Lithium ions induce prestalk-associated gene expression and inhibit prespore gene expression in Dictyostelium discoideum

We investigated the effect of Li+ on two types of cyclic AMP-regulated gene expression and on basal and cyclic AMP-stimulated inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) levels. Li+ effectively inhibits cyclic AMP-induced prespore gene expression, half-maximal inhibition occurring at about 2mM-LiCl. In contrast, Li+ (1-3 mM) promotes the cyclic AMP-induced increase of cysteine proteinase-2 mRNA levels, and induces the expression of this prestalk-associated gene in the absence of cyclic AMP stimuli. At concentrations exceeding 4-5 mM, LiCl inhibits cysteine proteinase-2 gene expression. LiCl reduces basal Ins(1,4,5)P3 levels and decreases the cyclic AMP-induced accumulation of Ins(1,4,5)P3; both effects occur half-maximally at 2-3 mM-LiCl. These results indicate that the induction of the cysteine proteinase-2 gene by Li+ is not due to elevated levels of Ins(1,4,5)P3. It is, however, possible that inhibition of prespore gene expression by Li+ is caused by Li+-induced reduction of basal and/or stimulated Ins(1,4,5)P3 levels

A Tier 3 Method for Enteric Methane in Dairy Cows Applied for Fecal N Digestibility in the Ammonia Inventory

The current inventory of N emission from cow excreta relies on fecal N digestibility data in Dutch feeding tables, assuming additivity of dietary ingredients to obtain diet values (CVB model). Alternatively, fecal N digestibility can be estimated by a dynamic, mechanistic model of digestion in the gastrointestinal tract, currently used as Tier 3 for enteric methane prediction in the Netherlands (Tier 3 model). Estimates of in situ rumen degradation characteristics for starch, neutral detergent fiber (NDF) and crude protein used as an input for the Tier 3 model were based on Dutch feeding tables (the protein evaluation system). Both methods were evaluated on independent dataset on fecal N digestibility that was constructed from peer-reviewed papers on N balance data for dairy cows published since 1999 (54 trials, 242 treatment means). Results indicate that observed apparent fecal N digestibility (67.0 ± 6.77%) was systematically over-predicted in particular by the CVB model (73.8 ± 4.35%) compared to the Tier 3 model (69.8 ± 4.52%). For the dataset including only observations from Dutch trials the observed fecal N digestibility (70.4 ± 7.33%) was also systematically over-predicted by the CVB model (76.4 ± 5.27%) but not by the Tier 3 model (69.7 ± 5.81%). Mixed model analysis with study as random factor indicated the slope of the regression between observed and predicted fecal N digestibility to be smaller than 1, in particular for the CVB model (CVB model slope varied between 0.405 and 0.560 and Tier 3 model slope between 0.418 and 0.657). The over-prediction by the CVB model with 6–7%-units of digestibility will lead to an over-predicted ammoniacal N excretion (urinary N) in the ammonia inventory, and biased estimation of N mitigating potential of nutritional measures. The present study demonstrates the benefit of using the Tier 3 model to predict the average level of apparent fecal N digestibility compared to the CVB model. The general estimates of in situ rumen degradation characteristics for starch, NDF and crude protein used as input for the Tier 3 model seemed applicable for the Dutch trials but less so for the non-Dutch trials

The effects of an Internet based self-help course for reducing panic symptoms - Don't Panic Online: study protocol for a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Internet based self-help for panic disorder (PD) has proven to be effective. However, studies so far have focussed on treating a full-blown disorder. Panic symptoms that do not meet DSM-IV criteria are more prevalent than the full-blown disorder and patients with sub-clinical panic symptoms are at risk of developing PD. This study is a randomised controlled trial aimed to evaluate an Internet based self-help intervention for sub-clinical and mild PD compared to a waiting list control group.</p> <p>Methods</p> <p>Participants with mild or sub-clinical PD (N = 128) will be recruited in the general population. Severity of panic and anxiety symptoms are the primary outcome measures. Secondary outcomes include depressive symptoms, quality of life, loss of production and health care consumption. Assessments will take place on the Internet at baseline and three months after baseline.</p> <p>Discussion</p> <p>Results will indicate the effectiveness of Internet based self-help for sub-clinical and mild PD. Strengths of this design are the external validity and the fact that it is almost completely conducted online.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1639">NTR1639</a> The Netherlands Trial Register is part of the Dutch Cochrane Centre.</p

Endoscopic full-thickness resection of T1 colorectal cancers:a retrospective analysis from a multicenter Dutch eFTR registry

Background Complete endoscopic resection and accurate histological evaluation for T1 colorectal cancer (CRC) are critical in determining subsequent treatment. Endoscopic full-thickness resection (eFTR) is a new treatment option for T1 CRC<2cm. We aimed to report clinical outcomes and short-term results. Methods Consecutive eFTR procedures for T1 CRC, prospectively recorded in our national registry between November 2015 and April 2020, were retrospectively analyzed. Primary outcomes were technical success and R0 resection. Secondary outcomes were histological risk assessment, curative resection, adverse events, and short-term outcomes. Results We included 330 procedures: 132 primary resections and 198 secondary scar resections after incomplete T1 CRC resection. Overall technical success, R0 resection, and curative resection rates were 87.0% (95% confidence interval [CI] 82.7%-90.3%), 85.6% (95%CI 81.2%-89.2%), and 60.3% (95%CI 54.7%-65.7%). Curative resection rate was 23.7% (95%CI 15.9%-33.6%) for primary resection of T1 CRC and 60.8% (95%CI 50.4%-70.4%) after excluding deep submucosal invasion as a risk factor. Risk stratification was possible in 99.3%. The severe adverse event rate was 2.2%. Additional oncological surgery was performed in 49/320 (15.3%), with residual cancer in 11/49 (22.4%). Endoscopic follow-up was available in 200/242 (82.6%), with a median of 4 months and residual cancer in 1 (0.5%) following an incomplete resection. Conclusions eFTR is relatively safe and effective for resection of small T1 CRC, both as primary and secondary treatment. eFTR can expand endoscopic treatment options for T1 CRC and could help to reduce surgical overtreatment. Future studies should focus on long-term outcomes

A significant proportion of classic Hodgkin lymphoma recurrences represents clonally unrelated second primary lymphoma

Despite high cure rates in classic Hodgkin lymphoma (cHL), relapses are observed. Whether relapsed cHL represents second primary lymphoma or an underlying T-cell lymphoma (TCL) mimicking cHL is under-investigated. To analyze the nature of cHL recurrences, in-depth clonality testing of immunoglobulin (IG) and T-cell receptor (TR) rearrangements was performed in paired cHL diagnosis and recurrences of 60 patients, supported by targeted mutation analysis of lymphoma-associated genes. Clonal IG rearrangements were detected by next-generation sequencing (NGS) in 69/120 (58%) diagnosis and recurrence samples. The clonal relationship could be established in 34 cases, identifying clonally related relapsed cHL in 24/34 patients (71%). Clonally unrelated cHL was observed in 10/34 patients (29%) as determined by IG-NGS clonality assessment, and confirmed by the identification of predominantly mutually exclusive gene mutations in the paired cHL samples. In recurrences of &gt;2 years, ~60% of cHL patients for which the clonal relationship could be established showed a second primary cHL. Clonal TR gene rearrangements were identified in 14/125 samples (11%), and TCL-associated gene mutations were detected in 7/14 samples. Retrospective pathology review with integration of the molecular findings were consistent with an underlying TCL in 5 patients aged &gt;50 years. This study shows that cHL recurrences, especially after 2 years, sometimes represent a new primary cHL or TCL mimicking cHL, as uncovered by NGS-based IG/TR clonality testing and gene mutation analysis. Given the significant therapeutic consequences, molecular testing of a presumed relapse in cHL is crucial for subsequent appropriate treatment strategies adapted to the specific lymphoma presentation.</p

A significant proportion of classic Hodgkin lymphoma recurrences represents clonally unrelated second primary lymphoma

Despite high cure rates in classic Hodgkin lymphoma (cHL), relapses are observed. Whether relapsed cHL represents second primary lymphoma or an underlying T-cell lymphoma (TCL) mimicking cHL is under-investigated. To analyze the nature of cHL recurrences, in-depth clonality testing of immunoglobulin (IG) and T-cell receptor (TR) rearrangements was performed in paired cHL diagnosis and recurrences of 60 patients, supported by targeted mutation analysis of lymphoma-associated genes. Clonal IG rearrangements were detected by next-generation sequencing (NGS) in 69/120 (58%) diagnosis and recurrence samples. The clonal relationship could be established in 34 cases, identifying clonally related relapsed cHL in 24/34 patients (71%). Clonally unrelated cHL was observed in 10/34 patients (29%) as determined by IG-NGS clonality assessment, and confirmed by the identification of predominantly mutually exclusive gene mutations in the paired cHL samples. In recurrences of &gt;2 years, ~60% of cHL patients for which the clonal relationship could be established showed a second primary cHL. Clonal TR gene rearrangements were identified in 14/125 samples (11%), and TCL-associated gene mutations were detected in 7/14 samples. Retrospective pathology review with integration of the molecular findings were consistent with an underlying TCL in 5 patients aged &gt;50 years. This study shows that cHL recurrences, especially after 2 years, sometimes represent a new primary cHL or TCL mimicking cHL, as uncovered by NGS-based IG/TR clonality testing and gene mutation analysis. Given the significant therapeutic consequences, molecular testing of a presumed relapse in cHL is crucial for subsequent appropriate treatment strategies adapted to the specific lymphoma presentation.</p

A significant proportion of classic Hodgkin lymphoma recurrences represents clonally unrelated second primary lymphoma

Despite high cure rates in classic Hodgkin lymphoma (cHL), relapses are observed. Whether relapsed cHL represents second primary lymphoma or an underlying T-cell lymphoma (TCL) mimicking cHL is under-investigated. To analyze the nature of cHL recurrences, in-depth clonality testing of immunoglobulin (IG) and T-cell receptor (TR) rearrangements was performed in paired cHL diagnosis and recurrences of 60 patients, supported by targeted mutation analysis of lymphoma-associated genes. Clonal IG rearrangements were detected by next-generation sequencing (NGS) in 69/120 (58%) diagnosis and recurrence samples. The clonal relationship could be established in 34 cases, identifying clonally related relapsed cHL in 24/34 patients (71%). Clonally unrelated cHL was observed in 10/34 patients (29%) as determined by IG-NGS clonality assessment, and confirmed by the identification of predominantly mutually exclusive gene mutations in the paired cHL samples. In recurrences of &gt;2 years, ~60% of cHL patients for which the clonal relationship could be established showed a second primary cHL. Clonal TR gene rearrangements were identified in 14/125 samples (11%), and TCL-associated gene mutations were detected in 7/14 samples. Retrospective pathology review with integration of the molecular findings were consistent with an underlying TCL in 5 patients aged &gt;50 years. This study shows that cHL recurrences, especially after 2 years, sometimes represent a new primary cHL or TCL mimicking cHL, as uncovered by NGS-based IG/TR clonality testing and gene mutation analysis. Given the significant therapeutic consequences, molecular testing of a presumed relapse in cHL is crucial for subsequent appropriate treatment strategies adapted to the specific lymphoma presentation.</p