Using dispersion models at microscale to assess long-term air pollution in urban hot spots: A FAIRMODE joint intercomparison exercise for a case study in Antwerp.

In the framework of the Forum for Air Quality Modelling in Europe (FAIRMODE), a modelling intercomparison exercise for computing NO2 long-term average concentrations in urban districts with a very high spatial resolution was carried out. This exercise was undertaken for a district of Antwerp (Belgium). Air quality data includes data recorded in air quality monitoring stations and 73 passive samplers deployed during one-month period in 2016. The modelling domain was 800 × 800 m2. Nine modelling teams participated in this exercise providing results from fifteen different modelling applications based on different kinds of model approaches (CFD - Computational Fluid Dynamics-, Lagrangian, Gaussian, and Artificial Intelligence). Some approaches consisted of models running the complete one-month period on an hourly basis, but most others used a scenario approach, which relies on simulations of scenarios representative of wind conditions combined with post-processing to retrieve a one-month average of NO2 concentrations. The objective of this study is to evaluate what type of modelling system is better suited to get a good estimate of long-term averages in complex urban districts. This is very important for air quality assessment under the European ambient air quality directives. The time evolution of NO2 hourly concentrations during a day of relative high pollution was rather well estimated by all models. Relative to high resolution spatial distribution of one-month NO2 averaged concentrations, Gaussian models were not able to give detailed information, unless they include building data and street-canyon parameterizations. The models that account for complex urban geometries (i.e. CFD, Lagrangian, and AI models) appear to provide better estimates of the spatial distribution of one-month NO2 averages concentrations in the urban canopy. Approaches based on steady CFD-RANS (Reynolds Averaged Navier Stokes) model simulations of meteorological scenarios seem to provide good results with similar quality to those obtained with an unsteady one-month period CFD-RANS simulations.

Fourteen-year study of the management of the odontogenic keratocyst. Are adjunctive therapies all they are cut out to be?

Odontogenic keratocysts (OKC) are benign, developmental, locally-aggressive odontogenic cystic lesions with a high risk of recurrence. As such, the most effective treatment modalities remain controversial. The mainstay of treatment remains enucleation with or without decompression. The use of adjunctive therapies is widely reported. Our aim was to review our experience of OKCs and therefore identify the treatment modality, if there is any single one, with the lowest rate of recurrence. We also aimed to identify any common themes linking those patients experiencing cystic recurrence. Data were collected on 50 patients treated at UHCW NHS Trust over a 14-year period (2005-2018) via an anonymised database. Surgical pathways were analysed, including details of the location of the cysts and the use of adjunctive therapies, namely; mechanical debridement, cryotherapy, and the use of Carnoy's solution. Fifty-six keratocysts, both primary (91%, n = 51) and recurrent (9%, n = 5) were included. A total of 6% of patients had a pre-existing diagnosis of Gorlin-Goltz Syndrome (n = 3). Enucleation was performed in an approximately 3:1 ratio to decompression with secondary enucleation (n = 41:15). Twenty-seven percent of patients had adjunctive therapies (n = 15). There was a 12% recurrence rate (n = 6) found only within the group of primary cysts that had been enucleated only. Notably, there were no recurrences in those cysts that had undergone adjunctive therapy. None of the cysts that underwent initial decompression or marsupialisation recurred. Following surgical intervention, no tertiary recurrent cysts were detected postoperatively. This study demonstrated the advantage of establishing a correct diagnosis prior to definitive treatment. Initial decompression in selected patients followed by enucleation, along with adjunctive therapies showed a benefit in reducing recurrences. However, in the absence of high-quality evidence for the most effective management of odontogenic keratocysts, finding a common approach will remain controversial.

Temporomandibular joint dysfunction following the use of a supraglottic airway device during general anaesthesia: a prospective observational study.

Supraglottic airway devices are commonly used to manage the airway during general anaesthesia. There are sporadic case reports of temporomandibular joint dysfunction and dislocation following supraglottic airway device use. We conducted a prospective observational study of adult patients undergoing elective surgery where a supraglottic airway device was used as the primary airway device. Pre-operatively, all participants were asked to complete a questionnaire involving 12 points adapted from the Temporomandibular Joint Scale and the Liverpool Oral Rehabilitation Questionnaire. Objective measurements included inter-incisor distance as well as forward and lateral jaw movements. The primary outcome was the inter-incisor distance, an accepted measure of temporomandibular joint mobility. Both the questionnaire and measurements were repeated in the postoperative period and we analysed data from 130 participants. Mean (SD) inter-incisor distance in the pre- and postoperative period was 46.5 (7.2) mm and 46.3 (7.5) mm, respectively (p = 0.521) with a difference (95%CI) of 0.2 (-0.5 to 0.9) mm. Mean (SD) forward jaw movement in the pre- and postoperative period was 3.6 (2.4) mm and 3.9 (2.4) mm, respectively (p = 0.018). Mean (SD) lateral jaw movement to the right in the pre- and postoperative period was 8.9 (4.1) mm and 9.1 (4.0) mm, respectively (p = 0.314). Mean (SD) lateral jaw movement to the left in the pre- and postoperative period was 8.8 (4.0) mm and 9.3 (3.6) mm, respectively (p = 0.008). The number of patients who reported jaw clicks or pops before opening their mouth as wide as possible was 28 (21.5%) vs. 12 (9.2%) in the pre- and postoperative period, respectively (p < 0.001) with a difference (95%CI) of 12.3% (6.7-17.9%). There was no significant difference in the responses to the other 11 questions or in the number of patients who reported pain in the temporomandibular joint area postoperatively. No clinically significant dysfunction of the temporomandibular joint following the use of supraglottic airway devices in the postoperative period was identified by either patient questionnaires or objective measurements.

Success Rates in a Diabetes Specialist Nurse-Led Education Programme: Re-setting the Glucostat.

Analysis of National Diabetes Audit data from 2011-2012 of newly diagnosed people with type 1 diabetes mellitus (DM) found low initial success rates in much of the UK at 20% on initial training, while an unusually high success rate of 75% achieving target HbA1C<58 mmol/mol (< 7.5%) was found in Cheshire (England average=40.8%). We present a review of the approach taken by the Cheshire Diabetes team in the 12 months following diagnosis. Between 2012 and 2013, 15 consecutive newly diagnosed people with type 1 DM were followed up for 18 months. All received support and advice by community Diabetes Specialist Nurses (DSNs) and Dieticians covering Central and Eastern Cheshire, UK. Mean±SD age at diagnosis was 23±3 years. The period of contact with the DSN service varied from 7-12 weeks. Baseline HbA1C of 99 mmol/mol [11.2%] (95% CI: 86-111 mmol/mol [10.0-12.3%]) declined by ~50% to 49 mmol/mol [6.6%] (41-57 mmol/mol [5.9-7.4%]; F=16.9, p<0.001) at 6 months and did not change between 6-12 months. Of those newly diagnosed with type 1 DM, 84.6% achieved a target HbA1C<58 mmol/mol (<7.5%) and 61.5% met a target<48 mmol/mol (<6.5%). There was no significant weight change during the study. The key elements of this bio-psycho-social approach by the DSN team included providing psychological support, patient engagement, demonstrating positive regard, gaining trust, identifying health-seeking behaviour, providing key decision-making skills and developing a self-management plan. This resulted in improvements in overall glycaemic control well above the national average without untoward weight gain. The UK National Diabetes Audit (2011-2012) in newly diagnosed type 1 diabetics in Cheshire, UK, showed a success rate at 6 months post-diagnosis of 75% achieving a target HbA1C<58 mmol/mol (<7.5%) compared with the national average of 40.8%. Initially thought to be erroneous, these excellent results were confirmed. The approach taken to achieve them is herein described.

Solid tumors of the peritoneum, omentum, and mesentery in children: radiologic-pathologic correlation: from the radiologic pathology archives.

Intraperitoneal solid tumors are far less common in children than in adults, and the histologic spectrum of neoplasms of the peritoneum and its specialized folds in young patients differs from that in older patients. Localized masses may be caused by inflammatory myofibroblastic tumor, Castleman disease, mesenteric fibromatosis, or other mesenchymal masses. Inflammatory myofibroblastic tumor is a mesenchymal tumor of borderline biologic potential that appears as a solitary circumscribed mass, possibly with central calcification. Castleman disease is an idiopathic lymphoproliferative disorder that appears as a circumscribed, intensely enhancing mass in the mesentery. Mesenteric fibromatosis, or intra-abdominal desmoid tumor, is a benign tumor of mesenchymal origin associated with familial adenomatous polyposis. Mesenteric fibromatosis appears as a mildly enhancing, circumscribed solitary mass without metastases. Diffuse peritoneal disease may be due to desmoplastic small round cell tumor (DSRCT), non-Hodgkin lymphoma, or rhabdomyosarcoma. DSRCT is a rare member of the small round blue cell tumor family that causes diffuse peritoneal masses without a visible primary tumor. A dominant mass is typically found in the retrovesical space. Burkitt lymphoma is a pediatric tumor that manifests with extensive disease because of its short doubling time. The bowel and adjacent mesentery are commonly involved. Rhabdomyosarcoma may arise as a primary tumor of the omentum or may spread from a primary tumor in the bladder, prostate, or scrotum. Knowledge of this spectrum of disease allows the radiologist to provide an appropriate differential diagnosis and suggest proper patient management.

Personal factors in systemic sclerosis and their coverage by patient-reported outcome measures. A multicentre European qualitative study and literature review.

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease where thickening of the skin can lead to reduced body function and limitations in activities. Severe forms can also affect and seriously damage inner organs. Patient-centred rehabilitation emphasises considerations of patients' background, experience and behavior which highlights the need to know if patient-reported outcome measures (PROMs) include such personal factors. AIM: To identify and describe personal factors in the experiences of functioning and health of persons with SSc and to examine if and to what extent PROMs in SSc research cover these factors. DESIGN: Data from a qualitative study with focus group interviews were analysed. PROMs in SSc research were identified in a literature review between 2008-2013. SETTING: Participants were recruited from outpatient clinics at rheumatology department. POPULATION: Sixty-three patients with SSc from four European countries participated. METHODS: Data from interviews were analysed using a structure of personal factors developed by Geyh et al. Identified PROMs were analysed and linked to main concepts, related to the personal factors, found in the interview data. RESULTS: Nineteen main concepts were related to the area "patterns of experience and behaviour" in the personal factor structure, 16 to "thoughts and beliefs", nine to "feelings", one to "motives" and one to "personal history and biography", respectively. Among the 35 PROMs identified, 15 did not cover any of the identified concepts. Concepts within the area "feelings" were mostly covered by the PROMs. Five of the PROMs covered "patterns of experience and behaviour", while "motives" and "personal history and biography" were not covered at all. Four of the identified PROMs covered concepts within the areas "feelings", "thoughts and beliefs" and "patterns of experience and behaviour" in the same instrument. The Illness Cognition Questionnaire and Illness Behaviour Questionnaire were such PROMs. CONCLUSION: Patterns of experience and behaviour had the highest number of concepts related to personal factors, but few of the PROMs in SSc research covered these factors. Only a few PROMs covered several personal factors areas in the same instrument. CLINICAL REHABILITATION IMPACT: The results would be of value when developing core sets for outcome measurements in SSc.

Spatially-varying surface roughness and ground-level air quality in an operational dispersion model.

Urban form controls the overall aerodynamic roughness of a city, and hence plays a significant role in how air flow interacts with the urban landscape. This paper reports improved model performance resulting from the introduction of variable surface roughness in the operational air-quality model ADMS-Urban (v3.1). We then assess to what extent pollutant concentrations can be reduced solely through local reductions in roughness. The model results suggest that reducing surface roughness in a city centre can increase ground-level pollutant concentrations, both locally in the area of reduced roughness and downwind of that area. The unexpected simulation of increased ground-level pollutant concentrations implies that this type of modelling should be used with caution for urban planning and design studies looking at ventilation of pollution. We expect the results from this study to be relevant for all atmospheric dispersion models with urban-surface parameterisations based on roughness.

Helminth protection against autoimmune diabetes in nonobese diabetic mice is independent of a type 2 immune shift and requires TGF-ß.

Leading hypotheses to explain helminth-mediated protection against autoimmunity postulate that type 2 or regulatory immune responses induced by helminth infections in the host limit pathogenic Th1-driven autoimmune responses. We tested these hypotheses by investigating whether infection with the filarial nematode Litomosoides sigmodontis prevents diabetes onset in IL-4-deficient NOD mice and whether depletion or absence of regulatory T cells, IL-10, or TGF-ß alters helminth-mediated protection. In contrast to IL-4-competent NOD mice, IL-4-deficient NOD mice failed to develop a type 2 shift in either cytokine or Ab production during L. sigmodontis infection. Despite the absence of a type 2 immune shift, infection of IL-4-deficient NOD mice with L. sigmodontis prevented diabetes onset in all mice studied. Infections in immunocompetent and IL-4-deficient NOD mice were accompanied by increases in CD4(+)CD25(+)Foxp3(+) regulatory T cell frequencies and numbers, respectively, and helminth infection increased the proliferation of CD4(+)Foxp3(+) cells. However, depletion of CD25(+) cells in NOD mice or Foxp3(+) T cells from splenocytes transferred into NOD.scid mice did not decrease helminth-mediated protection against diabetes onset. Continuous depletion of the anti-inflammatory cytokine TGF-ß, but not blockade of IL-10 signaling, prevented the beneficial effect of helminth infection on diabetes. Changes in Th17 responses did not seem to play an important role in helminth-mediated protection against autoimmunity, because helminth infection was not associated with a decreased Th17 immune response. This study demonstrates that L. sigmodontis-mediated protection against diabetes in NOD mice is not dependent on the induction of a type 2 immune shift but does require TGF-ß.

Cystic lung disease in infants and children.

Cysts within the lung are one of the more common pulmonary pathological findings seen in an active pediatric surgical pathology service. Of both developmental and acquired origin, they may present as respiratory distress in infants or may be asymptomatic lesions incidentally discovered by images studies of the thoracic for "non-pulmonary" reasons. The most frequently seen developmental cysts of the lung are those of Congenital Pulmonary Airway Malformations, types 1, 2 & 4. Other congenital cystic lesions include bronchogenic cysts (usually in older patients) and some of the enteric duplication lesions that contain cysts. Acquired cystic lung lesions include acute and persistent pulmonary interstitial emphysema, postinfarction peripheral cysts, postinfectious pulmonary cysts, and the cystic form of pleuropulmonary blastoma.

The impact of hemorrhoidectomy on sexual function in women: a preliminary study.

The purpose of this study was to explore the prevalence of sexual problems in post-hemorrhoidectomy females. The study consisted of a surgical group and a control group of women between the ages of 22 and 74 years, 39 with and 39 without hemorrhoidectomy. Female sexual function was evaluated using the Female Sexual Function Index (FSFI). The level of sexual function was calculated for each domain and compared across domains and demographic variables for each group. The prevalence of sexual dysfunction among the post-hemorrhoidectomy participants was 48.7% (19/39) and among the healthy women 7.7% (3/39). The average FSFI score was significantly lower in the surgical group (46.38+/-28.13) than in the control group (65.69+/-18.48) (P=0.001). All the FSFI domain scores, with the exception of the desire domain, were significantly lower for the surgical group relative to the healthy group (P<0.05). Logistic regression analysis revealed that group (P=0.001) and age (P=0.013) were predictors of problems in female sexual functioning. This preliminary study shows that women who have had a hemorrhoidectomy are at higher risk of sexual function problems. The sexual function of women with hemorrhoidectomy should be evaluated to provide them with a better quality of life.

From the archives of the AFIP: breast masses in children and adolescents: radiologic-pathologic correlation.

The spectrum of breast lesions in children and adolescents varies markedly from that for adults, with the former lesions being overwhelmingly benign. A breast mass in a young boy or girl may arise from normal and abnormal breast development. Other causes of masses include infection, trauma, and cyst formation. After onset of puberty, most cases of breast enlargement arise from benign fibroadenoma in girls and gynecomastia in boys. These conditions have specific imaging appearances, although juvenile (often giant) fibroadenoma cannot be distinguished from phyllodes tumor, which can be benign or malignant. In children, both conditions usually appear as well-circumscribed, hypoechoic masses at sonography and show diffuse enhancement except for nonenhancing septations at magnetic resonance imaging. A diagnosis of juvenile papillomatosis (a benign lesion) portends later development of breast cancer, and patients with this condition should be closely monitored. Malignant lesions of the breast in children are rare. The most common malignant lesions are metastases and are usually associated with widespread disease. The most common primary breast malignancy is malignant phyllodes tumor. Primary breast carcinoma is exceedingly rare in the pediatric age group, but its imaging appearance in children is the same as seen in adults and is different from that of almost all benign lesions. In girls, diagnostic interventions may injure the developing breast and cause subsequent disfigurement. Given this risk and the low prevalence of malignant disease in this population, a prudent course should be followed in the diagnosis of breast lesions. Imaging findings are very helpful for selecting patients for further diagnostic procedures. Although malignancy is rare, lesions with suspicious imaging findings or progressive growth should be subjected to cytologic or histologic examination.

Inhibition of type 1 diabetes in filaria-infected non-obese diabetic mice is associated with a T helper type 2 shift and induction of FoxP3+ regulatory T cells.

We sought to determine whether Litomosoides sigmodontis, a filarial infection of rodents, protects against type 1 diabetes in non-obese diabetic (NOD) mice. Six-week-old NOD mice were sham-infected or infected with either L3 larvae, adult male worms, or adult female worms. Whereas 82% of uninfected NOD mice developed diabetes by 25 weeks of age, no L. sigmodontis-infected mice developed disease. Although all mice had evidence of ongoing islet cell inflammation by histology, L. sigmodontis-infected mice had greater numbers of total islets and non-infiltrated islets than control mice. Protection against diabetes was associated with a T helper type 2 (Th2) shift, as interleukin-4 (IL-4) and IL-5 release from alpha-CD3/alpha-CD28-stimulated splenocytes was greater in L. sigmodontis-infected mice than in uninfected mice. Increased circulating levels of insulin-specific immunoglobulin G1, showed that this Th2 shift occurs in response to one of the main autoantigens in diabetes. Multicolour flow cytometry studies demonstrated that protection against diabetes in L. sigmodontis-infected NOD mice was associated with significantly increased numbers of splenic CD4(+) CD25(+) FoxP3(+) regulatory T cells. Interestingly, injection of crude worm antigen into NOD mice also resulted in protection against type 1 diabetes, though to a lesser degree than infection with live L. sigmodontis worms. In conclusion, these studies demonstrate that filarial worms can protect against the onset of type 1 diabetes in NOD mice. This protection is associated with a Th2 shift, as demonstrated by cytokine and antibody production, and with an increase in CD4(+) CD25(+) FoxP3(+) regulatory T cells.

Clinical and pathologic differential diagnosis of selected potential bioterrorism agents of interest to pediatric health care providers.

The early recognition of potential bioterrorism agents has been of increasing concern in recent years. The Centers for Disease Control and Prevention has categorized and listed biological terrorism agents. Although any or all of the highest risk biological agents (including inhalation anthrax, pneumonic plague, smallpox, tularemia, botulism, and viral hemorrhagic fevers) can be seen in the pediatric patient, several agents might closely resemble--at least in their initial stages-some of the more common childhood illnesses. The awareness of these similarities and, more importantly,their differences, are critical for all health care professionals. Selected examples of some typical childhood illnesses are presented and then compared with three of the most virulent biological agents (smallpox, anthrax and plague) that might be used in a bioterrorism attack.

From the archives of the AFIP: Lung disease in premature neonates: radiologic-pathologic correlation.

Pulmonary disease is the most important cause of morbidity in preterm neonates, whose lungs are often physiologically and morphologically immature. Surfactant deficiency in immature lungs triggers a cascade of alveolar instability and collapse, capillary leak edema, and hyaline membrane formation. The term respiratory distress syndrome (RDS) has come to represent the clinical expression of surfactant deficiency and its nonspecific histologic counterpart, hyaline membrane disease. Historically, chest radiographs of infants with RDS predictably demonstrated decreased pulmonary expansion, symmetric generalized reticulogranular lung opacities, and air bronchograms. Refinements in perinatal medicine, including antenatal glucocorticoid administration, surfactant replacement therapy, and increasingly sophisticated ventilatory strategies have decreased the prevalence of RDS and air leak, altered familiar radiographic features, and lowered the threshold of potential viability to a gestational age of approximately 23 weeks. Alveolar paucity and pulmonary interstitial thickness in these profoundly premature neonates impair normal gas exchange and may necessitate prolonged mechanical ventilation, increasing the risk of lung injury. Bronchopulmonary dysplasia (BPD), alternatively termed chronic lung disease of infancy, is a disorder of lung injury and repair originally ascribed to positive-pressure mechanical ventilation and oxygen toxicity. Before the advent of surfactant replacement therapy, chest radiographs of infants with classic BPD demonstrated coarse reticular lung opacities, cystic lucencies, and markedly disordered lung aeration that reflected alternating regions of alveolar septal fibrosis and hyperinflated normal lung parenchyma. In the current era of surfactant replacement, BPD is increasingly a disorder of very low-birth-weight neonates with arrested alveolar and pulmonary vascular development, minimal alveolar septal fibrosis and inflammation, and more subtle radiographic abnormalities.

Is the two week rule of any benefit to patients with oral cancer?

In the UK the government introduced the 'two week rule' for head and neck cancer in December 2000, which sought to guarantee that any patient with suspected cancer would be seen by a specialist within 2 weeks of being referred. Our aim was to find out whether referral under the 'two week rule' resulted in patients being given an appointment and starting treatment faster than those who had been referred urgently directly to a consultant surgeon. A retrospective review of case notes of all patients diagnosed with oral cancer over a six-month period showed that only 3 of 22 were referred under the 'two week rule'. A total of 48 referrals under the 'two week rule' were recorded during the same period. There was no significant difference between the two groups in terms of time waiting for an outpatient appointment and time spent waiting for treatment.

The morphologic spectrum of infantile lobar emphysema: a study of 33 cases.

Infantile lobar emphysema (ILE) is a relatively uncommon entity characterised by radiologic pulmonary lobar overinflation. The spectrum of underlying pathology in ILE has not been previously detailed. We have reviewed thirty-three cases of ILE accessioned to the Armed Forces Institute of Pathology, Washington D.C., since 1970. Seventeen (51.5%) presented in the first week of life, 27 (81.8%) presented within the first six months, and an additional six cases presented beyond six months including three beyond 18 months of age. Upper lobe involvement occurred in 96.9% cases and multiple lobes were involved in six cases. Nine infants had polyalveolar (hyperplastic) lobes determined on the basis of radial alveolar counts (RACs), while 21 were considered to be "classic ILE" since these showed lobar hyperexpansion without any other abnormality. RACs in infants with classic ILE remained fairly constant irrespective of age unlike a progressive increase seen in normal age-matched controls, suggesting a post-partum arrest of acinar development in ILE. Additional findings included serpiginous bronchioles resembling those seen in extralobar sequestration in two cases, bronchopulmonary dysplasia in two cases, and one case each showing "cystic alveoli" and peripheral subpleural cysts. ILE thus seems to be a composite of various pathologies resulting in a single clinical entity. We hypothesise that the timing of an inciting functional or anatomic bronchial obstruction during in-utero lung development determines morphologic variation in ILE.

Congenital pulmonary airway malformation (congenital cystic adenomatoid malformation) with multiple extrapulmonary anomalies: autopsy report of a fetus at 19 weeks of gestation.

Congenital pulmonary airway malformation, or congenital cystic adenomatoid malformation, is postulated to be a disorder of pulmonary airway morphogenesis and encompasses 5 different types with distinct levels or stages of tracheobronchial development. We present a unique case of type 2 congenital pulmonary airway malformation with a previously undocumented combination of multiple extrapulmonary anomalies, featuring ipsilateral multicystic renal dysgenesis, contralateral renal agenesis, and ovarian germ cell hypoplasia, diagnosed in a 19-week gestational age fetus by autopsy. Epithelial cells comprising the pulmonary lesions were positive for thyroid transcription factor-1, surfactant protein-B, and cytokeratin-7 but negative for cytokeratin-20 immunostainings, with the pattern seen in normal terminal bronchioles. Chromosomal analysis showed a normal female karyotype, despite a high estimated risk for Down syndrome suggested by the low maternal serum alpha-fetoprotein level.

Maurotoxin: a potent inhibitor of intermediate conductance Ca2+-activated potassium channels.

Maurotoxin, a 34-amino acid toxin from Scorpio maurus scorpion venom, was examined for its ability to inhibit cloned human SK (SK1, SK2, and SK3), IK1, and Slo1 calcium-activated potassium (K(Ca)) channels. Maurotoxin was found to produce a potent inhibition of Ca(2+)-activated (86)Rb efflux (IC(50), 1.4 nM) and inwardly rectifying potassium currents (IC(50), 1 nM) in CHO cells stably expressing IK1. In contrast, maurotoxin produced no inhibition of SK1, SK2, and SK3 small-conductance or Slo1 large-conductance K(Ca) channels at up to 1 microM in physiologically relevant ionic strength buffers. Maurotoxin did inhibit (86)Rb efflux (IC(50), 45 nM) through, and (125)I-apamin binding (K(i), 10 nM) to SK channels in low ionic strength buffers (i.e., 18 mM sodium, 250 mM sucrose), which is consistent with previous reports of inhibition of apamin binding to brain synaptosomes. Under similar low ionic strength conditions, the potency for maurotoxin inhibition of IK1 increased by approximately 100-fold (IC(50), 14 pM). In agreement with its ability to inhibit recombinant IK1 potassium channels, maurotoxin was found to potently inhibit the Gardos channel in human red blood cells and to inhibit the K(Ca) in activated human T lymphocytes without affecting the voltage-gated potassium current encoded by Kv1.3. Maurotoxin also did not inhibit Kv1.1 potassium channels but potently blocked Kv1.2 (IC(50), 0.1 nM). Mutation analysis indicates that similar amino acid residues contribute to the blocking activity of both IK1 and Kv1.2. The results from this study show that maurotoxin is a potent inhibitor of the IK1 subclass of K(Ca) potassium channels and may serve as a useful tool for further defining the physiological role of this channel subtype.