COVID-19: Seroprevalence and Vaccine Responses in UK Dental Care Professionals.

Dental care professionals (DCPs) are thought to be at enhanced risk of occupational exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, robust data to support this from large-scale seroepidemiological studies are lacking. We report a longitudinal seroprevalence analysis of antibodies to SARS-CoV-2 spike glycoprotein, with baseline sampling prior to large-scale practice reopening in July 2020 and follow-up postimplementation of new public health guidance on infection prevention control (IPC) and enhanced personal protective equipment (PPE). In total, 1,507 West Midlands DCPs were recruited into this study in June 2020. Baseline seroprevalence was determined using a combined IgGAM enzyme-linked immunosorbent assay and the cohort followed longitudinally for 6 mo until January/February 2021 through the second wave of the coronavirus disease 2019 pandemic in the United Kingdom and vaccination commencement. Baseline seroprevalence was 16.3%, compared to estimates in the regional population of 6% to 7%. Seropositivity was retained in over 70% of participants at 3- and 6-mo follow-up and conferred a 75% reduced risk of infection. Nonwhite ethnicity and living in areas of greater deprivation were associated with increased baseline seroprevalence. During follow-up, no polymerase chain reaction-proven infections occurred in individuals with a baseline anti-SARS-CoV-2 IgG level greater than 147.6 IU/ml with respect to the World Health Organization international standard 20-136. After vaccination, antibody responses were more rapid and of higher magnitude in those individuals who were seropositive at baseline. Natural infection with SARS-CoV-2 prior to enhanced PPE was significantly higher in DCPs than the regional population. Natural infection leads to a serological response that remains detectable in over 70% of individuals 6 mo after initial sampling and 9 mo from the peak of the first wave of the pandemic. This response is associated with protection from future infection. Even if serological responses wane, a single dose of the Pfizer-BioNTech 162b vaccine is associated with an antibody response indicative of immunological memory.

Cigarette smoke modifies neutrophil chemotaxis, neutrophil extracellular trap formation and inflammatory response-related gene expression.

BACKGROUND AND OBJECTIVE: Cigarette smoking is a major risk factor for periodontitis, and smoking perturbs neutrophil reactive oxygen species production. This study tested the hypothesis that cigarette smoke extract (CSE) and its components/metabolites nicotine, cotinine and thiocyanate (SCN-), may influence neutrophil functions. MATERIAL AND METHODS: Chemotaxis was assessed in neutrophils pre-treated with CSE using real-time video microscopy. Neutrophil extracellular trap (NET) release in response to CSE, nicotine, cotinine, SCN- as well as to phorbol 12-myristate-13-acetate and hypochlorous acid following pre-treatment with CSE, nicotine, cotinine or SCN- was assessed using fluorescence-based assays. The impact of CSE and SCN- treatment on neutrophil respiratory burst- and inflammation-related gene expression (NFKBIE, DNAJB1, CXCL8, NCF1, NCF2, CYBB) was determined by real-time polymerase chain reaction. RESULTS: Both CSE and SCN- pre-treatment inhibited phorbol 12-myristate-13-acetate-stimulated NET release. Additionally, SCN- inhibited hypochlorous acid-stimulated NET formation, while SCN- alone stimulated NET release. Overall, neutrophils pre-treated with CSE exhibited reduced speed, velocity and directionality relative to untreated neutrophils. Although CSE and SCN- promoted DNAJB1 expression, increased redox-related gene expression was only detected in response to SCN-. CONCLUSION: These results suggest that CSE can alter ex vivo neutrophil activation by mechanisms independent of SCN- and nicotine, and SCN- may contribute to the perturbed innate immune responses observed in smokers.

[Patient education for self-management of oral anticoagulation - situation in Hesse]. / Patientenschulungen zum Gerinnungsselbst-management - Angebotssituation in Hessen.

AIM: Oral anticoagulation (OAC) has been shown to be highly effective in preventing thromboembolic complications. Self-management can enable patients with a long-term indication for OAC to be actively involved in the therapy, but in Germany the implementation of self-management is linked to mandatory training. To illustrate significant structural disparities between education centres in Hesse, all such centres were identified and a list generated, specifying the differences. METHOD: Using our own questionnaire, we interviewed all known patient education centres in Hesse between January and July 2012, and conducted a descriptive analysis of their structural features. RESULTS: There were 44 datasets for statistical interpretation. We distinguished between centres with ASA certification (n=19) and centres without (n=25). On average, certified centres provide 6 h of training (range 2-9) compared to 5.5 h (range 1-12) in uncertified centers. Certified centres hold more group sessions per year (on average 17 vs. 8) and more individual training sessions (on average 10 vs. 5). Certified centres train 10-365 patients per year and uncertified centers between 5 and 77. Certified centres offer retraining more frequently (84% vs. 40%) and more often conclude the training with a written test (74% vs. 44%). Only 9 centres provide materials for patients with a migration background. CONCLUSION: The results show that in Hesse, severe structural discrepancies exist in training programmes for self-management of OAC, and it can be assumed that patients participating in trainings in different Hessian education centres face very differing conditions. To improve the quality of the trainings and to ensure patients have similar levels of knowledge, it is imperative that centres be regularly inspected with the help of proven quality indicators.

[Measurement of tissue-shift for head neck rotation]. / Messung von Strukturverschiebungen bei Kopf-Hals-Rotation.

BACKGROUND: During neck surgery the head of the patient is located in such a position that the neck-tissue is deformed compared to the normal head-position. The consideration of this tissue deformation of the neck during head rotation is the first step to using preoperative image data for medical navigation. MATERIAL AND METHODS: The tissue shift was measured and analyzed based on MRT-image data of a subject group of 5 patients. RESULTS: The big vessels, lying contralateral to the rotation, demonstrated a larger shift than those vessels, lying ipsilateral. The shift was nonlinear to the head rotation and the shift of the V. jugularis interna was less pronounced than the shift of the A. carotis communis even though they both run in the same adventitia. In the cranial neck section, the movement of the tissue was larger than in the caudal neck section. CONCLUSION: The knowledge about tissue shifts in different head positions should promote intraoperative, minimally invasive procedures. The expectation is that such examinations facilitate the navigation in neck surgery with online calculation of tissue shifts.

Finding stable minima using a nudged-elastic-band-based optimization scheme.

Optimization is essential in many scientific and economical areas, but it is often too complex to be tackled by simple straightforward calculations or by trial and error. Two well-known methods to find low-lying minima in such complex systems are simulated annealing and the genetic algorithm. In these methods artificial fluctuations control the probability of the system to overcome a local minimum having a certain depth. Here we present a complementary scheme that is based on the nudged-elastic-band method ordinarily used to find saddle points and we apply the scheme to find the most stable isomers of the phosphorus P(4), P(8) molecules and the corresponding molecules of As(n), Sb(n), and Bi(n) (n = 4,8) in the framework of the density functional theory. In the case of n = 8 we have found stable and metastable configurations, some of which are new and have similar energies. As a by-product we obtained an upper bound for the energy barriers between these configurations.

Analysis of body fluid mixtures by mtDNA sequencing: An inter-laboratory study of the GEP-ISFG working group.

The mitochondrial DNA (mtDNA) working group of the GEP-ISFG (Spanish and Portuguese Group of the International Society for Forensic Genetics) carried out an inter-laboratory exercise consisting of the analysis of mtDNA sequencing patterns in mixed stains (saliva/semen and blood/semen). Mixtures were prepared with saliva or blood from a female donor and three different semen dilutions (pure, 1:10 and 1:20) in order to simulate forensic casework. All labs extracted the DNA by preferential lysis and amplified and sequenced the first mtDNA hypervariable region (HVS-I). Autosomal and Y-STR markers were also analysed in order to compare nuclear and mitochondrial results from the same DNA extracts. A mixed stain prepared using semen from a vasectomized individual was also analysed. The results were reasonably consistent among labs for the first fractions but not for the second ones, for which some laboratories reported contamination problems. In the first fractions, both the female and male haplotypes were generally detected in those samples prepared with undiluted semen. In contrast, most of the mixtures prepared with diluted semen only yielded the female haplotype, suggesting that the mtDNA copy number per cell is smaller in semen than in saliva or blood. Although the detection level of the male component decreased in accordance with the degree of semen dilution, it was found that the loss of signal was not consistently uniform throughout each electropherogram. Moreover, differences between mixtures prepared from different donors and different body fluids were also observed. We conclude that the particular characteristics of each mixed stain can deeply influence the interpretation of the mtDNA evidence in forensic mixtures (leading in some cases to false exclusions). In this sense, the implementation of preliminary tests with the aim of identifying the fluids involved in the mixture is an essential tool. In addition, in order to prevent incorrect conclusions in the interpretation of electropherograms we strongly recommend: (i) the use of additional sequencing primers to confirm the sequencing results and (ii) interpreting the results to the light of the phylogenetic perspective.

Secretory responses of intact glomus cells in thin slices of rat carotid body to hypoxia and tetraethylammonium.

We have developed a thin-slice preparation of whole rat carotid body that allows us to perform patch-clamp recording of membrane ionic currents and to monitor catecholamine secretion by amperometry in single glomus cells under direct visual control. In normoxic conditions (P(O(2)) approximately 140 mmHg; 1 mmHg = 133 Pa), most glomus cells did not have measurable secretory activity, but exposure to hypoxia (P(O(2)) approximately 20 mmHg) elicited the appearance of a large number of spike-like exocytotic events. This neurosecretory response to hypoxia was fully reversible and required extracellular Ca(2+) influx. The average charge of single quantal events was 46 +/- 25 fC (n = 218), which yields an estimate of approximately 140,000 catecholamine molecules per vesicle. Addition of tetraethylammonium (TEA; 2-5 mM) to the extracellular solution induced in most (>95%) cells tested (n = 32) a secretory response similar to that elicited by low P(O(2)). Cells nonresponsive to hypoxia but activated by exposure to high external K(+) were also stimulated by TEA. A secretory response similar to the responses to hypoxia and TEA was also observed after treatment of the cells with iberiotoxin to block selectively Ca(2+)- and voltage-activated maxi-K(+) channels. Our data further show that membrane ion channels are critically involved in sensory transduction in the carotid body. We also show that in intact glomus cells inhibition of voltage-dependent K(+) channels can contribute to initiation of the secretory response to low P(O(2)).

K+ and Ca2+ channel activity and cytosolic [Ca2+] in oxygen-sensing tissues.

Ion channels are known to participate in the secretory or mechanical responses of chemoreceptor cells to changes in oxygen tension (P(O2)). We review here the modifications of K+ and Ca2+ channel activity and the resulting changes in cytosolic [Ca2+] induced by low P(O2) in glomus cells and arterial smooth muscle which are well known examples of O2-sensitive cells. Glomus cells of the carotid body behave as presynaptic-like elements where hypoxia produces a reduction of K+ conductance leading to enhanced membrane excitability, Ca2+ entry and release of dopamine and other neurotransmitters. In arterial myocytes, hypoxia can inhibit or potentiate Ca2+ channel activity, thus regulating cytosolic [Ca2+] and contraction. Ca2+ channel inhibition is observed in systemic myocytes and most conduit pulmonary myocytes, whereas potentiation is seen in a population of resistance pulmonary myocytes. The mechanism whereby O2 modulates ion channel activity could depend on either the direct allosteric modulation by O2-sensing molecules or redox modification by reactive chemical species.

[Spontaneous rupture of pheochromocytoma in a patient with polycystic kidneys. Apropos of a case]. / Rotura esponánea de feocromocitoma en paciente con riñones poliquísticos: A propósito de un caso.

OBJECTIVE: To report a case of spontaneous rupture of adrenal pheochromocytoma. METHODS/RESULTS: A patient previously diagnosed as having arterial hypertension and chronic renal failure secondary to adult polycystic renal disease was admitted to the emergency services with abdominal pain, signs of peripheral vasoconstriction and syncope. A CT scan showed a large perirenal hematoma. The patient underwent an extended left radical nephrectomy and evacuation of the hematoma. The histopathological analysis showed a polycystic kidney and a ruptura adrenal pheochromocytoma. The clinical features, diagnosis and treatment of this condition are discussed.

Aspirin reduces the incidence of second eye NAION: a retrospective study.

The objective of this study was to determine if aspirin reduces the incidence of second eye involvement after nonarteritic anterior ischemic optic neuropathy (NAION) in one eye. Records were reviewed of 131 patients who sustained unilateral NAION. Of these, the 33 patients who sustained second eye NAION were compared to those followed for a minimum of 2 years without sustaining a second eye NAION (67). Thirty-one of the 131 patients were excluded because of inadequate follow-up. Except for diabetes (relative risk [RR] 1.43, p = 0.05), the incidence of second eye NAION was independent of gender, age, cup/disk, hypertension, anemia, and migraine. The degree of visual acuity or field dysfunction in the first eye correlated poorly with the acuity (r = 0.28) and field (r = 0.33) loss in the second eye. Aspirin (65-1,300 mg) taken two or more times per week decreased the incidence (17.5% vs. 53.5%) and relative risk (RR = 0.44, p = 0.0002) of second eye AION regardless of the usual risk factors. Even after eliminating those patients who had bilateral disease when first referred, ASA still reduced the incidence of second eye involvement (35% vs. 13%, RR = 0.74, p = 0.01). Aspirin may be an effective means of reducing second eye NAION.

Classification of choroidal neovascularization by digital indocyanine green videoangiography.

PURPOSE: The majority of patients with exudative maculopathy due to age-related macular degeneration present with poorly defined or occult choroidal neovascularization (CNV) that cannot be imaged adequately by fluorescein angiography. Digital indocyanine green (ICG) videoangiography is a new technique that allows enhanced imaging of these poorly defined or occult vessels. The authors studied 1000 consecutive cases of occult CNV using digital ICG angiography to describe the various types of neovascularization observed by this technique and to determine the frequency and natural history of the various lesions. MATERIALS AND METHODS: Digital ICG videoangiography was performed as described previously on 1000 consecutive eyes with occult CNV by fluorescein angiography. RESULTS: One thousand consecutive eyes with occult CNV by fluorescein angiography were imaged using digital ICG videoangiography. Three morphologic types of CNV were noted by ICG videoangiography, which included focal spots, plaques (well-defined or poorly defined), and combination lesions (in which both focal spots and plaques are noted). Combination lesions can be subdivided into marginal spots (focal spots at the edge of plaques of neovascularization), overlying spots (hot spots overlying plaques of neovascularization), or remote spots (a focal spot remote from a plaque of neovascularization). The relative frequency of these lesions was as follows: there were 283 cases (29%) of focal spots; 597 cases (61%) of plaques, consisting of 265 cases (27%) of well-defined plaques and 332 cases (34%) of poorly defined plaques; and 84 cases (8%) of combination lesions, consisting of 35 cases (3%) of marginal spots, 37 cases (4%) of overlying spots, and 12 cases (1%) of remote spots. In seven additional cases (1%), a mixture of the above lesions was noted. In 13 additional eyes (1%), no lesions were noted on the ICG angiogram. The studies of 16 eyes were unreadable or unobtainable. CONCLUSIONS: There are three types of CNV that can be observed by digital ICG videoangiography. Plaques are the most common type and have a poor natural history. Focal spots or hot spots are the next most frequently seen lesion and can potentially be treated by ICG-guided laser photocoagulation. Combination lesions, in which both focal spots and plaques are present, are rare. This study of 1000 consecutive cases of eyes with occult neovascularization that were imaged with digital ICG videoangiography serves to classify the various types of neovascularization observed by this technique. Digital ICG videoangiography is an important tool in better delineating eyes with occult CNV. Future studies are necessary to validate our findings.

Emergency medical services for children in rural and frontier America: diverse and changing environments.

Rural emergency medical services for children is challenged by timely access to professional care at all levels. Particular issues of communication, providers, equipment, transport, education, legislation, financing, prevention, public awareness, data collection, and research are addressed as they confront the rural physician, with some established and suggested methods of solution. The most sophisticated health care provider, pediatrician, family practitioner, or emergency department physician must accept responsibility for implementing and facilitating the many diverse elements of rural emergency medical service for children, for structuring a functional and progressive whole that is germane to the community, and for improving rural child morbidity and mortality.

Intracellular free calcium responses to protons and capsaicin in cultured trigeminal neurons.

Acidic solutions and capsaicin are selective chemical stimuli for nociceptive neurons. The effect of these stimuli on intracellular calcium concentration was analysed in cultured trigeminal neurons of newborn rabbits. Rapid reductions in pH (from 7.4 to 5) evoked a transient rise in intracellular calcium concentration of 270% on average over the basal level (162.5 +/- 3.5 nM; n = 174) in 86% of the neurons. Maximal responses were found at pH 5.5. Proton-induced transients were diminished or abolished by 20 mM CaCl2, by zero CaCl2 and by 1 microM Ruthenium Red. In response to 1 microM capsaicin, 40% of the cells that were sensitive to protons also increased their intracellular calcium concentration to 218% of control. Capsaicin-induced intracellular calcium concentration rises were composed of an initial peak followed by a second, slower intracellular calcium concentration elevation. The capsaicin response was completely blocked by 1 microM Ruthenium Red, and disappeared in zero calcium, but was augmented in high extracellular calcium. Intracellular calcium concentration responses to capsaicin were still observed in neurons whose response to protons was desensitized by sustained exposure to low pH (pH 6.5). Cells surviving a 10-24h capsaicin (10 microM) treatment, still displayed responses to pH reductions. These results suggest that intracellular calcium concentration rises induced by moderate reductions in pH0 and capsaicin occur through different mechanisms.

Neurotrophic influences on corneal epithelial cells.

Innervation plays an important role in the maintenance of corneal structure and function. Neuropeptides contained in corneal nerves may be involved in these effects. This study was aimed to determine the influence of trigeminal and sympathetic neurons and of neuropeptides on proliferative activity of corneal epithelial cells in vitro. Corneal epithelial cells from adult rabbits were cultured alone or cocultured either with sensory neurons from the trigeminal ganglion or sympathetic cells from the superior cervical ganglion of newborn rabbits. Neurons and corneal epithelial cells shared the culture medium but lacked physical contact. After 2 or 7 days of coculture, or after treatment with substance P (SP) and/or calcitonin gene-related peptide (CGRP), the number of corneal cells was determined with a haemocytometer, and the incorporation of 3H-thymidine into corneal epithelial cells analysed by scintillation counting. Cell number and 3H-thymidine incorporation increased 3 and 2.5 times respectively (P < 0.01; P < 0.05), after 2 days of coculture of corneal epithelial cells with trigeminal neurons but this increase was reversed after 7 days of coculture. Sympathetic neurons had a stimulating effect on corneal epithelial cell proliferation that was apparent after 7 days of coculture (P < 0.01). A single administration of SP (10 microM) produced an increase in 3H-thymidine incorporation after 1 hr and an enhanced number of corneal epithelial cells 24 hr later. The same effect could be obtained by repeated administration of lower concentrations of SP (0.1 microM, six times over a 24 hr period). CGRP (1 microM) inhibited mitotic activity of corneal cells 12 hr after treatment. The effect could be reversed by simultaneous administration of SP (0.1 microM). These results indicate that trigeminal and sympathetic neurons modulate proliferation and perhaps differentiation of corneal epithelium cells in vitro. A stimulating effect was also obtained with SP while mitotic activity was inhibited by CGRP, thus suggesting that peptides contained in sensory nerve terminals may contribute to neural influences on epithelial cell proliferation.

Iodoaminopotentidine and related compounds: a new class of ligands with high affinity and selectivity for the histamine H2 receptor.

The synthesis and biological evaluation of a new class of histamine H2 antagonists with N-cyano-N'-[omega-[3-(1-piperidinylmethyl)phenoxy] alkyl]guanidine partial structure are described as part of an extensive research program to find model compounds for the development of new radioligands with high H2 affinity and specific activity. High receptor affinity is achieved by an additional (substituted) aromatic ring, which is connected with the third guanidine N by a carbon chain spacer and an amine, carboxamide, ester, or sulfonamide link ("polar group"). In functional studies for H2 antagonistic activity and other pharmacological actions [e.g. H1 antihistaminic, antimuscarinic, antiadrenergic (alpha 1, beta 1), 5-HT2 blocking activity] in the isolated guinea pig atrium and ileum and rat aorta and tail artery, the compounds proved to be highly potent and selective histamine H2 receptor antagonists. The H2 antagonistic activity is mainly depending on the length of both the N'-alkyl chain (chain A) and the N"-spacer (chain B). Compounds with a C3 chain A and a C2 chain B are most potent in the preferred group of substances, i.e., the carboxamide series. A wide variety of substituents at the aromatic ring is tolerated, among them iodine, amino, and azido groups. These compounds are up to 32 times more potent than cimetidine in the isolated guinea pig right atrium. The replacement of the carboxamide by an ester group (44c) is well tolerated, while replacement of the cyanoguanidine by an urea group results in nearly 100-fold decrease in activity (46c,e). The iodinated benzamides are among the most potent H2 antagonists known so far. The [125I]-labeled form of 31f ([125I]iodoaminopotentidine, [125I]-N-[2-(4-amino-3-iodobenzamido) ethyl]-N'-cyano-N"-[3-[3-(1-piperidinylmethyl) phenoxy]propyl]guanidine) and its photolabile analogue 31h ([125I]iodoazidopotentidine, [125I]-N-[2-(4-azido-3- iodobenzamido)ethyl]-N'-cyano-N"-[3-[3-(1-piperidinyl-methyl)pheno xy] propyl]guanidine) proved to be useful probes for reversible and irreversible labeling of the histamine H2 receptor. Radioligand binding studies in guinea pig cerebral membranes revealed considerably higher H2 receptor affinity for 31f (pKi = 9.15), 31h (pKi = 8.58), and some analogues than functional experiments (guinea pig atrium), presumably reflecting an easier access to the H2 receptors in membranes.

Reversible and irreversible labelling of H1- and H2 -receptors using novel [125I] probes.

We have recently designed the first 125I-labelled probes specific for the histamine H1 and H2 receptors. These reversible and irreversible antagonists are among the most potent H1 and H2 ligands and have enabled investigations into the biochemical and pharmacological properties of these two receptors. In various brain animal species, the ligand binding peptide of the H1 and H2 receptors, as determined by photoaffinity labeling, resides within 56-59 kDa peptides. In contrast, in guinea pig heart, the ligand binding domain of the H1 receptor is characterized by a higher molecular weight (68 kDa), suggesting the presence of an isoform of this protein, clearly differentiable by this biochemical property but not by its pharmacology. The reversible 125I-probes allowed us to extend the pharmacology of these receptors in several biological preparations and in human brain, and to establish their interaction with G-proteins. A detailed mapping of H1 and, for the first time, of H2 receptors, has been achieved in guinea pig brain, establishing their presence in almost all brain areas. These experiments show that there is no correlation between the density of H2 receptor and the activity of adenylate cyclase sensitive to histamine suggesting a molecular heterogeneity of this receptor.