Osteoradionecrosis incidence in pre-radiation teeth extractions: A prospective study.

AIMS: To evaluate osteoradionecrosis (ORN) incidence in a cohort of patients undergoing tooth extraction (TE) before radiotherapy (RT) for head and neck cancers. METHODS: The study protocol was approved by the Ethics Committee of Università Cattolica del Sacro Cuore (ID-2132) and registered at clinicaltrials.gov (ID: NCT04009161). TE was performed in case of signs of pericoronitis, periapical lesions, restorative impossibility, severe periodontitis. ORN was defined as exposed bone at an unhealed post-extraction socket in the absence of oncological recurrence. The RT plans were reviewed, and each post-extractive socket was contoured to calculate the received radiation dose. RESULTS: In total, 156 patients with 610 TE were enrolled. The mean follow-up was 567 days. ORN was diagnosed in four patients (2.6% of patients and 0.7% of TE). Need for osteotomy and radiation dose at the extraction site were associated with ORN (OR for osteotomy: 21.9, 95% CI: 2.17-222.2, p = 0.009; OR for RT dose: 1.1, 95% CI: 1-1.15, p = 0.05). CONCLUSIONS: TE appears to be a significant risk factor for ORN, particularly when osteotomy is required, and post-extraction sockets receive a high RT dosage. This study proposes a decision-making algorithm for TE and outlines a straightforward surgical protocol.

Speckle Tracking Echocardiography in Non-ST-Segment Elevation Acute Coronary Syndromes.

Non-ST-segment elevation acute coronary syndromes (NSTE-ACSs) are a group of clinical conditions characterized by acute myocardial ischemia. Conventional echocardiography is generally used to evaluate cardiac function using wall motion analysis and left ventricular ejection fraction but may be insufficient to explore all the complex features of NSTE-ACSs, which may vary substantially from patient to patient in terms of severity of ischemia and extent of involved myocardium. In the last years, speckle tracking echocardiography (STE) has become a widely available technique for the non-invasive assessment of cardiac function and has been repeatedly applied in the setting of NSTE-ACSs. In this review we summarize current evidence about the use of STE in patients with NSTE-ACSs, trying to underline advantages and limitations in comparison with conventional echocardiography for: diagnosis of NSTE-ACS, differential diagnosis, identification of high-risk patients, and prediction of outcome.

Predisposing factors of rhinitis medicamentosa: what can influence drug discontinuation?

BACKGROUND: the primary end point of our study was to define risk factors and identify the underlying conditions that may have led to the abuse of vasoconstrictors in rhinitis medicamentosa. Moreover, we analysed factors that may influence the vasoconstrictors discontinuation. METHODOLOGY: this was a prospective case-control observational study. Cases and controls were evaluated at the baseline in order define factors that may have influenced onset of rhinitis medicamentosa. They were re-evaluated at 3 months to verify symptoms control and drug discontinuation. Finally, they underwent a phone call questionnaire after 12 months regarding drug discontinuation. A potential bias of our study is that evaluating discontinuation we included subjects treated differently according to the main diagnosis. RESULTS: patients with rhinitis medicamentosa were more frequently smokers than controls, they had higher mean HAMA scores and positive psychiatric diseases history. Additionally, we frequently detected a local inflammation at nasal cytology in patients with rhinitis medicamentosa. A significant improvement in all nasal symptoms scores was observed in cases and controls but 29.4% of cases did not discontinue the vasoconstrictors. Two major factors negatively influenced discontinuation: positive nasal cytology and pathological HAMA score. CONCLUSION: we observed that positive local inflammation, anxiety and smoking habit correlate positively with vasoconstrictors abuse. In addition, we demonstrated that anxiety and local inflammation were the most important factors impairing drug discontinuation.

A corner reflector of graphene Dirac fermions as a phonon-scattering sensor.

Dirac fermion optics exploits the refraction of chiral fermions across optics-inspired Klein-tunneling barriers defined by high-transparency p-n junctions. We consider the corner reflector (CR) geometry introduced in optics or radars. We fabricate Dirac fermion CRs using bottom-gate-defined barriers in hBN-encapsulated graphene. By suppressing transmission upon multiple internal reflections, CRs are sensitive to minute phonon scattering rates. Here we report on doping-independent CR transmission in quantitative agreement with a simple scattering model including thermal phonon scattering. As a signature of CRs, we observe Fabry-Pérot oscillations at low temperature, consistent with single-path reflections. Finally, we demonstrate high-frequency operation which promotes CRs as fast phonon detectors. Our work establishes the relevance of Dirac fermion optics in graphene and opens a route for its implementation in topological Dirac matter.

Facial pain: sinus or not?

Facial pain remains a diagnostic and therapeutic challenge for both clinicians and patients. In clinical practice, patients suffering from facial pain generally undergo multiple repeated consultations with different specialists and receive various treatments, including surgery. Many patients, as well as their primary care physicians, mistakenly attribute their pain as being due to rhinosinusitis when this is not the case. It is important to exclude non-sinus-related causes of facial pain before considering sinus surgery to avoid inappropriate treatment. Unfortunately, a significant proportion of patients have persistent facial pain after endoscopic sinus surgery (ESS) due to erroneous considerations on aetiology of facial pain by physicians. It should be taken into account that neurological and sinus diseases may share overlapping symptoms, but they frequently co-exist as comorbidities. The aim of this review was to clarify the diagnostic criteria of facial pain in order to improve discrimination between sinogenic and non-sinogenic facial pain and provide some clinical and diagnostic criteria that may help clinicians in addressing differential diagnosis.

Seminal anti-Müllerian hormone levels during recombinant human follicle-stimulating hormone treatment in men with idiopathic infertility undergoing assisted reproduction cycles.

A prospective study was designed to investigate the effects of recombinant human follicle-stimulating hormone (rhFSH) on seminal anti-Müllerian hormone (AMH) levels in men with idiopathic oligoasthenoteratozoospermia (iOAT), researching possible relationships between the seminal AMH behavior and the response to the treatment. Thirty-nine men who were candidates for intracytoplasmic sperm injection (ICSI) because of iOAT were enrolled. Patients were treated on alternately days with 150 IU of rhFSH for at least 3 months before assisted reproduction cycles. Main outcome measures were seminal AMH concentrations before and after rhFSH therapy. After treatment, 16 subjects (responders) showed an improvement in their sperm count compared to baseline (7.6 ± 2.9 vs. 19.3 ± 7.7, p < 0.01) whereas 23 men (non-responders) experienced no sperm modifications. Baseline seminal AMH concentrations were significantly higher in responders than in non-responders (53.0 ± 30.6 vs. 34.6 ± 18.5, p < 0.025). Following therapy, a greater increase in AMH levels was observed in responders compared to non-responders (Δ = 24.8 ± 36.4 vs. Δ = 6.4 ± 11.2, p < 0.028). Seminal AMH levels significantly and positively correlated with sperm count (after rhFSH treatment rho = 0.647, p < 0.001). Our study suggests that rhFSH improves sperm count in a quota of iOAT men, and the subjects who respond to the treatment have higher baseline seminal AMH concentrations than the patients who are not responsive. Seminal AMH could be helpful to select those infertile men who may benefit from rhFSH treatment.

Environmental pollution due to cadmium: measure of semen quality as a marker of exposure and correlation with reproductive potential.

PURPOSE: Contradictory reports exist in the literature regarding an association of cadmium with parameters of semen quality. The aim of the study was to assess cadmium levels in both blood and seminal plasma and to analyze the relationships between cadmium concentrations and lifestyle and semen parameters. MATERIAL AND METHODS: Fifty healthy male volunteers were recruited to provide semen and blood samples. Each patient completed an extensive questionnaire regarding his occupation, residence, social status, diet, water source, smoking habits, and medical and surgical history. Semen analysis was carried out according to WHO guidelines. Detection of cadmium in both semen and blood samples was carried out by means of atomic absorption spectrophotometer. RESULTS: Mean concentrations of cadmium were 8.18 ± 1.6 ng/ml in blood samples and 2.56 ± 0.9 ng/ml in semen samples. Cadmium blood levels were significantly higher in men from industrialized areas and in current smokers, but were not correlated with semen levels. A significant positive correlation was found between cadmium blood levels, number of immotile spermatozoa, and teratozoospermia index (TZI). Significant inverse relationships between cadmium blood concentration and type-a and type a + b motility were found. CONCLUSIONS: The present data show a significant correlation between blood cadmium concentrations, cigarette smoking, occupational exposure, and parameters of semen quality. Such a reduction in spermiogenetic function could be an early marker of a toxic effect by cadmium pollution.

Skewed B cells in chronic hepatitis C virus infection maintain their ability to respond to virus-induced activation.

Chronic hepatitis C virus (HCV) infection is characterized by persistent B-cell activation, with enhanced differentiation and reduced proliferative ability. To assess the possible role of HCV in altering B-cell subset distribution, we examined ex vivo frequencies and B-cell inhibitory receptor expression in 37 chronic HCV-infected patients and 25 healthy donors (HD). In addition, we determined whether short-term exposure to culture-derived HCV (HCVcc) resulted in B-cell subset skewing and/or activation. There was a statistically significant increase in the frequencies of immature transitional, activated memory and tissue-like memory (TLM) B cells in HCV-infected patients compared with HD. We also found that the frequency of memory B cells correlated with serum HCV RNA levels. The proportion of B cells expressing the marker of exhaustion Fc receptor-like 4 (FcRL4) was generally low even though significantly higher in the patients' memory B-cell compartment compared with HD, and a positive correlation was found between the frequencies of the patients' TLM FcRL4+ B cells and serum alanine aminotransferase and histological activity index at liver biopsy. Exposure to cell-free HCVcc in vitro did not result in B-cell skewing but induced significant activation of naïve, TLM and resting memory B cells in HCV-infected patients but not in HD, in whom cell-associated virus was an absolute requirement for activation of memory B cells. These findings provide corroborative evidence in favour of significant B-cell subset skewing in chronic HCV infection and in addition show that expression of exhaustion markers in selected B-cell subsets does not impair virus-induced B-cell activation.

Therapeutic effects of L-carnitine and propionyl-L-carnitine on cardiovascular diseases: a review.

Several experimental studies have shown that levocarnitine reduces myocardial injury after ischemia and reperfusion by counteracting the toxic effect of high levels of free fatty acids, which occur in ischemia, and by improving carbohydrate metabolism. In addition to increasing the rate of fatty acid transport into mitochondria, levocarnitine reduces the intramitochondrial ratio of acetyl-CoA to free CoA, thus stimulating the activity of pyruvate dehydrogenase and increasing the oxidation of pyruvate. Supplementation of the myocardium with levocarnitine results in an increased tissue carnitine content, a prevention of the loss of high-energy phosphate stores, ischemic injury, and improved heart recovery on reperfusion. Clinically, levocarnitine has been shown to have anti-ischemic properties. In small short-term studies, levocarnitine acts as an antianginal agent that reduces ST segment depression and left ventricular end-diastolic pressure. These short-term studies also show that levocarnitine releases the lactate of coronary artery disease patients subjected to either exercise testing or atrial pacing. These cardioprotective effects have been confirmed during aortocoronary bypass grafting and acute myocardial infarction. In a randomized multicenter trial performed on 472 patients, levocarnitine treatment (9 g/day by intravenous infusion for 5 initial days and 6 g/day orally for the next 12 months), when initiated early after acute myocardial infarction, attenuated left ventricular dilatation and prevented ventricular remodeling. In treated patients, there was a trend towards a reduction in the combined incidence of death and CHF after discharge. Levocarnitine could improve ischemia and reperfusion by (1) preventing the accumulation of long-chain acyl-CoA, which facilitates the production of free radicals by damaged mitochondria; (2) improving repair mechanisms for oxidative-induced damage to membrane phospholipids; (3) inhibiting malignancy arrhythmias because of accumulation within the myocardium of long-chain acyl-CoA; and (4) reducing the ischemia-induced apoptosis and the consequent remodeling of the left ventricle. Propionyl-L-carnitine is a carnitine derivative that has a high affinity for muscular carnitine transferase, and it increases cellular carnitine content, thereby allowing free fatty acid transport into the mitochondria. Moreover, propionyl-L-carnitine stimulates a better efficiency of the Krebs cycle during hypoxia by providing it with a very easily usable substrate, propionate, which is rapidly transformed into succinate without energy consumption (anaplerotic pathway). Alone, propionate cannot be administered to patients in view of its toxicity. The results of phase-2 studies in chronic heart failure patients showed that long-term oral treatment with propionyl-L-carnitine improves maximum exercise duration and maximum oxygen consumption over placebo and indicated a specific propionyl-L-carnitine effect on peripheral muscle metabolism. A multicenter trial on 537 patients showed that propionyl-L-carnitine improves exercise capacity in patients with heart failure, but preserved cardiac function.

Oxidative stress during myocardial ischaemia and heart failure.

Oxidative stress is a condition in which oxidant metabolites exert their toxic effect because of an increased production or an altered cellular mechanism of protection. The heart needs oxygen avidly and, although it has powerful defence mechanisms, it is susceptible to oxidative stress, which occurs, for instance, during post-ischaemic reperfusion. Ischaemia causes alterations in the defence mechanisms against oxygen free radicals, mainly a reduction in the activity of mitochondrial superoxide dismutase and a depauperation of tissue content of reduced glutathione. At the same time, production of oxygen free radicals increases in the mitochondria and leukocytes and toxic oxygen metabolite production is exacerbated by re-admission of oxygen during reperfusion. Oxidative stress, in turn, causes oxidation of thiol groups and lipid peroxidation leading first to reversible damage, and eventually to necrosis. In man, there is evidence of oxidative stress (determined by release of oxidised glutathione in the coronary sinus) during surgical reperfusion of the whole heart, or after thrombolysis, and it is related to transient left ventricular dysfunction or stunning. Data on oxidative stress in the failing heart are scant. It is not clear whether the defence mechanisms of the myocyte are altered or whether the production of oxygen free radicals is increased, or both. Recent data have shown a close link between oxidative stress and apoptosis. Relevant to heart failure is the finding that tumour necrosis factor, which is found increased in failing patients, induces a rapid rise in intracellular reactive oxygen intermediates and apoptosis. This series of events is not confined to the myocytes, but occurs also at the level of endothelium, where tumour necrosis factor causes expression of inducible nitric oxide synthase, production of the reactive radical nitric oxide, oxidative stress and apoptosis. It is therefore, possible that the immunological response to heart failure results in endothelial and myocyte dysfunction through oxidative stress mediated apoptosis. Clarification of these mechanisms may lead to novel therapeutic strategies.

Impact of tissue harmonic imaging in patients with distorted left ventricles: improvement in accuracy and reproducibility of visual, manual and automated echocardiographic assessment of left ventricular ejection fraction.

AIMS: The aim of this study was to assess the incremental value of tissue harmonic imaging vs conventional echocardiography for evaluating left ventricular ejection fraction by manual and automated quantitation as well as visual estimation in patients with distorted left ventricles. METHODS AND RESULTS: In 25 patients unselected for image quality and with distorted left ventricles who underwent a nuclear study, digital cineloops of standard apical views were acquired by both tissue harmonic imaging and conventional echocardiography and sent to six observers for analysis of visual and quantitative left ventricular ejection fraction. Tissue harmonic imaging improved both the correlation and agreement of all echo techniques with nuclear measures, compared with conventional echocardiography echo, reducing standard errors (SE) to below 10%: for the visual estimate SE=7.5%, for manual tracing SE=6.3% and for automated tracing SE=8%. Tissue harmonic imaging decreased inter-observer variability compared with conventional echocardiography echo for both visual assessment (12.4% vs 18.4%, P<0.05) and quantitative measures (for manual tracing, 8.2% vs 11.8%, P<0.05; for automated tracing, 7.8% vs 16.8%, P<0.05). CONCLUSIONS: In patients with distorted left ventricles unselected for image quality, tissue harmonic imaging improves accuracy and reproducibility of both visual and quantitative echocardiographic assessment of left ventricular ejection fraction. In particular, it promotes automated quantitation by reducing its high standard error into a clinically reasonable range.

Effects of a short-term suspension of hormone replacement therapy on mammographic density.

OBJECTIVE: To evaluate the effects of hormone replacement therapy (HRT) and of a short-term suspension of HRT on mammographic density. DESIGN: Prospective clinical study. SETTING: Outpatient menopausal clinic of the Second University of Naples. PATIENT(S): Ninety-seven healthy postmenopausal women. INTERVENTION(S): Thirty-nine menopausal women with intact uterus (group A) were treated with continuous transdermal E(2) plus acetate nomegestrolo sequentially added, 37 women in surgical menopause (group B) were treated with transdermal E(2) continuously administered, and 21 menopausal women did not receive any medication (group C). At the entry and after 12 months, a mammography was performed without suspension of HRT (group A1: 19 women; group B1: 19 women) or after a short-term suspension (group A2: 20 women; group B2: 18 women). MAIN OUTCOME MEASURE(S): Mammographic density evaluated according to a quantitative method. RESULT(S): At the second mammography, seven patients in group A1, four patients in group B1, and one patient in both groups A2 and B2 showed an increase in mammographic density, whereas no mammographic density increase was observed in patients in group C. A statistically significant difference in the mammographic density increase was found between group A1 and group A2; no difference was found between group B1 and B2. CONCLUSION(S): Suspension of HRT for about 3 weeks may reverse mammographic density increase associated with its use.

A semiautomated objective technique for applying the proximal isovelocity surface area method to quantitate mitral regurgitation: Clinical studies with the digital flow map.

BACKGROUND: Clinical application of the color Doppler proximal isovelocity surface area (PISA) method to quantify mitral regurgitation (MR) has been limited by the often inaccurate assumption that isovelocity surfaces are hemispheric. This study applied an objective method for selecting the region where the hemispheric geometry holds best on the basis of mathematic analysis of results at different distances from the orifice. We aimed to demonstrate this approach can be applied accurately in the clinical setting and can be semiautomated to promote routine use by extracting velocities from the digital Doppler output and then performing all the calculations automatically. METHODS: In 75 patients with isolated MR, centerline velocities (V(r)) at each distance (r) from the orifice in the proximal flow field were extracted digitally. The automated analysis calculated peak MR flow rates as 2pir(2)V(r) and plotted these against their respective velocities. The optimal value for peak flow rate was obtained mathematically at the site where the slope of this curve was minimal (least inaccuracy). This value was combined with continuous wave Doppler data to provide regurgitant stroke volume (RSV) and orifice area (ROA), which were compared with quantitative Doppler in 75 patients and angiography in 42. RESULTS: RSV and ROA by this optimized, semiautomated PISA method correlated and agreed well with values from quantitative Doppler (y = 0.9x + 1.9, r = 0.90, standard error of the estimate [SEE] = 8.1 mL, mean difference = -0.7 +/- 8.5 mL for RSV; y = 0.9x + 0.02, r = 0.90, SEE = 0.048 cm(2), mean difference = -0.005 +/- 0.1 cm(2) for ROA) and correlated well with angiography (rho = 0.90 for both RSV and ROA). CONCLUSIONS: This objective PISA method for quantifying MR is accurate in the clinical setting and has been semiautomated by use of analysis of digital velocity data to provide a rapid and practical technique suitable to facilitate more extensive application in routine practice.

Tamoxifen effects on endometrium.

BACKGROUND: To evaluate the effects on the endometrium of a long term treatment with Tamoxifen in postmenopausal patients, asymptomatic for gynecologic disorders, surgically treated for breast cancer. SETTING: Outpatient menopausal clinic and endoscopic unit. PATIENTS AND INTERVENTIONS: 45 patients (Group I) were treated with 20 mg of Tamoxifen daily for a mean of 23.4 months. Seven patients (Group II) represented the control group and did not receive Tamoxifen. A transvaginal ultrasonography and a hysteroscopic guided biopsy were performed in all patients. RESULTS: Sagittal sonograms showed abnormal endometrial thickening (range 8-32 mm, mean 13 mm) in 17 patients (35.4%) of Group I and in 1 patient of Group II. Pathology on endometrial tissue sampling obtained at the time of hysteroscopy showed hyperplastic endometrial polyps in 3 patients (6.25%), endometrial hyperplasia in 16 patients (33.4%), while 1 patient had an endometrial polyp cancer on a background of hyperplasia and 1 had a superficial endometrial cancer (4.1%). Out of the 7 patients of Group II, one had an endometrial polyp, while 6 had no relevant endometrial abnormalities. CONCLUSIONS: Our study confirms that Tamoxifen treatment is associated with an increased incidence of proliferative and neoplastic endometrial changes. No obvious correlation was found between the length of Tamoxifen exposure time and occurrence of endometrial pathologies. It is mandatory to undertake twice per year gynecological evaluations for patients treated with Tamoxifen to promptly identify and correctly manage endometrial changes.

Underestimation of regional myocardial perfusion with Tc-99m sestamibi single-day rest-stress SPECT: a "drug washout" pitfall?

Myocardial perfusion scintigraphy with a Tc-99m sestamibi single-day SPECT protocol is a widely used technique to examine patients with possible or known coronary artery disease. A 76-year-old man with a clinical history suggestive of ischemic heart disease underwent Tc-99m sestamibi myocardial SPECT imaging with a same-day rest and stress protocol after temporary discontinuation of his current therapy, which included calcium channel and beta blockers and nitrates. The scintigraphic pattern was consistent with an asymptomatic infarction of the posterolateral myocardial wall and periinfarct ischemia. One week later, the patient had a Tc-99m sestamibi myocardial SPECT study at rest without discontinuing therapy, and scintigraphic images showed normalization of the posterolateral wall perfusion defect. The angiographic study showed a 90% stenosis of the circumflex artery. This case suggests that, during a 1-day cardiac SPECT protocol, washout of therapeutic pharmaceuticals may be responsible for underestimation of myocardial rest perfusion in territory supplied by a coronary artery with a critical stenosis.

Quantitation of ventricular size and function: principles and accuracy of transthoracic rotational scanning.

Two-dimensional echocardiography is a readily applicable method for the quantification of ventricular volumes. However, it is limited by assumptions regarding ventricular shape. Three-dimensional echocardiography has emerged as a more accurate and reproducible approach to ventricular volume and functional assessment compared with two-dimensional echocardiography. We review the principles of transthoracic rotational scanning and its clinical application for quantitative assessment of ventricular volume and function.

Atrioventricular nodal versus atrioventricular supraventricular reentrant tachycardias: characterization by an integrated Doppler electrophysiological hemodynamic study.

During reentrant supraventricular tachycardias involving the atrioventricular node (AVN-SVT) or an AV bypass tract (AV-SVT), atrial pressure increases. While in AVN-SVT this increase relates to atrial contraction during ventricular systole, the mechanism remains unclear in AV-SVT. This study sought to clarify this mechanism. During 11 AVN-SVTs and 9 AV-SVTs, anterograde flow through the AV valves and retrograde flow in the pulmonary and hepatic veins were studied by pulsed-wave (PW) Doppler measuring the time interval between the ECG-R wave and (1) the end of venous retrograde flows, and (2) the beginning of valvular anterograde flows. The positive or negative difference between these two time intervals guided recognizing the atrial contraction against open or closed AV valves. Intracavitary pressures and cardiac index were also measured. During AVN-SVTs, venous retrograde flows always ended before the anterograde valvular flows, indicating atrial contraction against closed AV valves. During AV-SVTs, pulmonary retrograde flow ended before the beginning of mitral anterograde flow in five cases, began before but ended during the anterograde flow in three cases, and overlapped to the anterograde flow in one case. A corresponding behavior was observed at the right side of the heart. In both SVTs, atrial pressures increased and end-diastolic ventricular pressure and cardiac index decreased similarly. During AVN-SVT, the atrial contraction always occurs against closed AV valves, and during AV-SVT it generally occurs against totally or partially closed AV valves, explaining similar atrial pressure and cardiac index changes in both SVTs.

Atrial and ventricular pressures in atrial flutter.

The hemodynamic effects of atrial flutter (AF) are unknown. The purpose of the present study was to investigate the changes in atrial and ventricular pressures after induction of AF. In 23 patients with paroxysmal AF (age 59 +/- 9 years), a hemodynamic study was performed both during sinus rhythm and after induction of the tachyarrhythmia. During AF, 13 patients showed a fixed 2:1 AV conduction and 10 patients showed variable conduction. Mean right and left atrial pressures increased (P < 0.001) and right and left ventricular end-diastolic pressures decreased (P < 0.001) after induction of AF. Both the increase in mean atrial pressures and the decrease in ventricular end-diastolic pressures were present either in the patients with fixed 2:1 AV (heart rate: 133 +/- 15 beats/min) or in those with variable conduction (heart rate 96 +/- 15 beats/min), but were more marked in the former. AF produces an impairment of atrial function, as evidenced by the increase in mean atrial pressures and reduction in ventricular end-diastolic pressures in the absence of an elevated heart rate. The mechanisms responsible for the increase in mean atrial pressures are unknown; however, atrial contractions against closed AV valves seem to play an important role.