An outbreak vector-host epidemic model with spatial structure: the 2015-2016 Zika outbreak in Rio De Janeiro.

BACKGROUND: A deterministic model is developed for the spatial spread of an epidemic disease in a geographical setting. The disease is borne by vectors to susceptible hosts through criss-cross dynamics. The model is focused on an outbreak that arises from a small number of infected hosts imported into a subregion of the geographical setting. The goal is to understand how spatial heterogeneity of the vector and host populations influences the dynamics of the outbreak, in both the geographical spread and the final size of the epidemic. METHODS: Partial differential equations are formulated to describe the spatial interaction of the hosts and vectors. The partial differential equations have reaction-diffusion terms to describe the criss-cross interactions of hosts and vectors. The partial differential equations of the model are analyzed and proven to be well-posed. A local basic reproduction number for the epidemic is analyzed. RESULTS: The epidemic outcomes of the model are correlated to the spatially dependent parameters and initial conditions of the model. The partial differential equations of the model are adapted to seasonality of the vector population, and applied to the 2015-2016 Zika seasonal outbreak in Rio de Janeiro Municipality in Brazil. CONCLUSIONS: The results for the model simulations of the 2015-2016 Zika seasonal outbreak in Rio de Janeiro Municipality indicate that the spatial distribution and final size of the epidemic at the end of the season are strongly dependent on the location and magnitude of local outbreaks at the beginning of the season. The application of the model to the Rio de Janeiro Municipality Zika 2015-2016 outbreak is limited by incompleteness of the epidemic data and by uncertainties in the parametric assumptions of the model.

Comparison of the head and neck position of elite dressage horses during top-level competitions in 1992 versus 2008.

Among veterinary surgeons, interest has recently increased in the role of the horse's neck as a causative factor in complex locomotor disturbances. Specifically, controversy surrounds the trend for the head to be carried behind the vertical (BHV) in contravention of Fédération Equestre Internationale (FEI) rules. The aim of this study was to determine whether the head angulation of elite dressage horses has changed over the last 25 years, and whether head angulation correlates with the competition score awarded. Head angle was measured from videos recorded during the Grand Prix test at the 1992 Olympic Games and the 2008 World Cup Final, during collected canter (CC), collected trot (CT), passage (Pa), and piaffe (Pi). Head angulations were BHV in CC and CT in both 1992 and 2008. The likelihood of being BHV during Pa or Pi was significantly greater in 2008 than in 1992 (P <0.05). Higher scores correlated significantly with head positions that were further BHV during Pi in 2008 (P <0.05). Head angulations were orientated BHV in all paces in 2008, whereas in 1992 this was only the case for CT and CC. These findings support the hypothesis that, in recent years, FEI dressage judges have not penalised horses for a head position BHV. The findings also support the need for further studies of the effects of head and neck position on the health of horses.

A mathematical model for indirectly transmitted diseases.

We consider a mathematical model for the indirect transmission via a contaminated environment of a microparasite between two spatially distributed host populations having non-coincident spatial domains. The parasite is benign in a first population and lethal in the second one. Global existence results are given for the resulting reaction-diffusion system coupled with an ordinary differential equation. Then, invasion and persistence of the parasite are studied. A simplified model for the transmission of a hantavirus from bank vole to human populations is then analysed.

Stereo-specific cytotoxic effects of gossypol enantiomers and gossypolone in tumour cell lines.

The naturally occurring compound, gossypol, has been previously used as a male oral contraceptive, for the treatment of benign gynaecological conditions and cancer patients. Long-term daily dosing with gossypol is associated with minimal side effects and no myelosuppression. Since gossypol exhibits atropisomerism due to the restricted rotation about the 2,2' carbon bond, we have isolated the l- and d-isomers by Schiff's base formation using a chiral amine and regenerated the enantiomers by acid hydrolysis. The enantiomers and the proposed oxidative metabolite, gossypolone, were characterized by HPLC, 1H-NMR and optical rotation. The cytotoxicity was assessed in cell cultures derived from melanoma, lung, breast, cervix, and leukaemia using the MTT viability assay. The cytotoxicity of gossypolone was similar to racemic gossypol in five out of the six cell lines studied. The l-enantiomer of gossypol induced a dose-dependent cell kill in all cell lines with a mean IC50 of 20 microM and was significantly more potent than racemic gossypol, the d-enantiomer of gossypol and gossypolone. In addition, when the leukaemia line was exposed to l-gossypol (0.5-10 microM) over a 4-day period, a schedule-dependent decrease in cell viability was observed. l-Gossypol was also compared with respective drugs used to treat patients with melanoma, lung cancer and leukaemia. The data indicate that l-gossypol was significantly more active than cisplatin, melphalan and dacarbazine in the two melanoma lines, cisplatin and daunorubicin in the lung line and hydroxyurea and busulphan in the leukaemia line. Preliminary studies using one melanoma line showed that the l-isomer induced cell shrinkage, membrane blebbing and DNA fragmentation, characteristics suggestive of apoptotic cell death.

Influence of protein supplements on the secretion of leukaemia inhibitory factor by mitomycin-pretreated Vero cells: possible application to the in vitro production of bovine blastocysts with high cryotolerance.

A co-culture system for bovine embryos using mitomycin-treated Vero cells and serum-supplemented modified synthetic oviduct fluid (mSOF) supports the development of in vitro maturation and fertilization-derived oocytes to hatched blastocysts. In this system, it has been suggested that one contribution made by the co-culture cells to embryo development is production of the cytokine leukaemia inhibitory factor (LIF). However, there are concerns about exposure of early embryos to serum due to its incompatibility with embryo cryosurvival. In this study, the influence of two protein supplements (synthetic serum substitute (SSS), a lipid-free human serum-derived product) and oestrous cow serum (ECS)) on Vero cell LIF secretion was compared, with the aim of designing a co-culture system that is supportive of bovine embryo cryopreservation. Vero cells cultured for 72 h in medium 199 + 5% fetal bovine serum (FBS) (recommended maintenance medium for this cell line) secreted detectable amounts of LIF (13.1 +/- 0.9 pg LIF per 10(5) cells). Culture in mSOF, the medium routinely used in this laboratory for embryo culture, also supported LIF secretion in Vero cells. However, the amount of LIF was tenfold higher (24.7 +/- 6.2 pg LIF per 10(5) cells; P < 0.05) when mSOF was supplemented with 10% (v/v) ECS compared with supplementation with 2% (v/v) SSS. Results of a second series of experiments in which supplementation with each protein was normalized to 10% revealed similar differences in LIF secretion, indicating that LIF secretion was affected by the type, not the amount, of protein. Time course analysis revealed stepwise increases (P < 0.05) in cumulative LIF secretion with every 24 h of culture in mSOF + either SSS or ECS. In terms of embryo development and post-cryopreservation viability, medium supplementation with 2% (v/v) SSS alone versus the two-step system of 2% (v/v) SSS (days 1-4) + 10% (v/v) ECS (days 4-10) had no influence (P > 0.05) on the ability of bovine blastocysts to hatch, with or without intervening cryostorage. However, the rate of blastocyst formation (expressed as the percentage of cleaved embryos) was only 27% in the presence of 2% (v/v) SSS, and increased almost twofold (P < 0.05) when ECS was added beginning on day 4 of co-culture. In summary, Vero cell LIF secretion was increased markedly by ECS. A two-step system of medium supplementation, in which embryos are exposed to ECS beginning on day 4 of in vitro development combined high rates of blastocyst formation with cryotolerance. This effect may be a result of limiting embryo exposure to serum-derived lipid until after the eight-cell stage and providing an increase in LIF during the critical developmental stages of compaction and cavitation.

Effects of a split keyboard design and wrist rest on performance, posture, and comfort.

The purpose of this study was to examine differences in experienced typists' performance, posture, and musculoskeletal pain when using a split, adjustable (SA) computer keyboard and when using a standard flat keyboard. In addition, the use of a wrist rest was examined for performance, posture, and musculoskeletal pain effects. Eighteen participants were exposed to the SA keyboard and a flat keyboard in a laboratory study of text typing for four consecutive hours on five days. The results indicated that after just 2 h of orientation and practice, the participants could perform as well on the SA keyboard as on the flat keyboard. The SA keyboard provided advantages for reduced wrist/hand pronation. There was no difference between the keyboards in the level of musculoskeletal pain reported by participants after typing. However, they reported increased pain in the back, neck, shoulders, and wrists from the beginning to the end of each of the experimental periods for both keyboards.

Vesicle-associated proteins and calcium in nerve terminals of chick ciliary ganglia during development of facilitation.

1. The developmental appearance of synaptic vesicle-associated proteins and nerve terminal calcium ([Ca2+]i) sequestering processes were determined for the chick ciliary ganglia in relation to the maturation of the different phase of increased efficacy of transmitter release following nerve impulses. The maturation phases studied were from stages 34-35, at the time of synapse formation, to stage 46 at hatching. 2. Western blots and immunohistochemical localization indicated that synaptotagmin 1 and synapsin IIa were detectable at stages 34-35 and were clearly localized at the nerve terminals by stage 37. Syntaxin was clearly localized at the nerve terminals at stage 34. 3. The relative size of the postganglionic compound action potential, used to measure the transmission efficacy through the ganglion, showed that the slope of the relationship between log efficacy and log extracellular calcium concentration ([Ca2+]o) in low [Ca2+]o was about 4 by stage 46. 4. A mature facilitatory mechanism for transmission was not present at stage 34 and did not emerge until stage 38. A mature augmentation was not present at stages 34 or 38 and was not established until stages 41-42. Post-tetanic potentiation (PTP) was not present at stage 34; it was evident at stages 37-38 and only reached maturity by stages 41-42. 5. The time course of calcium changes in the nerve terminals following trains of impulses that give rise to facilitation, augmentation and PTP was determined for different stages of development using the indicator Calcium Green-1 in the nerve terminal. The mature time course of the phases of calcium decline in the nerve terminal associated with facilitation and augmentation was observed as early as stage 38, whereas that of the PTP phase did not mature until after stage 42. 6. These results are discussed in terms of the maturation of the vesicle-associated proteins and calcium influx into the terminal following trains of impulses that give rise to the different components of increased synaptic efficacy.

Intracoronary stenting without intravascular ultrasound guidance followed by antiplatelet therapy with aspirin alone in selected patients.

One hundred selected patients with 103 lesions were treated with the deployment of 117 Palmaz-Schatz stents without the use of intravascular ultrasound, followed by antiplatelet therapy with aspirin alone. Angiographic and clinical follow-up revealed 2 stent thromboses; 3 stents required redilation, and 3 patients required intervention for disease progression elsewhere, suggesting that this approach can be applied effectively in selected patients.

Percutaneous balloon mitral valvotomy with the Inoue single-balloon catheter: commissural morphology as a determinant of outcome.

OBJECTIVES: The aim of this study was to determine the importance to outcome and the predictability of commissural splitting in patients undergoing percutaneous mitral valvotomy with the Inoue single-balloon catheter. BACKGROUND: Echocardiographic scoring systems devised to predict mitral valvotomy outcome are based on assessment of leaflet and subvalvular morphology, but the specific importance of commissural morphology has not been examined. METHODS: In 30 consecutive patients, commissural splitting was predicted on the basis of the two-dimensional echocardiographic commissural morphology: the extent of fusion, fibrosis or calcification of each commissure. Valve morphology also was evaluated according to a previously described echocardiographic scoring system. RESULTS: Splitting of one or both commissures occurred in 24 patients (80%) and was associated with a significantly greater mean increase in valve area (85%) than if neither commissure was split (13%). A good outcome from valvotomy (defined as valve area > 1.5 cm2 and increase in valve area > 25%) was achieved in 96% of those in whom one or both commissures split, but in none of the patients in whom neither commissure split. Whether or not splitting of at least one commissure would occur was predicted accurately in 28 (93%) of the 30 patients. Consequently, the prediction that one or both commissures would split was associated with a good outcome in 23 (89%) of 26 patients, whereas the prediction that neither commissure would split was not associated with a good outcome in any patient. There was no significant difference in the increase in mitral valve area between those with a mitral echocardiographic score < 8 and those with a score > or = 8. New or worsening mitral regurgitation occurred in nine patients, most commonly as a jet directed through a split commissure. CONCLUSIONS: Commissural splitting is the dominant mechanism by which mitral valve area is increased with the Inoue balloon technique, and it can be predicted by echocardiographic assessment of commissural morphology. Commissural morphology is a better predictor of outcome than is the mitral echocardiographic score.

EEG and pathologic findings in patients undergoing brain biopsy for suspected encephalitis.

Previous studies have suggested that EEG may be helpful in the diagnosis of herpes encephalitis (HE). To further define the value of EEG in an acutely ill, febrile, encephalopathic patient suspected as having encephalitis, we reviewed initial preoperative EEGs with the results of cerebral biopsies in 24 consecutive patients suspected of having encephalitis. Statistical analysis demonstrated that EEG patterns have only limited association with biopsy results. Since diseases which mimic encephalitis may also generate identical EEG changes, this is not an unexpected finding. EEG is useful in the evaluation and management of patients with encephalitis. However, the absence of specific wave forms or focal EEG abnormalities in the proper clinical setting should not deter consideration of HE or delay treatment.

Nitroglycerin has more favourable effects on left ventricular afterload than apparent from measurement of pressure in a peripheral artery.

Nitroglycerin (0.3 mg) was administered sublingually to 14 patients undergoing cardiac catheterization, and pressure waves compared in the ascending aorta and brachial artery. After nitroglycerin, ascending aortic systolic pressure fell in all cases (by 6-44, average 22 mmHg) whereas brachial systolic pressure remained unchanged (in three) or fell to a lesser degree (4-33, average 12 mmHg). Diastolic pressure did not change significantly. Alterations in pressure and in wave contour were explained on the basis of arterial dilation, with reduction in wave reflection. Nitroglycerin reduces left ventricular afterload through arterial dilation as well as preload through venous dilation. This effect on afterload is not apparent from measurement of pressure in the brachial artery.

Flecainide compared with a combination of digoxin and disopyramide for acute atrial arrhythmias after cardiopulmonary bypass.

Fifty six adult patients were randomised to treatment with flecainide (group 1, n = 29) or a combination of digoxin and disopyramide (group 2, n = 27) for acute atrial fibrillation and flutter after cardiac surgery. Intravenous flecainide was given as a 2 mg/kg bolus over 20 minutes followed by an infusion (0.2 mg/kg per hour) for 12 hours. Group 2 were given digoxin (0.75 mg) intravenously followed two hours later by an intravenous bolus of disopyramide (2 mg/kg) and an infusion (0.4 mg/kg per hour) for 10 hours. Within 12 hours sinus rhythm was restored in 86% of the group 1 (25 patients) and 89% of the group 2 (24 patients). The median time to reversion was significantly shorter in group 1 (80 minutes, range 30-180 minutes) than group 2 (220 minutes, range 138-523 minutes). None of the patients in group 1 and four of the patients in group 2 had transient relapses into atrial fibrillation during the 12 hours of intravenous treatment. There were five late relapses in group 1 and seven in group 2 during subsequent oral treatment. Two group 1 patients and two group 2 patients showed adverse drug effects. Intractable ventricular arrhythmias occurred after five days of oral treatment in one patient (group 1) who had poor left ventricular function, hepatic impairment, and toxic concentrations of drugs at the time of death. Flecainide was as effective as the combination of digoxin and disopyramide and it acted significantly faster and was associated with fewer relapses. Monitoring of blood concentrations of flecainide is essential in patients with poor left ventricular function and hepatic impairment.

Effect of glyceryl trinitrate on peripheral arteries alters left ventricular hydraulic load in man.

Effects of sublingual glyceryl trinitrate (GTN) were studied in ten patients without heart failure during diagnostic cardiac catheterisation following angiography. GTN caused substantial reduction in peak left ventricular and aortic pressure (19 mmHg) with lesser reduction in mean aortic pressure (9 mmHg) and no change in diastolic aortic pressure. Reduction in stroke volume (by 15%), associated with fall in left ventricular end diastolic pressure (by 4 mmHg) was insufficient to explain the marked (17 mmHg - 34%) reduction in pulse pressure. Decrease in pulse pressure was associated with loss of the late systolic peak on both the aortic and left ventricular pressure wave. This peak is caused by pulse wave reflection. GTN caused no change in peripheral resistance or in indices of aortic compliance (characteristic impedance, total arterial compliance) but was associated with reduction in fluctuations of both modulus and phase of aortic impedance. All these changes in pressure waves and in impedance spectra are explicable on the basis of decreased peripheral wave reflection. This can be attributed to the known vasodilatory effect of GTN on the peripheral arteries. Simulation of arterial vasodilatation in a multi-branched model of the systemic arterial system confirmed this interpretation. Dilatation of peripheral arteries explains in part the beneficial effects of GTN in adult man.

Intravenous sotalol for the treatment of atrial fibrillation and flutter after cardiopulmonary bypass. Comparison with disopyramide and digoxin in a randomised trial.

The efficacy of sotalol in treating acute atrial fibrillation and flutter after open heart surgery was compared with that of a digoxin/disopyramide combination. Forty adult patients with postoperative atrial arrhythmias were randomised into either group 1 (sotalol 1 mg/kg bolus intravenously plus 0.2 mg/kg intravenously over 12 hours) or group 2 (digoxin 0.75 mg intravenously, then two hours later disopyramide 2 mg/kg intravenous bolus and 0.4 mg/kg/h intravenously for 10 hours). In each group, 17 out of 20 patients reverted to sinus or junctional rhythm within 12 hours. The time to reversion in group 1 was significantly shorter than in group 2. Systolic blood pressure fell by greater than or equal to 20 mm Hg or to less than or equal to 90 mm Hg during drug administration in 17 out of 20 patients in group 1 (sotalol withdrawn in two) and in none out of 20 in group 2. Two patients in group 1 developed transient bradycardia (sotalol withdrawn in one). None of 17 patients in group 1 and two of 17 in group 2 relapsed temporarily into atrial fibrillation during the 12 hours of intravenous treatment. On continued oral treatment, one late relapse occurred in group 1 and five in group 2, and five patients in group 2 had disopyramide withdrawn because of anticholinergic side effects (acute urinary retention in four). Sotalol was as effective as the digoxin/disopyramide combination and acted significantly faster. Sensitivity to beta blockade in these patients may be related to high plasma catecholamine concentrations known to occur after cardiopulmonary bypass.