α_1L-adrenoceptors mediate contraction of human erectile tissue

α1-adrenoceptor antagonists can impact upon sexual function and have potential in the treatment of erectile dysfunction. Human erectile tissue contains predominantly α1A-adrenoceptors, and here we examined whether contractions of this tissue are mediated by the functional phenotype, the α1L-adrenoceptor. Functional experiments using subtype selective agonists and antagonists, along with radioligand ([3H]tamsulosin) binding assays, were used to determine the α1-adrenoceptor population. A61603, a α1A-adrenoceptor agonist, was a full agonist with a potency 21-fold greater than that of noradrenaline. The α1A- and α1D-adrenoceptor antagonist tamsulosin antagonized noradrenaline responses with high affinity (pKD = 9.7 ± 0.3), whilst BMY7378 (100 nM) (α1D-adrenoceptor antagonist) failed to antagonize responses. In contrast, relatively low affinity estimates were obtained for both prazosin (pKD = 8.2 ± 0.1) and RS17053 (pKD = 6.9 ± 0.2), antagonists which discriminate between the α1A- and α1L-adrenoceptors. [3H]Tamsulosin bound with high affinity to the receptors of human erectile tissue (pKD = 10.3 ± 0.1) with a receptor density of 28.1 ± 1.4 fmol mg−1 protein. Prazosin displacement of [3H]tamsulosin binding revealed a single homogenous population of binding sites with a relatively low affinity for prazosin (pKi = 8.9). Taken together these data confirm that the receptor mediating contraction in human erectile tissue has the pharmacological properties of the α1L-adrenoceptor. Keywords: Erectile tissue, α1-adrenoceptor subtypes, α1L-adrenoceptor, Tamsulosin, Prazosi

Could Reduced Fluid Intake Cause the Placebo Effect Seen in Overactive Bladder Clinical Trials? Analysis of a Large Solifenacin Integrated Database

Objective To assess the hypothesis that patients receiving placebo in overactive bladder (OAB) trials who experience less benefit from “treatment” continue with behavioral modifications such as fluid restriction, whereas those on active treatment adopt more normal drinking patterns. This may manifest itself as a reduction in micturition frequency (MF). Materials and Methods We interrogated a large integrated database containing pooled patient data from 4 randomized, placebo-controlled phase III OAB solifenacin studies. A statistical correction was applied to MF to remove the influence of fluid intake. Results Pooled analysis using patient-level data from 3011 patients and accounting for the studies within the models showed that all patients voided progressively less total urine per 24 hours during treatment than at baseline. However, reduction in total urine volume voided per 24 hours was larger in patients receiving placebo vs those on solifenacin; with a substantial decrease in 24-hour urine output in the placebo group from baseline to week 4, which was not the case in active groups. After correcting MF for volume voided for each patient using the statistical correction and averaging the corrected MF per treatment arm, the placebo effect almost disappeared. Patients on solifenacin voided less often, with a statistically significant increase in volume voided each time they voided, vs placebo. Conclusion Assuming volume voided is a good surrogate measure for fluid intake, this analysis shows that fluid restriction almost completely explains the reduction in MF in the placebo group. In contrast, patients receiving active treatment adopt more normal drinking patterns once they start to perceive improvement in their OAB symptoms

Nutrition support practices in critically ill head-injured patients: a global perspective

Background: Critical illness following head injury is associated with a hypermetabolic state but there are insufficient epidemiological data describing acute nutrition delivery to this group of patients. Furthermore, there is little information describing relationships between nutrition and clinical outcomes in this population. Methods: We undertook an analysis of observational data, collected prospectively as part of International Nutrition Surveys 2007-2013, and extracted data obtained from critically ill patients with head trauma. Our objective was to describe global nutrition support practices in the first 12 days of hospital admission after head trauma, and to explore relationships between energy and protein intake and clinical outcomes. Data are presented as mean (SD), median (IQR), or percentages. Results: Data for 1045 patients from 341 ICUs were analyzed. The age of patients was 44.5 (19.7) years, 78 % were male, and median ICU length of stay was 13.1 (IQR 7.9-21.6) days. Most patients (94 %) were enterally fed but received only 58 % of estimated energy and 53 % of estimated protein requirements. Patients from an ICU with a feeding protocol had greater energy and protein intakes (p <0.001, 0.002 respectively) and were more likely to survive (OR 0.65; 95 % CI 0.42-0.99; p = 0.043) than those without. Energy or protein intakes were not associated with mortality. However, a greater energy and protein deficit was associated with longer times until discharge alive from both ICU and hospital (all p <0.001). Conclusion: Nutritional deficits are commonplace in critically ill head-injured patients and these deficits are associated with a delay to discharge alive.Lee-anne S. Chapple, Marianne J. Chapman, Kylie Lange, Adam M. Deane and Daren K. Heylan

Is there a link between overactive bladder and the metabolic syndrome in women? : A systematic review of observational studies

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.To conduct a systematic review to determine whether there is an association between metabolic syndrome (MetS) and lower urinary tract symptoms (LUTS) or overactive bladder (OAB) in women. We systematically reviewed English language observational studies on the effect of MetS (or component factors) on the presence of OAB or LUTS in women. We searched PubMed, Web of Science and The Cochrane Library with no date restrictions, checked reference lists and undertook citation searches in PubMed and Google Scholar. Studies were assessed for risk of bias. Because of heterogeneity, results were not pooled, but are reported narrativelyPeer reviewe

Impact of Tail Loss on the Behaviour and Locomotor Performance of Two Sympatric Lampropholis Skink Species

Caudal autotomy is an anti-predator behaviour that is used by many lizard species. Although there is an immediate survival benefit, the subsequent absence of the tail may inhibit locomotor performance, alter activity and habitat use, and increase the individuals' susceptibility to future predation attempts. We used laboratory experiments to examine the impact of tail autotomy on locomotor performance, activity and basking site selection in two lizard species, the delicate skink (Lampropholis delicata) and garden skink (L. guichenoti), that occur sympatrically throughout southeastern Australia and are exposed to an identical suite of potential predators. Post-autotomy tail movement did not differ between the two Lampropholis species, although a positive relationship between the shed tail length and distance moved, but not the duration of movement, was observed. Tail autotomy resulted in a substantial decrease in sprint speed in both species (28–39%), although this impact was limited to the optimal performance temperature (30°C). Although L. delicata was more active than L. guichenoti, tail autotomy resulted in decreased activity in both species. Sheltered basking sites were preferred over open sites by both Lampropholis species, although this preference was stronger in L. delicata. Caudal autotomy did not alter the basking site preferences of either species. Thus, both Lampropholis species had similar behavioural responses to autotomy. Our study also indicates that the impact of tail loss on locomotor performance may be temperature-dependent and highlights that future studies should be conducted over a broad thermal range

The Oral-Vascular-Pulmonary Infection Route:a Pathogenic Mechanism Linking Oral Health Status to Acute and Post-Acute COVID-19

Purpose of Review: In recent years, much attention has focused on the role of poor oral health in the development or worsening of systemic diseases, including COVID-19. The mouth is an important site of cellular infection early in the disease course of COVID-19. We review how oral pathology, and specifically viral infection within the oral cavity, may mediate the disease severity and duration of COVID-19. In particular, the previously reported model of SARS-CoV-2 vascular delivery from the mouth to the lungs via the bloodstream is revisited.Recent Findings: We previously proposed that an oral-vascular-pulmonary route of infection could facilitate severe lung disease in COVID-19. This pathway could also explain the vital link between periodontitis and COVID-19 severity, including higher mortality risk. This model of pathogenesis is reconsidered in light of recent findings regarding the involvement of the mouth as a viral reservoir, and pathological processes in the blood, pulmonary vasculature, and elsewhere in the body. Oral dysbiosis in COVID-19 and the effect of oral hygiene in mitigating disease severity are discussed. The evidence for viral persistence in the mouth and intravascular viral passage from the mouth to the rest of the body via blood is also discussed in the context of post-acute COVID (long COVID).Summary: High viral load in the mouth and poor oral health status are associated with COVID-19 disease severity, increasing the risk of death. Pathophysiological links between viral activity in the mouth, oral health status, and disease outcome in the lungs and blood provide a rationale for further evaluation of the oral-vascular-systemic pathway in patients with acute COVID-19 and long COVID. The potential benefits of oral hygiene protocols and periodontal procedures in COVID-19 also warrant further investigation

Proteomic Analysis of a Noninvasive Human Model of Acute Inflammation and Its Resolution: The Twenty-one Day Gingivitis Model

The 21-day experimental gingivitis model, an established noninvasive model of inflammation in response to increasing bacterial accumulation in humans, is designed to enable the study of both the induction and resolution of inflammation. Here, we have analyzed gingival crevicular fluid, an oral fluid comprising a serum transudate and tissue exudates, by LC−MS/MS using Fourier transform ion cyclotron resonance mass spectrometry and iTRAQ isobaric mass tags, to establish meta-proteomic profiles of inflammation-induced changes in proteins in healthy young volunteers. Across the course of experimentally induced gingivitis, we identified 16 bacterial and 186 human proteins. Although abundances of the bacterial proteins identified did not vary temporally, Fusobacterium outer membrane proteins were detected. Fusobacterium species have previously been associated with periodontal health or disease. The human proteins identified spanned a wide range of compartments (both extracellular and intracellular) and functions, including serum proteins, proteins displaying antibacterial properties, and proteins with functions associated with cellular transcription, DNA binding, the cytoskeleton, cell adhesion, and cilia. PolySNAP3 clustering software was used in a multilayered analytical approach. Clusters of proteins that associated with changes to the clinical parameters included neuronal and synapse associated proteins

Do #BlackLivesMatter? Implicit Bias, Institutional Racism and Fear of the Black Body

The paper implores a brief cultural analysis to examine racial tensions and injustices in the U.S. that have led to the Black Lives Matter movement. Specifically, implicit bias is of primary focus as the authors examine how bias of the Black male frames the “Black-as-criminal” mentality, as well as connotes fear of the Black male body. The authors further discuss how fear of the Black face and Black male body has led to discriminatory actions such as institutional racism and, in the most vehement yet consistent cases, the killing of unarmed Black men and women. Cases such as Freddie Gray, Sandra Bland, Trayvon Martin, and Michael Brown are presented as exemplars of instances in which implicit bias and institutional racism result in malicious and racially framed discriminatory actions. The paper concludes with a presentation of how the Black Lives Matter movement is a modern-day representation of movements born from historical racial unrest for Black Americans around matters of social injustice, and how the movement can serve to project U.S. society toward an All Lives Matter position. The paper also presents implications that can be used for research and policy-level chang

The Oral-Vascular-Pulmonary Infection Route:a Pathogenic Mechanism Linking Oral Health Status to Acute and Post-Acute COVID-19

Purpose of Review: In recent years, much attention has focused on the role of poor oral health in the development or worsening of systemic diseases, including COVID-19. The mouth is an important site of cellular infection early in the disease course of COVID-19. We review how oral pathology, and specifically viral infection within the oral cavity, may mediate the disease severity and duration of COVID-19. In particular, the previously reported model of SARS-CoV-2 vascular delivery from the mouth to the lungs via the bloodstream is revisited.Recent Findings: We previously proposed that an oral-vascular-pulmonary route of infection could facilitate severe lung disease in COVID-19. This pathway could also explain the vital link between periodontitis and COVID-19 severity, including higher mortality risk. This model of pathogenesis is reconsidered in light of recent findings regarding the involvement of the mouth as a viral reservoir, and pathological processes in the blood, pulmonary vasculature, and elsewhere in the body. Oral dysbiosis in COVID-19 and the effect of oral hygiene in mitigating disease severity are discussed. The evidence for viral persistence in the mouth and intravascular viral passage from the mouth to the rest of the body via blood is also discussed in the context of post-acute COVID (long COVID).Summary: High viral load in the mouth and poor oral health status are associated with COVID-19 disease severity, increasing the risk of death. Pathophysiological links between viral activity in the mouth, oral health status, and disease outcome in the lungs and blood provide a rationale for further evaluation of the oral-vascular-systemic pathway in patients with acute COVID-19 and long COVID. The potential benefits of oral hygiene protocols and periodontal procedures in COVID-19 also warrant further investigation