Acute cutaneous graft-versus-host disease (acGVHD) following haematopoietic stem cell transplant (HSCT) is common but difficult to distinguish from other causes of rash. Plasma elafin has been proposed as a diagnostic and prognostic biomarker of skin GVHD.

To evaluate the role of plasma elafin as a biomarker in acGVHD in an Indian population.

Plasma elafin was evaluated in a prospective study of HSCT recipients, conducted over 2years, taking measurements at baseline and at onset of skin rash after HSCT. Patients were categorized into those with GVHD rash, those with non-GVHD rash and those with no rash and the three groups were compared.

Two hundred and sixty-one patients with a median age of 16years (range 1-61years) and a male predominance (17586M/F) underwent HSCT during the study period 56 patients in the GVHD group, 49 in the non-GVHD group and 156 in the no-rash group. The median baseline elafin was similar in all three groups. At the onset of rash, median elafin level was similar between GVHD and non-GVHD rash (34549 vs. 32077pg/mL; P=0.58) and between GVHD and no rash (34549 vs. 26197pg/mL; P=0.08). A rise in elafin from baseline was significantly different between GVHD and no rash (P<0.001) but not between GVHD and non-GVHD rash (P=0.44).

The utility of plasma elafin as a biomarker of skin GVHD is very limited. Plasma elafin, although elevated in cutaneous GVHD, is not helpful in distinguishing between GVHD rash and other causes of rash following HSCT.

The utility of plasma elafin as a biomarker of skin GVHD is very limited. Plasma elafin, although elevated in cutaneous GVHD, is not helpful in distinguishing between GVHD rash and other causes of rash following HSCT.Hypomagnesemia is common in kidney transplant recipients (KTRs). We sought to explore the relationship between Mg and outcomes in KTRs, which may be associated with mortality and thus may be a potential intervention target to improve outcomes. We followed KTRs performed between 01/2000 and 6/2016 at a large US transplant center from 6 months post-transplant to graft failure, death, or loss to follow-up. Using Mg as a time-dependent variable, associations between Mg and outcomes any time after 6 months post-transplant were evaluated. 3680 KTRs with 50 413 Mg measurements met inclusion criteria. 657 deaths occurred over a median follow-up of 5.1 years. Compared to Mg of 1.5-1.8 mg/dl, both lower (HR 1.17, 95% confidence interval (CI) 1.07-1.28) and higher (HR 1.16, 95% CI 1.09-1.23) Mg levels were associated with greater risk of mortality. Similar U-shaped associations were observed for Mg and cardiovascular disease-related mortality (HR for Mg ≤1.5 mg/dl 1.31; CI 1.03-1.68) and infection-related mortality (HR for Mg ≤1.5 mg/dl 1.28; CI 1.09-1.51), although relationships for Mg >1.8 mg/dl were not statistically significant. Mg exhibits a U-shaped association with mortality in KTRs, with levels between 1.5 and 1.8 mg/dl associated with the lowest risk.

Primary cutaneous anaplastic large-cell lymphoma (PC-ALCL) is a rare T-cell lymphoma. A prior analysis of the Surveillance, Epidemiology, and End Results (SEER) database reported only 157 cases of localized primary cutaneous CD30+ T-cell lymphoproliferative disorders (PC-ALCL and lymphomatoid papulosis) from 1973 to 2004. Our analysis of the SEER database since 2004 is the largest to date and our results improve our understanding of this disease and their potential prognostic factors.

We used the SEER database to retrospectively identify patients. Survival was analysed using the Kaplan-Meier method, and log-rank tests were used to compare survival distributions.

There were 501 cases of PC-ALCL recorded from 2005 to 2016. Overall survival rates at 5 and 10years were found to be 80.6% (95% CI 76.3%-84.3%) and 61.5% (95% CI 54.1%-68.1%) respectively. Age ≥60years [hazard ratio (HR)=1.09, P=0.001 and use of chemotherapy (HR=1.86, P=0.01)] were associated with lower overall survival. In contrast to the 1973-2004 cohort, the head and neck site was not significantly associated with prognosis on multivariate analysis.

PC-ALCL has been increasingly recognized over the past decade. Age >60years and use of chemotherapy are associated with a worse outcome. Contrary to prior studies, location was not associated with poor survival.

60 years and use of chemotherapy are associated with a worse outcome. Contrary to prior studies, location was not associated with poor survival.

Inappropriate platelet transfusions represent an opportunity for improvements in patient care. Use of a best practice alert (BPA) as clinical decision support (CDS) for red cell transfusions has successfully reduced unnecessary red blood cell (RBC) transfusions in prior studies. We studied the impact of a platelet transfusion BPA with visibility randomized by patient chart.

A BPA was built to introduce CDS at the time of platelet ordering in the electronic health record. Alert visibility was randomized at the patient encounter level. BPA eligible platelet transfusions for patients with both visible and non-visible alerts were recorded along with reasons given for override of the BPA. Focused interviews were performed with providers who interacted with the BPA to assess its impact on their decision making.

Over a 9-month study period, 446 patient charts were randomized. The visible alert group used 25.3% fewer BPA eligible platelets. Mean monthly usage of platelets eligible for BPA display was 65.7 for the control group and 49.1 for the visible alert group (p=0.07). BPA-eligible platelets used per inpatient day at risk per month were not significantly different between groups (2.4 vs. 2.1, p=0.53).

It is feasible to study CDS via chart-based randomization. A platelet BPA reduced total platelets used over the study period and may have resulted in $151,069 in yearly savings, although there were no differences when adjusted for inpatient days at risk. During interviews, providers offered additional workflow insights allowing further improvement of CDS for platelet transfusions.

It is feasible to study CDS via chart-based randomization. A platelet BPA reduced total platelets used over the study period and may have resulted in $151,069 in yearly savings, although there were no differences when adjusted for inpatient days at risk. During interviews, providers offered additional workflow insights allowing further improvement of CDS for platelet transfusions.

During coronavirus disease 2019 (COVID-19) pandemic, various adverse skin reactions to long-term mask wearing have been reported.

We aimed to assess the clinical features of mask-induced dermatoses and recommend prevention and treatment options.

From April to August 2020, questionnaires including preexisting skin disorders, patients’ reported mask-related symptoms, their daily mask wearing duration and frequency, types of masks used, whether they are health care workers, and demographic information were distributed to patients of 12 hospitals. Dermatologists assessed skin lesions, confirmed diagnosis, and recorded treatment modalities.

Itchiness was the most frequent symptom, mostly affecting the cheeks. Most common skin disease was new-onset contact dermatitis (33.94%), followed by new-onset acne (16.97%) and aggravation of preexisting acne (16.97%). Daily wearing (p=0.018) was significantly associated with new-onset contact dermatitis. More than half of the patients with preexisting skin problems experienced aggravation while wearing masks. Longer duration (more than 6 hours/day, p=0.043) and cotton masks (p<0.001) significantly increased acne flare-up. Healthcare workers had a higher incidence of skin disease. Skin lesions were generally mild and well tolerated with topical agents.

Effect of seasonal characteristics and other risk factors were not assessed. The patients were visiting dermatologic clinics and had interest in their skin status. Thus, a selection bias may exist.

Mask-induced/triggered dermatoses contribute to increase the dermatological burden during pandemic.

Mask-induced/triggered dermatoses contribute to increase the dermatological burden during pandemic.Atypical connectivity between brain regions and altered structure of the corpus callosum (CC) in imaging studies supports the long-distance hypoconnectivity hypothesis proposed for autism spectrum disorder (ASD). The aim of this study was to unveil the CC ultrastructural and cellular changes employing the valproic acid (VPA) rat model of ASD. Male Wistar rats were exposed to VPA (450 mg/kg i.p.) or saline (control) during gestation (embryonic day 10.5), and maturation, exploration, and social behavior were subsequently tested. Myelin content, ultrastructure, and oligodendroglial lineage were studied in the CC at post-natal days 15 (infant) and 36 (juvenile). As a functional outcome, brain metabolic activity was determined by positron emission tomography. Concomitantly with behavioral deficits in juvenile VPA rats, the CC showed reduced myelin basic protein, conserved total number of axons, reduced percentage of myelinated axons, and aberrant and less compact arrangements of myelin sheath ultrastructure. Mature oligodendrocytes decreased and oligodendrocyte precursors increased in the absence of astrogliosis or microgliosis. In medial prefrontal and somatosensory cortices of juvenile VPA rats, myelin ultrastructure and oligodendroglial lineage were preserved. VPA animals exhibited global brain hypometabolism and local hypermetabolism in brain regions relevant for ASD. In turn, the CC of infant VPA rats showed reduced myelin content but preserved oligodendroglial lineage. Our findings indicate that CC hypomyelination is established during infancy and prior to oligodendroglial pattern alterations, which suggests that axon-oligodendroglia communication could be compromised in VPA animals. Thus, CC hypomyelination may underlie white matter alterations and contribute to atypical patterns of connectivity and metabolism found in ASD.Despite the dramatic efficacy of EGFR-TKIs, most of non-small cell lung cancer patients ultimately develop resistance to these agents. In this study, we explored the effects of miRNA-125a-5p and miRNA-145, alone or in combination, EGFR expression, cell growth and sensitivity of the NSCLC cells to erlotinib. The expression of EGFR was measured using RT-qPCR and Western blotting. The effect of miRNAs and erlotinib on cell growth and survival was assessed by trypan blue assay and MTT assay, respectively. Apoptosis was measured using ELISA cell death assay. We found that transfection of miRNA-125a-5p and miRNA-145 significantly inhibited the expression of EGFR mRNA and protein in a time-dependent manner (p less then 0.05 vs. blank control or negative control miRNA). ANOVA and Bonferroni’s test were used to ascertain significant differences between groups. Other experiments indicated that upregulation of each of miRNA-125a-5p or miRNA-145 inhibited cell growth, induced apoptosis, and markedly decreased the IC50 value of erlotinib in A549 lung cancer cells (p less then 0.05). Moreover, the combination of two miRNAs showed a stronger effect on cells survival, apoptosis, and drug sensitivity, relative to single miRNA (p less then 0.05). The results of our study indicate that the therapeutic delivery of miRNA-145 and miRNA-125a-5p to lung cancer may inhibit cell proliferation, trigger apoptosis, and sensitize lung cancer cells to EGFR-TKIs.Communities commonly warn against heavy alcohol and other substance use during natural disasters like hurricanes, because such use may produce risk for individuals and communities, with studies showing deleterious effects persisting months or even years. Examining patterns and emotional correlates of use in the immediate presence of hurricanes may identify useful risk prevention targets. We assessed self-reported substance use and emotions in a university community (faculty, staff, and students) having the unlucky fate of experiencing hurricanes in early September 2 years in a row. Participants (403 in 2018, 76.0% female; M age 28.82; SD = 12.36 and 292 in 2019, 72.6% female; M age 30.63; SD = 13.96) reported typical weekly substance use and emotions and then the same data during each hurricane day. Results showed elevated use of alcohol, caffeine and tobacco before and during each hurricane, but a rapid drop-off of alcohol and caffeine (but not tobacco) use immediately after-although anxiety remained high. Findings are interpreted using both tension-reduction and stress-coping models and suggestions are made for future risk mitigation.Cefuroxime (CFX) is a broad-spectrum second-generation cephalosporin and one of the best choices for antibiotic prophylaxis. However, when used in critically ill patients, it may present changes in its pharmacokinetic properties. Therefore, therapeutic drug monitoring of CFX is necessary for effective dosing strategies. A simple, rapid and sensitive liquid chromatographic method with UV detection was developed and validated for the quantification of CFX in plasma. The method involved a single-step precipitation of proteins with methanol and trifluoroacetic acid. Cefuroxime was analyzed on a Brisa LC2 C18 column in isocratic mode consisting of 0.1% trifluoroacetic acid in water and acetonitrile (7525) with UV detection at a wavelength of 280 nm. The retention times of CFX and cephazolin (internal standard) were 9.8 and 7.4 min, respectively. The calibration curve was linear over a concentration range of 0.25-50 μg/ml. The limits of detection and quantification were 0.1 μg/ml and 0.25 μg/ml, respectively. The accuracy and precision were always less then 10%. The mean recovery was 93.52%. This fast and simple method could be applied in routine analysis and pharmacokinetic studies.Transcriptomic responses combined with apical adverse ecologically relevant outcomes have proven to be useful to unravel and anchor molecular mechanisms of action to adverse outcomes. This is the case for feeding inhibition responses in the model ecotoxicological species Daphnia magna. The aim of the present study was to assess the transcriptomic responses in guts dissected from D. magna individuals exposed to concentrations of selected compounds that inhibit feeding and compare them with the responses associated to 2 levels of food restriction (low food and starvation). Chemical treatments included cadmium, copper, fluoranthene, λ-cyhalothrin, and the cyanotoxin anatoxin-a. Although the initial hypothesis was that exposure to chemical feeding inhibitors should elicit similar molecular responses as food limitation, the corresponding gut transcriptomic responses differed significantly. In moderate food limitation conditions, D. magna individuals increased protein and carbohydrate catabolism, likely to be used as energetic sources, whereas under severe starving conditions most metabolism-related pathways appeared down-regulated. Treatment with chemical feeding inhibitors promoted cell turnover-related signaling pathways in the gut, probably to renew tissue damage caused by the reported oxidative stress effects of these compounds, and inhibited the transcription of gut digestive gene enzymes and energetic metabolic pathways. We conclude that chemical feeding inhibitors, rather than mimicking the physiological response to low- or no-food conditions, cause specific toxic effects, preventing Daphnia both from feeding and from adjusting its metabolism to the resulting low energy intake. Environ Toxicol Chem 2021;001-11. © 2021 SETAC.PM2.5 is a well-known air pollutant threatening public health. Studies confirmed that exposure to the particles could impair pulmonary function, cause chronic obstructive pulmonary disease, and increase the incidence of lung cancer. The characteristic of PM2.5 varies across regions. The toxic function of PM2.5 in southwest China remains to be elucidated. This study aimed to investigate lung injury and its mechanisms induced by PM2.5 collected in Chengdu. Rats were administered with PM2.5 by intratracheal instillation for 4 weeks. Biochemical, cell count, and inflammation-related parameters were measured. Lung tissues were obtained for hematoxylin and eosin and Masson’s trichrome staining. The expression levels of vascular endothelial growth factor (VEGF), Janus tyrosine protein kinase-2 (JAK-2), and signal transducer and activator of transcription-3 (STAT-3) were detected by immunohistochemistry assays. Meanwhile, A549 cells were treated with the PM2.5. The cell cycle, and apoptosis were measured by flow cytometry. mRNA and protein expressions of JAK-2, STAT-3, p-STAT-3, and VEGFA were detected using qPCR and Western blot analysis respectively. Results of in vivo study showed that PM2.5 induced lung pathological injury, aggravated the accumulation of inflammatory cells, and increased the serum levels of inflammatory factors. In vitro experiments showed that PM2.5 disrupted the cell growth cycle and increased cell apoptosis through the activation of the JAK-2/STAT-3 signaling pathway. Taken together, this study provided convincing experimental evidence that PM2.5 collected in southwest China could induce pulmonary injury as manifested by inflammatory response and lung fibrosis, possibly through the modulation of the JAK-2/STAT-3 signaling pathway.

Surgical margin status remains a controversial factor in predicting the outcome of colorectal liver metastases (CRLM) resection. Our study aims to evaluate the effects of surgical margins on oncologic outcomes with regard to the genetic and morphological evaluation (GAME) score.

R1 resection was defined as having a less than 1 mm margin width. Patients who underwent surgery for CRLM from January 2005 to December 2018 were recruited. The patients were divided into two risk subgroups, namely, the low or medium risk (GAME 0-3) and high-risk (GAME score 4 or more) groups. The effects of margin status on overall survival (OS) and recurrence-free survival rate (RFS) were examined.

In total, 661 patients were recruited, among which 159 (24.1%) had R1 resection. Before hepatectomy, 514 patients showed a low or medium risk (R1 resection n = 124), while 147 patients demonstrated a high risk (R1 resection n = 35). In the whole cohort, multivariable analysis did show that R1 resection was associated with worse RFS and OS. While further research only found that in the low or medium risk group, R1 resection was related to poor OS and RFS. Meanwhile, in the high risk group, no significant difference was found in the median OS and RFS among patients with R0 or R1 resection.

The prognostic role of margin status varied according to the GAME score. Margin clearance only improved survival rates in patients with low or medium GAME score. In contrast, R1 resection demonstrated similar oncologic outcomes with R0 resection in patients with high GAME score.

The prognostic role of margin status varied according to the GAME score. Margin clearance only improved survival rates in patients with low or medium GAME score. In contrast, R1 resection demonstrated similar oncologic outcomes with R0 resection in patients with high GAME score.

To evaluate whether the 15-day threshold of headache days per month adequately reflects substantial differences in disability across the full spectrum of migraine.

The monthly frequency of headache days defines migraine subtypes and has crucial implications for epidemiological and clinical research as well as access to care.

The patients with migraine (N=836) who participated in the American Registry for Migraine Research, which is a multicenter, longitudinal patient registry, between February 2016 and March 2020, were divided into four groups based on monthly headache frequency Group 1 (0-7headache days/month, n=286), Group 2 (8-14headache days/month, n=180), Group 3 (15-23headache days/month, n=153), Group 4 (≥24headache days/month, n=217). Disability (MIDAS), Pain intensity (NRS), Work Productivity and Activity Impairment (WPAI), Pain Interference (PROMIS-PI), Patient Health Questionnaire-4 (PHQ-4), and General Anxiety Disorder-7 (GAD-7) scores were compared.

Mean (standard deviation [SD]) age was e refinements in the classification of migraine.

Our data suggest that the use of a 15 headache day/month threshold to distinguish episodic and chronic migraine does not capture the burden of illness nor reflect the treatment needs of patients. These results have important implications for future refinements in the classification of migraine.AkaLumine hydrochloride, named TokeOni, is one of the firefly luciferin analogs, and its reaction with firefly luciferase produces near-infrared (NIR) bioluminescence. Prior to studying the bioluminescence mechanism, basic knowledge about the chemical structures, electronic states, and absorption properties of TokeOni at various pH values of solution has to be acquired. In this paper, the absorption spectra for TokeOni and AkaLumine at pH 2-10 were measured. Density functional theory (DFT) calculations, time-dependent DFT calculations, and the vibrational analyses were carried out. The absorption spectra indicate that the chemical forms of TokeOni in solutions are same as those of AkaLumine. The peaks at pH 7-10 in the absorption spectra correspond to the excitation from the ground state of a carboxylate anion of AkaLumine, the peak at pH 2 corresponds to the excitation from the ground state of a carboxylate anion with an N-protonated thiazoline ring and N-protonated dimethylamino group of AkaLumine, and the peak at pH 4 corresponds to the excitation from the ground state of a carboxylate anion with an N-protonated thiazoline ring of AkaLumine.

Implantable cardioverter defibrillator (ICD) and permanent pacemaker (PPM) lead placement may worsen or result in tricuspid regurgitation (TR). While the association between lead placement and the incidence of TR has been established, current understanding of this problem remains incomplete. This systematic review and meta-analysis sought to pool the existing evidence to better understand the occurrence and severity of TR associated with cardiac implantable electrical device (CIED) insertion.

An electronic search was performed to identify all relevant studies published from 2000 to 2018. Overall, 15 studies were selected for the analysis comprising 4019 patients with data reported on TR development following ICD or PPM lead placement. Demographic information, perioperative clinical variables, and clinical outcome measures, including pre and postoperative echocardiographic TR grade changes, were extracted and pooled for systematic review.

Mean patient age was 69 years [95% CI 64.62-73.59], and 63% [95% Cd PPM lead placement is associated with increased TR post-procedure. Further studies are warranted to evaluate changes in TR grade in the long term.The SARS-CoV-2 pandemic has evolved to a global health problem with a dramatic morbidity and mortality rate impacting our daily life and those of many patients. While there is evidence that some diseases are associated with an increased risk for development of a more severe course of COVID-19, little is known on protective conditions. Importantly, clearance of viral infection and protection against disease manifestation crucially depends on functional innate and adaptive immunity and the interferon signalling axis. Here, we hypothesize that patients with non-segmental vitiligo (NSV), an autoimmune skin (and mucosal) disorder, may clear SARS-CoV-2 infection more efficiently and have a lower risk of COVID-19 development. Conversely, in case of COVID-19 development, vitiligo autoimmunity may influence the cytokine storm-related disease burden. In addition, immune activation during SARS-CoV-2 infection or COVID-19 disease might increase vitiligo disease activity. Our hypothesis is based on the shift of the immune system in NSV towards adaptive type 1 (IFNγ and CD8 T cells) and innate immune responses. Identified susceptibility genes of NSV patients may further confer increased antiviral activity. To validate our hypothesis, we suggest an international consortium to perform a retrospective data registry and patient-reported study on a large number of NSV patients worldwide during the COVID-19 pandemic.Electrokinetically driven insulator-based microfluidic devices represent an attractive option to manipulate particle suspensions. These devices can filtrate, concentrate, separate, or characterize micro and nanoparticles of interest. Two decades ago, inspired by electrode-based dielectrophoresis, the concept of insulator-based dielectrophoresis (iDEP) was born. In these microfluidic devices, insulating structures (i.e., posts, membranes, obstacles, or constrictions) built within the channel are used to deform the spatial distribution of an externally generated electric field. As a result, particles suspended in solution experience dielectrophoresis (DEP). Since then, it has been assumed that DEP is responsible for particle trapping in these devices, regardless of the type of voltage being applied to generate the electric field-direct current (DC) or alternating current. Recent findings challenge this assumption by demonstrating particle trapping and even particle flow reversal in devices that prevent DEP from occurring (i.e., unobstructed long straight channels stimulated with a DC voltage and featuring a uniform electric field). The theory introduced to explain those unexpected observations was then applied to conventional „DC-iDEP” devices, demonstrating better prediction accuracy than that achieved with the conventional DEP-centered theory. This contribution summarizes contributions made during the last two decades, comparing both theories to explain particle trapping and highlighting challenges to address in the near future.A GGGGCC hexanucleotide repeat expansion in the C9orf72 gene is linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (C9-ALS/FTD). Unconventional translation of the hexanucleotide repeat expansion generates five dipeptide repeat proteins (DPRs). The molecular mechanism underlying the DPR-linked neurotoxicity is under investigation. In this study, using cell-based models, we show that poly-proline-arginine DPR (poly-PR), the most neurotoxic DPR in vitro, binds to adenosine deaminase acting on RNA (ADAR)1p110 and ADAR2 and inhibits their RNA editing activity. We further show that poly-PR impairs cellular stress response that is mediated by ADAR1p110. These results together suggest that the poly-PR-mediated inhibition of the ADAR activity contributes to C9-ALS/FTD-linked neurotoxicity.Enamel Hypoplasia (EH) is known to be a useful indicator for wide range of detrimental factors in early childhood in past populations, such as nutritional disturbances, mechanical trauma, disease, metabolic, and/or genetic disorders. EH may be divided into three categories pits, grooves, and lines, where the last two are referred to as „Linear Enamel Hypoplasia” (LEH). The regularity of enamel formation allows retrospective determination of the age of LEH formation. The current article reviews and compares the best-known methods used to estimate age at LEH formation and provides a new computational tool. Growth curves for canines and incisors were developed based on tooth growth tables by previous authors. Optimal models were selected using the Akaike Information Criterion. A Microsoft Excel spreadsheet was created to calculate age at LEH formation using the most common methods. All method results were compared with an archaeological sample (44 teeth of 18 individuals from an early modern cemetery from Wrocław, Poland) and a theoretical model. The results of the methods were compared pairwise with Bland-Altman plots. The current article provides a quick and easy-to-use tool for analyzing LEH chronology and comparing the results of different methods. As shown by the Bland-Altman plots, most methods provide approximately consistent results for LEHs formed at around 2-3 years of age. However, LEHs formed particularly early or late are more prone to discrepancies between different methods. Comparison of the age at LEH formation obtained by different methods should be done carefully – and the new LEH calculation tool with optimized equations provided in this publication can facilitate this process.

A profound feeling of guilt and its role in complicating psychological reactions are accepted as central issues in suicide bereavement. However, research examining the relationship of guilt with mental disorders commonly following suicide bereavement is still lacking. This study aimed to examine the association between guilt and symptoms of depression, prolonged grief disorder, and posttraumatic stress disorder (PTSD) after suicide bereavement, as well as its moderating role in the association between the time which elapsed since bereavement and psychopathological symptoms.

154 self-selected adult German participants bereaved by suicide completed online questionnaires assessing sociodemographics, characteristics related to the loss, guilt, depression, prolonged grief, and PTSD.

Significant positive correlations were found between guilt and all assessed psychopathological symptoms. Further, guilt was a significant correlate with symptoms of depression, prolonged grief, PTSD over and above sociodemographic factors, and time that elapsed since the loss. Guilt furthermore moderated the link between the time which elapsed since bereavement and depressive symptoms, while this effect was not observed for prolonged grief and posttraumatic stress symptoms.

Our findings replicate theoretical frameworks linking feelings of guilt with mental disorders after suicide bereavement. Accordingly, they highlight the necessity to adapt psychotherapeutic interventions according to the specific needs of this population to maximize treatment effectiveness.

Our findings replicate theoretical frameworks linking feelings of guilt with mental disorders after suicide bereavement. Accordingly, they highlight the necessity to adapt psychotherapeutic interventions according to the specific needs of this population to maximize treatment effectiveness.

To evaluate preclinical education in Endodontology at Austrian, German and Swiss dental schools using an online survey.

An online survey divided into nine categories was sent using SurveyMonkey software to 37 dental schools, before the spread of the COVID-19 pandemic. The questionnaire included 50 questions to evaluate preclinical endodontic education, such as faculty-to-student ratios, topics taught and materials used, in preclinical phantom head courses. Seven and 14days after the first e-mail contact, dental schools received a reminder e-mail. After four and six weeks, the dental schools were contacted by telephone and asked to participate in the online survey. The processing time was eight weeks in total.

The response rate was 89%. Preclinical endodontic education at the participating dental schools differs considerably. Theory classes ranged from 1 to 70h (15h mean), and practical classes ranged from 3 to 78h (39h mean). The faculty-to-student ratio varied between 14 and 138 (115mean). Forty-five per cent of the dental schools had a specialist in endodontics teaching theory. Several dental microscopes were available for preclinical teaching purposes at 82% of the dental schools. The majority (82%) taught root canal preparation with rotary or reciprocating NiTi instruments. Overall, 85% of the dental schools taught lateral compaction, amongst other methods, for canal filling.

A substantial divergence amongst the dental schools regarding the time dedicated to theory and practical instruction in Endodontology was reported. However, convergence in the use of root canal treatment techniques and materials was reported.

A substantial divergence amongst the dental schools regarding the time dedicated to theory and practical instruction in Endodontology was reported. However, convergence in the use of root canal treatment techniques and materials was reported.

To investigate (1) the cytotoxic potential of the brown precipitate (BP) formed with sodium hypochlorite (NaOCl) and chlorhexidine gluconate (CHX), using both a small animal model of Caenorhabditis elegans (C.elegans) and cultured human gingival fibroblasts; and (2) the chemical composition of BP using Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS).

Brown precipitate was obtained by mixing equal volumes of 6% NaOCl and 2% CHX and separating the BP from clear supernatant by centrifugation. The brown precipitate was weighed and solubilized in dimethyl sulfoxide for cytotoxicity experiments. The cytotoxic effect of BP was assessed using C.elegans larvae and primary immortalized human gingival fibroblasts-hTERT (hTERT-hNOF) cells. Various dilutions of BP (25ng/µL-150ng/µL), supernatant (0.15% v/v), NaOCl (1100-11000 dilutions of 6% NaOCl) or CHX (1500-11000 dilutions of 2% CHX) along with vehicle control (0.5% v/v ethanol and 0.15% v/v DMSO) or untreated control (growth medium) were tested on C.eleicities observed in C.elegans larvae and human gingival fibroblasts. Because of the insoluble and toxic nature of BP, consecutive use of CHX and NaOCl irrigants should be avoided in root canal treatment.

Brown precipitate was toxic in both C. elegans larvae and hTERT-hNOF cells. The ToF-SIMS analysis of BP revealed ions characteristic of CHX and PCA that could account for the toxicities observed in C. elegans larvae and human gingival fibroblasts. Because of the insoluble and toxic nature of BP, consecutive use of CHX and NaOCl irrigants should be avoided in root canal treatment.

Haematopoietic cell transplantation (HCT) therapy tends to be associated with various complications including engraftment failure, regimen-related toxicities, and infectious diseases. In addition, HC infusion itself occasionally elicits adverse events (AEs), one of the most common AEs is an allergic reaction. As appropriate laboratory tests have not yet been established to distinguish allergy-mediated AEs from other complications, clinical responses for HCT-related AEs can only be nonspecific. In this pilot study, using passive immune basophil activation test (pi-BAT), we attempted to distinguish an HC infusion-induced allergic reaction from various HCT-related AEs.

Using pi-BAT, we examined 34 patients who underwent HCT, that is, 11 with AEs and 23 without AEs as controls.

Two of the eleven AE cases were pi-BAT positive and, the rest of nine AE cases were negative, while all non-AE cases were negative. Both of the two positive cases showed erythema, tachycardia, plus cough. Because erythema is one of the representative symptom of allergy, those cases could be classified as allergic reaction cases or anaphylaxis cases if tachycardia and cough were concomitant symptoms of erythema. Among the nine AEs with pi-BAT negative result, four cases showed urticaria, four showed vomiting plus diarrhoea, and one showed cough. Urticaria case was strongly suspected of allergy, however, the AE cases were pi-BAT negative.

The pi-BAT may be useful as an auxiliary diagnostic tool to confirm the possible involvement of HC infusion in HCT-related AEs and identify an immunologic mechanism for HCT-related hypersensitivity reactions.

The pi-BAT may be useful as an auxiliary diagnostic tool to confirm the possible involvement of HC infusion in HCT-related AEs and identify an immunologic mechanism for HCT-related hypersensitivity reactions.Lipid rafts, membrane microdomains enriched with (glyco)sphingolipids, cholesterol, and select proteins, act as cellular signalosomes. Various methods have been used to separate lipid rafts from bulk (non-raft) membranes, but most often, non-ionic detergent Triton X-100 has been used in their isolation. However, Triton X-100 is a reported disruptor of lipid rafts. Histological evidence confirmed raft disruption by Triton X-100, but remarkably revealed raft stability to treatment with a related polyethylene oxide detergent, Brij O20. We report isolation of detergent-resistant membranes from mouse brain using Brij O20 and its use to determine the distribution of major mammalian brain gangliosides, GM1, GD1a, GD1b and GT1b. A different distribution of gangliosides-classically used as a raft marker-was discovered using Brij O20 versus Triton X-100. Immunohistochemistry and imaging mass spectrometry confirm the results. Use of Brij O20 results in a distinctive membrane distribution of gangliosides that is not all lipid raft associated, but depends on the ganglioside structure. This is the first report of a significant proportion of gangliosides outside raft domains. We also determined the distribution of proteins functionally related to neuroplasticity and known to be affected by ganglioside environment, glutamate receptor subunit 2, amyloid precursor protein and neuroplastin and report the lipid raft populations of these proteins in mouse brain tissue. This work will enable more accurate lipid raft analysis with respect to glycosphingolipid and membrane protein composition and lead to improved resolution of lipid-protein interactions within biological membranes.

To better characterize the ways that migraine affects multiple domains of life.

Further understanding of migraine burden is needed.

Adults with migraine randomized to mindfulness-based stress reduction or headache education arms (n=81) in two separate randomized clinical trials participated in semistructured in-person qualitative interviews conducted after the interventions. Interviews queried participants on migraine impact on life and were audio-recorded, transcribed, and summarized into a framework matrix. A master codebook was created until meaning saturation was reached and magnitude coding established code frequency. Themes and subthemes were identified using a constructivist grounded theory approach.

Despite most participants being treated with acute and/or prophylactic medications, 90% (73/81) reported migraine had a negative impact on overall life, with 68% (55/81) endorsing specific domains of life impacted and 52% (42/81) describing impact on emotional health. Six main themes of migraine imding of the deep burden of this chronic neurological disease is needed to effectively target and treat what is most important to those living with migraine.

Migraine has a global negative impact on overall life, cognitive and emotional health, work, family, and social life. Migraine contributes to isolation, frustration, guilt, fear, avoidance behavior, and stigma. A greater understanding of the deep burden of this chronic neurological disease is needed to effectively target and treat what is most important to those living with migraine.Gangliosides are glycosphingolipids abundantly expressed in the vertebrate nervous system, and are classified into a-, b-, or c-series according to the number of sialic acid residues. The enzyme GD3 synthase converts GM3 (an a-series ganglioside) into GD3, a b-series ganglioside highly expressed in the developing and adult retina. The present study evaluated the visual system of GD3 synthase knockout mice (GD3s-/- ), morphologically and functionally. The absence of b- series gangliosides in the retinas of knockout animals was confirmed by mass spectrometry imaging, which also indicated an accumulation of a-series gangliosides, such as GM3. Retinal ganglion cell (RGC) density was significantly reduced in GD3s-/- mice, with a similar reduction in the number of axons in the optic nerve. Knockout animals also showed a 15% reduction in the number of photoreceptor nuclei, but no difference in the bipolar cells. The area occupied by GFAP-positive glial cells was smaller in GD3s-/- retinas, but the number of microglial cells/macrophages did not change. In addition to the morphological alterations, a 30% reduction in light responsiveness was detected through quantification of pS6-expressing RGC, an indicator of neural activity. Furthermore, electroretinography (ERG) indicated a significant reduction in RGC and photoreceptor electrical activity in GD3s-/- mice, as indicated by scotopic ERG and pattern ERG (PERG) amplitudes. Finally, evaluation of the optomotor response demonstrated that GD3s-/- mice have reduced visual acuity and contrast sensitivity. These results suggest that b-series gangliosides play a critical role in regulating the structure and function of the mouse visual system.

Electronic Health (eHealth) tools offer opportunities for people to access health information online; yet, most tools are not designed to meet the unique needs of diverse older adults, leading to health disparities. Our goal was to provide guidance for the development of eHealth tools for diverse older populations for use in geriatric care models.

Guidance for eHealth tools was compiled from user design resources and eHealth design literature. Pragmatic examples were provided from an evidenced-based eHealth tool called PREPAREforYourCare.org (PREPARE). We used quantitative feasibility data from PREPARE research studies and qualitative analysis of PREPARE focus groups, cognitive interviews, and feedback from randomized trials to further inform our recommendations.

Guidance and lessons learned include (1) define clear objectives and a conceptual framework; (2) co-create with the target population; (3) optimize the design and layout for accessibility and ease of use, such as text at the 5th grade reading level, closed captioning, etc.; (4) use simple, standardized navigation design; (5) use actionable information to enhance behavior change, such as modeling of behaviors; (6) align accompanying written materials with the eHealth tool; and (7) create tracking mechanisms for ongoing user feedback. PREPARE is used as a case example to provide pragmatic illustrations for how the guidance may be operationalized.

eHealth tools can be tailored to the unique characteristics, preferences, and needs of diverse older populations. Following the „lessons learned” may help decrease health disparities among diverse older adults and ensure eHealth tools are readily accessible and culturally appropriate.

eHealth tools can be tailored to the unique characteristics, preferences, and needs of diverse older populations. Following the „lessons learned” may help decrease health disparities among diverse older adults and ensure eHealth tools are readily accessible and culturally appropriate.

Patients with cancer have played a key role in advocating for legal access to cannabis, but little is known about links between cancer and cannabis use or cannabis-related beliefs. The authors used data from a national survey to study these relationships.

Nationally representative data collected by the National Survey on Drug Use and Health from 2015 to 2019 were acquired. Patterns of cannabis use and cancer history were examined and tested within age group subpopulations via domain analysis using survey weights.

Data for 214,505 adults, including 4741 individuals (3.8%) with past (>1 year ago) cancer diagnosis and 1518 individuals (1.2%) with recent (≤1 year ago) cancer diagnosis, were examined. Cannabis use was less common in those with past (8.9%; 95% CI, 8.0%-9.8%) or recent (9.9%; 95% CI, 6.9%-11.1%) cancer diagnosis than in those without a history of cancer (15.9%; 95% CI, 15.7%-16.1%). However, when analyses were stratified by age group, those 18 to 34 years of age were more likely to report p should account for patient age, and accurate information about cannabis should be provided to help patients with cancer make decisions about cannabis use.

Cannabis (marijuana) use is increasing in the United States, but we do not have much information on the relationship between cannabis use and cancer. We studied information from a representative group of people and found that younger patients generally reported more past and/or recent cannabis use if they had been diagnosed with cancer whereas older individuals did not. Beliefs about cannabis risk and accessibility differed by age. Clinical trials to study cannabis should account for patient age, and accurate information about cannabis should be provided to help patients with cancer make decisions about cannabis use.A new device for monitoring the laryngeal nerves during thyroid surgery has been developed. NIM Vital™ (Medtronic Xomed, Inc., Jacksonville, FL, USA) incorporates (a) a new wireless design, (b) NIM NerveTrendTM (Medtronic Xomed) EMG reporting, (c) intelligent noise-reduction technology that suppresses artifacts, (d) smart troubleshooting pop-up alerts, and (e) NIM Nervassure ™ (Medtronic Xomed) for continuous monitoring. This device offers enhanced stability and flexibility for both intermittent and continuous laryngeal nerve monitoring. The new NIM NerveTrend ™ EMG reporting makes it possible to track the recurrent laryngeal nerve condition throughout a procedure, even when using intermittent nerve monitoring. During both continuous and intermittent monitoring, green, yellow and red status bars provide visual information and associated tones provide audible cues, making it easy to monitor nerve function and interpret EMG trends. This new tool for laryngeal nerve monitoring has the potential to augment nerve dissection during surgery. Measurements of long-term outcome are needed to establish their efficacy.Interventional cardiovascular medicine has seen constant progress over the last few decades. Since the first angiograms and percutaneous transluminal coronary angioplasty were carried out, this progress has been tremendous and has led to a substantial decline in cardiovascular morbidity and mortality. The purpose of this article is to report and review the latest developments and evidence in robotics-assisted percutaneous coronary intervention (rPCI) and its potential future applications, opportunities, and limitations. Contemporary evidence shows that rPCI can lead to a significant reduction in radiation exposure as well as medical hazards for cardiologists. Rates of device and procedural success remain high and there is no evidence of a disadvantage for the patient. The accuracy of implantation with a reduced geographic mismatch is a further advantage that can result in a higher quality of treatment. Even in complex coronary lesions and procedures, rPCI seems to be safe and efficient. The latest developments include telestenting over hundreds of kilometers from a remote platform. Currently, the main limitations are the absence of large-scale randomized trials for the valid assessment of the benefits and disadvantages of rPCI as well as the technical limitations of the currently available rPCI systems. rPCI is a forward-looking innovation in cardiology that is applicable to a wide range of coronary interventions. Despite the present lack of knowledge and the limited data concerning the outcome for the patient, the available literature reveals promising results that should lead to improvements for physicians and patients.Oncologic visceral surgery has recently been revolutionized by robotics, artificial intelligence (AI), sparing of functionally important structures and innovative intraoperative imaging tools. These techniques enable new dimensions of precision surgery and oncology. Currently, data-driven, cognitive operating rooms are standing at the forefront of the latest technical and didactic developments in abdominal surgery. Rectal low anterior resection with total mesorectal excision (TME) for lower- and middle-third rectal cancer is a challenging operation due to the narrow pelvis and the tender guiding structures. Thus, new approaches have been needed to simplify the procedure and to upgrade the results. The combination of robotics with pelvic intraoperative neuromonitoring (pIONM) and new possibilities of visualization, such as multi- and hyperspectral imaging (MSI / HSI) or fluorescence imaging (FI) with indocyanine green (ICG) is a forward-looking modality to enhance surgical precision and reduce postoperative complications while improving oncologic and functional outcomes with a better quality of life. The aim of our video-paper is to show how to achieve maximum precision by combining robotic surgery with pelvic intraoperative neuromonitoring and new imaging devices for rectal cancer.Head and neck squamous cell carcinomas (HNSCC) take many lifes worldwide. Patients with recurrent/metastatic disease receive combination chemotherapy containing anti-EGFR antibody cetuximab. However, resistance often hurdles therapy. The mechanism is yet to unveil, although EGFR extracellular alterations and activity of c-Met signaling were accused. We investigated the effects of EGFR-vIII and EGFR-R521K on cetuximab efficacy in HNSCC in cellular, xenograft, and clinical setup. Furthermore, we investigated the efficacy of c-Met inhibition in HNSCC in vitro and in vivo. We showed that EGFR-vIII is very rare in HNSCC, while the common R521K polymorphism abolishes antibody-dependent cellular cytotoxicity and in vivo antitumor effect of cetuximab. This selectivity was not reflected in immunophenotype or survival data of HNSCC patients, suggesting a more complex mechanism behind. Interestingly, c-Met inhibitor SU11274 was more effective in cetuximab-resistant, EGFR R521K heterozygous cells and xenografts, raising the possible importance of simultaneous targeting of the two receptors.There are about 14 million new cancer cases and 8 million deaths every year. Every second man and one in every three women will get cancer during their lifetimes. Following decades of steady increase, death rates have stabilized due to increased awareness and prevention, early detection, and the emergence of more effective therapy. Yet despite all the advances cancer remains a major killer. Despite improved therapies, nearly all current treatments face the same problem for many patients, they ultimately stop working. Therapy resistance is the ultimate challenge facing cancer researchers and patients today. In this review we present an overview of the most important resistance mechanisms, discussing progress in therapies designed to prevent or overcome anticancer therapy resistance. Finally, we present recent findings from our own laboratory on the development of new experimental models and new therapeutic approaches to combat multidrug resistant cancer.Chemotherapy plays an important role in the treatment of cancer. While clinical chemotherapy protocols can lead to remission in some patients, in many cases tumor progression occurs despite continued treatment. In the present study we summarize mathematical approaches to model tumor growth and response to treatment, focusing on anticancer therapy resistance. We present results obtained at the recently founded Cybermedical Competence Center at Óbuda University, focusing on the development of a new therapy optimization concept that aims to optimize traditional chemotherapy.