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We study the dynamics of threads of monodisperse droplets, including droplet chains and multi-chains, in which the droplets are interconnected by capillary bridges of another immiscible liquid phase. This system represents wet soft-granular matter - a class of granular materials in which the grains are soft and wetted by thin fluid films-with other examples including wet granular hydrogels or foams. In contrast to wet granular matter with rigid grains (

PURPOSE This study aimed to determine the relationship between age of first exposure (AFE) to repetitive head impacts through contact/collision sports and patient-reported outcomes in community rugby players. METHODS We recruited community rugby players older than 18 yr with at least 1 yr of contact rugby participation to complete an online survey. Participants completed the Brief Symptom Inventory-18 (BSI-18), Short-Form Health Survey 12 (SF-12), and Satisfaction with Life Scale (SWLS) via Qualtrics. We used generalized linear models to examine the association between AFE (continuous) and patient-reported outcomes by sex, while controlling for cumulative years contact/collision sport history, age, and concussion history (yes/no). In addition, we used Mann-Whitney U tests to compare patient-reported outcomes between AFE

Background and aim Adenocarcinoma of the esophagus is still burdened by low 5-year survival. A complete pathologic response after neoadjuvant treatment is associated with improved long-term survival, however this result is rarely achieved. The aim of this study was to evaluate the impact of tumor regression grade (TRG), according to Mandard, on long-term survival. The primary endpoint was to determine whether the survival benefit associated with a complete tumor regression could be achieved also with a subtotal tumor response (TRG2). Secondly, we analyzed how TRG predicts survival in chemotherapy (CT) or chemoradiotherapy (CRT) treated patients and the relationship with nodal status (ypN). Methods We evaluated all consecutive patients who underwent esophagectomy for cancer at Padova University Hospital and Mainz University Hospital. Inclusion criteria were histologically confirmed ADK involving the thoracic esophagus or Siewert I and II cancers, treated by neoadjuvant CT or CRT and surgery. Patients with Siewert III or cervical cancer and those who underwent upfront surgery were excluded from the study. Kaplan-Maier analysis was used to estimate overall survival (OS) according to the TRG and ypN. Results Overall, 270 patients were recruited in the study period. The median OS was 50 months (range 1–134). TRG 1 and 2 were associated with improved survival (P Conclusion Tumor regression after neoadjuvant treatment is significantly associated with long term survival irrespective of the nodal status. In the overall study population and among CRT treated patients, the long-term survival was comparable between TRG 1 and TRG 2 patients. This finding allowed us to support the criterion of a Major Pathologic Response, which includes both TRG 1 and 2 ypN0 patients, potentially creating a homogeneous and larger subgroup of subjects to be evaluated in future clinical trials and studies.

Background and aim Laparoscopic Heller-Dor (LHD) is an effective treatment for esophageal achalasia, with good long-term results in more than 85–90% of patients. It remains controversial whether LHD is also indicated in the end-stage disease when the esophagus has a sigmoid shape. The aim of this study was to evaluate the outcome of LHD in patients with end-stage achalasia, as compared to patients with megaesophagus but without a sigmoid shape. Methods From 1992 to 2020, patients with a radiological diagnosis of sigmoid-shaped esophagus (radiological stage IV achalasia: group SE) and patients with straight, larger than 6 cm in diameter esophagus (radiological stage III achalasia: group NSE), both treated with LHD, were compared. Treatment failure was defined as the persistence or reoccurrence of an Eckardt score > 3, or the need for retreatment. Results During the study period, 164 such patients were observed: 73 patients in the SE group and 91 in the NSE group. The patients’ demographic and clinical parameters are summarised in Table 1. The median follow-up was 67 months (IQR: 24–106). No intra or postoperative mortality was recorded. There were 7 mucosal lesions: 2 in the SE group and 5 in the NSE group (P = 0.45). A positive outcome was obtained in 73% of patients in the SE group, as compared to 90% in the NSE group (P = 0.007, Table 2). All the patients whose surgery failed subsequently underwent one or more endoscopic pneumatic dilations. The overall success rate of the combination of LHD and endoscopic dilations was 83.6% in the SE group and all patients in the NSE group. The persisting failures had additional treatments: 4 patients a redo-myotomy, one each a botox injection, POEM and only one patient had an esophagectomy; the remaining 5 patients refused additional treatments. Postoperative 24-hour pH-monitoring was abnormal in 16.6% in SE group and 8.3% in NSE group (P = 0.33). Conclusion In end-stage achalasia patients, LHD may still achieve good results by relieving symptoms in more than 70% of patients. Therefore, LHD may still be the first surgical option to be offered to these patients before esophagectomy.

Background and aim Esophageal perforation (EP) is characterized by high morbidity and mortality. In recent years, non-operative management has proved to be successful in selected patients. However, there is a lack of data supporting the superiority of one approach over the others and there is no consensus on the treatment algorithm. The Pittsburgh Severity Score (PSS) is a scoring system based on clinical factors at the time of EP presentation, intended to guide treatment. The aim of the study is to verify PSS usefulness in stratifying EP severity and in guiding clinical decisions. Methods All patients referred to our Unit for EP between January 2005 and January 2020 were enrolled. Patients were stratified according to their PSS into 3 groups (PSS ≤ 2; 3–5 and > 5): the postoperative outcomes were compared. The predictive value of the PSS was evaluated by simple linear and logistic regression for the following outcomes: need for surgery, complications, in-hospital mortality, ICU and hospital stay, time to refeeding and need for reintervention. Results Seventy-three patients were referred for EP (M/F: 46/27). Perforations were more frequently iatrogenic (41.1%) or spontaneous (37.0%). The median PSS was 4 (IQR 2–6). Surgery was required in 60.3% of cases. The median PSS was significantly lower in the conservative group (P Conclusion PSS is useful in stratifying patients in risk groups with different morbidity and mortality. It is also useful in guiding the therapeutic conduct, selecting patients for nonoperative management. Prospective studies are needed to confirm the role of the PSS in the treatment of esophageal perforation.

Background and aim The current standard of care in treating locally-advanced esophageal cancer has been established after the publication of the landmark CROSS trial and several others, which demonstrated an overall survival benefit from preoperative chemoradiation prior to esophagectomy in this setting. However, elderly patients have been generally excluded from randomized study protocols, so literature regarding the choice of the best treatment approach for resectable esophageal cancer in patients older than 75 years old is limited. The aim of this study was to characterize outcomes associated with neoadjuvant chemoradiation prior to esophagectomy, compared to esophagectomy alone, in older patients with esophageal cancer. Methods We conducted a retrospective study in patients ≥75 years with locally-advanced esophageal cancer (both adenocarcinoma -EAC and squamous cell carcinoma -SCC) undergoing esophagectomy ± neoadjuvant chemoradiation at our Center between 2000 and 2020. Results A total of 141 patients were included in the study. Patients were subcategorized into two groups: patients undergoing upfront surgery (SURG, n = 97) and patients undergoing neoadjuvant therapy before surgery (NAT, n = 44). Patients in the NAT group experienced a significantly higher postoperative morbidity when compared to the SURG group. Overall survival (21 months and 25 months, p = 0.8883) and cancer-related survival (20 and 25 months, p 0.8052) were not statistically different between the SURG and the NAT group. When looking to the histology, OS for EAC and for SCC did not significantly differ between the 2 groups. We subcategorized patients according to their final pathological stage into patients with pTNM stage I and II, and patients with stage III and IV. Among patients with EACs stage III-IV, the NAT group experienced a significant benefit in OS when compared to the SURG group. Univariate analysis for risk factors for postoperative morbidity showed a significant association between NAT and postoperative complications (p 0,0336). Multivariate analysis confirmed neoadjuvant therapy as an independent prognostic factor for morbidity (P 0,0226). Conclusion In our study, patients undergoing NAT before surgery experienced a higher postoperative morbidity when compared to patients undergoing upfront esophagectomy. Further studies are needed to identify which older patients are most suitable for neoadjuvant therapy before esophagectomy.

Background and aim Esophago-gastric junction outflow obstruction (EGJOO) is a relatively new clinical entity revealed by high-resolution manometry (HRM) that can have two different etiologies, i.e. idiopathic or secondary (esophageal strictures, eosinophilic esophagitis, giant hiatal hernia, prior fundoplication or bariatric surgery, malignancy). Treatment of EGJOO currently mirrors that of achalasia, but this is based only on few studies with small case series. The aim of this study was to assess the outcome of laparoscopic Heller-Dor (LHD) in patients with EGJOO, as compared with patients with esophageal achalasia. Methods Between 2016–2019, all patients with a diagnosis of idiopathic EGJOO and referred to our Centre for dysphagia or food regurgitation were prospectively collected. Naïve EGJOO patients were first given medical treatment with Ca2+ channel blockers for 6 months. Then patients were ‘restaged’: patients without clinical improvement and/or whose integrated relaxation pressure (IRP) had not decreased were scheduled for LHD. EGJOO patients who had already been treated elsewhere with botox injections, pneumatic dilations or Ca2+ channel blockers were scheduled upfront for LHD. Patients with EGJOO who underwent LHD were compared with patients with radiological stage I achalasia. The achalasia group was further analyzed by subgrouping the patients based on the manometric-pattern. Treatment failure was defined as the persistence or reoccurrence of a Eckardt score > 3 or the need for retreatment. Results During the study period, 150 patients were enrolled: 25 EGJOO patients and 125 radiological stage I achalasia (25 pattern I, 74 pattern II, and 26 pattern III). The median follow-up was 24 months (IQR: 34–16). Treatment was successful in 96% of patients in the EGJOO group and in 96% of achalasia patients with pattern I, 98.7% in those with pattern II, and 96.2% of those with pattern III (P = 0.50). Six-month post-operative HRM showed a reduction in the LES resting pressure and IRP for all patients in all 4 groups (P Conclusion This is the first comparative study based on prospective data collection to assess the outcome of LHD in patients with EGJOO. LHD emerged as an effective treatment for EGJOO, with an excellent success rate, comparable with the procedure’s efficacy in treating early-stage achalasia.

This study aimed to determine the relationship between age of first exposure (AFE) to repetitive head impacts through contact/collision sports and patient-reported outcomes in community rugby players.We recruited community rugby players older than 18 yr with at least 1 yr of contact rugby participation to complete an online survey. Participants completed the Brief Symptom Inventory-18 (BSI-18), Short-Form Health Survey 12 (SF-12), and Satisfaction with Life Scale (SWLS) via Qualtrics. We used generalized linear models to examine the association between AFE (continuous) and patient-reported outcomes by sex, while controlling for cumulative years contact/collision sport history, age, and concussion history (yes/no). In addition, we used Mann-Whitney U tests to compare patient-reported outcomes between AFE12 and AFE ≥12.A total of 1037 rugby players (31.6 ± 11.3 yr (range, 18-74 yr), 59.1% men) participated in this study. Whether analyzed continuously or dichotomously at age 12 yr, younger AFE was not associated with worse patient-reported outcomes for either men or women. Positive concussion history was a significant predictor of worse BSI-18 subscores, SF-12 subscores, and SWLS in women and worse BSI-18 subscores in men. Cumulative contact/collision sport history was a significant predictor of better BSI-18 Depression and SF-12 (Mental Component Summary) subscores in men only. In men and women, older age was a significant predictor of better BSI-18 Depression, Anxiety, and GSI subscores; better SWLS (in men only); and better SF-12 Mental Component Summary, but worse SF-12 (Physical Component Summary).Younger AFE to contact/collision sport is not associated with worse patient-reported outcomes in early adult rugby players. Concussion history was predictive of worse patient-reported outcomes.

In this article, I explore the performative nature of ghost bike memorials across the United States. Ghost bikes, flat-white painted immobile bicycles, are installed roadside to mark the location o...

To provide a summary of the evidence on the comparative effectiveness of two surgical treatment strategies, sentinel node biopsy (SNB) and elective neck dissection (END), in patients with T1-T2 oral cancer and clinically negative (cN0) neck, in terms of overall survival (OS), disease-free survival (DFS) and neck recurrence rates (NRRs).A systematic review was performed by including studies published up to April 2019. Meta-analysis was performed to compare NRRs between SNB and END. A narrative summary of the results was generated for OS, DFS and morbidity outcomes. The certainty of evidence was assessed according to the GRADE methodology.No randomized studies were retrieved. Five observational studies were included in the comparative effectiveness analysis and four observational studies were included in the comparative morbidity analysis. The pooled risk ratio showed no differences in NRRs between SNB and END (10.5% vs 11.6%; pooled RR 1.09; 95% CI 0.67-1.76). No differences in OS or DFS between the two treatments were found. SNB appears to be associated with a lower rate of postoperative complications and lower shoulder dysfunction than END. Conversely, the results of the quality of life (QoL) questionnaires are not sufficient to advocate a particular strategy.Our review highlights the lack of well conducted and randomized studies comparing SNB to END, leading to poor clinical evidence. Although our findings suggest no significant differences in OS, DFS and NRR between the two strategies, the certainty of our evidence is too low to make it useful for clinical decision making.

The HIV-1 envelope glycoprotein, gp120, binds the host cell receptor, CD4, in the initial step of HIV viral entry and infection. This process is an appealing target for the development of inhibitory drugs and neutralizing antibodies. To study gp120 binding and intracellular trafficking, we engineered a fluorescent fusion of the humanized gp120 JRFL HIV-1 variant and GFP. Gp120-sfGFP is glycosylated with human sugars, robustly expressed, and secreted from cultured human cells. Protein dynamics, quality control, and trafficking can be visualized in live cells. The fusion protein can be readily modified with different gp120 variants or fluorescent proteins. Finally, secreted gp120-sfGFP enables a sensitive and easy binding assay that can quantitatively screen potential inhibitors of gp120-CD4 binding on live cells via fluorescence imaging or laser scanning cytometry. This adaptable research tool should aid in studies of gp120 cell biology and the development of novel anti-HIV drugs.

Vinculin and its splice isoform metavinculin play key roles in regulating cellular morphology, motility, and force transduction. Vinculin is distinct from metavinculin in its ability to bundle filamentous actin (F-actin). To elucidate the molecular basis for these differences, we employed computational and experimental approaches. Results from these analyses suggest that the C terminus of both vinculin and metavinculin form stable interactions with the F-actin surface. However, the metavinculin tail (MVt) domain contains a 68 amino acid insert, with helix 1 (H1) sequestered into a globular subdomain, which protrudes from the F-actin surface and prevents actin bundling by sterically occluding actin filaments. Consistent with our model, deletion and selective point mutations within the MVt H1 disrupt this protruding structure, and facilitate actin bundling similar to vinculin tail (Vt) domain.

Fluorescent protein (FP) technologies suitable for use within the eukaryotic secretory pathway are essential for live cell and protein dynamic studies. Localization of FPs within the endoplasmic reticulum (ER) lumen has potentially significant consequences for FP function. All FPs are resident cytoplasmic proteins and have rarely been evolved for the chemically distinct environment of the ER lumen. In contrast to the cytoplasm, the ER lumen is oxidizing and the site where secretory proteins are post-translationally modified by disulfide bond formation and N-glycosylation on select asparagine residues. Cysteine residues and N-linked glycosylation consensus sequences were identified within many commonly utilized FPs. Here, we report mTagBFP is post-translationally modified when localized to the ER lumen. Our findings suggest these modifications can grossly affect the sensitivity and reliability of FP tools within the secretory pathway. To optimize tools for studying events in this important intracellular environment, we modified mTagBFP by mutating its cysteines and consensus N-glycosylation sites. We report successful creation of a secretory pathway-optimized blue FP, secBFP2.

Several fluorescent proteins (FPs) are prone to forming low-affinity oligomers. This undesirable tendency is exacerbated when FPs are confined to membranes or when fused to naturally oligomeric proteins. Oligomerization of FPs limits their suitability for creating fusions with proteins of interest. Unfortunately, no standardized method evaluates the biologically relevant oligomeric state of FPs. Here, we describe a quantitative visual assay for assessing whether FPs are sufficiently monomeric under physiologic conditions. Membrane-associated FP-fusion proteins, by virtue of their constrained planar geometry, achieve high effective concentrations. We exploited this propensity to develop an assay to measure FP tendencies to oligomerize in cells. FPs were fused on the cytoplasmic end of an endoplasmic reticulum (ER) signal-anchor membrane protein (CytERM) and expressed in cells. Cells were scored based on the ability of CytERM to homo-oligomerize with proteins on apposing membranes and restructure the ER from a tubular network into organized smooth ER (OSER) whorl structures. The ratio of nuclear envelope and OSER structures mean fluorescent intensities for cells expressing enhanced green fluorescent protein (EGFP) or monomeric green fluorescent protein (mGFP) CytERM established standards for comparison of uncharacterized FPs. We tested three FPs and identified two as sufficiently monomeric, while a third previously reported as monomeric was found to strongly oligomerize.

Background: Many alcoholic patients have serum protein deficiency that contributes to their systemic problems. The unfolded protein response (UPR) is induced in response to disequilibrium in the protein folding capability of the endoplasmic reticulum (ER) and is implicated in hepatocyte lipid accumulation and apoptosis, which are associated with alcoholic liver disease (ALD). We investigated whether alcohol affects ER structure, function, and UPR activation in hepatocytes in vitro and in vivo. Methods: HepG2 cells expressing human cytochrome P450 2E1 and mouse alcohol dehydrogenase (VL-17A) were treated for up to 48 hours with 50 and 100 mM ethanol. Zebrafish larvae at 4 days postfertilization were exposed to 350 mM ethanol for 32 hours. ER morphology was visualized by fluorescence in cells and transmission electron microscopy in zebrafish. UPR target gene activation was assessed using quantitative PCR, in situ hybridization, and Western blotting. Mobility of the major ER chaperone, BIP, was monitored in cells by fluorescence recovery after photobleaching (FRAP). Results: VL-17A cells metabolized alcohol yet only had slight activation of some UPR target genes following ethanol treatment. However, ER fragmentation, crowding, and accumulation of unfolded proteins as detected by immunofluorescence and FRAP demonstrate that alcohol induced some ER dysfunction despite the lack of UPR activation. Zebrafish treated with alcohol, however, showed modest ER dilation, and several UPR targets were significantly induced. Conclusions: Ethanol metabolism directly impairs ER structure and function in hepatocytes. Zebrafish are a novel in vivo system for studying ALD.

The occurrence of neonatal sandbar sharks Carcharhinus plumbeus in the Adriatic Sea is reported; however, nursery areas still need to be identified.

We have used electron spin resonance spectroscopy to study the defects induced in yttria-stabilized zirconia (YSZ) single crystals by 2.5-MeV electron irradiations. Two paramagnetic centers are produced: the first one with an axial symmetry is similar to the trigonal Zr 3+ electron center (T center) found after X-ray irradiation or thermochemical reduction, whereas the second one is a new oxygen hole center with an axial symmetry different from the orthorhombic O - center induced by X-ray irradiation. At a fluence around 10 18 e/cm , both centers are bleached out near 600 K, like the corresponding X-ray induced defects. At a fluence around 10 19 e/cm 2 , defects are much more stable, since complete thermal bleaching occurs near 1000 K. Accordingly, ageing of as-irradiated samples shows that high-dose defects at more stable than the low-dose ones.