290 research outputs found
Diagnosis and management of iridocorneal endothelial syndrome
The iridocorneal endothelial (ICE) syndrome is a rare ocular disorder that includes a group of conditions characterized by structural and proliferative abnormalities of the corneal endothelium, the anterior chamber angle, and the iris. Common clinical features include corneal edema, secondary glaucoma, iris atrophy, and pupillary anomalies, ranging from distortion to polycoria. The main subtypes of this syndrome are the progressive iris atrophy, the Cogan-Reese syndrome, and the Chandler syndrome. ICE syndrome is usually diagnosed in women in the adult age. Clinical history and complete eye examination including tonometry and gonioscopy are necessary to reach a diagnosis. Imaging techniques, such as in vivo confocal microscopy and ultrasound biomicroscopy, are used to confirm the diagnosis by revealing the presence of "ICE-cells" on the corneal endothelium and the structural changes of the anterior chamber angle. An early diagnosis is helpful to better manage the most challenging complications such as secondary glaucoma and corneal edema. Treatment of ICE-related glaucoma often requires glaucoma filtering surgery with antifibrotic agents and the use of glaucoma drainage implants should be considered early in the management of these patients. Visual impairment and pain associated with corneal edema can be successfully managed with endothelial keratoplasty
Differential Recruitment of Auditory Cortices in the Consolidation of Recent Auditory Fearful Memories.
Memories of frightening events require a protracted consolidation process. Sensory cortex, such as the auditory cortex, is involved in the formation of fearful memories with a more complex sensory stimulus pattern. It remains controversial, however, whether the auditory cortex is also required for fearful memories related to simple sensory stimuli. In the present study, we found that, 1 d after training, the temporary inactivation of either the most anterior region of the auditory cortex, including the primary (Te1) cortex, or the most posterior region, which included the secondary (Te2) component, did not affect the retention of recent memories, which is consistent with the current literature. However, at this time point, the inactivation of the entire auditory cortices completely prevented the formation of new memories. Amnesia was site specific and was not due to auditory stimuli perception or processing and strictly related to the interference with memory consolidation processes. Strikingly, at a late time interval 4 d after training, blocking the posterior part (encompassing the Te2) alone impaired memory retention, whereas the inactivation of the anterior part (encompassing the Te1) left memory unaffected. Together, these data show that the auditory cortex is necessary for the consolidation of auditory fearful memories related to simple tones in rats. Moreover, these results suggest that, at early time intervals, memory information is processed in a distributed network composed of both the anterior and the posterior auditory cortical regions, whereas, at late time intervals, memory processing is concentrated in the most posterior part containing the Te2 region
Resting state functional thalamic connectivity abnormalities in patients with post-stroke sleep apnoea: a pilot case-control study
OBJECTIVE: Sleep apnoea is common
after stroke, and has adverse effects on the
clinical outcome of affected cases. Its pathophysiological
mechanisms are only partially known. Increases
in brain connectivity after stroke might influence
networks involved in arousal modulation
and breathing control. The aim of this study was to
investigate the resting state functional MRI thalamic
hyper connectivity of stroke patients affected
by sleep apnoea (SA) with respect to cases not
affected, and to healthy controls (HC).
PATIENTS AND METHODS: A series of stabilized
strokes were submitted to 3T resting state
functional MRI imaging and full polysomnography.
The ventral-posterior-lateral thalamic nucleus was
used as seed.
RESULTS: At the between groups comparison
analysis, in SA cases versus HC, the regions significantly
hyper-connected with the seed were
those encoding noxious threats (frontal eye
field, somatosensory association, secondary visual
cortices). Comparisons between SA cases
versus those without SA, revealed in the former
group significantly increased connectivity with
regions modulating the response to stimuli independently
to their potentiality of threat (prefrontal,
primary and somatosensory association, superolateral
and medial-inferior temporal, associative
and secondary occipital ones). Further
significantly functionally hyper connections were
documented with regions involved also in the modulation
of breathing during sleep (pons, midbrain,
cerebellum, posterior cingulate cortices), and in
the modulation of breathing response to chemical
variations (anterior, posterior and para-hippocampal
cingulate cortices).
CONCLUSIONS: Our preliminary data support
the presence of functional hyper connectivity in
thalamic circuits modulating sensorial stimuli, in
patients with post-stroke sleep apnoea, possibly
influencing both their arousal ability and breathing
modulation during sleep
La valutazione degli interventi di prossimità . Uno studio pilota
Nonostante negli ultimi anni le attività di prevenzione dell’addiction da sostanze e da comportamenti si siano moltiplicate, nella maggior parte dei casi per tali attività , e per gli interventi di prossimità in particolare, non vengono attuati adeguati processi di valutazione. Ciò anche a causa della mancanza di sistemi di valutazione e di modelli teorici di riferimento condivisi. Il presente studio costituisce il primo passo di un progetto di ricerca più ampio finalizzato alla valutazione degli effetti degli interventi di prossimità . Lo studio descrive, in particolare, i rapporti esistenti tra frequenza di assunzione della sostanza o di attuazione del comportamento problematico, stadio del cambiamento e fattori di vulnerabilità e di protezione. Lo studio dimostra, inoltre, che il sistema di valutazione adottato è in grado di rilevare le differenze esistenti tra momenti diversi del percorso di cambiamento, in cui la frequenza di attuazione del comportamento problematico assume significato in relazione a variabili psicologiche e di contesto
Deriving Natural Background Levels of Arsenic at the Meso-Scale Using Site-Specific Datasets: An Unorthodox Method
Arsenic is found in groundwater above regulatory limits in many countries and its origin is often from natural sources, making the definition of Natural Background Levels (NBLs) crucial. NBL is commonly assessed based on either dedicated small-scale monitoring campaigns or large-scale national/regional groundwater monitoring networks that may not grab local-scale heterogeneities. An alternative method is represented by site-specific monitoring networks in contaminated/polluted sites under remediation. As a main drawback, groundwater quality at these sites is affected by human activities. This paper explores the potential for groundwater data from an assemblage of site-specific datasets of contaminated/polluted sites to define NBLs of arsenic (As) at the meso-scale (order of 1000 km2). Common procedures for the assessment of human influence cannot be applied to this type of dataset due to limited data homogeneity. Thus, an \u201cunorthodox\u201d method is applied involving the definition of a consistent working dataset followed by a statistical identification and critical analysis of the outliers. The study was conducted in a highly anthropized area (Ferrara, N Italy), where As concentrations often exceed national threshold limits in a shallow aquifer. The results show that site-specific datasets, if properly pre-treated, are an effective alternative for the derivation of NBLs when regional monitoring networks fail to catch local-scale variability
Mechanisms of endothelial cell dysfunction in cystic fibrosis
Although cystic fibrosis (CF) patients exhibit signs of endothelial perturbation, the functions of the cystic fibrosis
conductance regulator (CFTR) in vascular endothelial cells (EC) are poorly defined. We sought to uncover
biological activities of endothelial CFTR, relevant for vascular homeostasis and inflammation. We examined cells
from human umbilical cords (HUVEC) and pulmonary artery isolated from non-cystic fibrosis (PAEC) and CF
human lungs (CF-PAEC), under static conditions or physiological shear. CFTR activity, clearly detected in
HUVEC and PAEC, was markedly reduced in CF-PAEC. CFTR blockade increased endothelial permeability to
macromolecules and reduced trans‑endothelial electrical resistance (TEER). Consistent with this, CF-PAEC displayed
lower TEER compared to PAEC. Under shear, CFTR blockade reduced VE-cadherin and p120 catenin
membrane expression and triggered the formation of paxillin- and vinculin-enriched membrane blebs that
evolved in shrinking of the cell body and disruption of cell-cell contacts. These changes were accompanied by
enhanced release of microvesicles, which displayed reduced capability to stimulate proliferation in recipient EC.
CFTR blockade also suppressed insulin-induced NO generation by EC, likely by inhibiting eNOS and AKT
phosphorylation, whereas it enhanced IL-8 release. Remarkably, phosphodiesterase inhibitors in combination
with a β2 adrenergic receptor agonist corrected functional and morphological changes triggered by CFTR dysfunction
in EC. Our results uncover regulatory functions of CFTR in EC, suggesting a physiological role of CFTR
in the maintenance EC homeostasis and its involvement in pathogenetic aspects of CF. Moreover, our findings
open avenues for novel pharmacology to control endothelial dysfunction and its consequences in CF
Medial pivot vs posterior stabilized total knee arthroplasty designs: a gait analysis study
Aim To compare a medial pivot (MP) total knee arthroplasty (TKA) with posterior stabilized (PS) TKA designs from a subjective, clinical and biomechanical point of view, in a single-centre, single-surgeon, case-control non-randomized trial. Methods Sixteen patients were randomly picked up from case series into each group. Subjective outcome was assessed using the Forgotten Joint Score Questionnaire (FJSQ). Clinical evaluation included range of motion (ROM). All patients underwent gait analysis by a treadmill with force-measuring plaques and videorecording device; data were recorded for 30 seconds and included cadence, step length, stance time and walking speed. A blinded qualitative analysis of the pattern of gait was defined as biphasic or non-biphasic. Descriptive statistics for the continuous study variables and statistical significance were calculated for all parameters with independent-samples t-test and χ2 test to analyse difference in pattern of gait between groups. Results Mean FJSQ in the MP group was 91.87 (CI 95%: 88.12- 95.46) and 75.31 (CI 95%: 67.97-81.56) in the PS group (p=0.029). Mean post-operative ROM was 117° (CI 95%: 113°-122°) in the MP group and 112° (CI 95%: 108°-117°) in the PS group (p=0.14). No statistical difference was found between groups regarding all gait analysis parameters which have been recorded. Conclusion MP TKA design showed better subjective results using the FJSQ, but it did not improve significantly clinical and functional outcomes compared to PS TKA design, at a short-term follow-up
Genetic deletion of fibroblast growth factor 14 recapitulates phenotypic alterations underlying cognitive impairment associated with schizophrenia
Cognitive processing is highly dependent on the functional integrity of gamma-amino-butyric acid (GABA) interneurons in the brain. These cells regulate excitability and synaptic plasticity of principal neurons balancing the excitatory/inhibitory tone of cortical networks. Reduced function of parvalbumin (PV) interneurons and disruption of GABAergic synapses in the cortical circuitry result in desynchronized network activity associated with cognitive impairment across many psychiatric disorders, including schizophrenia. However, the mechanisms underlying these complex phenotypes are still poorly understood. Here we show that in animal models, genetic deletion of fibroblast growth factor 14 (Fgf14), a regulator of neuronal excitability and synaptic transmission, leads to loss of PV interneurons in the CA1 hippocampal region, a critical area for cognitive function. Strikingly, this cellular phenotype associates with decreased expression of glutamic acid decarboxylase 67 (GAD67) and vesicular GABA transporter (VGAT) and also coincides with disrupted CA1 inhibitory circuitry, reduced in vivo gamma frequency oscillations and impaired working memory. Bioinformatics analysis of schizophrenia transcriptomics revealed functional co-clustering of FGF14 and genes enriched within the GABAergic pathway along with correlatively decreased expression of FGF14, PVALB, GAD67 and VGAT in the disease context. These results indicate that Fgf14(-/-) mice recapitulate salient molecular, cellular, functional and behavioral features associated with human cognitive impairment, and FGF14 loss of function might be associated with the biology of complex brain disorders such as schizophrenia
The higher order auditory cortex is involved in the assignment of affective value to sensory stimuli
The sensory cortex participates in emotional memory but its role is poorly understood. Here we show that inactivation of the higher order auditory cortex Te2 in rats during early memory consolidation impairs remote first- and second-order fear memories but not the association between two neutral cues. Furthermore, Te2 inactivation prevents changes in the valence of such information. Following the presentation of two auditory cues previously paired with either pleasant or painful stimuli, a large percentage of cells responds to both experiences but also a small fraction of neurons responds exclusively to one of them. The latter type of neurons signals the valence rather than the salience or the motor responses associated with the stimuli, and reflects selective associative processes. Pharmacogenetic silencing of memory-activated neurons causes amnesia. Thus, Te2 represents a crucial node for the assignment of the affective value to sensory stimuli and for the storage of such information
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