Sapienza Global Bedside Evaluation of Swallowing after Stroke: the GLOBE-3S study.

BACKGROUND AND PURPOSE: Dysphagia occurs in up to 50% of all patients with acute stroke. There is debate regarding which is the most effective screening tool in identifying aspiration in patients with acute stroke. We assessed the accuracy of the Sapienza Global Bedside Evaluation of Swallowing after Stroke (GLOBE-3S), which combines the Toronto Bedside Swallowing Screening Test (TOR-BSST©) with oxygen desaturation and laryngeal elevation measurement during swallowing. METHODS: We prospectively enrolled consecutive patients with stroke within 72 h of symptom onset. All patients with stroke firstly underwent a standard neurological examination, then the GLOBE-3S evaluation and finally the fiberoptic endoscopic evaluation of swallowing (FEES). Two different assessors, a neurologist and a speech pathologist, blind to both the clinical data and each other's evaluation, administered the GLOBE-3S and FEES examination. We assessed the accuracy of the GLOBE-3S in detecting post-stroke swallow impairment with aspiration using the FEES as the standard. RESULTS: We enrolled 50 patients with acute stroke, 28 of whom (56%) had swallowing impairment with aspiration at FEES evaluation. A total of 33 patients (66%) failed the GLOBE-3S evaluation. The GLOBE-3S reached a sensitivity of 100% and a specificity of 77.3% (negative predictive value, 100%; positive likelihood ratio, 4.34). The median time required for the GLOBE-3S to be performed was 297 s. CONCLUSIONS: GLOBE-3S is quick to perform at the bedside and can accurately identify aspiration in patients with acute stroke. By including the measurement of laryngeal elevation and monitoring of oxygen desaturation, it could represent a highly sensitive instrument to avoid the misdiagnosis of silent aspirators.

Insomnia as a predictor of high-lethality suicide attempts.

INTRODUCTION: Research has demonstrated that patients with insomnia are at an increased risk of experiencing suicidal ideation and/or making a suicide attempt. OBJECTIVES: To evaluate the relation between insomnia and suicidal behaviour. AIMS: To examine factors associated with a diagnosis of insomnia in patients admitted to an Emergency Department (ED) and assessed by the psychiatrist in charge. METHODS: Participants were 843 patients consecutively admitted to the ED of Sant'Andrea Hospital in Rome, between January 2010 and December 2011. All patients admitted were referred to a psychiatrist. A clinical interview based on the Mini International Neuropsychiatric Interview (MINI) and a semi-structured interview was conducted. Patients were asked about 'ongoing' suicidal ideation or plans for suicide. RESULTS: Forty-eight percent of patients received a diagnosis of bipolar disorder (BD), major depressive disorder (MDD) or an anxiety disorder; whereas, 17.1% were diagnosed with Schizophrenia or other non-affective psychosis. Patients with insomnia (compared to patients without insomnia) more frequently had a diagnosis of BD (23.9% vs. 12.4%) or MDD (13.3% vs. 9.5%; p < 0.001). Moreover, patients with insomnia less frequently had attempted suicide in the past 24 h (5.3% vs. 9.5%; p < 0.05) as compared with other patients, but those patients with insomnia who attempted suicide more frequently used a violent method (64.3% vs. 23.6%; p < 0.01) compared to other suicide attempters. CONCLUSIONS: Our results do not support an association between insomnia and suicidal behaviour. However, suicide attempters with insomnia more frequently used violent methods, and this phenomenon should be taken into serious consideration by clinicians.

Morpho-chemical characterization of individual ancient starches retrieved on ground stone tools from Palaeolithic sites in the Pontic steppe.

Despite the extensive literature on the retrieval of digestible starches from archaeological contexts, there are still significant concerns regarding their genuine origin and durability. Here, we propose a multi-analytical strategy to identify the authenticity of ancient starches retrieved from macrolithic tools excavated at Upper Paleolithic sites in the Pontic steppe. This strategy integrates the morphological discrimination of starches through optical microscopy and scanning electron microscopy with single starch chemo-profiling using Fourier transform infrared imaging and microscopy. We obtained evidence of aging and biomineralization in the use-related starches from Palaeolithic sites, providing a methodology to establish their ancient origin, assess their preservation status, and attempt their identification. The pivotal application of this multidisciplinar approach demonstrates that the macrolithic tools, from which starches were dislodged, were used for food-processing across the Pontic Steppe around 40,000 years ago during the earliest colonization of Eurasia by Homo sapiens.

Unilateral vocal fold paralysis post-thyroidectomy: does early intervention allow for better voice recovery?

OBJECTIVE: Thyroidectomy is the primary cause of unilateral vocal fold paralysis (UVFP). A delay in rehabilitation may cause dysfunctional phenomena and worsen dysphonia. The main aim is to investigate the impact of early Speech Therapy (ST) on voice recovery in UVFP post-thyroidectomy and propose an appropriate treatment schedule. PATIENTS AND METHODS: 93 patients with UVFP were analysed. 72 presented transient paralysis and 21 permanent ones. Individuals with permanent paralysis were retrospectively divided in two groups. Group A was composed of 11 patients (8 F, 3 M; mean age: 50.5 ± 8.6) who received ST within 8 weeks; Group B comprised 10 patients (7 F, 3 M; mean age: 57 ± 11.5) treated after more than 8 weeks. Videolaryngostroboscopy (VLS) was assessed and both objective and subjective voice parameters were collected. The non-parametric Wilcoxon test was applied to the sample. RESULTS: The resolution of supraglottic compensations was observed in 91% of cases in Group A, whereas in only 40% of cases in Group B. A functional glottal closure occurred in 73% of patients in group A, while it was completely absent in group B. Group A showed a statistically significant difference between the values of Jitter, NHR, TMF and VHI collected pre-ST compared to that collected after 1 year. Conversely, a statistically significant difference was found only for VHI values in group B. CONCLUSIONS: Early ST brings benefits to patients with permanent UVFP, both on voice recovery and on quality of life. A ST protocol should be applied both before and after thyroidectomy. The ST treatment should start early after surgery.

Rearrangements and aberrant expression of the retinoic acid receptor alpha gene in acute promyelocytic leukemias.

Although acute promyelocytic leukemias (APLs) are consistently associated with a reciprocal chromosome 15;17 translocation, the gene(s) directly affected by the breakpoints have never been isolated. The chromosome 17 breakpoint maps to near the retinoic acid receptor alpha (RAR alpha) locus. Investigation of 20 APLs and a large series of other neoplastic patients and normal controls revealed RAR alpha gene rearrangements and aberrant transcripts only in the APL cases. These findings suggest that the RAR alpha gene is involved in the APL chromosome 17 breakpoint, is implicated in leukemogenesis, and could be used as a marker for identifying leukemic promyelocytes.

Morpho-functional patterns of physiologic oropharyngeal swallowing evaluated with dynamic fast MRI.

With the advent of dynamic fast MRI sequences the act of deglutition can be dynamically visualized in cine-mode. Twenty-three healthy volunteers were enrolled in this study to define the morpho-functional patterns of oral and pharyngeal deglutition using new dynamic MRI techniques. All subjects were previously submitted to video endoscopic assessment, to exclude swallowing abnormalities. As contrast material a combination of yogurt mixed with gadolinium-diethylene diamine pentaacetic acid was used. The protocol was divided into three parts: (a) preliminary assessment of the oral cavity, pharynx and laryngeal structures; (b) morphologic assessment of tongue, soft palate, pharynx, epiglottis and larynx-hyoid bone; (c) dynamic assessment of swallowing without administrating any contrast media and, in subsequent phase, by injecting 5 ml of yogurt-based contrast medium in the patient's mouth. The time resolution was 3-4 images/s. The MR protocol revealed to be effective in the evaluation of normal motility patterns of the structures involved in swallowing. Moreover, the evaluation of the bolus progression, slowdown or stagnation, was possible. On the contrary problems were encountered in calculating precisely the bolus progression time, because of the insufficient temporal resolution. However, more energy should be invested to optimize the spatial and temporal resolution of turbo-FLASH sequences, to obtain a better dynamic representation of a complex function such as deglutition.

Carbon monoxide: effects on oxygenation of the fetus in utero.

The partial pressure of oxygen in fetal blood decreases in proportion to the carboxyhemoglobin concentrations in fetal and maternal blood. Because fetal oxygen tensions normally equal 20 to 30 percent of the values for adults, this reduction can result in severe hypoxia of vital tissues. Decreases in oxygen tension may be a factor in the lower birth weights of infants born to women who smoke or are exposed to severe air pollution.

PHOX2A and PHOX2B genes are highly co-expressed in human neuroblastoma.

The detection of PHOX2B mutations in a small proportion of patients affected with either familial or sporadic neuroblastoma (NB), has arisen interest on the possible pathogenic role of this gene in the disease determination. In this light, we have carried out a quantitative expression analysis of PHOX2B and its paralogue PHOX2A on a panel of NB cell lines and NB tumour samples to identify a possible differential expression between NB cells and their normal counterpart (adrenal medulla cells). Our results revealed that both PHOX2A and PHOX2B are over-expressed in tumour samples and NB cell lines. Particularly, the expression levels of the two genes in NB cell lines show a highly significant correlation, suggesting their possible synergistic role or a coordinated expression regulation. Furthermore, PHOX2 gene over-expression in NB tumours and cell lines suggests these genes may be widely involved in NB development through either a direct mechanism of up-regulation or a failure in maintaining proper transcript levels after embryonic development.

Methylene blue MMX® tablets for chromoendoscopy. Bioavailability, colon staining and safety in healthy volunteers undergoing a full colonoscopy.

Methylene blue-MMX® tablets are proposed as an aid for detection and visualisation of adenomas and carcinomas in patients undergoing colonoscopy, by improving their detection rate and highlighting the presence of the intestinal dysplastic lesions. Single total doses of 100 and 200 mg were administered to healthy volunteers undergoing a bowel cleansing preparation and a full colonoscopy to investigate the colonic staining. The pharmacokinetics of methylene blue and the safety after exposure to the tablets were also investigated. With 200 mg, the best staining, assessed as the sum of acceptable and good staining, was achieved in the ascending colon and rectosigmoid (75% subjects each), the transverse and the descending colon (approximately 63% each). Absence of staining or overstaining were reported for no colonic region of interest in any subject. Similar results were observed in the 100 mg dose group. Methylene blue blood concentrations reached a peak (Cmax) in a median time (Tmax) of 12 h with 100 mg and 16 h with 200 mg. AUC0-t was 10.7 ±â€¯6.7 µg/mLxh after 100 mg and 25.2 ±â€¯7.4 µg/mLxh after 200 mg. Half-life ranged between 9 and 22 h after the lower dose and between 6 and 26 h after the higher dose. The cumulative urinary excretion was about 28% after 100 mg and about 39% after 200 mg up to 60 h post-dose. The overall frequency of adverse events after single dose of the test product administered along with a bowel cleansing preparation was 39%, but only one was related to the test product: abnormal transaminases. The most frequent adverse event was a transient polyuria (17%). One serious adverse event (gastrointestinal haemorrhage) led the subject to study discontinuation and hospitalisation and another subject withdrew the study due to one adverse event (haematemesis). Either event was not related to methylene blue.

Respiratory function of the placenta as determined with carbon monoxide in sheep and dogs.

A technique is described for studying the respiratory function of the placenta using carbon monoxide, a gas whose exchange across the placenta between the maternal and fetal circulations is limited by diffusion rather than blood flow. During the steady state before the introduction of CO, the normal concentration of carboxyhemoglobin in the ewe, [COHb](M), is approximately 0.90%, and that in the fetus is 2.9%, the ratio [COHb](F)/[COHb](M) being 3.2. In dogs the corresponding values are 1.9%, 4.8%, and 2.4%. After the introduction of CO into the mother animal, CO diffused across the placenta slowly with an equilibration half-time of approximately 2 hours. The average carbon monoxide diffusing capacity (D(Pco)) of the placenta during maternal to fetal exchange was 0.54 ml per (minute x mm Hg x kg fetal weight) (SD +/- 0.13) in sheep and 0.57 ml per (minute x mm Hg x kg) (SD +/- 0.18) in dogs. The fetal to maternal placental diffusing capacity in two sheep was 0.54 ml per (minute x mm Hg x kg). Calculations considering the relative rates of reaction of O(2) and CO with red cell hemoglobin and the relative rates of diffusion of the two gases suggest that the true D(Po2) should be about 1.2 to 2 times greater than the D(Pco) or 0.65 to 1.1 per (minute x mm Hg x kg). This is about 5 times greater than the reported value of D(Po2) calculated from measurements of P(O2) in the mixed uterine and umbilical venous blood. With a diffusing capacity of this magnitude the maternal and fetal placental end capillary P(O2) would approach equilibrium, becoming too small to measure, and the calculation of D(Po2) would be unreliable. We suggest that the apparent end capillary P(o2) gradients of 15 to 20 mm Hg, obtained from sampling uterine and umbilical venous blood, result from a combination of uneven distribution of maternal and fetal placental blood flow and from placental oxygen consumption.

Uneven distribution of maternal and fetal placental blood flow, as demonstrated using macroaggregates, and its response to hypoxia.

A technique is described for studying the distribution of blood flow to the maternal and fetal placental vessels in sheep and dogs with radioactive labeled macroaggregates of albumin. When the maternal animal breathed room air the distribution of maternal placental blood flow was uneven among the cotyledons as well as within a given cotyledon. Fetal blood flow was also distributed nonuniformly among and within the cotyledons. The relation of maternal to fetal placental blood flow was also markedly uneven (coefficient of correlation, tau = 0.066). After the animal was made hypoxic by breathing 10-12% O(2) the distribution of maternal, fetal, and maternal/fetal placental flows became more uniform. The coefficient of correlation of maternal to fetal flow was high (tau = 0.53, P < 0.01). While the maternal animal breathed room air, after ligation of a major branch of the umbilical artery the distribution of maternal, fetal, and maternal/fetal flows in the remaining two-thirds to three-fourths of the placenta became more uniform. The correlation coefficient for maternal to fetal flow was high (tau = 0.35, P < 0.01).It appears that under normal circumstances with uneven distribution of blood flows there is a considerable portion of the placenta that does not receive blood flow in optimum quantities to promote efficient O(2) exchange. Failure to consider the influence of nonuniform maternal flow/fetal flow will result in overestimation of mean maternal-fetal oxygen tension gradients, and thus underestimation of the placental diffusing capacity for oxygen. In response to maternal hypoxia or compromise of the fetal placental circulation the distribution of maternal, fetal, and maternal/fetal flows becomes more uniform, thereby increasing the efficiency of placental O(2) exchange.

Chronic lurasidone treatment normalizes GABAergic marker alterations in the dorsal hippocampus of mice exposed to prenatal immune activation.

Prenatal maternal infection represents a risk factor for the development of psychopathologic conditions later in life. Clinical evidence is also supported by animal models in which the vulnerability to develop a schizophrenic-like phenotype likely originates from inflammatory processes as early as in the womb. Prenatal immune challenge, for example, induces a variety of long-term behavioral alterations in mice, such as deficits in recognition and spatial working memory, perseverative behaviors and social impairments, which are relevant to different symptom clusters of schizophrenia. Here, we investigated the modulation of GABAergic markers in the dorsal and ventral hippocampus of adult mice exposed to late prenatal immune challenge with the viral mimetic Poly(I:C) (polyriboinosinic-polyribocytidilic-acid) at gestational day 17, and we evaluated the ability of chronic treatment with the multi-receptor antipsychotic lurasidone to modulate the alterations produced by maternal infection. Poly(I:C) mice show a significant reduction of key GABAergic markers, such as GAD67 and parvalbumin, specifically in the dorsal hippocampus, which were normalized by chronic lurasidone administration. Moreover, chronic drug administration increases the expression of the pool of brain derived neurotrophic factor (BDNF) transcripts with the long 3'-UTR as well as the levels of mature BDNF protein in the synaptosomal compartment, selectively in dorsal hippocampus. All in all, our findings demonstrate that lurasidone is effective in ameliorating molecular abnormalities observed in Poly(I:C) mice, providing further support to the neuroplastic properties of this multi-receptor antipsychotic drug.

ALK-positive adenocarcinoma of the lung expressing neuroendocrine markers and presenting as a "pituitary adenoma".

We report an ALK-rearranged adenocarcinoma of the lung presenting as a pituitary metastasis, clinically simulating a pituitary adenoma. The patient, a 50 year-old, former-smoking woman was admitted with a Parinaud's syndrome characterized by progressive oculomotor impairment of visual verticality, bitemporal hemianopsia and nystagmus. Imaging studies showed a sellar tumor and the biopsy revealed a TTF-1 and napsin positive lung adenocarcinoma strongly expressing synaptophysin and CD56, also harboring ALK rearrangement. A subsequent CT scan disclosed the primary lung mass of the left upper lobe. The patient progressed after 4 cycles of cisplatin/pemetrexed as first line treatment, but showed a partial response and a significant clinical benefit from the combination of ceritinib and nivolumab in a phase Ib trial. Despite its central nervous system tropism, ALK-rearranged adenocarcinoma manifesting with pituitary gland involvement was never reported. Second generation ALK inhibitors seem the best therapeutic strategy.

Mapping of chromosome 17 breakpoints in acute myeloid leukemias.

The 17q11-21 chromosomal region is frequently involved in non-random structural rearrangements associated with the M1 and M2 subtypes of acute myeloid leukemias (AML), as well as with the 15;17 translocation typical of the promyelocytic subtype. A number of genes have been localized in this region including the c-erbA-1 and c-erbB-2 proto-oncogenes, the genes coding for the granulocyte-colony stimulating factor (G-CSF), the retinoic acid receptor alpha (RAR alpha) and the myeloperoxidase enzyme (MPO). However, the precise location of these genes in relationship to the 17q11-21 breakpoint(s) has not been determined. Using in situ hybridization on metaphase chromosomes, we established the position of the breakpoints in relationship to the c-erbA-1, c-erbB-2, G-CSF, RAR alpha and MPO loci in a series of AML cases bearing 17q11-21 rearrangements. We report: (i) that the respective position of the five genes is centromere - c-erbA-1 - G-CSF - c-erbB-2 - RAR alpha - MPO - telomere; (ii) that the breakpoints of the various AML subtypes are variably located between the centromere and c-erbB-2 in M1 and M2; (iii) that the breakpoints are consistently located between c-erbB-2 and RAR alpha/MPO in M3; and (iv) that the breakpoint on chromosome 17 in the 15;17 translocation is located on 17q21 and not on 17q11-12 as previously reported.

Amino acid transport in placental slices. Mechanism of increased accumulation by prolonged incubation.

The accumulation of alpha-aminoisobutyric acid by placental slices is increased dramatically upon prior incubation of the slices in amino acid-free, buffered saline. This increase is inhibited by inhibitors of protein synthesis and is accompanied by an increased V for the transport process. While alternative explanations are discussed, these data suggest that the incubation effect may be mediated through an increase in the number of available transport sites which are synthesized during the incubation period. Incubation with an amino acid mixture diminishes the increase as well as general protein synthesis, suggesting that a reduced availability of amino acids may initiate compensatory changes in the synthesis of cellular transport proteins.

Formation and characterization of glutamate dehydrogenase monolayers on silicon supports.

In this paper we have tested two different procedures (the "three-step" and the "four-step" procedures) for the covalent immobilization of glutamate dehydrogenase (GDH) onto silicon supports. Atomic force microscopy (AFM), Fourier-transform infrared spectroscopy (FT-IR), fluorescence spectroscopy and an enzymatic assay were used to probe the structure and activity of the immobilized enzyme. Our results demonstrate that coupling through the "three-step" procedure does not significantly affect either the fold pattern or the activity of the enzyme, suggesting that this method could be ideally suited to the development of high quality monolayers for use in enzyme-based planar biosensors.

808-nm laser with exogenous chromophores for the treatment of benign oral lesions.

OBJECTIVE: The aim of this study was to verify the effectiveness and safety of the 808-nm wavelength for use on benign lesions of the oral cavity that are stained with toluidine blue solution. MATERIALS AND METHODS: The toluidine blue solution according to Mashberg is used in stomatology for the detection of leuko-erythroplasic lesions. In our experience, we have used it to stain even serous cysts, angiomas, and fibromas. We chose a 808-nm wavelength emitted from a power diode laser, because it is well absorbed by the blue color and barely by the healthy mucosa. The non-contact photocoagulation kept the surrounding borders intact when we used the pulsed-emission, 50 ms 7 W, without anesthesia. No sutures were needed. The leukoplasic borders of the lesions were histologically examined before and after the treatment. RESULTS: The vaporized lesions healed completely in about 5-7 days without any kind of treatment, leaving some slight elastic white scars. A mild edema-erythema followed the treatment for 5-7 days. CONCLUSIONS: The selective results confirm the effectiveness of this therapeutic procedure on pigmented benign lesions, pre-treated with exogenous chromophores and photocoagulated without bleeding, with a minimum energy 808-nm laser.

[The sclero-atrophic lichen as principal cause of acquired phimosis in pediatric age]. / II lichen sclero-atrofico come causa principale di fimosi acquisita in età pediatrica.

Lichen sclerosus et atrophicus is main cause of phimosis in pediatric age and require surgical therapy. This one, characterized by partial circumcision followed by topical treatment with steroids, is safe and effective.

A methodological approach for determination of maximal inspiratory pressure in patients undergoing invasive mechanical ventilation.

BACKGROUND: Maximal inspiratory pressure (MIP) can help to evaluate inspiratory muscle strength. However its determination in ventilated patients is cumbersome and needs special equipment. We hypothesized that MIP could be obtained by using the expiratory hold knob of the ventilator. The aim of this study was to verify whether: 1) the end expiratory occlusion technique can be used for MIP determination; and 2) if this technique provides different results compared to those obtained by the traditional method of MIP calculation. METHODS: We studied 23 consecutive patients undergoing mechanical ventilation for acute respiratory failure. The MIP was determined by two different methods, both based on occluding the airway for 20 seconds. This occlusion was obtained either by pressing the expiratory hold knob of the ventilator; or by detaching the patient from the ventilator circuit and using a noiseless pneumatic shutter placed on the inspiratory line of a two-way valve that allows expiration but prevents inspiration. RESULTS: The average values of MIP obtained by using either the hold knob of the ventilator or the noiseless pneumatic shutter were -46±14 cmH2O and -56±13 cmH2O, respectively. The linear regression analysis showed a significant correlation between MIPVent and MIPOcc (r2=0.95), although the Bland- Altman analysis revealed that they are not clinically comparable. CONCLUSION: MIP can be easily determined at the bedside by pressing the expiratory hold knob of ventilator. However, MIPVent and MIPOcc are different in terms of absolute value probably because they were determined at diverse lung volume.