"Vascular tuft sign" in neuroendocrine tumors of the pancreas.

The often well-developed microvasculature in pancreatic neuroendocrine tumors (PanNETs) has been studied from different perspectives. However, some detailed structural findings have received less attention. Our objective is to study an overlooked event in PanNETs: "enclosed vascular tufts" (EVTs). For this purpose, 39 cases of PanNETs were examined with conventional (including serial sections) and immunochemistry procedures. In typical EVTs, the results show: 1) an insulated terminal vascular area, with a globular (glomeruloid) aspect, formed by a cluster of coiled microvessels, presenting CD31-, CD34-positive endothelial cells, αSMA-positive pericytes, and perivascular CD34-positive stromal cells/telocytes, separated by a pseudoglandular space from the surrounding trabeculae of tumor neuroendocrine cells; and 2) a pedicle joining the insulated terminal vascular area, with connective tissue tracts around the enclosing tumor trabeculae. EVTs predominate in the trabecular and nested gyriform pattern of PanNETs, with tumor trabeculae that follow a ribbon coil (winding ribbon pattern) around small vessels, which acquire a tufted image. In EVTs, secondary modifications may occur (fibrosis, hyalinization, myxoid changes, and calcification), coinciding or not with those of the connective tracts. In conclusion, the typical characteristics of unnoticed EVTs allow them to be considered as a morphological sign of PanNETs (a vascular tuft sign). Further in-depth studies are required, mainly to assess the molecular pathways that participate in vascular tuft formation and its pathophysiological implications.

Circadian temperature rhythm in breeding sows: differences between days in oestrus and anoestrus after weaning.

BACKGROUND: Mammals are subject to circadian rhythms for the control of various physiological events. One of the parameters known to be subject to variations throughout the day is body temperature, which is also subject to influences such as environmental temperature. However, there are not many studies on these rhythms in breeding sows. The aim of this study was to determine the circadian parameters for body temperature in post-weaning sows during oestrus period, throughout the seasons in a warm climate. RESULTS: Differences were observed in inter-daily stability, intra-daily fragmentation and cycle length comparing the summer sows with the other seasons. Differences were also observed in the period that the sows were in oestrus compared to the non-oestrus period for intra-daily fragmentation, with these differences being more important in the warm seasons compared to the cold seasons. The parameters normalised by COSINOR also showed significant differences when comparing seasons, especially in the acrophase of the temperature maximum. Another significant finding was an increase in vaginal temperature during oestrus in sows monitored in summer compared to the other seasons. Correlations between body, vaginal and environmental temperature were observed. CONCLUSION: There is a seasonal influence on the circadian rhythm of temperature and summer is clearly the season with the greatest differences in circadian parameters when compared to the other seasons. The extreme summer conditions seem to definitely influence this rhythm and make the body and vaginal temperature of the sows different from the rest of the year. The increase in period robustness in both body and vaginal temperature during the days when sows are in oestrus could be related to the hormonal events of oestrus and ovulation and seems to be independent of weather since it occurs in all controlled seasons. However, this robustness is significantly higher in summer than in the other seasons both in the oestrus period and on days when sows are not in oestrus.

Cumplimentación del consentimiento informado en cirugía radioguiada por los servicios de Cirugía General y Medicina Nuclear de una unidad de cirugía radioguiada / Completion of the informed consent in radioguided surgery by the General Surgery and Nuclear Medicine services of a radioguided surgery unit

Objetivo Identificar la frecuencia de errores en los documentos de consentimiento informado en cirugía radioguiada en un hospital de tercer nivel y detectar posibles causas o factores asociados a un mayor riesgo de error. Material y método Se analizaron los consentimientos informados de un total de 369 intervenciones de cirugía radioguiada, cumplimentados por los servicios de Medicina Nuclear y Cirugía General, y se analizó el grado de cumplimentación de los mismos y su correlación con facultativos responsables, tipo de enfermedad e intervención, tiempo de espera y cumplimentación del consentimiento de la otra especialidad. Resultados Se identificaron errores en 22 consentimientos de Medicina Nuclear y 71 consentimientos de Cirugía General. El error más común fue la ausencia de identificación del facultativo responsable (17 en Medicina Nuclear, 51 en Cirugía General), y el segundo más común la ausencia de documento (2 en Medicina Nuclear, 20 en Cirugía General). Existieron diferencias significativas en los errores cometidos en función del médico responsable, sin encontrarse correlación significativa con el resto de las variables. Conclusiones Los médicos responsables fueron el principal factor asociado a un mayor riesgo de error en la cumplimentación de consentimientos informados. Serían recomendables nuevos estudios para analizar factores casuales y posibles intervenciones para minimizar errores (AU)

Objective To identify the frequency of errors in the informed consent documents in radioguided surgery in a third level hospital and to detect possible causes or factors associated with a greater risk of error. Material and method The informed consents of a total of 369 radioguided surgery interventions, completed by the Nuclear Medicine and General Surgery services, were analyzed, as well as their degree of completion and its correlation with responsible physicians, type of pathology and intervention, waiting time and completion of the consent of the other specialty. Results Errors were identified in 22 consent forms for Nuclear Medicine and 71 consent forms for General Surgery. The most common error was the absence of identification of the responsible physician (17 in Nuclear Medicine, 51 in General Surgery), and the second most common was the absence of a document (2 in Nuclear Medicine, 20 in General Surgery). There were significant differences in the errors made depending on the doctor in charge, without finding a significant correlation with the other variables. Conclusions The responsible physicians were the main factor associated with a greater risk of error in the completion of informed consent. New studies would be recommended to analyze causal factors and possible interventions to minimize errors (AU)

Completion of the informed consent in radioguided surgery by the General Surgery and Nuclear Medicine services of a radioguided surgery unit.

OBJECTIVE: To identify the frequency of errors in informed consent documents in radioguided surgery in a third level hospital and to detect possible causes or factors associated with a greater risk of error. MATERIAL AND METHODS: Informed consent forms of a total of 369 radioguided surgery interventions, completed by the Nuclear Medicine and General Surgery services, were analyzed, and the degree of completion of the forms and its correlation with the physicians responsible, type of pathology, intervention, and waiting time were compared with the completion of consent by another specialty. RESULTS: Errors were identified in 22 consent forms from Nuclear Medicine and 71 from General Surgery. The most common error was the absence of identification of the physician responsible (17 in Nuclear Medicine, 51 in General Surgery), and the second most common was the absence of a document (2 in Nuclear Medicine, 20 in General Surgery). There were significant differences in the errors made depending on the doctor in charge, with no significant correlation with the other variables. CONCLUSIONS: The physicians responsible were the main factor associated with a greater risk of error in the completion of informed consent forms. Further studies are needed to analyze the causal factors and possible interventions to minimize errors.

2-years retrospective observational case-control study on survival and marginal bone loss of implants in patients with hereditary coagulopathies.

BACKGROUND: Evaluating 2-years implant loss and marginal bone loss in patients with hereditary coagulopathies, comparing with a healthy control group. MATERIAL AND METHODS: 37 implants in 13 patients (17 haemophilia A, 20 Von-Willebrand disease) versus 26 implants in 13 healthy patients. Data measured through Lagervall-Jansson index (after surgery, at prosthetic loading, at 2 years). STATISTICS: Chi-square, Haberman's, ANOVA, Mann-Whitney-U. Significance p<0.05. RESULTS: Haemorrhagic accidents in 2 coagulopathies patients (non-statistical differences). Hereditary coagulopathies patients suffered more hepatitis (p<0.05), HIV (p<0.05) and less previous periodontitis (p<0.01). Non-statistical differences in marginal bone loss among groups. 2 implants were lost in the hereditary coagulopathies and none in the control group (non-statistical differences). Hereditary coagulopathies patients had longer (p<0.001), and narrower implants (p<0.05) placed. 43.2% external prosthetic connection in hereditary coagulopathies patients (p<0.001); change of prosthetic platform more frequent in control group (p<0.05). 2 implants lost: external connection (p<0.05). Survival rate 96.8% (hereditary coagulopathies 94.6%, control group 100%). CONCLUSIONS: Implant and marginal bone loss at 2 years is similar in patients with hereditary coagulopathies and control group. Precautions should be taken on the treatment for hereditary coagulopathies patients, through prior haematological protocol. Implant loss only occurred in in a patient with Von-Willebrand´s disease.

Exposure to Cigarette Smoke Impedes Human Osteoblast Differentiation Independently of Nicotine.

INTRODUCTION: Tobacco smoking has been implicated in an array of adverse health outcomes, including those that affect adult bone. However, little is known about the impact of tobacco products on developing bone tissue as it develops in the embryo. AIMS AND METHODS: Here, human embryonic stem cells were differentiated into osteoblasts in vitro and concomitantly exposed to various concentrations of smoke solutions from two conventional, one additive-free and two harm-reduction brands of cigarettes. Differentiation inhibition was determined by calcium assays that quantified matrix mineralization and compared to the cytotoxicity of the tobacco product. RESULTS: Exposure to mainstream smoke from conventional and additive-free cigarettes caused no inhibition of cell viability or mineralization, while sidestream smoke (SS) concentration-dependently produced cell death. In contrast, mineralization was inhibited only by the highest mainstream concentration of harm-reduction smoke solution. Additionally, sidestream smoke solution from the harm-reduction cigarettes impeded calcification at concentrations lower than those determined to be cytotoxic for conventional products. CONCLUSIONS: Sidestream smoke impaired in vitro osteogenesis at subtoxic concentrations. In addition, though often perceived as safer, smoke from harm-reduction cigarettes was more potent in inhibiting in vitro osteogenesis than smoke from conventional cigarettes. IMPLICATIONS: This study adds to a growing list of adverse outcomes associated with pre-natal tobacco exposure. Specifically, in vitro exposure to tobacco products interfered with osteogenic differentiation of human embryonic stem cells, a well-established surrogate model for human embryonic bone development. Contrasting a diverse array of tobacco products unveiled that sidestream smoke was generally more developmentally osteotoxic than mainstream smoke and that harm-reduction products may not be less harmful than conventional products, adverse effects that were seemingly independent of nicotine.

Effects of the feeding level in early gestation on body reserves and the productive and reproductive performance of primiparous and multiparous sows.

Early gestation may be the best period for sows to recover body reserve losses from previous lactation. The aim of this study was to investigate the effect of different levels of restricted feeding in early gestation on the body status, productive and reproductive performance, and hormonal-metabolic status of primiparous and multiparous sows. A total of 130 sows were randomly assigned to one of three feeding levels: Treatment I, which sows were fed at the level commonly used from day 3 to 28 of gestation (2.5 kg·d-1 of a diet with 2.18 Mcal NE·kg-1 and 13.72 g CP·kg-1), and Treatments II and III, where feed was increased by 25% and 50%, respectively. Sow body status, litter size and weight, early mortalities, reproductive rates, weaning-to-estrus interval, and hormones linked to metabolism were recorded. The highest weight gain, body condition score, and backfat thickness were found in sows fed Treatment III compared to those fed the usual feeding level (Treatment I). No differences among treatment groups were found in litter size or litter weight, although a tendency for more live born piglets and fewer stillbirths was found in sows fed Treatment III. In contrast, litters from sows fed at higher feeding levels had a higher mortality at 72 h compared to those fed at the lowest feeding level (I), which was partly linked to a higher percentage of piglets culled at birth and piglets weighing less than 800 g. There were no differences in conception and farrowing rates, leptin, progesterone, insulin, or cortisol among treatment groups applied in early gestation. In conclusion, increasing the feeding level in sows during early gestation to improve their short-term productive and reproductive performance remains controversial. Further studies are needed to focus on how the restricted feeding level applied could affect the viability and proportion of low-weight piglets.

Intussusceptive angiogenesis and its counterpart intussusceptive lymphangiogenesis.

Intussusceptive angiogenesis (IA) is currently considered an important alternative and complementary form of sprouting angiogenesis (SA). Conversely, intussusceptive lymphangiogenesis (IL) is in an initial phase of study. We compare their morphofunctional characteristics, since many can be shared by both processes. To that end, the following aspects are considered: A) The concept of IA and IL as the mechanism by which blood and lymphatic vessels split, expand and remodel through transluminal pillar formations (hallmarks of intussusception). B) Terminology and historical background, with particular reference to the group of Burri, including Djonov and Patan, who initiated and developed the vessel intussusceptive concept in blood vessels. C) Incidence in normal (e.g. in the sinuses of developing lymph nodes) and pathologic conditions, above all in vessel diseases, such as dilated veins in hemorrhoidal disease, intravascular papillary endothelial hyperplasia (IPEH), sinusoidal hemangioma, lobular capillary hemangioma, lymphangiomas/lymphatic malformations and vascular transformation of lymph nodes. D) Differences and complementarity between vessel sprouting and intussusception. E) Characteristics of the cover (endothelial cells) and core (connective tissue components) of pillars and requirements for pillar identification. F) Structures involved in pillar formation, including endothelial contacts of opposite vessel walls, interendothelial bridges, merged adjacent capillaries, vessel loops and spilt pillars. G) Structures resulting from pillars with intussusceptive microvascular growth, arborization, remodeling and segmentation (compartmentalization). H) Influence of intussusception in the morphogenesis of vessel tumors/ pseudotumors; and I) Hemodynamic and molecular control of vessel intussusception, including VEGF, PDGF BB, Hypoxia, Notch, Endoglobin and Nitric oxide.

First passage time distribution of multiple impatient particles with reversible binding.

Consider N independently diffusing particles that reversibly bind to a target. We study a problem recently introduced by Grebenkov of finding the first passage time (FPT) for K of the N particles to be simultaneously bound to the target. Since binding is reversible, bound particles may unbind before the requisite K particles bind to the target. This so-called "impatience" leads to a delicate temporal coupling between particles. Recent work found the mean of this FPT in the case that N = K = 2 in a one-dimensional spatial domain. In this paper, we approximate the full distribution of the FPT for any N ≥ K ≥ 1 in a broad class of domains in any space dimension. We prove that our approximation (i) is exact in the limit that the target and/or binding rate is small and (ii) is an upper bound in any parameter regime. Our approximation is analytically tractable and we give explicit formulas for its mean and distribution. These results reveal that the FPT can depend sensitively and nonlinearly on both K and N. The analysis is accompanied by detailed numerical simulations.

Increase of germ cell nuclear factor expression in globozoospermic Gopc-/- knockout mice.

BACKGROUND: Golgi-associated PDZ and coiled-coil motif-containing protein (GOPC) is a Golgi protein that plays a role in vesicular transport and intracellular protein trafficking and degradation. Mice deficient in GOPC protein have globozoospermia and are infertile. The germ cell nuclear factor (GCNF) is a member of the nuclear receptor superfamily which is expressed in male germ cells, from spermatocytes and spermatids, both in the nucleus and the acrosomal region. It is not known if its expression could be altered in Gopc-/- mice with defective acrosomes. OBJECTIVES: The aim of the present work was to analyze the distribution of GCNF protein in spermatids of Gopc-/- knockout mice. MATERIALS AND METHODS: We have analyzed the expression and distribution during spermatogenesis of GCNF and its deregulation in Gopc-/- mutant mice by RT-qPCR, Western blot, immunohistochemistry and immunogold. RESULTS: Germ cell nuclear factor was localized in the nucleus of all the cell types in the seminiferous tubules. Despite being a nuclear protein, it was also located in the acrosome and in the manchette of elongating spermatids. We have found that in the absence of GOPC, the expression of GCNF was increased in the nucleus of spermatocytes, mainly in leptotene, and in the nucleus and the manchette during the spermatid elongation. DISCUSSION AND CONCLUSION: Gopc-/- mice have defective acrosome and manchette. The manchette is involved in the transport of proteins through the cytoplasm and the nucleus. Considering that the GCNF protein is normally transported to the acrosome and the nucleus, it can be thought that transport deficiencies in Gopc-/- mice are responsible for the increased expression of this protein.

Update on radioguided surgery: from international consensus on sentinel node in head and neck cancer to the advances on gynaecological tumors and localization of non-palpable lesions. / Actualización en cirugía radioguiada: del consenso internacional en ganglio centinela de cabeza y cuello a los avances en tumores ginecológicos y localización de lesiones no palpables.

The aim of this review is to provide an updated perspective on different fields of radioguided surgery. With reference to the sentinel lymph node biopsy in oral squamous cell carcinoma, we present the results of the interactive debate held at the recent Congress of our specialty about the more relevant aspects of the London Consensus. Drainage peculiarities and indications according to the current guidelines on gynaecological tumours, endometrial and cervical cancer, are detailed and new scenarios for nuclear medicine physicians are presented; robotic surgery and hybrid tracers, for instance. Moreover, the notable growth in radioguided surgery indications for non-palpable lesions, widely used in mammary pathology, make it advisable to update two procedures which have shown satisfying results, such as the solitary pulmonary nodule and the osteoid osteoma.

67-Gallium SPECT/CT in febrile syndromes of unknown origin. / SPECT/TC con galio-67 en los síndromes febriles sin foco conocido.

INTRODUCTION AND OBJECTIVE: Febrile syndromes of unknown origin (FSUO) are complex processes in hospital practice. Their management includes an exhaustive medical history and examination, as well as an extensive number of biochemical tests. If these are inconclusive, diagnostic imaging techniques such as SPECT/CT with 67-Gallium Citrate (67Ga-SPECT/CT) could play an important role. We evaluated its role in the management of FSUO in our healthcare area. MATERIAL AND METHODS: We reviewed 57 patients who underwent a 67Ga-SPECT/CT due to a FSUO (32 women and 25 men, age range: 32-83 years old) obtaining scintigraphic findings, previous treatments and final diagnosis. Values of sensitivity, specificity, positive predictive values (VPP) and negative values (NPV) were obtained and compared with the results for PET/CT with 18Fluor-deoxy-glucose (18F-FDG PET/CT) found in the literature. RESULTS: The diagnoses found were: infection in 27/57 (47%), inflammatory disease in 15/57 (26%), neoplasm in 1/57 (1.75%) and patients without final diagnosis in 14/57 (24%). The statistical values of 67Ga-SPECT/CT were: sensitivity, specificity, PPV and NPV of 67%, 93%, 97% y 48%, respectively which were slightly lower than those found for the 18F-FDG PET/CT (86%, 52%, 70% and 92%, respectively). The diagnostic yield was 73% which increased to 80% in the patients who lacked empirical treatment. CONCLUSION: Despite the better results of 18F-FDG PET/CT, 67Ga-SPECT/CT behaved as a useful technique in the management of FSUO. It is advisable to use it if 18F-FDG PET/CT is not available.

Circadian monitoring as an aging predictor.

The ageing process is associated with sleep and circadian rhythm (SCR) frailty, as well as greater sensitivity to chronodisruption. This is essentially due to reduced day/night contrast, decreased sensitivity to light, napping and a more sedentary lifestyle. Thus, the aim of this study is to develop an algorithm to identify a SCR phenotype as belonging to young or aged subjects. To do this, 44 young and 44 aged subjects were recruited, and their distal skin temperature (DST), activity, body position, light, environmental temperature and the integrated variable TAP rhythms were recorded under free-living conditions for five consecutive workdays. Each variable yielded an individual decision tree to differentiate between young and elderly subjects (DST, activity, position, light, environmental temperature and TAP), with agreement rates of between 76.1% (light) and 92% (TAP). These decision trees were combined into a unique decision tree that reached an agreement rate of 95.3% (4 errors out of 88, all of them around the cut-off point). Age-related SCR changes were very significant, thus allowing to discriminate accurately between young and aged people when implemented in decision trees. This is useful to identify chronodisrupted populations that could benefit from chronoenhancement strategies.

Impact of a shift work-like lighting schedule on the functioning of the circadian system in the short-lived fish Nothobranchius furzeri.

Adult Nothobranchius furzeri of the MZM-04/10 strain were individually kept and subjected to a "5 + 2" shifting lighting schedule (SHIFT) for 8 weeks in order to evaluate the desynchronizing effects of a simulated human-like shift-work schedule on the functioning of the circadian system (CS). With this aim, sixteen 21-week-old N. furzeri were placed into a Morning, Night and Evening schedule (lights on from 08:00 to 16:00, 00:00 to 08:00 and 16:00 to 00:00 h, respectively) and fed once a day in the middle of the corresponding photophase (12:00, 04:00 and 20:00 h, respectively). Then, in the weekends (2 days), fish were always returned to the Morning shift. As controls, 16 fish were maintained under a non-shifting LD cycle condition (CONTROL) throughout the whole experiment, with lights on from 08:00 to 16:00 h. Rest-activity rhythm (RAR) of fish subjected to SHIFT showed several symptoms of chronodisruption, such as a decrease in the percentage of diurnal activity and a reduction of the relative amplitude and the circadian function index with time. When a periodogram analysis was performed, RAR of N. furzeri under SHIFT conditions showed up to three separate circadian components: one longer than 24 h (26.5 h) that followed the weekly 8 h delays; a short-period component (~23 h) that was related to the weekend's phase advances, and finally, a 24 h component. The shifting LD schedule also affected fish CS at a molecular level, with several significant differences in the expression of core genes of the molecular clock (bmal1, clock, rorα, rev-erbα) between SHIFT and CONTROL animals. RAR impairment along with changes in clock gene expression could be associated with high stress and accelerated aging in these fish.

Hepatocellular carcinoma treatment: ablation and arterial embolization. / Tratamiento del hepatocarcinoma: ablación y embolización arterial.

Percutaneous and endovascular techniques take an important role in the therapeutic management of patients with hepatocarcinoma. Different techniques of percutaneous ablation, especially indicated in tumors up to 2cm diameter offer, at least, similar results to surgical resection. Taking advantage of double hepatic vascularization and exclusive tumor nutrition by the artery, several endovascular techniques of treating the tumor have been developed. Intra-arterial administration of embolizing particles, alone or charged with drug (chemoembolization), will produce ischemia and consequent necrosis with excellent results in selected patients. Certain types of particles may exclusively be carriers of a therapeutic agent when they incorporate a radioisotope that facilitates the direct intratumoral selective irradiation (radioembolization). This technique has demonstrated its efficacy in lesions not susceptible to be treated with other methods and should be considered, together with ablation and chemoembolization, in the therapeutic algorithms of hepatocarcinoma.

Heritability of siesta and night-time sleep as continuously assessed by a circadian-related integrated measure.

Siesta is a relevant aspect of sleep due to its posited relationship with health or cognitive function. However, unlike night-time sleep, studies about daytime-sleep determinants and characteristics are scarce, and the genetic/environmental structure of siesta is still unknown. Our aim was to explore the relative contribution of genetic and environmental factors to variation in sleep-wake rhythm, measured by a continuous assessment of temperature-activity-position (TAP), which allows for diurnal sleep analysis. The sample comprised 53 pairs of female twins (28 MZ and 25 DZ), selected from the Murcia Twin Register. Mean age of participants was 52 (SD: 6.03). Zygosity was determined by DNA. We conducted separate univariate analyses to study the sources of variance of daytime and night-time sleep parameters. About 60% of the sample reported to take siesta at least once a week. Heritability of taking siesta and daytime sleep duration was 65 and 61% respectively. Other sleep parameters obtained by TAP showed heritability estimates between 36 and 69%, suggesting a relevant impact of genetic factors on sleep rhythm. This is the first study to investigate the relative contribution of genetic factors to siesta. By using TAP, we introduce a novel approach to the study of diurnal sleep characteristics.