Retroclavicular vs Infraclavicular block for brachial plexus anesthesia: a multi-centric randomized trial.

BACKGROUND: The coracoid approach is a simple method to perform ultrasound-guided brachial plexus regional anesthesia (RA) but its simplicity is counterbalanced by a difficult needle visualization. We hypothesized that the retroclavicular (RCB) approach is not longer to perform when compared to the coracoid (ICB) approach, and improves needle visualization. METHODS: This randomized, controlled, non-inferiority trial conducted in two hospitals, included patients undergoing distal upper limb surgery. Patients were randomly assigned to a brachial plexus block (ICB or RCB). The primary outcome was performance time (sum of visualization and needling time), and was analyzed with a non-inferiority test of averages. Depth of sensory and motor blockade, surgical success, total anesthesia time, needle visualization, number of needle passes and complications were also evaluated. Subgroup analysis restricted to patients with higher body mass index was completed. RESULTS: We included 109 patients between September 2016 and May 2017. Mean RCB performance time was 4.8 ± 2.0 min while ICB was 5.2 ± 2.3 min (p = 0.06) with a 95% CI reaching up to 5.8% longer. RCB conferred an ultrasound-needle angle closer to 0° and significantly improved needle visibility after the clavicle was cleared and before local anesthetic administration. No differences were found in the secondary outcomes. Similar results were found in the subgroup analysis. CONCLUSION: RCB approach for brachial plexus anesthesia was similar to ICB approach in terms of time performance. Needle visibility, which represent an important clinical variable, was superior and angle between needle and ultrasound probe was close to 0° in the RCB group. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT02913625), registered 26 September 2016.

Postoperative analgesic effect, of preoperatively administered dexamethasone, after operative fixation of fractured neck of femur: randomised, double blinded controlled study.

BACKGROUND: Fractured neck of femur is a common cause of hospital admission in the elderly and usually requires operative fixation. In a variety of clinical settings, preoperative glucocorticoid administration has improved analgesia and decreased opioid consumption. Our objective was to define the postoperative analgesic efficacy of single dose of dexamethasone administered preoperatively in patients undergoing operative fixation of fractured neck of femur. METHODS: Institutional ethical approval was granted and written informed consent was obtained from each patient. Patients awaiting for surgery at Cork University Hospital were recruited between July 2009 and August 2012. Participating patients, scheduled for surgery were randomly allocated to one of two groups (Dexamethasone or Placebo). Patients in the dexamethasone group received a single dose of intravenous dexamethasone 0.1 mg kg -1 immediately preoperatively. Patients in the placebo group received the same volume of normal saline. Patients underwent operative fixation of fractured neck of femur using standardised spinal anaesthesia and surgical techniques. The primary outcome was pain scores at rest 6 h after the surgery. RESULTS: Thirty seven patients were recruited and data from thirty patients were analysed. The groups were similar in terms of patient characteristics. Pain scores at rest 6 h after the surgery (the principal outcome) were lesser in the dexamethasone group compared with the placebo group [0.8(1.3) vs. 3.9(2.9), mean(SD) p = 0.0004]. Cumulative morphine consumption 24 h after the surgery was also lesser in the dexamethasone group [7.7(8.3) vs. 15.1(9.4), mean(SD) mg, p = 0.04]. CONCLUSIONS: A single dose of intravenous dexamethasone 0.1 mg kg -1 administered before operative fixation of fractured neck of femur improve significantly the early postoperative analgesia. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01550146 , date of registration: 07/03/2012.

The development of a custom-built portable impact-testing device for assessing the cushioning properties of athletic socks.

Despite manufacturer claims that athletic socks attenuate force during exercise, no device exists to assess this. Therefore, this study outlines the development of a custom-built impact-testing device for assessing the cushioning properties of socks. The device used a gravity-driven impact striker (8.5 kg), released from 0.05 m, which impacted a no-sock, sock or a basic shoe/sock condition in the vertical axis. A load cell (10,000 Hz) assessed peak impact force, time to peak impact force and loading rate. Reliability was investigated between day, between trial and within trial. Excellent reliability (coefficient of variation < 5% adjusted for 95% confidence limits) was reported for peak impact force in all conditions, with no evidence of systematic bias. Good reliability (coefficient of variation < 10% adjusted for 68% confidence limits) was reported for time to peak impact force and loading rate with some evidence of systematic bias. It was concluded that the custom-built impact-testing device was reliable and sensitive for the measurement of peak impact force on socks.

The Development of a Custom Built Portable Impact Testing Device for Assessing the Cushioning Properties of Athletic Socks.

Despite manufacturer claims that athletic socks attenuate force during exercise, no device exists to assess this. Therefore, this study outlines the development of a custom built impact testing device for assessing the cushioning properties of socks. The device utilised a gravity driven impact striker (8.5 kg), released from 0.05 m, which impacted a no sock, sock or a basic shoe/sock condition in the vertical axis. A load cell (10000 Hz) assessed peak impact force, time to peak impact force and loading rate. Reliability was investigated between day, between trial and within trial. Excellent reliability (coefficient of variation < 5% adjusted for 95% confidence limits) was reported for peak impact force in all conditions, with no evidence of systematic bias. Good reliability (coefficient of variation < 10% adjusted for 68% confidence limits) was reported for time to peak impact force and loading rate with some evidence of systematic bias. It was concluded that the custom built impact testing device was reliable and sensitive for the measurement of peak impact force on socks.

WITHDRAWN: The Development of a Custom Built Portable Impact Testing Device for Assessing the Cushioning Properties of Athletic Socks.

Ahead of Print article withdrawn by publisher.

Metallome deregulation and health-related impacts due to long-term exposure to recent volcanic ash deposits: New chemical and isotopic insights.

Volcanic ash exposure can lead to significant health risks. Damage to the respiratory and pulmonary systems are the most evident toxic side effects although the causes of these symptoms remain unclear. Conversely, the effects on other organs remain largely under-explored, limiting our understanding of the long-term volcanic ash-related risk at the whole-body scale. The metallome i.e. metal concentrations and isotopic compositions within the body, is suspected to be affected by volcanic ash exposure, having thus the potential for capturing some specificities of ash toxicity. However, the means by and extent to which the metallome is affected at the entire body scale and how the consequent chemical and isotopic deregulations correlate with pathophysiological dysfunctions are currently poorly understood. Here, we adopt a transdisciplinary approach combining high precision chemical analyses (major and trace element concentrations) and CuZn isotope measurements in seven organs and two biological fluids of isogenic mice (C57BL/6) exposed to eruption products from La Soufrière de Guadeloupe (Eastern Carribean), in tandem with biological parameters including physiological and morphological data. Based on principal component analysis, we show that after one month of exposure to volcanic ash deposits, the mice metallome; originally organ-specific and isotopically-typified, is highly disrupted as shown for example by heavy metal accumulation in testis (e.g., Fe, Zn) and Cu, Zn isotopic divergence in liver, intestine and blood. These metallomic variations are correlated with early testicular defects and might reflect the warning signs of premature (entero)hepatic impairments that may seriously affect fertility and favor the emergence of liver diseases after prolonged exposure. Monitoring the temporal evolution of the Cu and Zn isotope compositions seems to be a promising technique to identify the main biological processes and vital functions that are vulnerable to environmental volcanogenic pollutants although this will require further validation on human subjects.

The SARS-CoV-2 viral load in COVID-19 patients is lower on face mask filters than on nasopharyngeal swabs.

Face masks and personal respirators are used to curb the transmission of SARS-CoV-2 in respiratory droplets; filters embedded in some personal protective equipment could be used as a non-invasive sample source for applications, including at-home testing, but information is needed about whether filters are suited to capture viral particles for SARS-CoV-2 detection. In this study, we generated inactivated virus-laden aerosols of 0.3-2 microns in diameter (0.9 µm mean diameter by mass) and dispersed the aerosolized viral particles onto electrostatic face mask filters. The limit of detection for inactivated coronaviruses SARS-CoV-2 and HCoV-NL63 extracted from filters was between 10 to 100 copies/filter for both viruses. Testing for SARS-CoV-2, using face mask filters and nasopharyngeal swabs collected from hospitalized COVID-19-patients, showed that filter samples offered reduced sensitivity (8.5% compared to nasopharyngeal swabs). The low concordance of SARS-CoV-2 detection between filters and nasopharyngeal swabs indicated that number of viral particles collected on the face mask filter was below the limit of detection for all patients but those with the highest viral loads. This indicated face masks are unsuitable to replace diagnostic nasopharyngeal swabs in COVID-19 diagnosis. The ability to detect nucleic acids on face mask filters may, however, find other uses worth future investigation.

Sex differences in hypothalamic-pituitary-adrenal axis function in patients with chronic pain syndrome.

Chronic pain is often equated with chronic stress yet the relationship between chronic pain and hypothalamic-pituitary-adrenal (HPA) axis activity is poorly understood. The objective of this study was to examine diurnal functioning of the HPA axis in patients with clinically defined non-inflammatory chronic pain syndrome (CPS) compared to controls. The sample consisted of 37 adults with CPS and 47 healthy controls. All participants provided saliva samples at awakening, 12:00, 18:00 and 21:00 h on two consecutive days, as well as completing self-report questionnaires relating to anxiety and depression. The CPS group had a significantly lower overall mean diurnal salivary cortisol concentration compared to the control group (p < 0.01) but no significant differences were found between the two groups for repeated cortisol sampling across the day. However, a three-way interaction of time of day by patient status by sex was found (p < 0.032), with lower cortisol concentration in male patients compared to female patients in the afternoon period. No significant group effect was found for the rate of decline in the circadian rise in cortisol concentration. These data demonstrate that CPS is associated with a degree of hypocortisolemia, particularly in male patients. The altered dynamics of cortisol secretion in CPS in relation to the onset and duration of pain in patients remains to be determined.

New insights into cytokine gene expression in the rat hypothalamus following endotoxin challenge.

Peripheral injection of the endotoxin LPS in rats 3 weeks prior to a second injection of LPS derived from another bacterial strain results in elevated corticosterone and decreased pro-inflammatory cytokines in the blood. We further investigated this model by measuring cytokine expression in the hypothalamus and spleen. In LPS-pretreated rats, hypothalamic expression of a range of cytokines was attenuated in response to the second injection of LPS while splenic expression was elevated. This is the first demonstration that prior exposure to an endotoxin can differentially affect cytokine expression in the brain and peripheral tissues when a host is confronted with a second, acute, pro-inflammatory stimulus. Changes in hypothalamic cytokine expression in endotoxin pretreated rats may provide new evidence for the involvement of central cytokine pathways in modulating peripheral inflammation and mediating psychopathological alterations associated with inflammatory diseases.

Diurnal cortisol and coping responses in close relatives of persons with acquired brain injury: a longitudinal mixed methods study.

OBJECTIVE: To examine the impact of having a close relative experience a severe brain injury. DESIGN: Six-month longitudinal mixed methods concurrent embedded study. Quantitative data provided the primary database and qualitative data provided the secondary source. METHODS: Assessment included psychosocial factors of perceived stress, traumatic stress symptoms, coping and social support in addition to salivary cortisol as a biological marker of stress. Written accounts of the experience were provided in response to an open-ended question. Participants composed 15 close relatives of adults with severe brain injury admitted to a specialist rehabilitation facility (mean age 49.4 years; SD 11.79). Assessments were conducted on admission, at 6 weeks, 3 months and 6 months post-admission. RESULTS: Quantitative data revealed high traumatic stress at admission, with a non-significant decline at follow-up. Diurnal cortisol output declined significantly from baseline to all follow-up assessments. Coping sub-scales of acceptance and religion were repeated associated with cortisol indices at baseline, 6 weeks, 3 months and 6 months follow-up. Qualitative data revealed two themes; 'relational impact' and 'passage of time'. CONCLUSIONS: Findings offer the potential for effective and timely intervention in family members of persons with severe brain injury.

Isolated Lumbar Extension Resistance Training Improves Strength, Pain, and Disability, but Not Spinal Height or Shrinkage ("Creep") in Participants with Chronic Low Back Pain.

Objective. Loss of disc height is commonly associated with chronic low back pain (CLBP). Isolated lumbar extension (ILEX) exercise for the lumbar extensors is recommended to treat CLBP and is suggested such exercise might promote disc healing and regeneration. This study examined a 12-week ILEX intervention on indirect determination of disc height and shrinkage through seated stadiometry, strength, pain, and disability. Design. A quasi-experimental wait-list controlled design was used. Nine participants underwent pretesting (T1), a 12-week control period, retesting (T2), a 12-week intervention period, and finally posttesting (T3). Seated stadiometry, ILEX strength, pain, and disability were measured at each time point. Results. No significant repeated-measures effects for any seated stadiometry variables occurred. Significant improvement across the intervention period (T2 to T3) was found for strength (P <0.0001; effect size [ES] = 2.42). Change in pain was not significant for repeated effects (P = 0.064); however, ES for the intervention period (T2 to T3) was moderate (ES = -0.77). Change in disability was significant between time point T1 and T3 (P = 0.037) and ES for the intervention period (T2 to T3) was large (ES = -0.92). Pain and disability achieved minimal clinically important changes. Conclusions. This is apparently the first study to examine disc change in vivo after exercise in CLBP. Results of the present study, though supporting ILEX resistance training to improve strength, pain, and disability, did not find any effect on spinal height.

Re-exposure to endotoxin induces differential cytokine gene expression in the rat hypothalamus and spleen.

This study was designed to investigate whether the pattern of hypothalamic and splenic cytokine expression induced by peripheral administration of a bacterial lipopolysaccharide (LPS) is affected by prior exposure to LPS derived from another bacterial strain. Injection of LPS from Salmonella enteritidis (LPS(2)) alone resulted in increased hypothalamic gene expression of IL-1beta, IL-6, TNFalpha, IL-1ra and IL-10. However, pre-exposure to LPS derived from Escherichia coli (LPS(1)) 3 weeks before, significantly attenuated hypothalamic IL-1ra, IL-6 and IL-10 expression. IL-1beta expression also tended to be lower. This pattern contrasted with the robust cytokine expression in the spleen of LPS(2)-treated rats previously exposed to LPS(1), since pre-treatment with endotoxin resulted in a significantly greater response of IL-1beta and IL-1ra to LPS(2). Expression of TNFalpha and IL-10 also tended to be higher. Pre-treatment with LPS(1) did not significantly affect the marked increase in corticosterone and adrenaline blood levels induced by LPS(2). Thus, while endotoxin pre-exposure seemed not to induce a "tolerant" state in the periphery as judged by the immune and endocrine parameters evaluated upon re-stimulation, expression of four of the six cytokines measured was decreased in the hypothalamus. This is the first demonstration that endotoxin priming can differentially affect cytokine expression in the central nervous system and peripheral tissues when a host is confronted with a second, acute, pro-inflammatory stimulus. These results may provide new evidence for the involvement of cytokine pathways in the central nervous system in modulating peripheral inflammation and mediating cognitive and behavioural alterations during inflammatory diseases.

Modulation of stress by imidazoline binding sites: implications for psychiatric disorders.

In this review, we present evidence for the involvement of imidazoline binding sites (IBS) in modulating responses to stress, through central control of monoaminergic and hypothalamo-pituitary-adrenal (HPA) axis activity. Pharmacological and physiological evidence is presented for differential effects of different IBS subtypes on serotoninergic and catecholaminergic pathways involved in control of basal and stress-stimulated HPA axis activity. IBS ligands can modulate behavioural and neuroendocrine responses in animal models of stress, depression and anxiety, and a body of evidence exists for alterations in central IBS expression in psychiatric patients, which can be normalised partially or fully by treatment with antidepressants. Dysfunction in monoaminergic systems and the HPA axis under basal and stress-induced activation has been extensively reported in psychiatric illnesses. On the basis of the literature, we suggest a potential therapeutic role for selective IBS ligands in the treatment of depression and anxiety disorders.

Effects of chronic treatment with citalopram on cannabinoid and opioid receptor-mediated G-protein coupling in discrete rat brain regions.

RATIONALE: There is growing interest in investigating the mechanisms of action of selective serotonin reuptake inhibitors (SSRIs), beyond their association with the serotonergic system, due to their wide therapeutic potential for disorders including depression, pain and addiction. OBJECTIVE: The aim of this study was to investigate whether chronic treatment with the SSRI, citalopram, alters the functional coupling of G(i/o)-associated cannabinoid type 1 (CB(1)) and mu-opioid receptors in selected areas of rat brain implicated in psychiatric disorders and pain. METHODS: Using an autoradiographic approach, the effects of the cannabinoid receptor agonist, HU210 (in the presence or absence of the CB(1) receptor antagonist AM251), or the mu-opioid receptor agonist, [D: -Ala(2),N-Me-Phe4,Gly(5)-ol]-enkephalin (DAMGO; in the presence or absence of the mu-opioid receptor antagonist D: -Phe-Cys-Tyr-D: -Trp-Orn-Thr-Pen-Thr-NH(2)), on [(35)S]GTPgammaS binding in discrete brain regions of citalopram-treated (10 mg kg(-1) day(-1) for 14 days by subcutaneous minipump) and control rats were investigated. RESULTS: The HU210-induced increase in [(35)S]GTPgammaS binding observed in the hypothalamic paraventricular nucleus of control rats was abolished after chronic treatment with citalopram. Reduced response to HU210 in rats receiving chronic treatment with citalopram was also observed in the hippocampus and medial geniculate nucleus. Citalopram had no significant effect on DAMGO-induced [(35)S]GTPgammaS binding in the brain regions investigated, with the exception of the medial geniculate nucleus where a modest impairment was observed. CONCLUSIONS: These data provide evidence for reduced cannabinoid receptor-mediated G-protein coupling in the hypothalamus, hippocampus and medial geniculate nucleus of rats chronically treated with citalopram, effects which may, in part, underlie the mechanism of action of SSRIs.

The regulation of vestibular afferent information during monocular vision while standing.

The purpose of this study was to investigate the contribution of the vestibular system to postural control during monocular vision using binaural-bipolar galvanic vestibular stimulation (GVS). Four visual (both eyes, dominant eye, non-dominant eye, and no vision) conditions were tested during GVS in five healthy subjects while focusing on a target placed in front of them. GVS evoked similar upper body postural sway during both monocular and no vision conditions that were significantly greater to those during binocular vision. Changes in ground reaction forces to the anode side followed that same trend, although data for vision with the dominant eye were not significantly different from that for binocular vision. These data suggest an increase in the weighting of vestibular afferent information during monocular vision for standing postural control.

A prospective study of diurnal cortisol responses to the social experience of school transition in four-year-old children: anticipation, exposure, and adaptation.

This study examined psychosocial influences on hypothalamic-pituitary-adrenal axis activity in 105 4-year-old children transitioning to primary school. Measuring before, during, and after school transition over a period of up to 12 months, salivary cortisol was assessed on awakening and early evening. Parents reported child temperament and teachers recorded adaptive behavior. Whilst cortisol at awakening and early evening increased from baseline to school transition, effects were not significant. A significant decrease occurred between transition and follow-up and from baseline to follow-up for both awakening and evening cortisol. Poorer effortful control was associated with high morning and steeper diurnal slope of cortisol at transition whilst surgency/extroversion was associated individually with greater morning and evening cortisol at transition and adaptation. Greater increase in internalizing social isolation during the first 6 months of school in more surgent/extrovert children predicted higher morning and evening cortisol at follow-up. This study is the first to explore these adaptive relationships over a 12-month period and supports social isolation over time as a key element in developmental endocrine activation.

The hypothalamic-pituitary-adrenal axis response to stress in mice lacking functional vasopressin V1b receptors.

The role of arginine vasopressin (Avp) as an ACTH secretagogue is mediated by the Avp 1b receptor (Avpr1b) found on anterior pituitary corticotropes. Avp also potentiates the actions of CRH (Crh) and appears to be an important mediator of the hypothalamic-pituitary-adrenal axis response to chronic stress. To investigate the role of Avp in the hypothalamic-pituitary-adrenal axis response to stress, we measured plasma ACTH and corticosterone (CORT) levels in Avpr1b knockout (KO) mice and wild-type controls in response to two acute (restraint and insulin administration) and one form of chronic (daily restraint for 14 d) stress. No significant difference was found in the basal plasma levels of ACTH and CORT between the two genotypes. Acute restraint (30 min) increased plasma ACTH and CORT to a similar level in both the Avpr1b mutant and wild-type mice. In contrast, plasma ACTH and CORT levels induced by hypoglycemia were significantly decreased in the Avpr1b KO mice when compared with wild-type littermates. There was no difference in the ACTH response to acute and chronic restraint in wild-type mice. In the Avpr1b KO group subjected to 14 sessions of daily restraint, plasma ACTH was decreased when compared with wild-type mice. On the other hand, the CORT elevations induced by restraint did not adapt in the Avpr1b KO or wild-type mice. The data suggest that the Avpr1b is required for the normal pituitary and adrenal response to some acute stressful stimuli and is necessary only for a normal ACTH response during chronic stress.

Contactless graphene conductivity mapping on a wide range of substrates with terahertz time-domain reflection spectroscopy.

We demonstrate how terahertz time-domain spectroscopy (THz-TDS) operating in reflection geometry can be used for quantitative conductivity mapping of large area chemical vapour deposited graphene films on sapphire, silicon dioxide/silicon and germanium. We validate the technique against measurements performed with previously established conventional transmission based THz-TDS and are able to resolve conductivity changes in response to induced back-gate voltages. Compared to the transmission geometry, measurement in reflection mode requires careful alignment and complex analysis, but circumvents the need of a terahertz transparent substrate, potentially enabling fast, contactless, in-line characterisation of graphene films on non-insulating substrates such as germanium.

Endomorphins as agents for the treatment of chronic inflammatory disease.

Endomorphin (EM)-1 and EM-2 are tetrapeptides located within the mammalian central nervous system and immune tissues, with high affinity and specificity for micro-opioid receptors. Most of the literature has focused on the analgesic properties of EM-1 and EM-2 in animal models of neuropathic or neurogenic pain, but there is persuasive evidence emerging that EMs can also exert potent anti-inflammatory effects in both acute and chronic peripheral inflammation. The purpose of this review is to present and evaluate the evidence for anti-inflammatory properties of EM-1 and EM-2 with a view to their potential for use in chronic human inflammatory disease. Distribution of EMs within the immune system and functional roles as immunomodulatory agents are summarized and discussed. Possible milestones to be met revolve around issues of peptide stability, biodegradability problems and optimal route and method of delivery. The potential for delivery of a low-cost drug with both peripheral anti-inflammatory and analgesic properties, effective in low doses, and targeted to the site of inflammation, should focus our attention on further development of EMs as potent therapeutic agents in chronic inflammation.