pathogens in culture, and CCT reduced A. alternata lesions on detached leaves. Factors including concentration, microbial communities and physio-chemical properties could not be consistently linked to NCT efficacy. SIGNIFICANCE AND IMPACT OF THE STUDY: This study particularly highlights the application of scanning microscopy to study the interaction between pathogens and putative NCT microbes on foliar surfaces. This adds insight to mechanisms of NCT efficacy, along with physico-chemical and microbial characterization of the teas. This study shows the potential for the use of NCTs as a crop protection tool of low-cost which could be of particular benefit in smallholder agriculture.

Diverse microbial communities in non-aerated compost teas suppress bacterial wilt.

Non-aerated compost teas (NCTs) are water extracts of composted organic materials and are used to suppress soil borne and foliar disease in many pathosystems. Greenhouse trials were used to test the effectiveness of NCTs to suppress potato bacterial wilt caused by Ralstonia solanacearum on plants grown in soils inoculated with a virulent isolate of the pathogen (biovar II). NCTs prepared from matured compost sources: agricultural waste (AWCT), vermicompost (VCT) and solid municipal waste (SMWCT) were evaluated at three initial application times (7 days before inoculation, at time of inoculation and 7 days after inoculation) prior to weekly applications, in a randomized complete-block design. AWCT applied initially at the time of inoculation resulted in the greatest disease suppression, with the disease severity index 2.5-fold less than the non-treated plants and the "area under the disease progress curve" (AUDPC) 3.2-fold less. VCT and SMWCT were less suppressive than AWCT regardless of initial application time. Next generation sequencing of the v4 region of 16S rRNA gene and the internal transcribed spacer region (ITS1) revealed that diversity and composition of the bacterial and fungal communities across the NCTs varied significantly. Dominant bacterial phyla such as Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria, Verrucomicrobia, Chloroflexi, Planctomycetes, Acidobacteria, and a fungal phylum Ascomycota were detected in all NCTs. AWCT had optimum physico-chemical measurements with higher bacterial Shannon diversity indices (H) and fungal richness (S) than the other treatments. We conclude that bacterial wilt of potatoes grown in controlled conditions can be suppressed by a non-aerated compost tea with a high microbial diversity when applied at planting and weekly thereafter.

Modulation of medial geniculate nucleus neuronal activity by electrical stimulation of the nucleus accumbens.

Dysfunctional sensory gating has been proposed to result in the generation of phantom perceptions. In agreement, it has been recently suggested that tinnitus, a phantom perception of sound commonly associated with hearing loss, is the result of a breakdown of circuitry involving the limbic system and the medial geniculate nucleus (MGN) of the thalamus. In humans with tinnitus, structural changes and abnormal activity have been found to occur in the auditory pathway as well as parts of the limbic system such as the nucleus accumbens (NAc). However, at present, no studies have been conducted on the influence of the NAc on the MGN. We investigated the functional connectivity between the NAc and MGN single neurons. Bipolar electrical stimulation was delivered to the NAc while recording single neuron activity in MGN in anesthetized Wistar rats. Histological analysis was used to confirm placement of electrodes. NAc electrical stimulation generally decreased spontaneous firing rates in MGN neurons and, in a limited number of neurons, caused an increase in firing rate. This suggests that NAc can modulate the activity of auditory neurons in the MGN and may play a role in the development of tinnitus.

Benign subcutaneous emphysema: A case report with bite.

INTRODUCTION: Subcutaneous emphysema is the presence of air/gas within the subcutaneous tissue plane. Though there are numerous causative factors, benign subcutaneous emphysema is rare. CASE REPORT: We report a very rare case of benign subcutaneous emphysema following an insect bite on the forearm of a 48-year old man. The puncture area was erythematous and the emphysema extended to the whole arm, axilla and superior mediastinum. Despite, conservative management, the patient had residual discomfort and erythema around the puncture site. Surgical debridement resulted in resolution of symptoms. DISCUSSION: Subcutaneous emphysema affecting an isolated limb is extremely rare. It is vital to differentiate it from life-threatening soft-tissue infections secondary to a gas-forming organism. Immunodeficiency states are key factors in the development and the outcomes of patients with subcutaneous emphysema. Medical management successfully resolves symptoms in the majority of cases. However, surgical debridement of the puncture site and surrounding fibrotic tissue has been advocated for those with persistent symptoms. CONCLUSION: This case highlights a rare cause of benign subcutaneous emphysema, highlighting key issues surrounding its management for a successful outcome.

Identification of hydrolysable tannins in the reaction zone of Eucalyptus nitens wood by high performance liquid chromatography--electrospray ionisation mass spectrometry.

The first detailed analysis of the phenolic constituents of the reaction zones (tissue of antimicrobial defence) from the sapwood of a Eucalyptus spp. is presented. Plantation-grown Eucalyptus nitens trees with stem decay resulting from pruning wounds were sampled and extracts were prepared from healthy sapwood and from reaction zone tissue. Analysis by HPLC with ESI-MS revealed that a diverse range of hydrolysable tannins are present in both healthy sapwood and in reaction zone extracts, including over 30 gallotannins, ellagitannins and phenols. Eight tannins were unequivocally identified, including the gallotannins tri-O-galloyl-beta-D-glucose, tetra-O-galloyl-beta-D-glucose and penta-O-galloyl-beta-D-glucose, and the ellagitannins pedunculagin, tellimagrandin I, casuarinin, casuarictin and tellimagrandin II. The phenols gallic acid, ellagic acid and catechin were also identified. The ellagitannins (particularly pedunculagin) are considerably more abundant in the reaction zone than in the healthy sapwood and may contribute to the effectiveness of the reaction zone as an antimicrobial barrier.

Changes in regional renal blood flow after unilateral nephrectomy using the techniques of autoradiography and microautoradiography.

PURPOSE: To determine alterations in regional renal blood flow following unilateral nephrectomy using an autoradiographic technique. The role of prostaglandins and the sympathetic nervous system in the mediation of these changes was assessed. MATERIALS AND METHODS: C-14 iodoantipyrine was used as a tracer to measure intrarenal blood flow in anaesthetised rats at multiple time points following nephrectomy. Autoradiographs were produced from tissue sections. C-14 concentrations were measured from standards thus allowing blood flow values to be calculated. RESULTS: Base line values for cortical and medullary blood flow were 806 +/- 63 and 373 +/- 39 ml./100 gm./min. (mean +/- SEM) respectively. At 2 hours post nephrectomy blood flow to both the cortex and medulla increased significantly (1152 +/- 54 and 594 +/- 37; p < 0.05). Blood flow had returned to control levels by 24 hours and was maintained at 5 days post-nephrectomy. Multiple discrete regions of high blood flow within the cortex were observed. Microautoradiography defined the morphological location of these discrete regions of higher blood flow as periglomerular vasculature. Diclofenac administration did not inhibit the augmentation in cortical blood flow post-nephrectomy, while medullary blood flow fell below base line values at both 30 minutes and 2 hours following nephrectomy. Sympathetic denervation did not affect the changes in cortical blood flow seen following nephrectomy, but did ameliorate the changes in medullary blood flow. CONCLUSIONS: Significant, transient changes in regional renal blood flow occur in the residual kidney following unilateral nephrectomy. The interaction between vasoactive mediators and the autonomic nervous system which produces changes in cortical blood flow is complex. It is evident, however, that medullary blood flow is dependent on local prostaglandin production and is also influenced by sympathetic nervous supply.

Plasma levels of amino acids correlate with motor fluctuations in parkinsonism.

Seven patients with Parkinson's disease who experienced severe motor fluctuations in response to levodopa were studied in detail with relation to the effect of dietary protein on their motor function. The levodopa dose for each patient was not changed during the period of study, and no other antiparkinsonian drugs were used. Regular and high-protein diets resulted in a marked elevation in the plasma concentrations of large neutral amino acids (LNAAs) that are known to compete with levodopa for transport across the blood-brain barrier. Despite elevated plasma levodopa levels, all patients with elevated LNAA levels experienced parkinsonian symptoms. When the amino acid level dropped while plasma levodopa levels were elevated, patients experienced relief of these symptoms. On a low-protein diet, LNAA levels remained low and all patients were consistently dyskinetic throughout the day, even though the mean plasma levodopa levels were somewhat lower than when the patients consumed a high-protein diet. A redistribution diet that is virtually protein free until supper and then unrestricted until bedtime is tolerated by patients because this simple manipulation permits near-normal daytime motor function.

Dietary method for reducing fluctuations in Parkinson's disease.

Motor fluctuations and non-response to carbidopa-levodopa (Sinemet) therapy are major problems in the long-term management of Parkinson's disease. Levodopa manipulation, addition of adjuvants, and drug holidays are often unsuccessful. Others have shown that the clinical state of stabilized Parkinsonians can be reversed with intravenous administration of large neutral amino acids. Reasoning that dietary protein might precipitate motor oscillations and non-response, a low-protein daytime diet (7 g) was offered to fifteen patients. Eighty-six percent of this sample demonstrated immediate sensitivity to Sinemet. While on a low-protein diet, patients' clinical function was predominantly choreatic. Eight patients required a 10-60 percent reduction in their daily levodopa dose in order to minimize this choreatic tendency. Discontinuation of adjuvants did not compromise motor independence. Conversely, while on a high-protein diet (160 g), patients were predominantly immobile with markedly elevated plasma amino acid and levodopa levels. Consequently, elimination of dietary protein from breakfast and lunch can offer an effective and easily modified method for the amelioration of motor fluctuations and non-response to Sinemet in Parkinson's disease during working hours.

Technicium as a radiolabel in the assessment of in vivo human Fc clearance.

99m-Tc was used as a radiolabel to study in vivo human clearance of IgG sensitized erythrocytes. Stannous chloride pretreatment at different doses and varying amounts of 99m-Tc were studied with respect to radiolabelling efficiency and elution. Mean in vivo clearance rates in systemic lupus erythematosus patients were significantly prolonged compared to controls. Using as little as 200 microCi of 99m-Tc per patient, in vivo human immune clearance can be determined with a minimal radiation biohazard. With this method, serial immune determinations can be performed within very short time frames, allowing for monitoring effects of immunomodulatory therapy as well as variations in disease activity.