Effectiveness of diagnosis and early treatment of ocular motility alterations in premature infants.

Objective: Prematurity often results in important developmental sequelae of brain structures, particularly those involved in processing visual information, such as the optic nerve, primary visual cortex and visuomotor integration areas. The aim of this study is to analyse the functionality of the sensory and motor pathways of the visual system by means of an orthoptic-ophthalmological assessment. Materials and methods: In this retrospective study, 151 records were examined, covering a period from 2000 to 2020, of preterm patients with gestational age < 32 weeks and birth weight ≤ 1,500 g up to an average age of about 8 years, referred to the Centre for Paediatric Ophthalmology and Strabology of the Ophthalmology Clinic of the Policlinico Umberto I, La Sapienza University of Rome, who underwent a complete ophthalmological and orthoptic assessment including the following tests measurement of ocular deviations according to the Hirschberg method, Lang I-II test, Titmus Stereotest, objective convergence assessment and ocular motility examination. Results: From the charts reviewed, 24.5% (37/151) of patients had Retinopathy of the Premature (ROP); while 38% of the whole sample (57/151) had strabismic amblyopia, of the latter only 31.5% (18/57) had ROP. In 8% of patients (12/151) the stereoscopic sense was absent, in 45% (8/151) stereopsis was gross (> 60 seconds of arc). In addition, 20.52 % (31/151) had a manifest eye deviation. 7.28% (11/151) had hypermetropia in the right eye (RE); 7.95% (12/151) hypermetropia in the left eye (OS); 3.31% of the patients (5/151) had myopia in the RE; 2% (3/151), myopia in the left eye (LE). In addition, the study of ocular motility revealed varying degrees of alteration poorly correlated with prematurity status. Conclusion: It was found that amblyopia, stereopsis and objective convergence are more affected by ROP than strabismus, refractive defects and ocular motility, indicating that premature children are particularly susceptible to ophthalmological and orthoptical alterations.

Anisometropia and isoametropia associated with microstrabismus: effectiveness of late anti-amblyopia treatment.

PURPOSE: Outcomes Research Study on patients suffering from anisometropia or isoametropia associated with amblyopia and microstrabismus to show the impact of late occlusion treatment on therapeutic prognosis. MATERIALS AND METHODS: Enrollment of all the eligible patients presenting to recruiting centers at the Department of Pediatric Ophthalmology and Strabismus - Ophthalmological Clinic - Policlinico Umberto I - Rome. At baseline, all patients will undergo an opthalmologic evaluation. Recruited patients will be followed for a 2-year period. Our test group was composed of 31 patients, 11 with bilateral and 20 with monolateral amblyopia, totalling 42 amblyopic eyes, and it was assessed - always by the same examiner - with the help of the following orthoptic examinations: Wirt test, Irvine-Jampolsky test (4 dioptre fixation task), Visuscope, Cover Test, Bagolini striated glasses, and Worth lights test. We assessed pre-post treatment variations observed in the overall group of amblyopic eyes, regardless of the differences between RE and LE. OUTCOMES: Of the 31 children, 58.1% were males and 41.9% female, average age between 6 and 14 years. Of the 42 amblyopic eyes, after daily occlusion of 8 hours ± 2.30 SD, we recorded an improvement of 71.4%, and visual acuity increased from an average of 0.4 LogMAR to 0.1 LogMAR. CONCLUSION: Late anti-amblyopic occlusion treatment proved effective in the long term for children 6 to 12 years, specifically regarding visual acuity, fixation, stereopsis, and binocular collaboration in patients suffering from anisometropia or isoametropia and microstrabismus.

Ocular motility alterations in orbital fractures: pre-post evaluation in maxillofacial surgical treatment.

PURPOSE: The study aims to investigate the ability of maxillofacial surgery to reduce strabismus and improve ocular clinical symptomatology in patients with fracture of the medial or lateral floor of the orbit, or both, and to evaluate such abilities relative to the temporal distance between trauma and surgery. PATIENTS AND METHODS: 25 patients with traumatic diplopia were evaluated by CT, Goldman manual field of view, Hess-Lancaster test, eye examination and orthoptic examination, before and after surgery. RESULTS: We observed: a statistically significant reduction of the deviation angle, both from close and long distance (P = 0.0054 and P = 0.0051 respectively) with a 38% reduction of the deviation from short distance and 54% from afar; a regression of diplopia in 20% of the surgically treated cases (CL from 0 to 39%), significant at the Mc Nemar test; a negative correlation with the time elapsed between the onset of the fracture and maxillofacial surgery (R = -0.26), even if the analysis did not show a statistical significance of the data (P = 0.2). However, it is evident that the maximum improvement is observed only in cases operated within 5 months of the trauma, while the failures (worsening or persistence of diplopia) were observed only in the cases operated later. CONCLUSION: We can state that the intervention reduces strabismus and improves ocular symptomatology, as it statistically significantly reduces cases of diplopia; furthermore, it would seem preferable to intervene early, especially when damage to a muscular structure is suspected, even if the data do not allow definitive conclusions in this regard.

Management della retinopatia diabetica e dell'edema maculare diabetico: linee guida "Euretina 2017".

Si prevede che la malattia diabetica con tutte le sue complicanze avrà un forte aumento di incidenza con un grosso impatto socioeconomico nei prossimi decenni in tutto il mondo. Pertanto ben si comprende l'importanza di individuare attraverso una fine diagnostica quanto più precocemente la comparsa dei sintomi diabetici, migliorare lo stile di vita ed impostare cure efficienti. Riportiamo la serie di raccomandazioni EURETINA 2017, dei maggiori esperti in Europa per la gestione della malattia diabetica e delle complicanze della retina. Per combattere questa "pestilenza" occorre un team medico preparato. Il trattamento laser è stato considerato sino a non molto tempo fa il Gold standard della retinopatia diabetica e dell'edema diabetico (RD e EMD). Recenti studi hanno dimostrato, invece, che si possono raggiungere risultati migliori mediante l'iniezione diretta di farmaci nella cavità vitreale. In particolare è emerso terapia di prima linea, molecole in grado di inibire il fattore di crescita endoteliale vascolare (anti VEGF) mentre non è più raccomandata la fotocoagulazione laser per il trattamento del DME. Nell'ambito delle molecole farmacologiche gli steroidi hanno mantenuto un ruolo nella gestione del DME cronicamente persistente.

Inferior Oblique Weakening and Abnormal Head Position: Controlled Myotomy versus Recession.

Purpose. Randomized controlled trial aimed at comparing surgical outcomes in a group of patients suffering from hyperfunction of the inferior oblique (IO) muscle with abnormal head position (AHP). The surgical techniques being compared are Recession and (thread) Controlled Myotomy. Materials and Methods. The group of 20 patients suffering from medium-high hyperfunction of the IO was assessed through an ophthalmological and orthoptic examination. 10 patients underwent traditional Recession (Group A) and 10 were treated with Controlled Myotomy (Group B). Results. The average age was 19 years ± 10.7 SD. After 1 year, 20% of Group A showed a small Vertical Deviation associated with a small AHP, while 80% had orthophoria and 40% of them had a small AHP. 80% of Group B showed a small Vertical Deviation associated with an equally small AHP, while 20% had orthophoria with a full resolution of AHP. Conclusion. Based on the results obtained and the fewer intrasurgical risks involved, thread Controlled Myotomy proved to be a valid alternative to Recession. Furthermore, in case of Recession, over the long period a small residual AHP remained in the patients who had orthophoria, unlike Myotomy which led to a total resolution.

The economic burden of musculoskeletal disorders on the Italian social security pension system estimated by a Monte Carlo simulation.

The aim of the study is to estimate the pension costs incurred for patients with musculoskeletal disorders (MDs) and specifically with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) in Italy between 2009 and 2012. We analyzed the database of the Italian National Social Security Institute (Istituto Nazionale Previdenza Sociale i.e. INPS) to estimate the total costs of three types of social security benefits granted to patients with MDs, RA and AS: disability benefits (for people with reduced working ability), disability pensions (for people who cannot qualify as workers) and incapacity pensions (for people without working ability). We developed a probabilistic model with a Monte Carlo simulation to estimate the total costs for each type of benefit associated with MDs, RA and AS. We also estimated the productivity loss resulting from RA in 2013. From 2009 to 2012 about 393 thousand treatments were paid for a total of approximately €2.7 billion. The annual number of treatments was on average 98 thousand and cost in total €674 million per year. In particular, the total pension burden was about €99 million for RA and €26 million for AS. The productivity loss for AR in 2013 was equal to €707,425,191 due to 9,174,221 working days lost. Our study is the fi rst to estimate the burden of social security pensions for MDs based on data of both approved claims and benefits paid by the national security system. From 2009 to 2012, in Italy, the highest indirect costs were associated with disability pensions (54% of the total indirect cost), followed by disability benefits (44.1% of cost) and incapacity pensions (1.8% of cost). In conclusion, MDs are chronic and highly debilitating diseases with a strong female predominance and very significant economic and social costs that are set to increase due to the aging of the population.

Reliability study of biometrics "do not contact" in myopia.

PURPOSE: The aim of the study is a comparison between the actually achieved after surgery condition versus the expected refractive condition of the eye as calculated via a biometer. MATERIALS AND METHODS: The study was conducted in a random group of 38 eyes of patients undergoing surgery by phacoemulsification. RESULTS: The mean absolute error was calculated between the predicted values from the measurements with the optical biometer and those obtained in the post-operative error which was at around 0.47% CONCLUSIONS: Our study shows results not far from those reported in the literature, and in relation, to the mean absolute error is among the lowest values at 0.47 ± 0.11 SEM.

Temporary diplopia upon hyoscine-N-butyl bromide administration: case report.

Hyoscine-N-butyl bromide is a widely used antispasmodic belonging to the belladonna alkaloid class of semisynthetic quaternary ammonium compounds. These compounds exert a spasmolytic action on the smooth muscles of the bile-gastrointestinal tract, genitourinary tract, salivary glands (xerostomia), and also on the visual apparatus - in particular, the irido-ciliary complex. As a consequence, they provoke collateral effects such as mydriasis and accommodation disturbances. We report the case of a 23-year-old woman who complained of not only "dry mouth" but also "cloudy vision" and a "diplopia", both of temporary type, 2 hours after oral administration of hyoscine-N-butyl bromide.

Persistent vertical diplopia after cataract surgery: a case report.

Diplopia is an event that can occur following cataract surgery, although its rate of occurrence is limited and ranges from 0.67% to 0.85%. The authors present a case of vertical diplopia arising after peribulbar anaesthesia for cataract surgery in a 78-year-old woman. Diplopia appeared at distance in primary position, while at near there was binocular single vision. Stereopsis was present at the Lang I - II Test, but the Wirth Test was incomplete. Although in the literature the frequency of these "accidents" is very limited, we think it is relevant to emphasize the need to perform pre-operative routine using a careful orthoptic examination along with a thorough medical, especially strabological, history.

Adolescents' fMRI activation to a response inhibition task predicts future substance use.

BACKGROUND: Deficient behavioral regulation may be a risk factor for substance use disorders in adolescents. Abnormalities in brain regions critical to cognitive control have been linked to more intense and problematic future substance use (e.g., Durazzo, Gazdzinski, Mon, & Meyerhoff, 2010; Falk, Berkman, Whalen, & Lieberman, 2011; Paulus, Tapert, & Schuckit, 2005). The goal of this study was to examine the degree to which brain response to an inhibition task measured in mid-adolescence can predict substance use 18 months later. METHOD: Adolescents aged 16-19 (N=80) performed a go/no-go response inhibition task during fMRI at project baseline, and were followed 18 months later with a detailed interview on substance use and dependence symptoms. Participants were 39 high frequency users and 41 demographically similar low frequency users (458 versus 2 average lifetime drug use occasions at baseline, respectively). RESULTS: Across all subjects, no-go trials produced significant increases in neural response in the ventromedial prefrontal cortex and a region including the left angular and supramarginal gyri (p(FWE)<.01, cluster threshold ≥ 30 voxels). Less ventromedial prefrontal activation but more left angular gyrus activation predicted higher levels of substance use and dependence symptoms in the following 18 months, particularly for those who were high frequency users in mid-adolescence (p<.05). CONCLUSIONS: These findings are consistent with studies showing that impairments in cognitive control have strong associations with substance use. We found a predictive relationship between atypical activation patterns at baseline and substance use behavior 18 months later, particularly among adolescents with histories of previous heavy use.

Ocular traumatology in children. A retrospective study.

UNLABELLED: OBIECTIVE: This study assesses the descriptive epidemiology of children with eye injuries presenting to the Emergency Department of a non exclusive Paediatric University Hospital - First Division of Ophthalmology of "Sapienza" University of Rome - over a period of 12 years. STUDY DESIGN: A retrospective long term study of 12 years. PARTICIPANTS: All paediatric patients (up to 14 years of age) presenting with ocular injuries and hospitalized. METHODS: It was analyzed the incidence of the ocular trauma among males and females. The situation in which the trauma occurred, type of trauma (contusive or perforating), the presence of endo-bulbar foreign bodies, visual acuity outcome. RESULTS: There were 203 patients who presented to the Emergency Department in the period examined. Contusive traumas were 130 (90 males, 40 females). The perforating trauma were 73 (63 males, 10 females). The presence of an endo-bulbar foreign body was registered in 10 patients. A detailed analysis of the causes of the trauma is therefore provided. We evidence that males were almost exclusively involved in sport traumas (60 males versus 2 females), and in second instance accidental trauma is almost equally divided between two genders. CONCLUSIONS: Our retrospective study presents the paediatric cases of a non exclusive Paediatric University Hospital where 3% of ocular traumas requiring hospitalization were in children. Therefore our data could be useful in order to bring about the necessary preventive measures to minimize paediatric eye injuries.

Pneumotrabeculoplasty as treatment for primary open angle glaucoma: critical review of the literature.

PURPOSE: To evaluate with criticism the available evidence shown in the literature about the efficacy of pneumotrabeculoplasty (PNT) as a treatment for primary open angle glaucoma. MATERIALS AND METHODS: PNT is a recent non-surgical and noninvasive technique to safely reduce the intraocular pressure (IOP) in eyes suffering from ocular hypertension or primary open angle glaucoma. The technique consists in the application on the ocular surface of a disposable suction ring that induces a temporary trabecular meshwork stretching, increasing outflow of aqueous humor in the Schlemm's canal. In our study, we compared the results on the efficacy and safety of this treatment published to date in the literature. RESULTS: During follow-up, Authors have observed significant reductions in IOP in about 70% of treated eyes. The first treatment consists in 3 applications at day 0, 7 and 90, repeatable every 90 days. Immediately after suction ring application there is a significant elevation of IOP, however, of short duration and without demonstrable visual field worsening. Side effects observed are of little clinical significance and spontaneously resolving in a short time. CONCLUSIONS: The PNT is a safe and effective technique to reduce IOP in patients with ocular hypertension or open-angle glaucoma. It is repeatable, but can not replace drug treatment in patients already receiving topical therapy for glaucoma; however, it has proven effectiveness in maintaining an IOP target over time if accompanied with only a single topical drug, favoring a reduction of antiglaucoma drugs in polytherapy and increasing the compliance with treatment.

Clinical manifestations due to pharmacological interactions in pediatric ophthalmic surgery: topical drugs and general anaesthesia.

INTRODUCTION: The authors consider the type and the incidence of the adverse effects due to the interaction between ophthalmic drugs and general anaesthesia in pediatric ophthalmic surgery. PATIENTS AND METHODS: The experience included 176 general anaesthesia in 100 children aged between 9,2 months and 11,4 years (mean age 4,9 years). RESULTS: In the 100 patients we reported: 4 cases (2.7% general anaesthesias) of sinus tachycardia with heart rhythm varying between 170 and 180 beats per minute (3.6%); 5 cases of sinus bradycardia, varying between 60 and 70 beats per minute (3.3%); 3 cases of bronchospasm (2%); 2 cases of psychomotor agitation/disturbances in pre-convulsive state after anaesthesia (1.3%); 3 cases of arterial hypotension (60-70 mmHg) (2%); 7 cases of skin rush around neck and chest (4.6%); 1 case of prolonged apnoea (0.6%). CONCLUSIONS: The clinical manifestations, principally on the cardio-circulatory and nervous system are subjected to critical revision, to foresee the pharmacological interferences and therefore to prepare the necessary measure of medical treatment.

Adaptation to a high protein, carbohydrate-free diet induces a marked reduction of fatty acid synthesis and lipogenic enzymes in rat adipose tissue that is rapidly reverted by a balanced diet.

We have previously shown that in vivo lipogenesis is markedly reduced in liver, carcass, and in 4 different depots of adipose tissue of rats adapted to a high protein, carbohydrate-free (HP) diet. In the present work, we investigate the activity of enzymes involved in lipogenesis in the epididymal adipose tissue (EPI) of rats adapted to an HP diet before and 12 h after a balanced diet was introduced. Rats fed an HP diet for 15 days showed a 60% reduction of EPI fatty acid synthesis in vivo that was accompanied by 45%-55% decreases in the activities of pyruvate dehydrogenase complex, ATP-citrate lyase, acetyl-CoA carboxylase, glucose-6-phosphate dehydrogenase, and malic enzyme. Reversion to a balanced diet for 12 h resulted in a normalization of in vivo EPI lipogenesis, and in a restoration of acetyl-CoA carboxylase activity to levels that did not differ significantly from control values. The activities of ATP-citrate lyase and pyruvate dehydrogenase complex increased to about 75%-86% of control values, but the activities of glucose-6-phosphate dehydrogenase and malic enzyme remained unchanged 12 h after diet reversion. The data indicate that in rats, the adjustment of adipose tissue lipogenic activity is an important component of the metabolic adaptation to different nutritional conditions.

Dietary sodium restriction exacerbates age-related changes in rat adipose tissue and liver lipogenesis.

To investigate the effects of prolonged dietary sodium restriction on lipid metabolism, male rats weighing 35 to 40 g (just weaned) were fed either a low-salt (LSD) or a normal salt diet (NSD) and used in metabolic experiments after 1, 2, or 3 months of diet consumption. After 2 and 3 months on the diet, LSD rats showed increased amounts of lipid in carcass and retroperitoneal tissue. In both LSD and NSD, extending the feeding period from 2 to 3 months resulted in a marked reduction in the in vivo rates of adipose tissue fatty acid synthesis that was accompanied by increases in liver lipogenesis and in the activity of adipose tissue lipoprotein lipase (LPL). However, these increases were more marked in LSD rats. Thus, in vivo rates of liver fatty synthesis and LPL activity in LSD rats, which were already higher (by about 35% and 20%, respectively) than in controls after 2 months, attained levels 50% higher than those in NSD animals after another month on the diet. Brown adipose tissue (BAT) thermogenic capacity, estimated after 2 and 3 months by the tissue temperature response to norepinephrine (NE) injection and by guanosine diphosphate (GDP) binding to BAT mitochondria, did not change in controls, but was significantly reduced in LSD rats. This raises the possibility that a decrease in overall energy expenditure, together with an LPL-induced increased uptake of preformed fatty acids from the circulation, may account for the excessive lipid accumulation in LSD rats. Taken together, the data indicate that prolonged dietary sodium restriction exacerbates normal, age-related changes in white and BAT metabolism.

Management of patients with syncope referred urgently to general hospitals.

OBJECTIVE: To evaluate the incidence and the strategy of management of syncope admitted urgently to a general hospital. BACKGROUND: The management of patients with syncope is not standardized. METHODS: The study was a prospective observational registry from a sample of 28 general hospitals in Italy and enroled all consecutive patients referred to their emergency rooms from November 5th 2001 to December 7th 2001 who were affected by transient loss of consciousness as the principal symptom. RESULTS: The incidence of syncope was 0.95% (996 of 105,173 patients attending). Forty-six percent were hospitalized, mostly in the Department of Internal Medicine. The mean in-hospital stay was 8.1+/-5.9 days. A mean of 3.48 tests was performed per patient. A definite diagnosis was made in 80% of cases, neurally-mediated syncope being the most frequent. The findings of each of the 28 hospitals participating in the survey were separately evaluated. We observed great inter-hospital and inter-department heterogeneity regarding the incidence of emergency admission, in-hospital pathways, most of the examinations performed and the final assigned diagnosis. For example, the execution of carotid sinus massage ranged from 0% in one hospital to 58% in another (median 12.5%); tilt testing ranged from 0 to 50% (median 5.8%); the final diagnosis of neurally-mediated syncope ranged from 10 to 78.6% (median 43.3%). CONCLUSION: Great inter-hospital and inter-department heterogeneity in the incidence and management of syncope was observed in general hospitals. As a consequence, we were unable to describe a uniform strategy for the management of syncope in everyday practice.

Control of glyceroneogenic activity in rat brown adipose tissue.

Brown adipose tissue (BAT) glyceroneogenesis was evaluated in rats either fasted for 48 h or with streptozotocin-diabetes induced 3 days previously or adapted for 20 days to a high-protein, carbohydrate-free (HP) diet, conditions in which BAT glucose utilization is reduced. The three treatments induced an increase in BAT glyceroneogenic activity, evidenced by increased rates of incorporation of [1-14C]pyruvate into triacylglycerol (TAG)-glycerol in vitro and a marked, threefold increase in the activity of BAT phosphoenolpyruvate carboxykinase (PEPCK). BAT glycerokinase activity was not significantly affected by fasting or diabetes. After unilateral BAT denervation of rats fed either the HP or a balanced diet, glyceroneogenesis activity increased in denervated pads, evidenced by increased rates of nonglucose carbon incorporation into TAG-glycerol in vivo (difference between 3H2O and [14C]glucose incorporations) and of [1-14C]pyruvate in vitro. PEPCK activity was not significantly affected by denervation. The data suggest that BAT glyceroneogenesis is not under sympathetic control but is sensitive to hormonal/metabolic factors. In situations of reduced glucose use there is an increase in BAT glyceroneogenesis that may compensate the decreased generation of glycerol-3-phosphate from the hexose.

Beta2-agonists and cAMP inhibit protein degradation in isolated chick (Gallus domesticus) skeletal muscle.

1. The role of beta2-agonist and of cAMP in chick skeletal muscle proteolytic pathways and protein synthesis was investigated using an in vitro preparation that maintains tissue glycogen stores and metabolic activity for several hours. 2. In extensor digitorum longus (EDL) muscle total proteolysis decreased by 15 to 20% in the presence of equimolar concentrations of epinephrine, clenbuterol, a selective hbetaagonist, or dibutyryl-cAMP. Rates of protein synthesis were not altered by clenbuterol or dibutyryl-cAMP. 3. The decrease in the rate of total protein degradation induced by 10(-5)M clenbuterol was paralleled by a 44% reduction in Ca2+-dependent proteolysis, which was prevented by 10(-5)M ICI 118.551, a selective fbeta2antagonist. 4. No change was observed in the activity of the lysosomal, ATP-dependent, and ATP-independent proteolytic systems. Ca2+-dependent proteolytic activity was also reduced by 58% in the presence of 10(-4)M dibutyryl-cAMP or isobutylmethylxanthine. 5. The data suggest that catecholamines exert an inhibitory control of Ca2+-dependent proteolysis in chick skeletal muscle, probably mediated by fbeta2adrenoceptors, with the participation of a cAMP-dependent pathway.

Expression of glycerokinase in brown adipose tissue is stimulated by the sympathetic nervous system.

The effect of cold exposure (4 degrees C) or prolonged norepinephrine infusion on the activity and mRNA levels of glycerokinase (GyK) was investigated in rat interscapular brown adipose tissue (BAT). Cold exposure for 12 and 24 h induced increases of 30% and 100%, respectively, in the activity of BAT GyK, which was paralleled by twofold and fourfold increase in enzyme mRNA levels. BAT hemidenervation resulted in reductions of 50% and 30% in GyK activity and in mRNA levels, respectively, in denervated pads from rats kept at 25 degrees C, and suppressed in these pads the cold-induced increases in both GyK activity and mRNA levels. The increase in GyK activity induced by cold exposure was not affected by phenoxybenzamine, but was markedly inhibited by previous administration of propranolol or actinomycin D. BAT GyK activity did not change significantly after 6 h of continuous subcutaneous infusion of norepinephrine (20 microg/h), but increased twofold and fourfold after 12 and 24 h, with no further increase after 72 h of infusion. Norepinephrine infusion also activated mRNA production, but the effect was comparatively smaller than that on enzyme activity. beta-Adrenergic agonists also stimulated GyK activity with the following relative magnitude of response: CL316243 (beta(3)) > isoproterenol (non-selective) > dobutamine (beta(1)). In vitro rates of incorporation of glycerol into glyceride-glycerol were increased in BAT from rats exposed to cold. The data suggest that in conditions of a sustained increase in BAT sympathetic flow there is a stimulation of GyK gene expression at the pretranslational level, with increased enzyme activity, mediated by beta-adrenoreceptors, mainly beta(3).