Ruolo dei Test provocativi a basso ed alto volume durante Manometria Esofagea ad Alta risoluzione in pazienti affetti da JackHammer esophagus: studio prospettico

Introduction. Jackhammer esophagus (JE) is a hypercontractile disorder, the pathogenesis of which is incompletely understood. Multiple rapid swallows (MRS) and rapid drink challenge (RDC) are complementary tests used during high resolution manometry (HRM) that evaluate inhibitory and excitatory neuromuscular function and latent obstruction respectively. Aims & Methods. Our aim was to evaluate esophageal pathophysiology using MRS and RDC in 83 JE patients (28 males; 63; 54‐70 years). Twenty one healthy subjects (11 males; 28; 26-30 years) were used as a control group. All patients underwent solid state HRM with ten 5 ml single swallows (SS) and one to three 10 ml MRS; 34 patients also underwent RDC. Data are shown as median‐IQ range. Results. Abnormal motor inhibition was noted during at least one MRS in 48% of JE vs 29% of controls (p=0.29). Mean DCI after MRS was significantly lower than after SS [6028 (3678-9267) mmHg.cm.s vs 7514 (6238-9197) mmHg.cm.s, p=0.02], as was highest DCI (p<0.0001). Consequently, 66% of JE patients had no contraction reserve. At least one variable of obstruction during RDC was outside the normal range in 74% of JE. Both highest DCI after SS and pressure gradient across the esophagogastric junction during RDC were higher in patients with dysphagia vs those without (p=0.04 and 0.01 respectively). Conclusions. Our data suggest altered neural control in JE patients with heterogeneity in inhibitory function. Furthermore, some patients had latent esophagogastric junction obstruction during RDC which correlated with the presence of dysphagia

Requirement of the nicotinic acetylcholine receptor β2 subunit for the anatomical and functional development of the visual system

In the mammalian visual system the formation of eye-specific layers at the thalamic level depends on retinal waves of spontaneous activity, which rely on nicotinic acetylcholine receptor activation. We found that in mutant mice lacking the β2 subunit of the neuronal nicotinic receptor, but not in mice lacking the α4 subunit, retinofugal projections do not segregate into eye-specific areas, both in the dorso-lateral geniculate nucleus and in the superior colliculus. Moreover, β2−/− mice show an expansion of the binocular subfield of the primary visual cortex and a decrease in visual acuity at the cortical level but not in the retina. We conclude that the β2 subunit of the nicotinic acetylcholine receptor is necessary for the anatomical and functional development of the visual system

Pattern Electroretinogram in Ocular Hypertension, Glaucoma Suspect and Early Manifest Glaucoma Eyes: A Systematic Review and Meta-analysis

To provide standardized confidence limits of the transient pattern electroretinogram (tPERG) P50 and N95 and steady state pattern electroretinogram (ssPERG) amplitudes in normal controls as compared to ocular hypertension (OHT), glaucoma suspect (GS), or early manifest glaucoma (EMG) eyes. The identification of standardized confidence limits in the context of pattern electroretinogram (PERG) might overcome the high intrinsic variability of the measure, and it might lead to a more intuitive understanding of the results as well as to an easier comparison of data from multiple tests, sites, and operators. The study protocol was prospectively registered on the International Prospective Register of Systematic Reviews (ID: CRD42022370032). A literature search was conducted on PubMed, Web of Science, and Scopus. Studies comparing PERG raw data in normal control eyes as compared to OHT, GS, and/or EMG were included. The risk of bias was assessed using the National Institute for Health and Clinical Excellence quality assessment tool. The main outcome was the P50, N95, and ssPERG amplitude difference between the control and the study groups’ eyes. The standardized mean difference was calculated as a measure of the effect size for the primary outcome. A subanalysis was conducted based on the type of electrodes adopted for the PERG measurements (invasive vs. noninvasive). Of the 4580 eligible papers, only 23 were included (1754 eyes). Statistically significant amplitude differences were found in the P50, N95, and ssPERG amplitudes between normal controls and OHT, GS, and EMG eyes. The highest standardized mean difference values were observed in the ssPERG amplitude in all 3 sets of comparison. The subanalysis did not reveal any statistically significant differences between invasive and noninvasive recording strategies. The use of standardized values as the main outcome measures in the context of the PERG data analysis is a valid approach, normalizing several confounding factors which have affected the clinical utility of PERG both for individual patients and in clinical trials. ssPERG apparently better discriminates diseased eyes compared to tPERG. The adoption of skin-active electrodes is able to adequately discriminate between healthy and diseased statuses. Proprietary or commercial disclosure may be found after the references

The pacemaker current I(f) in single human atrial myocytes and the effect of β-adrenoceptor and A(1)-adenosine receptor stimulation

1. We used single human atrial myocytes to study I(f) occurrence, properties and pharmacological modulation. Cells were obtained by chunk enzymatic digestion from samples of right atrial appendages of patients undergoing corrective cardiac surgery. 2. Patch-clamped cells in the whole-cell configuration were superfused with a modified Tyrode solution to reduce contamination by interfering currents and to amplify I(f). The average cell membrane capacitance was 85.06±2.41 pF (n=531). Data were consistent with the geometrical dimensions of the cells (length 94.2±1.89 μm, width 17.9±0.42 μm, n=126). 3. When hyperpolarizing to −120 mV from a holding potential of −40 mV, 252 of 306 tested cells (82%) expressed a hyperpolarization-activated inward current (I(f) density =3.77±0.25 pA pF(−1)); the current was considered to be present in a given cell if its density at −120 mV was larger than 0.5 pA pF(−1). 4. Current activation was sigmoidal and fitted a Boltzmann model; the average activation curve (n=25) showed a maximum current amplitude of 205.97±19.94 pA, corresponding to 3.87±0.63 pA pF(−1), voltage of half-maximal activation (V(1/2)) at −86.68±2.19 mV and a slope of −11.39±0.69 mV. The reversal potential of I(f) measured by tail-current analysis was −13.07±1.92 mV (n=6). The addition of CsCl (5 mM) fully and reversibly blocked the current. 5. In the presence of the β-adrenoceptor agonist isoprenaline (Iso, 1 μM), V(1/2) was significantly shifted toward less negative potentials by 6.06±1.96 mV (n=16, P=0.0039). The selective A(1)-adenosine receptor agonist cyclopentyladenosine (CPA, 1 μM) caused a statistically significant shift of V(1/2) toward more negative potentials with respect to the control curve, both in the absence (−7.37±1.83 mV, P=0.0005, n=11) and in the presence of 1 μM Iso (−4.97±1.78, P=0.031, n=6). 6. These results demonstrate that a current with the properties of I(f) described in cardiac primary and secondary pacemakers occurs in the majority of human atrial cells. While the pathophysiological relevance of I(f) in human atrial tissue remains to be defined, our data clearly show that it is modulated through stimulation of β-adrenoceptors and A(1)-adenosine receptors

Pattern Electroretinogram in Ocular Hypertension, Glaucoma Suspect and Early Manifest Glaucoma Eyes

Topic: To provide standardized confidence limits of the transient pattern electroretinogram (tPERG) P50 and N95 and steady state pattern electroretinogram (ssPERG) amplitudes in normal controls as compared to ocular hypertension (OHT), glaucoma suspect (GS), or early manifest glaucoma (EMG) eyes. Clinical Relevance: The identification of standardized confidence limits in the context of pattern electroretinogram (PERG) might overcome the high intrinsic variability of the measure, and it might lead to a more intuitive understanding of the results as well as to an easier comparison of data from multiple tests, sites, and operators. Methods: The study protocol was prospectively registered on the International Prospective Register of Systematic Reviews (ID: CRD42022370032). A literature search was conducted on PubMed, Web of Science, and Scopus. Studies comparing PERG raw data in normal control eyes as compared to OHT, GS, or EMG were included. The risk of bias was assessed using the National Institute for Health and Clinical Excellence quality assessment tool. The main outcome was the P50, N95, and ssPERG amplitude difference between the control and the study groups’ eyes. The standardized mean difference was calculated as a measure of the effect size for the primary outcome. A subanalysis was conducted based on the type of electrodes adopted for the PERG measurements (invasive vs. noninvasive). Results: Of the 4580 eligible papers, only 23 were included (1754 eyes). Statistically significant amplitude differences were found in the P50, N95, and ssPERG amplitudes between normal controls and OHT, GS, and EMG eyes. The highest standardized mean difference values were observed in the ssPERG amplitude in all 3 sets of comparison. The subanalysis did not reveal any statistically significant differences between invasive and noninvasive recording strategies. Conclusions: The use of standardized values as the main outcome measures in the context of the PERG data analysis is a valid approach, normalizing several confounding factors which have affected the clinical utility of PERG both for individual patients and in clinical trials. Steady state PERG apparently better discriminates diseased eyes compared to tPERG. The adoption of skin-active electrodes is able to adequately discriminate between healthy and diseased statuses. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references

Evaluation of the Anti-Spike (RDB) IgG Titer among Workers Employed at the University of Pisa Vaccinated with Different Types of SARS-CoV-2 Vaccines

With the development of SARS-CoV-2 vaccines, many authors started evaluating the immunization efficacy of the available vaccines mainly through sero-positivity tests or by a quantitative assessment of the IgG against the spike protein of SARS-CoV-2 virus in vaccinated subjects. In this work, we compared the titers resulting from vaccination and tried to understand the potential factors affecting the immune response to the available SARS-CoV-2 vaccines. This study was conducted on 670 volunteers employed at the University of Pisa and undergoing a health surveillance program at the University Hospital of Pisa. For each participant, 10 mL of blood, information about contacts with confirmed cases of COVID-19, age, sex, SARS-CoV-2 vaccination status, previous SARS-CoV-2 infection and symptoms, type of vaccine and the date of administration were collected. In the multivariate analysis, the type of vaccine, the presence of symptoms in SARS-CoV-2 positive individuals, and the distance from the second dose significantly affected the antibody titer; the combined vaccination resulted in a faster decay over time compared with the other types of vaccination. No significant differences were observed between Spikevax and Comirnaty (p &gt; 0.05), while the antibody levels remain more stable in subjects undergoing Vaxzevria vaccination (p &lt; 0.01) compared with mRNA-based ones