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Engineered miniprotein host–small-molecule guest pairs could be utilized to design new processes within cells as well as investigate fundamental aspects of cell signaling mechanisms. However, the development of host–guest pairs capable of functioning in living systems has proven challenging. Moreover, few examples of host–guest pairs with stoichiometries other than 2:1 exist, significantly hindering the ability to study the influence of oligomerization state on signaling fidelity. Herein, we present an approach to identify host–guest systems for relatively small green fluorescent guests by incorporation into cyclic peptides. The optimal host–guest pair produced a 10-fold increase in green fluorescence signal upon binding. Biophysical characterization clearly demonstrated higher order supramolecular assembly, which could be visualized on the surface of living yeast cells using a turn-on fluorescence readout. This work further defines evolutionary design principles to afford host–guest pairs with stoichiometries other than 2:1 and enables the identification of spectrally orthogonal host–guest pairs.

Protein phosphatases, while long overlooked, have recently become appreciated as drivers of both normal- and disease-associated signaling events. As a result, the spotlight is now turning torwards this enzyme family and efforts geared towards the development of modern chemical tools for studying these enzymes are well underway. This Minireview focuses on the evolution of chemical activity probes, both optical and covalent, for the study of protein phosphatases. Small-molecule probes, global monitoring of phosphatase activity through the use of covalent modifiers, and targeted fluorescence-based activity probes are discussed. We conclude with an overview of open questions in the field and highlight the potential impact of chemical tools for studying protein phosphatases.

Lacking protein synthesis machinery and organelles necessary for autophagy or apoptosis, aged red blood cells (RBCs) are marked by circulating auto-antibodies for macrophage-mediated clearance. The antigen recognized by these auto-antibodies is the major protein of the RBC membrane, Band 3. To ensure regulation and specificity in clearance, the molecular "clock" must mark senescent cells in a way that differentiates them from younger cells, to prevent premature clearance. Predominant models of Band 3 senescence signaling are reviewed, and merits are discussed in light of the recently published crystal structure of the Band 3 membrane domain. © 2017 IUBMB Life, 70(1):32-40, 2018.

The success of hemodialysis depends on functional vascular access but such an invasive, semipermanent intervention can be confronting for patients. Vascular access complications are potentially life threatening and reduce treatment satisfaction and quality of life. This study aims to describe patient perspectives on vascular access. Face-to-face, semistructured interviews were conducted with 26 adult patients receiving hemodialysis with any form of vascular access at two dialysis units in Australia. The transcripts were analyzed using thematic analysis. We identified five major themes describing patient perspectives on vascular access: developing mental fortitude for access (accepting necessity for survival, self-advocacy, experiential confidence and competency, dependency on others, gaining vascular knowledge), device intrusiveness on the body (restricting normal function, finding compensatory solutions, bodily invasion, confronting appearance), inhibiting pain (aversion to surgery, persisting needle anxieties), exposure to dire health consequences (resigning to inevitable failure, anticipating serious complications, technological skepticism, wary of medical incompetence), and imposing burdens (generating additional expenses, encumbering family members). Patients with a vascular access rely on a precarious lifeline, which is confronting, intrusive, and burdensome. Some develop mental resilience to cope with the pain and invasiveness of vascular access. The results suggest that more attention to address needle anxieties, self-advocacy, lifestyle disruption, fear of complications, and concern for caregiver burden may improve treatment satisfaction and outcomes for patients on hemodialysis.

pH is a profound regulator of cellular function. It is, therefore, often important to assess intracellular pH. Given the small size of individual cells and their sensitivity to perturbation, measurement of intracellular pH requires sensitive, indirect measurement approaches. These include equilibration of weak acids/bases, nuclear magnetic resonance spectroscopy, pH microelectrodes, fluorescent pH indicator dyes and pH-sensitive fluorescent proteins. Presently, the use of fluorescence techniques predominates, as these permit sensitive detection and the possibility to discretely measure pH in different cellular compartments. The selection of intracellular pH measurement technique is guided by consideration of their strengths and weaknesses, in addition to technical considerations. Cells resist changes of pH through pH buffering molecules, including proteins and bicarbonate, which together are called the cell's buffer capacity. Key Concepts Cellular processes are highly sensitive to pH, so cells have redundant mechanisms to control their pH. Buffer capacity is the ability of cells to control pH by absorbing or releasing H+ from chemical pH buffering molecules. Cell membranes contain embedded transport proteins able to move H+, or pH-buffering HCO3− in order to tightly control cytosolic and organellar pH. pH of the cytosol and other intracellular compartments can be measured. Certain molecules will absorb light and release a photon of light at a longer wavelength, a process known as fluorescence. Fluorescent dyes and proteins are the most common means to report on intracellular pH. Keywords: cytosolic pH; organellar pH; pH indicator dye; fluorescent protein; nuclear magnetic resonance; ionophore; buffer capacity; microelectrode; fluorescence spectroscopy

Purpose In rural communities that experience high rates of cardiovascular disease (CVD) morbidity and mortality, family history education may enhance risk awareness and support engagement in healthy behaviors but could also engender fatalism. This study was conducted to assess if the relationship between family history and adherence to healthy lifestyle behaviors is moderated by fatalism. Methods Baseline data were obtained from 1,027 adult participants in the HeartHealth in Rural Kentucky study. Multiple linear regression was used to determine whether fatalism moderated the relationship between high-risk family history of CVD and adherence to healthy lifestyle behaviors, controlling for sociodemographic variables and CVD risk factors. The relationship between family history and healthy behaviors was assessed for subgroups of participants divided according to the upper and lower quartiles of fatalism score. Findings The relationship between high-risk family history of CVD and adherence to healthy behaviors was moderated by fatalism. Among those with the highest quartile of fatalism scores, high-risk family history predicted greater adherence to healthy behaviors, while among those in the lowest quartile, and among those with the middle 50% of fatalism scores, there was no association between family history and healthy behavior scores. Conclusions Family history education can provide people at increased risk for CVD important information to guide health practices. This may be particularly relevant for those with a high degree of fatalistic thinking. In rural communities with limited health resources, family history education, combined with assessment of fatalism, may support better targeted interventions to enhance engagement in healthy behaviors.

Objectives/Hypothesis Acute otitis media (AOM) is a common bacterial infection in childhood that causes an inflammatory response in the middle ear. Leukocytes produce different inflammatory molecules in vitro when stimulated with Gram-positive and Gram-negative bacteria. The major causes of AOM are Streptococcus pneumoniae, nontypeable Haemophilus influenza, and Moraxella catarrhalis. We sought to assess differences in cytokines, chemokines, and expression of Toll-like receptors (TLRs) at onset of AOM based on bacterial culture results. Study Design Middle ear fluid (MEF) from 66 children with AOM was studied. Methods Innate immune genes, cytokines (interleukin [IL]-6, IL-8, IL-10, IL1-β; tumor necrosis factor-α), chemokines (CCL2, CCL3, CCL4, CCR5, CXCR3), and Toll-like receptors (TLR2, TLR4, TLR9) expression was measured using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) from MEF collected in vivo by tympanocentesis. Results Culture-positive MEF had higher levels of all cytokines and chemokines (9–300-fold) as compared to MEF that was culture negative. Polymerase chain reaction (PCR)-positive/culture-negative MEF for otopathogens showed significant differences (P

Bicarbonate (HCO3(-)) has a central place in human physiology as the waste product of mitochondrial energy production and for its role in pH buffering throughout the body. Because bicarbonate is impermeable to membranes, bicarbonate transport proteins are necessary to enable control of bicarbonate levels across membranes. In humans, 14 bicarbonate transport proteins, members of the SLC4 and SLC26 families, function by differing transport mechanisms. In addition, some anion channels and ZIP metal transporters contribute to bicarbonate movement across membranes. Defective bicarbonate transport leads to diseases, including systemic acidosis, brain dysfunction, kidney stones, and hypertension. Altered expression levels of bicarbonate transporters in patients with breast, colon, and lung cancer suggest an important role of these transporters in cancer.

BACKGROUND AND PURPOSE Na+/HCO3- co-transport (NBC) regulates intracellular pH (pHi) in the heart. We have studied the electrogenic NBC isoform NBCe1 by examining the effect of functional antibodies to this protein. EXPERIMENTAL APPROACH We generated two antibodies against putative extracellular loop domains 3 (a-L3) and 4 (a-L4) of NBCe1 which recognized NBCe1 on immunoblots and immunostaining experiments. pHi was monitored using epi-fluorescence measurements in cat ventricular myocytes. Transport activity of total NBC and of NBCe1 in isolation were evaluated after an ammonium ion-induced acidosis (expressed as H+ flux, JH, in mmol·L−1 min−1 at pHi 6.8) and during membrane depolarization with high extracellular potassium (potassium pulse, expressed as ΔpHi) respectively. KEY RESULTS The potassium pulse produced a pHi increase of 0.18 ± 0.006 (n= 5), which was reduced by the a-L3 antibody (0.016 ± 0.019). The a-L-3 also decreased JH by 50%. Surprisingly, during the potassium pulse, a-L4 induced a higher pHi increase than control,(0.25 ± 0.018) whereas the recovery of pHi from acidosis was faster (JH was almost double the control value). In perforated-patch experiments, a-L3 prolonged and a-L4 shortened action potential duration, consistent with blockade and stimulation of NBCe1-carried anionic current respectively. CONCLUSIONS AND IMPLICATIONS Both antibodies recognized NBCe1, but they had opposing effects on the function of this transporter, as the a-L3 was inhibitory and the a-L4 was excitatory. These antibodies could be valuable in studies on the pathophysiology of NBCe1 in cardiac tissue, opening a path for their potential clinical use.

Summary Undesired behaviours are a common problem amongst leisure and sporting horses in the UK and have a significant impact on the work of equine practitioners. In most cases, behaviours considered aberrant by owners are normal responses for their horses. Behaviours perceived as ‘naughtiness’ may in fact signify direct actions to avoid pain- or fear-inducing stimuli. Examples that practitioners might deal with include trailer loading problems, avoidance of having saddlery equipment applied or reluctance to leave the yard. Even where no evidence of physical problems or pain can be detected, avoidance behaviours may reflect learnt responses that previously led to success in evading unpleasant consequences. Because owners often misunderstand the reason for such behaviours to develop in their horses, attempts at resolution often involve suppression or punishment based approaches. Although repeated subjugation of undesirable responses may ultimately appear to resolve the overt behavioural problem in some cases, in many others it can lead to a worsening of the problem, the development of alternative avoidance strategies or the horse learning that escaping the source of its pain or anxiety is impossible and ceasing to respond. Some horses develop abnormal or repetitive behaviours, which are not in the ‘normal’ behavioural repertoire. These stereotypic behaviours, sometimes termed ‘vices’, can indicate strategies to cope with a suboptimal environment. Indeed, their performance may serve to improve the situation for the animal. Attempts to suppress or prevent horses showing stereotypies, therefore, will generally exacerbate the underlying welfare problem. When dealing with either stereotypies or avoidance behaviours, it is important to recognise the role of learning in their development and maintenance. Resolution involves both understanding the underlying motivation for showing the behaviour and how it has become reinforced and established over time, for each individual case. The use of environmental change and/or behavioural modification techniques that are both successful and welfare compatible, are important in dealing with undesired behaviour in horses and selection of suitable professionals for referral an important responsibility for the equine practitioner.

Purpose: To contrast rates of initial HPV vaccine uptake, offered at no cost, between a rural clinic, a rural community college, and an urban college clinic and to identify rural versus urban differences in uptake of free booster doses. Methods: Young rural women attending rural clinics (n = 246), young women attending a rural community college (n = 251) and young women attending an urban university health clinic (n = 209) were recruited in Kentucky. After completing a brief questionnaire, women received a free voucher for HPV vaccination. Whether women redeemed the voucher for the initial dose of vaccine served as the study outcome variable. Findings: In controlled analyses, the contrast in initial uptake between urban clinic women (reference category) and rural college women was significant (P < .0001). However, the contrast in initial uptake between urban clinic women (reference category) and rural clinic women was not significant (P = .42). The model predicting uptake of subsequent doses among those with initial uptake (n = 235) also indicated significant differences as a function of recruitment location, with rural clinic women being about 7 times more likely than urban clinic women (P < .0001) to not return for at least 1 follow-up dose. The contrast between urban clinic women and rural college women was also significant (P = .014). Conclusion: Initial uptake of free HPV vaccination among young rural college women may be problematic. Moreover, uptake of subsequent free doses among rural women may be problematic regardless of whether contact is made in a clinic or through college recruitment.

BACKGROUND: It has been claimed that beer is one of the richest sources of silicon in the diet; however, little is known of the relationship between silicon content and beer style and the manner in which beer is produced. The purpose of this study was to measure silicon in a diversity of beers and ascertain the grist selection and brewing factors that impact the level of silicon obtained in beer. RESULTS: Commercial beers ranged from 6.4 to 56.5 mg L−1 in silicon. Products derived from a grist of barley tended to contain more silicon than did those from a wheat-based grist, likely because of the high levels of silica in the retained husk layer of barley. Hops contain substantially more silicon than does grain, but quantitatively hops make a much smaller contribution than malt to the production of beer and therefore relatively less silicon in beer derives from them. During brewing the vast majority of the silicon remains with the spent grains; however, aggressive treatment during wort production in the brewhouse leads to increased extraction of silicon into wort and much of this survives into beer. CONCLUSION: It is confirmed that beer is a very rich source of silicon. Copyright © 2010 Society of Chemical Industry

This study investigates hydrological controls on E. coli concentration and loading in two artificially drained agricultural watersheds (58 and 23 km 2 ) of the U.S. Midwest. Stream E. coli concentrations are significantly (p < 0.02) lower at base flow than high flow; however, E. coli load is significantly higher at high flow than at low flow (p < 0.001). Although E. coli concentrations are not significantly higher (p = 0.253) in summer/fall (3269 MPN/100 mL) than in the winter/ spring (2411 MPN/100 mL), E. coli load is significantly higher (p < 0.05) in winter/spring (346 MPN/day) than in summer/ fall season (75 MPN/day). Correlation analysis indicates that discharge and precipitation are the best indicators of E. coli concentration and 7-d antecedent precipitation (7dP), the best indicator of E. coli loading in the watersheds studied regardless of flow conditions and location. However, E. coli concentration and loading best correlate to 7dP and turbidity at base flow. A spatial dependency is also observed at base flow with E. coli concentration and load correlating better to 7dP in the headwaters and to turbidity in the lower reaches of the watersheds studied. For high flow conditions, E. coli concentration and loading are poorly correlated to most variables, except stream water temperature and 7-d antecedent discharge. These results are consistent with those reported in the literature and suggest that, at least during base flow conditions, turbidity and 7dP may be usable in artificially drained landscapes of the Midwest to identify potential hot spots of E. coli contamination.

Background Recent analysis of clinical data and a clearer understanding of the role of chemical structure in the development of cross-reactivity indicate that the increased risk of an allergic reaction to a cephalosporin in penicillin-allergic patients is smaller than previously postulated. Method Medline and EMBASE databases were searched with the keywords: cephalosporin, penicillin, allergy, and cross-sensitivity for the years 1960 through 2005. Among 219 articles retrieved, 9 served as source material for this evidence-based meta-analysis. Results A significant increase in allergic reactions to cephalothin (odds ratio [OR] = 2.5; 95% confidence interval [CI] = 1.1 to 5.5), cephaloridine (OR = 8.7; CI = 5.9 to 12.8), and cephalexin (OR = 5.8; CI = 3.6 to 9.2), and all first generation cephalosporins plus cefamandole (OR = 4.8; CI = 3.7 to 6.2) were observed in penicillin allergic patients; no increase was observed with second generation cephalosporins (OR = 1.1; CI, 0.6 to 2.1) or third generation cephalosporins (OR = 0.5; CI = 0.2 to 1.1). Clinical challenges, skin testing, and monoclonal antibody studies point to the paramount importance of similarities in side chain structure to predict cross-allergy between cephalosporins and penicillins. Conclusion First-generation cephalosporins have cross-allergy with penicillins, but cross-allergy is negligible with second- and third-generation cephalosporins. Particular emphasis should be placed on the role of chemical structure in determining the risk of cross-reactivity between specific agents.

Hypertrophic cardiomyocyte growth contributes substantially to the progression of heart failure. Activation of the plasma membrane Na+-H+ exchanger (NHE1) and Cl- -HCO3- exchanger (AE3) has emerged as a central point in the hypertrophic cascade. Both NHE1 and AE3 bind carbonic anhydrase (CA), which activates their transport flux, by providing H+ and HCO3-, their respective transport substrates. We examined the contribution of CA activity to the hypertrophic response of cultured neonatal and adult rodent cardiomyocytes. Phenylephrine (PE) increased cell size by 37 +/- 2% and increased expression of the hypertrophic marker, atrial natriuretic factor mRNA, twofold in cultured neonatal rat cardiomyocytes. Cell size was also increased in adult cardiomyocytes subjected to angiotensin II or PE treatment. These effects were associated with increased expression of cytosolic CAII protein and the membrane-anchored isoform, CAIV. The membrane-permeant CA inhibitor, 6-ethoxyzolamide (ETZ), both prevented and reversed PE-induced hypertrophy in a concentration-dependent manner in neonate cardiomyocytes (IC50=18 microm). ETZ and the related CA inhibitor methazolamide prevented hypertrophy in adult cardiomyocytes. In addition, ETZ inhibited transport activity of NHE1 and the AE isoform, AE3, with respective EC50 values of 1.2 +/- 0.3 microm and 2.7 +/- 0.3 microm. PE significantly increased neonatal cardiomyocyte Ca2+ transient frequency from 0.33 +/- 0.4 Hz to 0.77 +/- 0.04 Hz following 24 h treatment; these Ca2+ -handling abnormalities were completely prevented by ETZ (0.28 +/- 0.07 Hz). Our study demonstrates a novel role for CA in mediating the hypertrophic response of cardiac myocytes to PE and suggests that CA inhibition represents an effective therapeutic approach towards mitigation of the hypertrophic phenotype.

In the second of two parts, Kevin R. Casey, of Malvern, Pa., provides the tools to establish a comprehensive law firm alternative dispute resolution department. He covers ways to address attorney ambivalence, and lists implementation steps that will help the prospects for a well-rounded, profitable program

Carbonic anhydrases (CA) catalyze the reversible conversion of CO2 to HCO3-. Some bicarbonate transporters bind CA, forming a complex called a transport metabolon, to maximize the coupled catalytic/transport flux. SLC26A6, a plasma membrane Cl-/HCO3- exchanger with a suggested role in pancreatic HCO3- secretion, was found to bind the cytoplasmic enzyme CAII. Mutation of the identified CAII binding (CAB) site greatly reduced SLC26A6 activity, demonstrating the importance of the interaction. Regulation of SLC26A6 bicarbonate transport by protein kinase C (PKC) was investigated. Angiotensin II (AngII), which activates PKC, decreased Cl-/HCO3- exchange in cells coexpressing SLC26A6 and AT1a-AngII receptor. Activation of PKC reduced SLC26A6/CAII association in immunoprecipitates. Similarly, PKC activation displaced CAII from the plasma membrane, as monitored by immunofluorescence. Finally, mutation of a PKC site adjacent to the SLC26A6 CAB site rendered the transporter unresponsive to PKC. PKC therefore reduces CAII/SLC26A6 interaction, reducing bicarbonate transport rate. Taken together, our data support a mechanism for acute regulation of membrane transport: metabolon disruption.

A 7-year old female with global cognitive impairment, short attention span, hyperactivity, impulsivity, and many compulsive behaviors was referred to the Genetics Clinic. Height was below the 5th centile and weight was at the 5th centile while head circumference was at the 50th centile. Minor anomalies included bluish sclera, low set and slightly posteriorly rotated auricles and a narrow palate with marked overbite. There was no significant family history. Chromosome analysis showed an unbalanced, mosaic female karyotype consisting of three cell lines: 46,X,+r[46]/45,X[37]/45,X,dup(1)(q11q21.3) [17] de novo.ish r(X)(DXZ1+,XIST+). Expression of XIST was observed in cDNA from the patient, suggesting the presence of an inactive X chromosome. Inactivation was confirmed by detection of a methylated allele of androgen receptor. This methylated allele was under-represented in undigested DNA, consistent with it arising from the r(X) which was present in only a minority of the patient's cells. The clinical phenotype of the tiny r(X) syndrome in our patient is obviously further influenced by mosaicism for the dup(1). Few cases of duplication of the proximal portion of chromosome 1 have been reported. Of these, the duplication either was present in all cells or involved different band regions so that a direct comparison would be difficult. However, the lower percentage of mosaicism for the dup(1) in our patient would suggest a milder influence on the clinical phenotype. © 2003 Wiley-Liss, Inc.

Author(s): Chang, KJ; Nguyen, PT; Thompson, JA; Kurosaki, TT; Casey, LR; Leung, EC; Granger, GA | Abstract: BackgroundTo the authors' knowledge, there are no other published clinical studies that have employed either systemic or local biologic response modifiers in the treatment of patients with pancreatic carcinoma. The purpose of this study was to determine the feasibility and safety of allogeneic mixed lymphocyte culture (cytoimplant) delivered by endoscopic ultrasound (EUS)-guided fine-needle injection (FNI) in patients with advanced pancreatic carcinoma.MethodsEight patients with unresectable adenocarcinoma of the pancreas were enrolled: 4 patients in Stage II, 3 in Stage III, and 1 in Stage IV. Cytoimplants were delivered locally into the tumor using a novel EUS-guided FNI technique. Escalating doses of 3, 6, or 9 billion cells were implanted into the pancreatic tumor by a single EUS-guided FNI. Toxicity (modified National Cancer Institute criteria) was assessed at Day 1, Week 1, and Months 1 and 3. Clinical endpoints included Karnofsky performance status (KPS), CA 19-9, tumor response (computed tomography and/or EUS), and survival with follow-up examinations and imaging tests on months 3, 6, 9, 12, and 24.ResultsThere were no bone marrow, hemorrhagic, infectious, renal, cardiac, or pulmonary toxicities. There were 3 transient Grade 3 gastrointestinal toxicities, and 3 patients had transient episodes of hyperbilirubinemia that were reversed by replacement of biliary stents. Seven of 8 patients (86%) experienced low grade fever that responded to acetaminophen, and all fever was resolved within the first 4 weeks. There were no procedure-related complications. There were 2 partial responses and 1 minor response, with a median survival of 13.2 months.ConclusionsA single injection of cytoimplant immunotherapy by EUS-guided FNI appears to be feasible and is not associated with substantial toxicity.

Objectives In 1984 females made up 45% of medical undergraduates in Ireland. By 1996 this proportion had increased to 57%. This study examines gender differences in performance at final medical examinations, with a view to ascertaining the impact of the change in proportion of females attending medical school. Design Final year examination results of medical students over a 5-year period (1992–96) were obtained from the broadsheets of University College Dublin (UCD) examinations office. The results of 557 students (females n=277; males=280) were analysed for all final year examinations (n=5). Setting University College Dublin. Subjects Final year medical students. Results Overall females were found to have performed better than their male counterparts. They were more likely to achieve an honours grade and had a similar or lower likelihood of passing or failing. Gender differences in performance were most marked in paediatrics (P

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The outcome for patients with pineoblastoma has historically been very poor, with most patients dying of disseminated disease despite irradiation. Furthermore, the low incidence of this tumor has hindered progress toward defining better treatment strategies. Here we report the activity and toxicity of cyclophosphamide administered as a single agent at a dose schedule of 2 g/m2/day for 2 successive days at monthly intervals for a maximum of four courses. Eight patients were evaluated, six newly diagnosed and two recurrent. Amongst the six newly diagnosed patients, there were three patients demonstrating partial responses, and three had stable disease throughout the cyclophosphamide treatment period. All six patients are alive and disease free after further therapy. One patient with recurrent disease demonstrated tumor progression on cyclophosphamide, and the other had stable disease throughout the cyclophosphamide treatment period. Both patients subsequently died of progressive disease. The major toxicity of high dose cyclophosphamide was hematopoietic, with one patient requiring a dose reduction after three courses due to prolonged thrombocytopenia. One patient was also withdrawn from treatment with cyclophosphamide due to impaired pulmonary function. This study demonstrates the activity of high dose cyclophosphamide in the treatment of pineoblastoma and may serve as basis for the design of future studies of this tumor.

A 74-year-old man presenting for aortic reconstructive surgery showed severe, previously undiagnosed obstructive sleep apnoea during overnight oximetry monitoring before operation. Postoperatively, in the first 4 hours following extubation, he suffered 238 episodes of respiratory obstruction. These events were associated with frequent arousals, large fluctuations in systolic and diastolic blood pressure. Administration of nasal continuous positive airways pressure abolished the obstructions and allowed an uninterrupted night's sleep, with a significantly reduced blood pressure. Subsequent dips in oxygen saturation as a result of respiratory obstruction recurred on the fifth postoperative night. We conclude that pre-operative overnight oximetry may be useful in identifying those patients at risk of postoperative upper airway obstruction. Use of nasal continuous positive airway pressure may prevent the occurrence of early postoperative obstruction and the associated haemodynamic changes.

The personality characteristics of 77 patients seen in general practice with a Catego diagnosis of anxiety state (including phobic state) or depressive neurosis derived from the Present State Examination were compared with those in 77 normal subjects chosen at random from the list of the same general practitioner. Each patient was matched with a normal subject of the same age and sex. The personality characteristics were rated using the Personality Assessment Schedule, an interview schedule designed to elicit the premorbid personality of the subject. The neurotic patients had significantly higher scores for the personality charcteristics of anxiousness, vulnerability, resourcelessness, hypochondriasis and other features commonly described as oral and hysterical. Schizoid features were absent in the neurotic group. The results suggest that there are common personality attributes in neurotic disorder and that these have clinical significance.

A 63-year-old man with erythraemia was found to have a high affinity haemoglobin which was subsequently identified as Hb San Diego beta 109 (G11) Val leads to Met, recently described in a Filipino family (Nute et al, 1974). The oxygen affinity of the haemolysates was increased approximately two-fold at pH values between 6.04 and 7.90. The n value was nearly normal (2.5-2.9) in the upper range of saturation (70-95% oxygenation) but was somewhat diminished (1.9-2.1) below this range. In vitro biosynthesis of globin by reticulocytes showed that there was balanced synthesis of alpha and beta chains (alpha:beta ratio = 1).

A 7-year-old English girl was found to have a lobar pneumonia with a marked haemolytic anaemia. Routine electrophoresis revealed no abnormal haemoglobin but, as anticipated, an unstable haemoglobin fraction readily formed in haemolysates on routine in vitro instability tests. From the subsequent structural and biosynthetic studies it was concluded that the propositus' red cells contained, in addition to Hbs A, A2 and F, two unstable haemoglobins with abnormalities in the primary structure of their non α-chains: Hb Sydney and Hb Coventry. The first has an amino acid substitution ValAla at position β67 (E11), while the other, Hb Coventry, is a new variant with a non α-chain which resembles the βA-chain except that the leucine residue at position β141(H19) is deleted. This suggests that, instead of the normal complement of two β-chain genes, the propositus' genome has three, i.e. βA-, βSydney- and βCoventry-chain genes. Evidence is presented from which it can be concluded that the non α-chain of Hb Coventry, whilst being structurally a β-chain variant is, in fact, a βδ fusion chain variant with 140β- and 5δ-chain residues. The oxygen dissociation curve of the propositus showed a reduced affinity at the upper part of the curve, a feature which she shared with a straightforward heterozygote for Hb Sydney, and a slight shift to the left in the lower part, a feature which she shared with her father who possessed Hb Coventry.

Studies of suicide intent have found a link between seriousness of the attempt and personality. Following a parasuicide, 60 patients were assessed using measures of depression, suicide intent and personality. Personality disorder was found to be present in over 65% of these and was mainly of explosive type. It was significantly more common in men than women and the dimension measuring sociopathy was equivocally linked to male gender. There were no other associations between gender and the other dimensions measured. Using a categorical approach to personality, suicide intent was not significantly different between the categories of personality; there was no correlation between dimensional or categorical measures of personality and suicide intent, when the severity of depression was controlled. By itself personality did not contribute significantly in determining variance in intent but it did interact significantly with age. Language: en