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The impact of cirrhosis and portal hypertension on perioperative outcomes of minimally invasive left lateral sectionectomies remains unclear. We aimed to compare the perioperative outcomes between patients with preserved and compromised liver function (noncirrhotics versus Child-Pugh A) when undergoing minimally invasive left lateral sectionectomies. In addition, we aimed to determine if the extent of cirrhosis (Child-Pugh A versus B) and the presence of portal hypertension had a significant impact on perioperative outcomes. This was an international multicenter retrospective analysis of 1,526 patients who underwent minimally invasive left lateral sectionectomies for primary liver malignancies at 60 centers worldwide between 2004 and 2021. In the study, 1,370 patients met the inclusion criteria and formed the final study group. Baseline clinicopathological characteristics and perioperative outcomes of these patients were compared. To minimize confounding factors, 1:1 propensity score matching and coarsened exact matching were performed. The study group comprised 559, 753, and 58 patients who did not have cirrhosis, Child-Pugh A, and Child-Pugh B cirrhosis, respectively. Six-hundred and thirty patients with cirrhosis had portal hypertension, and 170 did not. After propensity score matching and coarsened exact matching, Child-Pugh A patients with cirrhosis undergoing minimally invasive left lateral sectionectomies had longer operative time, higher intraoperative blood loss, higher transfusion rate, and longer hospital stay than patients without cirrhosis. The extent of cirrhosis did not significantly impact perioperative outcomes except for a longer duration of hospital stay. Liver cirrhosis adversely affected the intraoperative technical difficulty and perioperative outcomes of minimally invasive left lateral sectionectomies. [ABSTRACT FROM AUTHOR]

Data on the effect of body mass index on laparoscopic liver resections are conflicting. We performed this study to investigate the association between body mass index and postoperative outcomes after laparoscopic major hepatectomies. This is a retrospective review of 4,348 laparoscopic major hepatectomies at 58 centers between 2005 and 2021, of which 3,383 met the study inclusion criteria. Concomitant major operations, vascular resections, and previous liver resections were excluded. Associations between body mass index and perioperative outcomes were analyzed using restricted cubic splines. Modeled effect sizes were visually rendered and summarized. A total of 1,810 patients (53.5%) had normal weight, whereas 1,057 (31.2%) were overweight and 392 (11.6%) were obese. One hundred and twenty-four patients (3.6%) were underweight. Most perioperative outcomes showed a linear worsening trend with increasing body mass index. There was a statistically significant increase in open conversion rate (16.3%, 10.8%, 9.2%, and 5.6%, P <.001), longer operation time (320 vs 305 vs 300 and 266 minutes, P <.001), increasing blood loss (300 vs 300 vs 295 vs 250 mL, P =.022), and higher postoperative morbidity (33.4% vs 26.3% vs 25.0% vs 25.0%, P =.009) in obese, overweight, normal weight, and underweight patients, respectively (P <.001). However, postoperative major morbidity demonstrated a "U"-shaped association with body mass index, whereby the highest major morbidity rates were observed in underweight and obese patients. Laparoscopic major hepatectomy was associated with poorer outcomes with increasing body mass index for most perioperative outcome measures. [ABSTRACT FROM AUTHOR]

Currently, the impact of body mass index (BMI) on the outcomes of laparoscopic liver resections (LLR) is poorly defined. This study attempts to evaluate the impact of BMI on the peri-operative outcomes following laparoscopic left lateral sectionectomy (L-LLS). A retrospective analysis of 2183 patients who underwent pure L-LLS at 59 international centers between 2004 and 2021 was performed. Associations between BMI and selected peri-operative outcomes were analyzed using restricted cubic splines. A BMI of >27kg/m2 was associated with increased in blood loss (Mean difference (MD) 21 mls, 95% CI 5–36), open conversions (Relative risk (RR) 1.13, 95% CI 1.03–1.25), operative time (MD 11 min, 95% CI 6–16), use of Pringles maneuver (RR 1.15, 95% CI 1.06–1.26) and reductions in length of stay (MD -0.2 days, 95% CI -0.3 to −0.1). The magnitude of these differences increased with each unit increase in BMI. However, there was a "U" shaped association between BMI and morbidity with the highest complication rates observed in underweight and obese patients. Increasing BMI resulted in increasing difficulty of L-LLS. Consideration should be given to its incorporation in future difficulty scoring systems in laparoscopic liver resections. [ABSTRACT FROM AUTHOR]

Minimal invasive liver resections are a safe alternative to open surgery. Different scoring systems considering different risks factors have been developed to predict the risks associated with these procedures, especially challenging major liver resections (MLR). However, the impact of neoadjuvant chemotherapy (NAT) on the difficulty of minimally invasive MLRs remains poorly investigated. Patients who underwent laparoscopic and robotic MLRs for colorectal liver metastases (CRLM) performed across 57 centers between January 2005 to December 2021 were included in this analysis. Patients who did or did not receive NAT were matched based on 1:1 coarsened exact and 1:2 propensity-score matching. Pre- and post-matching comparisons were performed. In total, the data of 5189 patients were reviewed. Of these, 1411 procedures were performed for CRLM, and 1061 cases met the inclusion criteria. After excluding 27 cases with missing data on NAT, 1034 patients (NAT: n = 641; non-NAT: n = 393) were included. Before matching, baseline characteristics were vastly different. Before matching, the morbidity rate was significantly higher in the NAT-group (33.2% vs. 27.2%, p-value = 0.043). No significant differences were seen in perioperative outcomes after the coarsened exact matching. After the propensity-score matching, statistically significant higher blood loss (mean, 300 (SD 128–596) vs. 250 (SD 100–400) ml, p-value = 0.047) but shorter hospital stay (mean, 6 [ 4-8] vs. 6 [ 5-9] days, p-value = 0.043) were found in the NAT-group. The current study demonstrated that NAT had minimal impact on the difficulty and outcomes of minimally-invasive MLR for CRLM. Abbreviated abstract: The impact of neoadjuvant chemotherapy (NAT) on the difficulty of minimally invasive major liver resections (MLRs) remains poorly investigated. NAT had minimal impact on the difficulty and outcomes of minimally-invasive MLR for colorectal liver metastases. [ABSTRACT FROM AUTHOR]

Although alterations of the default mode network (DMN) in schizophrenia (SZ) have been largely investigated, less research has been carried out on DMN alterations in different sub-phenotypes of this disorder. The aim of this pilot study was to compare DMN features among SZ patients with and without auditory verbal hallucinations (AVH). Three groups of 17 participants each were considered: patients with hallucinations (AVH-SZ), patients without hallucinations (nAVH-SZ) and age-matched healthy controls (HC). The DMN spatial pattern was similar between the nAVH-SZ and HC, but the comparison between these two groups and the AVH-SZ group revealed alterations in the left Angular Gyrus (lAG) node of the DMN. Using a novel approach based on normalized fractional Amplitude of Low-Frequency Fluctuations (fALFF), the AVH-SZ subgroup showed altered spectral activity in the DMN compared with the other two groups, especially in the lower-frequency bands (0.017–0.04 Hz). Significant positive correlations were found for both SZ groups collapsed, and for the nAVH-SZ group alone between delusional scores (PANSS-P1) and slow fALFF bands of the DMN. Narrowing the analysis to the ROI centered on the lAG, significant correlations were found in the AVH-SZ group for hallucination scores (PANSS-P3) and Slow-5 and Slow-4 (both positive), and Slow-3 (negative) fALFF bands. Our results reveal the central role of the lAG in relation to hallucinations, an important cortical area connecting auditory cortex with several hubs (including frontal linguistic centers) and involved in auditory process monitoring. • Schizophrenia (SZ) patients might experience auditory verbal hallucinations (AVH). • Default Mode Network (DMN) is unaltered for SZ patients, but not in presence of AVH. • Alterations in DMN might be linked to the presence of AVH in SZ patients. • Left Angular Gyrus (lAG) might play a key role in the generation of AVH. • Fluctuations derived from DMN and lAG correlates with the severity of hallucinations. [ABSTRACT FROM AUTHOR]

Despite the rapid advances that minimally invasive liver resection has gained in recent decades, open conversion is still inevitable in some circumstances. In this study, we aimed to determine the risk factors for open conversion after minimally invasive left lateral sectionectomy, and its impact on perioperative outcomes. This is a post hoc analysis of 2,445 of 2,678 patients who underwent minimally invasive left lateral sectionectomy at 45 international centers between 2004 and 2020. Factors related to open conversion were analyzed via univariate and multivariate analyses. One-to-one propensity score matching was used to analyze outcomes after open conversion versus non-converted cases. The open conversion rate was 69/2,445 (2.8%). On multivariate analyses, male gender (3.6% vs 1.8%, P =.011), presence of clinically significant portal hypertension (6.1% vs 2.6%, P =.009), and larger tumor size (50 mm vs 32 mm, P <.001) were identified as independent factors associated with open conversion. The most common reason for conversion was bleeding in 27/69 (39.1%) of cases. After propensity score matching (65 open conversion vs 65 completed via minimally invasive liver resection), the open conversion group was associated with increased operation time, blood transfusion rate, blood loss, and postoperative stay compared with cases completed via the minimally invasive approach. Male sex, portal hypertension, and larger tumor size were predictive factors of open conversion after minimally invasive left lateral sectionectomy. Open conversion was associated with inferior perioperative outcomes compared with non-converted cases. [ABSTRACT FROM AUTHOR]

In the last three decades, minimally invasive liver resection has been replacing conventional open approach in liver surgery. More recently, developments in neoadjuvant chemotherapy have led to increased multidisciplinary management of colorectal liver metastases with both medical and surgical treatment modalities. However, the impact of neoadjuvant chemotherapy on the surgical outcomes of minimally invasive liver resections remains poorly understood. A multicenter, international, database of 4998 minimally invasive minor hepatectomy for colorectal liver metastases was used to compare surgical outcomes in patients who received neoadjuvant chemotherapy with surgery alone. To correct for baseline imbalance, propensity score matching, coarsened exact matching and inverse probability treatment weighting were performed. 2546 patients met the inclusion criteria. After propensity score matching there were 759 patients in both groups and 383 patients in both groups after coarsened exact matching. Baseline characteristics were equal after both matching strategies. Neoadjuvant chemotherapy was not associated with statistically significant worse surgical outcomes of minimally invasive minor hepatectomy. Neoadjuvant chemotherapy had no statistically significant impact on short-term surgical outcomes after simple and complex minimally invasive minor hepatectomy for colorectal liver metastases. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BD) is a psychiatric condition causing acute dysfunctional mood states and emotion regulation. Specific neuropsychological features are often present also among patients in euthymic phase, who do not show clear psychotic symptoms, and for whom the characterization from functional magnetic resonance imaging (fMRI) is very limited. This study aims at identifying the neural and behavioral correlates of the default mode network (DMN) using the fractional amplitude of low frequency fluctuations (fALFF). Eighteen euthymic BD patients (10 females; age = 54.50 ± 11.38 years) and sixteen healthy controls (HC) (8 females; age = 51.16 ± 11.44 years) underwent a 1.5T fMRI scan at rest. The DMN was extracted through independent component analysis. Then, DMN time series was used to compute the fALFF, which was correlated with clinical scales. From the between-group comparison, no significant differences emerged in correspondence to regions belonging to the DMN. For fALFF analysis, we reported significant increase of low-frequency fluctuations for lower frequencies, and decreases for higher frequencies compared to HC. Correlations with clinical scales showed that an increase in higher frequency spectral content was associated with lower levels of mania and higher levels of anxious symptoms, while an increase in lower frequencies was linked to lower depressive symptoms. Starting from our findings on the DMN in euthymic BD patients, we suggest that the fALFF derived from network time series represents a viable approach to investigate the behavioral correlates of resting state networks, and the pathophysiological mechanisms of different psychiatric conditions. • Euthymic bipolar disorder (BD) patients show no current clinical symptoms. • Spatial pattern of Default Mode Network (DMN) in euthymic BD patients is unaltered. • Fractional amplitude of low-frequency fluctuations (fALFF) ground on DMN time series. • fALFF derived from DMN correlates with the severity of depressive and manic symptoms. • fALFF allows investigating the clinical correlates of DMN in euthymic BD patients. [ABSTRACT FROM AUTHOR]

The fluorescence properties of Indocyanine Green (ICG) make it a useful technique in the armamentarium of liver surgeons in order to enhance the visualization of anatomical structures by providing a real-time liver mapping. We have analyzed the impact of ICG-fluorescence staining technique in 40 consecutive patients who underwent robotic-assisted liver resection for malignancies from June 2014 to November 2017. For the 55% of patients the surgical indication was colorectal liver metastasis followed by hepatocarcinoma in 35% of cases. The R0 resection rate was 100%, and the mean resection margin was 12 mm. Twenty percent of patients experienced tumor recurrence. The 1-year and 2-year overall survival rates were 91% and 84%, respectively. The 1-year and 2-year disease free survival were 77.2% and 65%, respectively. The previously marked transaction line was changed after the staining method in 12 out of 40 patients. Through intra-operative ultrasonography and white-light exploration of the liver surface 43 lesions were detected, whereas with the ICG-F 52 lesion of the liver surface were identified, including two superficial colorectal metastases missed at the intra-operative ultrasonography. The ICG-F is a promising navigational tool, that can potentially overcome the limitations of the minimally invasive liver surgery. [ABSTRACT FROM AUTHOR]

We performed this study in order to investigate the impact of liver cirrhosis (LC) on the difficulty of minimally invasive liver resection (MILR), focusing on minor resections in anterolateral (AL) segments for primary liver malignancies. This was an international multicenter retrospective study of 3675 patients who underwent MILR across 60 centers from 2004 to 2021. 1312 (35.7%) patients had no cirrhosis, 2118 (57.9%) had Child A cirrhosis and 245 (6.7%) had Child B cirrhosis. After propensity score matching (PSM), patients in Child A cirrhosis group had higher rates of open conversion (p = 0.024), blood loss >500 mls (p = 0.001), blood transfusion (p < 0.001), postoperative morbidity (p = 0.004), and in-hospital mortality (p = 0.041). After coarsened exact matching (CEM), Child A cirrhotic patients had higher open conversion rate (p = 0.05), greater median blood loss (p = 0.014) and increased postoperative morbidity (p = 0.001). Compared to Child A cirrhosis, Child B cirrhosis group had longer postoperative stay (p = 0.001) and greater major morbidity (p = 0.012) after PSM, and higher blood transfusion rates (p = 0.002), longer postoperative stay (p < 0.001), and greater major morbidity (p = 0.006) after CEM. After PSM, patients with portal hypertension experienced higher rates of blood loss >500 mls (p = 0.003) and intraoperative blood transfusion (p = 0.025). The presence and severity of LC affect and compound the difficulty of MILR for minor resections in the AL segments. These factors should be considered for inclusion into future difficulty scoring systems for MILR. [ABSTRACT FROM AUTHOR]

To assess the impact of cirrhosis and portal hypertension (PHT) on technical difficulty and outcomes of minimally invasive liver resection (MILR) in the posterosuperior segments. This is a post-hoc analysis of patients with primary malignancy who underwent laparoscopic and robotic wedge resection and segmentectomy in the posterosuperior segments between 2004 and 2019 in 60 centers. Surrogates of difficulty (i.e, open conversion rate, operation time, blood loss, blood transfusion, and use of the Pringle maneuver) and outcomes were compared before and after propensity-score matching (PSM) and coarsened exact matching (CEM). Of the 1954 patients studied, 1290 (66%) had cirrhosis. Among the cirrhotic patients, 310 (24%) had PHT. After PSM, patients with cirrhosis had higher intraoperative blood transfusion (14% vs. 9.3%; p = 0.027) and overall morbidity rates (20% vs. 14.5%; p = 0.023) than those without cirrhosis. After coarsened exact matching (CEM), patients with cirrhosis tended to have higher intraoperative blood transfusion rate (12.1% vs. 6.7%; p = 0.059) and have higher overall morbidity rate (22.8% vs. 12.5%; p = 0.007) than those without cirrhosis. After PSM, Pringle maneuver was more frequently applied in cirrhotic patients with PHT (62.2% vs. 52.4%; p = 0.045) than those without PHT. MILR in the posterosuperior segments in cirrhotic patients is associated with higher intraoperative blood transfusion and postoperative morbidity. This parameter should be utilized in the difficulty assessment of MILR. [ABSTRACT FROM AUTHOR]

Danon disease, an X-linked multisystemic disorder, is due to deficiency of Lysosome-Associated Membrane Protein 2 (LAMP2). It is usually characterized by hypertrophic cardiomyopathy, mental retardation and skeletal myopathy, sometimes also with atypical features. A 20-year-old man with cognitive impairment was admitted to the Emergency Room because of a sudden chest pain. ECG showed Wolff–Parkinson–White syndrome; echocardiography revealed hypertrophic cardiomyopathy, and, shortly after, he experienced a cardiac arrest followed by an occipital ischemic stroke. On neurological examination, he complained of visual loss, and diffuse muscle wasting and weakness were also unexpectedly noted. Electromyography evidenced a myopathic pattern and a peripheral neuropathy. A muscle biopsy disclosed vacuolar myopathy with glycogen storage; immunohistochemical studies demonstrated a LAMP-2 deficiency. LAMP2 molecular analysis identified a “de novo” mutation (p. Q353X). This patient with a neglected Danon disease, experienced an unusual complication as a stroke due to cerebral hypoperfusion after cardiac arrest caused by WPW syndrome. [ABSTRACT FROM AUTHOR]

Pancreatic tumors are very rare diseases in very young children. Most information about those diseases in children was published in cases reports. Due to the rare nature of pancreatic tumors in children, there remains the absence of diagnostic algorithms, clear radiographic and morphological assessments as well as evidence based best treatment options. Because of the young age of patients and the rare occurrence of pancreatic neoplasms, tumor detection remains poor. For malignancies affecting the head of the pancreas the only possibility for achieving clear surgical margins is performing a pancreaticoduodenectomy (PD). We describe two cases of diagnostic and treatment of pancreatic tumor of very young children what was done in our institute. [ABSTRACT FROM AUTHOR]

Background Quantification of left ventricular (LV) volume from cardiovascular magnetic resonance images relies on subjective and often challenging selection of short-axis (SAX) slices. We hypothesized that this could be solved by defining mitral annular (MA) plane and apex in long-axis (LAX) views, which could be combined with automated LV volume analysis that does not rely on manual tracing of the endocardial border. Methods SAX images from 50 subjects were analyzed using custom software. LV apex and insertion points of the mitral leaflets were marked on LAX views and used to approximate MA plane. End-systolic and end-diastolic LV volumes (ESV, EDV) were measured while including only slices or their parts located between MA plane and LV apex. Endocardial borders were automatically detected using our previously validated algorithm and also manually traced to obtain reference values. Results Selection of anatomic landmarks in LAX views allowed automated measurement of LV volumes without the need for subjective slice selection. Intertechnique comparisons resulted in high correlations (EDV: r = 0.95; ESV: r = 0.96) and small biases (1 and 9 ml). Combined three-dimensional displays of LAX and SAX views with the MA plane showed that in 7/10 worst cases, intertechnique discordance was due to incorrect manual tracing at LV base that erroneously included part of atrial cavity in LV volume or excluded part of LV cavity, i.e., incorrect reference values. Conclusion Defining the MA plane and apex in the LAX views obviates the need for subjective slice selection and eliminates errors in LV volume measurements. [ABSTRACT FROM AUTHOR]

Introduction: Despite the potential advantages in terms of microdissection and microsuturing capabilites, the robotic approach for borderline resectable pancreatic cancer is scarcely reported. Methods: We report our technique for a robotic-assisted pancreaticoduodenectomy with tangential Portal/ Superior Mesenteric Vein resection/reconstruction (RPD PV/SMV).We also compared the surgical outcomes of eight consecutive patients undergoing RPD PV/SMV with that of sixty patients who underwent robotic-assisted pancreaticoduodenectomy (RPD) in the same period of time. Results: A total of eight consecutive patients underwent RPD PV/SMV. We observed an increased estimated blood loss (550 vs 280 mL, p = 0.003) and operative time (438 vs 350 min, p = 0.002) in the RPD PV/SMV group of patients compared with RPD group, whereas the complication rate (28% vs 31%, p = 0.726) was similar. No venous-congestion related complications were observed in the postoperative course. The median length of hospital stay was similar in the RPD group in comparison to that in the RPD PV/SMV group (10 vs 13 range 6-19 days, p = 0.313). Conclusion: RPD PV/SMV is a challenging operation. It is associated with higher operative time and increased estimated blood loss in comparison to standard RPD. [ABSTRACT FROM AUTHOR]

Summary: Titin is a gigantic elastic filament that determines sarcomere ultrastructure and stretch response in vertebrate muscle. It folds into numerous Ig and FnIII domains connected in tandem. Data on interdomain arrangements and dynamics are essential for understanding the function of this filament. Here, we report a mechanistic analysis of the conformational dynamics of two Ig domains from the N terminus of titin, Z1Z2, by using X-ray crystallography, SAXS, NMR relaxation data, and residual dipolar couplings in combination. Z1Z2 preferentially adopts semiextended conformations in solution, with close-hinge arrangements representing low-probability states. Although interdomain contacts are not observed, the linker appears to acquire moderate rigidity via small, local hydrophobic interactions. Thus, Z1Z2 constitutes an adaptable modular system with restricted dynamics. We speculate that its preexistent conformation contributes to the selective recruitment of the binding partner telethonin onto the repetitive surface of the filament. The structural interconversion of four Z1Z2 conformers is analyzed. [Copyright &y& Elsevier]

The metabolic synthesis and degradation of essential nucleotide compounds are primarily carried out by phosphoribosyltransferases (PRT) and nucleoside phosphorylases (NP), respectively. Despite the resemblance of their reactions, five classes of PRTs and NPs exist, where anthranilate PRT (AnPRT) constitutes the only evolutionary link between synthesis and degradation processes. We have characterized the active site of dimeric AnPRT from Sulfolobus solfataricus by elucidating crystal structures of the wild-type enzyme complexed to its two natural substrates anthranilate and 5-phosphoribosyl-1-pyrophosphate/Mg2+. These bind into two different domains within each protomer and are brought together during catalysis by rotational domain motions as shown by small angle x-ray scattering data. Steady-state kinetics of mutated AnPRT variants address the role of active site residues in binding and catalysis. Results allow the comparative analysis of PRT and pyrimidine NP families and expose related structural motifs involved in nucleotide/nucleoside recognition by these enzyme families. [ABSTRACT FROM AUTHOR]

• Spectral activity changes following tDCS depend on the initial state of the brain. • State-dependent tDCS modulates power but not connectivity in somatomotor areas. • Generalized additive mixed models account for non-linear properties of tDCS effects. Transcranial direct current stimulation (tDCS) is a non-invasive technique widely used to investigate brain excitability and activity. However, the variability in both brain and behavioral responses to tDCS limits its application for clinical purposes. This study aims to shed light on state-dependency, a phenomenon that contributes to the variability of tDCS. To this aim, we investigated changes in spectral activity and functional connectivity in somatomotor regions after Real and Sham tDCS using generalized additive mixed models (GAMMs), which allowed us to investigate how modulation depends on the initial state of the brain. Results showed that changes in spectral activity, but not connectivity, in the somatomotor regions depend on the initial state of the brain, confirming state-dependent effects. Specifically, we found a non-linear interaction between stimulation conditions (Real vs Sham) and initial state: a reduction of alpha and beta power was observed only in participants that had higher alpha and beta power before Real tDCS. This study highlights the importance of considering state-dependency to tDCS and shows how it can be taken into account with appropriate statistical models. Our findings bear insight into tDCS mechanisms, potentially leading to discriminate between tDCS responders and non-responders. [ABSTRACT FROM AUTHOR]

Introduction: The application of indocyanine green (icg) properties in the field of HPB surgery is gaining momentum. The adoption of the staining technique for the visualization of hepatic liver parenchyma is still preliminary.Methods: We performed a 1:1 case- matched comparison among 20 patients who underwent robotic liver resection with or without the application of icg fluorescence.Results: The icg enabled the reduction of postoperative liver abscess and bile leakage rate. The staining technique was not time-consuming and provided excellent enhancement of liver transection line.Conclusion: The routine use of icg-fluorescence could potentially reduce the postoperative complications during robotic liver surgery. [ABSTRACT FROM AUTHOR]

We investigated the perioperative outcomes of our experience in robotic PD including patients who underwent to resection and reconstruction of superior mesenteric/portal vein (PD-SMV/PV) in order to evaluate the safety and feasibility of this approach. We performed 45 robotic PD and 10 robotic PD-SMV/PV. We achieved a R0 resection rate in 51/55 (92.7%) of patients with a mean lymph nodes retrieved of 20.5 (17-25). [Extracted from the article]

Background Celiac disease (CD) is an immune-mediated disorder characterized by an accumulation of immune cells in the duodenal mucosa as a consequence of both adaptive and innate immune responses to undigested gliadin peptides. Mast cells (MCs) are innate immune cells that are a major source of costimulatory signals and inflammatory mediators in the intestinal mucosa. Although MCs have previously been associated with CD, functional studies have never been performed. Objective We aimed at evaluating the role of MCs in the pathogenesis of CD. Methods Intestinal biopsy specimens of patients with CD were scored according to the Marsh classification and characterized for leukocyte infiltration and MC distribution. Moreover, MC reactivity to gliadin and its peptides was characterized by using in vitro assays. Results Infiltrating MCs were associated with the severity of mucosal damage, and their numbers were increased in patients with higher Marsh scores. MCs were found to directly respond to nonimmunodominant gliadin fragments by releasing proinflammatory mediators. Immunohistochemical characterization of infiltrating MCs and the effects of gliadin peptides on intestinal MCs indicated an increase in proinflammatory MC function in advanced stages of the disease. This was also associated with increased neutrophil accumulation, the prevalence of M1 macrophages, and the severity of tissue damage. Conclusion We provide a description of the progressive stages of CD, in which MCs are the hallmark of the inflammatory process. Thus the view of CD should be revised, and the contribution of MCs in the onset and progression of CD should be reconsidered in developing new therapeutic approaches. [ABSTRACT FROM AUTHOR]

The single nucleotide polymorphism p.N680S of the follicle-stimulating hormone (FSH) receptor (FSHR) is a discrete marker of ovarian response but previous in vitro studies failed to demonstrate differences in the response to FSH between N and S carrier cells. Here we demonstrate that p.N680S mediates different kinetics of the response to FSH in vitro. Intracellular cAMP production is faster in p.N680S N than in S homozygous human granulosa cells (45 versus 90 min to achieve the plateau, respectively; Mann-Whitney's U-test; p < 0.005; n = 4). Reflecting the cAMP kinetics, phospho-ERK1/2 and -CREB activation, AREG and STARD1 gene expressions and progesterone production were qualitatively and quantitatively different in N versus S homozygous cells. Finally, the blockade of ERK pathway by U0126 abolishes the genotype-mediated different effects on gene expression and progesterone production (Mann-Whitney's U-test; p ≥ 0.005; n = 3). [ABSTRACT FROM AUTHOR]

Abstract: UHV evaporation of Sn on (1×2) Pt(110), followed by UHV annealing, provides three different PtSn/Pt(110) surface alloys, each characterized by a specific low energy electron diffraction (LEED) and scanning tunneling microscopy (STM) pattern. When annealed in a controlled oxygen background, the PtSn/Pt(110) surface alloys can be transformed into SnOx/Pt(110) nano-oxides. This paper reports the experimental phase diagram of the metallic and oxidized surface superstructures. [Copyright &y& Elsevier]