Modeling circuit mechanisms of opposing cortical responses to visual flow perturbations.

In an ever-changing visual world, animals' survival depends on their ability to perceive and respond to rapidly changing motion cues. The primary visual cortex (V1) is at the forefront of this sensory processing, orchestrating neural responses to perturbations in visual flow. However, the underlying neural mechanisms that lead to distinct cortical responses to such perturbations remain enigmatic. In this study, our objective was to uncover the neural dynamics that govern V1 neurons' responses to visual flow perturbations using a biologically realistic computational model. By subjecting the model to sudden changes in visual input, we observed opposing cortical responses in excitatory layer 2/3 (L2/3) neurons, namely, depolarizing and hyperpolarizing responses. We found that this segregation was primarily driven by the competition between external visual input and recurrent inhibition, particularly within L2/3 and L4. This division was not observed in excitatory L5/6 neurons, suggesting a more prominent role for inhibitory mechanisms in the visual processing of the upper cortical layers. Our findings share similarities with recent experimental studies focusing on the opposing influence of top-down and bottom-up inputs in the mouse primary visual cortex during visual flow perturbations.

Relationship of Frailty, Nutritional Status and Oral Health-Related Quality of Life in Mexico City Nursing Home Residents.

BACKGROUND: We aimed to identify the association among nutritional status, Oral Health-Related Quality of Life (OHRQoL) and frailty, and to estimate the mediation effect of these conditions between age and frailty in a group of Mexico City nursing home residents. METHODS: We conducted a cross-sectional study. Fried's phenotype criteria, Full Mini Nutritional Assessment, and General Oral Health Assessment Index was applied. RESULTS: The participants (n = 286) mean age was 82.4 (± 9.2) years. The prevalence of frailty was 58%, and the prevalence of malnutrition and the risk of malnutrition were 22.7% and 59.5%, respectively. A higher risk of frailty was associated with older age (p = 0.015), sex (women) (p = 0.041), poor nutritional status (p <0.001) and compromised OHRQoL (p <0.001). Approximately 40% of the effect of age on frailty was mediated by nutritional status and OHRQoL (p <0.05). CONCLUSION: A strong association between nutritional status and frailty was observed. Additionally, OHRQoL was associated with frailty. The effect of age on frailty was mediated by OHRQoL and nutritional status. Interventions targeted to improve nutritional status and oral health may contribute to preventing or delaying the onset of frailty.

100 Years since Robert Barany's visit to the Zaragoza medical faculty.

In December 1923, a twelve-day course took place at the University of Zaragoza, specifically at the Faculty of Medicine, given by Professor Róbert Bárány, who was awarded the Nobel Prize for Medicine in 1914 for his discoveries on the vestibular apparatus.Professor Robert Bárány came to the faculty at the invitation of Professor Victor Fairén through the University Exchange programme. This course consisted of four lectures and twelve lessons a day in which he presented his knowledge of the physiopathology of the vestibule and cerebellum, as well as practical demonstrations of the physical examination of nystagmus and cerebellar pathology.Lorente de Nó, a doctorate student of medicine, was one of the most outstanding students on the course. His intellect was already outstanding in those years, which helped him to discuss the physiopathology of nystagmus with Professor Bárány. The relationship he forged with the Nobel laureate in Zaragoza would be decisive for his future as a researcher.The aim of this work is to compile and integrate the available information on the course that Professor Bárány took in the city of Zaragoza, consulting official documents from the university and the city, articles, books and the press of the time.

Brimonidine-LAPONITE® intravitreal formulation has an ocular hypotensive and neuroprotective effect throughout 6 months of follow-up in a glaucoma animal model.

Intravitreal administration is widely used in ophthalmological practice to maintain therapeutic drug levels near the neuroretina and because drug delivery systems are necessary to avoid reinjections and sight-threatening side effects. However, currently there is no intravitreal treatment for glaucoma. The brimonidine-LAPONITE® formulation was created with the aim of treating glaucoma for extended periods with a single intravitreal injection. Glaucoma was induced by producing ocular hypertension in two rat cohorts: [BRI-LAP] and [non-bri], with and without treatment, respectively. Eyes treated with brimonidine-LAPONITE® showed lower ocular pressure levels up to week 8 (p < 0.001), functional neuroprotection explored by scotopic and photopic negative response electroretinography (p = 0.042), and structural protection of the retina, retinal nerve fibre layer and ganglion cell layer (p = 0.038), especially on the superior-inferior axis explored by optical coherence tomography, which was corroborated by a higher retinal ganglion cell count (p = 0.040) using immunohistochemistry (Brn3a antibody) up to the end of the study (week 24). Furthermore, delayed neuroprotection was detected in the contralateral eye. Brimonidine was detected in treated rat eyes for up to 6 months. Brimonidine-LAPONITE® seems to be a potential sustained-delivery intravitreal drug for glaucoma treatment.

Association between superior semicircular canal dehiscence and other dehiscences in temporal bone.

BACKGROUND: The study of the association between superior semicircular canal and other dehiscences in the temporal bone. MATERIALS AND METHODS: We have studied computed tomography of radiologically diagnosed people with superior or posterior semicircular canal dehiscences, in four health centres. In addition, we have studied one isolated human temporal bone, one skull and one cadaver head belonging to the collection of the Department of Human Anatomy and Histology of the University of Zaragoza that had dehiscence in the superior semicircular canal. RESULTS: The most frequent association that we observed was between superior semicircular canal dehiscence and tegmen tympani dehiscence (37.33%). Three cases (two clinical cases and one isolated temporal bone) showed multiple associated dehiscences (tegmen tympani, mastoid antrum, posterior semicircular canal, internal auditory canal, glenoid cavity, tympanum bone and geniculate ganglion) associated with superior semicircular canal dehiscence. CONCLUSIONS: When the superior semicircular canal dehiscence is associated to other in the petrous bone (tegmen tympani, mastoid antrum, posterior semicircular canal, internal auditory canal) could be grouped into the same syndrome called "otic capsule syndrome", since they have the same origin and common aetiology (otic capsule).

Unexpected obstetric haemorrhage. Krukenberg tumour. / Hemorragia obstétrica de causa inesperada. Tumor de Krukenberg.

Obstetric haemorrhage can endanger the lives of mother and foetus. It often occurs unexpectedly without clear predictors. A high degree of suspicion helps to avoid delaying resuscitation measures. We present the case of a ruptured ovarian metastasis that occurred during labour. It caused a massive bleed forcing a caesarean section due to non-reassuring foetal status. This was an unprecedented and undescribed onset of Krukenberg tumour formation. Malignant tumours in pregnancy are rare and difficult to diagnose due to their clinical manifestations which often overlap with those of pregnancy itself (dyspepsia, nausea and bloating). Despite the available therapeutic measures, a delay in diagnosis is a determining factor for long-term prognosis. We review the causes of obstetric bleeding, and underline how rare Krukenberg tumours concomitant to pregnancy are.

Extended phenotype and clinical subgroups in unilateral Meniere disease: A cross-sectional study with cluster analysis.

OBJECTIVES: To define clinical subgroups by cluster analysis in patients with unilateral Meniere disease (MD) and to compare them with the clinical subgroups found in bilateral MD. DESIGN: A cross-sectional study with a two-step cluster analysis. SETTINGS: A tertiary referral multicenter study. PARTICIPANTS: Nine hundred and eighty-eight adult patients with unilateral MD. MAIN OUTCOME MEASURES: best predictors to define clinical subgroups with potential different aetiologies. RESULTS: We established five clusters in unilateral MD. Group 1 is the most frequently found, includes 53% of patients, and it is defined as the sporadic, classic MD without migraine and without autoimmune disorder (AD). Group 2 is found in 8% of patients, and it is defined by hearing loss, which antedates the vertigo episodes by months or years (delayed MD), without migraine or AD in most of cases. Group 3 involves 13% of patients, and it is considered familial MD, while group 4, which includes 15% of patients, is linked to the presence of migraine in all cases. Group 5 is found in 11% of patients and is defined by a comorbid AD. We found significant differences in the distribution of AD in clusters 3, 4 and 5 between patients with uni- and bilateral MD. CONCLUSIONS: Cluster analysis defines clinical subgroups in MD, and it extends the phenotype beyond audiovestibular symptoms. This classification will help to improve the phenotyping in MD and facilitate the selection of patients for randomised clinical trials.

[Anaesthetic implications in a pregnant patient with an extreme thrombocytopenia due to a May-Hegglin anomaly: general o regional anaesthesia?]. / Implicaciones anestésicas en gestante con trombocitopenia extrema por síndrome de May-Hegglin: ¿anestesia regional o general?

The May-Hegglin anomaly is an inherited disorder, so uncommon that the incidence is still unknown. It is characterized by macro-thrombocytopenia with normal platelet function and cytoplasmic inclusion bodies in granulocytes. The case is reported of a 28-year-old primiparous patient who had an urgent caesarean section due to failed induction of labour. The patient had no history of abnormal bleeding. Other causes of thrombocytopenia or platelet dysfunction, such as preeclampsia, HELLP syndrome, or placental abruption, were ruled out. The platelet count prior to surgery was 20,900/mm(3) with normal platelet function. General anaesthesia was performed. No excessive bleeding occurred and a platelet transfusion was not needed.

Familial clustering and genetic heterogeneity in Meniere's disease.

The aims of this study were to estimate the prevalence of familial cases in patients with Meniere's disease (MD) and to identify clinical differences between sporadic and familial MD. We recruited 1375 patients with definite MD according to the American Academy of Otolaryngology-Head and Neck Surgery criteria, obtaining the familial history of hearing loss or episodic vertigo by direct interview or a postal survey in 1245 cases in a multicenter study. Familial clustering was estimated by the recurrence risk ratio in siblings (λs ) and offspring (λo ) using intermediate and high prevalence values for MD in European population. A total of 431 patients (34%) reported a familial history of hearing loss or recurrent vertigo and 133 patients had a relative with possible MD. After clinical reevaluation, 93 relatives in 76 families were diagnosed of definite MD (8.4%), including three pairs of monozygotic twins. λs and λo were 16-48 and 4-12, respectively. We observed genetic heterogeneity, but most families had an autosomal dominant inheritance with anticipation. No clinical differences were found between sporadic and familial MD, except for an early onset in familial cases. We may conclude that MD has a strong familial aggregation and that sporadic and familial MDs are clinically identical.

Determining triple gauge boson couplings from Higgs data.

In the framework of effective Lagrangians with the SU(2)(L)×U(1)(Y) symmetry linearly realized, modifications of the couplings of the Higgs field to the electroweak gauge bosons are related to anomalous triple gauge couplings (TGCs). Here, we show that the analysis of the latest Higgs boson production data at the LHC and Tevatron give rise to strong bounds on TGCs that are complementary to those from direct TGC analysis. We present the constraints on TGCs obtained by combining all available data on direct TGC studies and on Higgs production analysis.

A minimally invasive surgery robotic assistant for HALS-SILS techniques.

This paper is focused in the design and implementation of a robotic surgical motion controller. The proposed control scheme addresses the issues related to the application of a robot assistant in novel surgical scenario, which combines hand assisted laparoscopic surgery (HALS) with the single incision laparoscopic surgery (SILS) techniques. It is designed for collaborating with the surgeon in a natural way, by performing autonomous movements, in order to assist the surgeon during a surgical maneuver. In this way, it is implemented a hierarchical architecture which includes an upper auto-guide velocity planner connected to a low-level force feedback controller. The first one, based on a behavior approach, computes a collision free trajectory of the surgical instrument tip, held by the robot, for reaching a goal location inside of the abdominal cavity. On the other hand, the force feedback controller uses this trajectory for performing the instrument displacement by taking into account the holonomic movement constraints introduced by the fulcrum point. The aim of this controller is positioning the surgical instrument by minimizing the forces exerted over the abdominal wall due to the fulcrum location uncertainty. The overall system has been integrated in the control architecture of the surgical assistant CISOBOT, designed and developed at the University of Malaga. The whole architecture performance has been tested by means of in vitro trials.

[Labor pain worries future fathers more than the mothers]. / El dolor del parto preocupa más a los futuros padres que a las madres.

OBJECTIVE: To evaluate the concerns of the future father about labor pain and another 9 items which could be important to the well-being of the mother during delivery. To investigate any possible differences in opinion between the future father and mother. PATIENTS AND METHODS: An anonymous and voluntary questionnaire was offered to the father and the pregnant patient during the last month of pregnancy. They had to answer the questionnaire separately, scoring 10 items in a 0-10 point ordinal scale, according to their concerns and the importance for the good development of the delivery (0= not concerned about/insignificant to 10=concerned about/great importance). The items included were: 1) esthetic aftermath, 2) embarassment, 3) continous information, 4) walking during labor, 5) drinking during labor, 6) companionship, 7) labor pain, 8) keeping composure, 9) kindness, 10) room comfortability. Data on age, education, parity and nationality were recorded. RESULTS: A total of 147 questionnaires were completed, 99 by mothers, and 48 by fathers. Pain was the most important concern for the future fathers scoring a mean (SD) of 8.15 (2), while continuous information 7.71 (2.5), kindness 7.9 (2.1), and companionship 8.21 (2.3) were more important than pain for mothers. A statistically significant difference was found between fathers and mothers regarding labor pain (P=.001), walking during labor (P=.003), and drinking during labor (P=.009). CONCLUSIONS: The result of our study suggests that increasing the presence of the father during the delivery process, and taking care of the emotional aspects and the quality of the information given could be very important for the perception of satisfaction.

Deubiquitinases in cancer: new functions and therapeutic options.

Deubiquitinases (DUBs) have fundamental roles in the ubiquitin system through their ability to specifically deconjugate ubiquitin from targeted proteins. The human genome encodes at least 98 DUBs, which can be grouped into 6 families, reflecting the need for specificity in their function. The activity of these enzymes affects the turnover rate, activation, recycling and localization of multiple proteins, which in turn is essential for cell homeostasis, protein stability and a wide range of signaling pathways. Consistent with this, altered DUB function has been related to several diseases, including cancer. Thus, multiple DUBs have been classified as oncogenes or tumor suppressors because of their regulatory functions on the activity of other proteins involved in tumor development. Therefore, recent studies have focused on pharmacological intervention on DUB activity as a rationale to search for novel anticancer drugs. This strategy may benefit from our current knowledge of the physiological regulatory mechanisms of these enzymes and the fact that growth of several tumors depends on the normal activity of certain DUBs. Further understanding of these processes may provide answers to multiple remaining questions on DUB functions and lead to the development of DUB-targeting strategies to expand the repertoire of molecular therapies against cancer.

Metabolic syndrome characteristics in gout patients.

Gout is commonly associated with obesity, arterial hypertension, diabetes, and dyslipidemia. However, the prevalence of metabolic syndrome has not been widely recognized in patients with gout. We studied 41 patients (37 males) with primary gout to assess the prevalence and characteristics of the associated metabolic syndrome. Twenty-one patients with gout (51%) showed >or=3 criteria for the metabolic syndrome. Pathological conditions associated were obesity (21/41), high blood pressure (30/41), dyslipidemia (30/41), and fasting plasma glucose >or= 100 mg/dL (22/41). The most frequent triad was the presence of increased waist circumference, elevated fasting plasma glucose, and hypertension. Mean serum urate concentration did not differ significantly in gout patients with the metabolic syndrome (8.5 mg/dl) and without (8.1 mg/dl). Given the complications associated with metabolic syndrome, its diagnosis may determine the long-term treatment of patients with gout.

Uric acid metabolism in patients with primary gout and the metabolic syndrome.

Forty-four patients (40 males) with a mean age of 58 years were included in this pilot study. Mean serum urate concentration in patients with and without the metabolic syndrome (MS) was 8.8 mg/dL and 8.1 mg/dL, respectively. Urinary uric acid excretion was 543 mg/day/1.73 m(2) in the former and 609 mg/day/1.73 m(2) in the latter. Uric acid to creatinine ratio was 0.37 mg/mg in patients with the MS and 0.42 mg/mg in those without the MS. Mean serum urate increased from 8.6 mg/dL in subjects with three or more MS components to 10.3 mg/dL in those with five MS components. Serum urate was markedly lower in patients with mild MS (9 patients, 8.6 mg/dL) as compared to severe MS (10 patients, 9.2 mg/dL). In contrast, urinary uric acid to creatinine ratio was 0.42 mg/mg in patients with gout and mild MS and 0.33 mg/mg in gout patients with severe MS. Uric acid underexcretion appears to be more severe in gout patients with the MS. This disturbance appears to be related to the severity of the MS.

Tympanic ossicles and pharyngeal arches.

We have performed a study on 11 human embryos regarding the development of the tympanic ossicles and their relationship with the first pharyngeal arch. After performing measurements to date the embryos and foetuses chronologically, we performed a meticulous dissection of the temporal bones. Subsequently, they were fixed in 10% formol, decalcified with 2% nitric acid, embedded in Paraplast, sectioned in 7-mm sequences and stained with Martin's trichrome technique. In the 21- and 24-mm cranium-raquis (CR) length human embryos, we have observed the head of the malleus and the body of the incus close to Meckel's cartilage, in addition to the handle of the malleus, the long limb of the incus and the stapes. Between them there was a mesenchymal band inside the primordium of the tympanic cavity. In the 27-mm CR embryo, the various components of the malleus and incus were fusing, and in the 30-mm CR embryo the union was complete. From our observations, we can conclude that the malleus and the incus are derived from the first and second pharyngeal arches.

An unusual patient with hypothyroidism, tophaceous gout, and marked joint destruction.

This report describes a 75-year-old Caucasian man with extensive urate deposits and severe gouty arthropathy that confined him to a wheelchair. Since age 50, he suffered multiple acute gout flares and progressive deformities in his hands, feet, knees, and elbows (tophi). Serum creatinine was 1.4 mg/dL and serum urate 9.4 mg/dL. Conditions known to increase uric acid production (psoriasis, chronic bronchitis) and to decrease uric acid excretion (hypothyroidism, metabolic syndrome, and nephroangiosclerosis) may operate in a single patient, illustrating the dramatic clinical course of untreated gout.