Extent of Shisham (Dalbergia sissoo Roxb.) Decline in Sialkot, Gujranwala, Lahore and Sargodha Districts

A thorough survey of four districts of Punjab viz. Sialkot, Gujranwala, Lahore and Sargodha was carried out during May-June 2003 to study the present scenario of shisham (Dalbergia sissoo Roxb.) decline in these areas and to find out relationship, if any, between disease severity and edaphic conditions. From each of the four districts, canal banks, highways and roadsides, and agricultural lands were surveyed. In Lahore surveyed areas also included University of the Punjab, Aitchison College and roadside along the canal bank of BRB Lahore Branch. From each district 700 – 1200 plants were observed. Shisham trees were found to be attacked with two types of diseases viz. wilting and dieback, the latter being the more prevalent than the former. Maximum mortality of 75 – 80 % was observed along the canal banks except BRB Lahore branch. Along the highways and roadsides 20 – 40 % plants were found dead. In the Punjab University about 10 % plants were found dead while 17 % were affected with dieback and wilting ranging from mild infection to highly diseased. The least disease incidence and mortality rate was observed on plants growing on agricultural lands, along the roadside of BRB Lahore branch and in Aitchison College. Disease incidence and severity seemed to have no relation with soil pH. Generally older plants were found to be more susceptible to the disease attack than the younger ones. It was concluded that plant resistance to disease attack was associated with proper irrigation management. Apparently stressed conditions especially high soil moisture content is responsible for the attack and severity of the disease. It is recommended that along the canal bank shisham should be replaced with Eucalyptus spp. Furthermore, seeds from the resistant shisham plants, standing healthy among the hundreds of dead ones along the canal banks, should be used to raise nurseries for shisham plantation on suitable places away from the canals.&nbsp

Dieback Resistance Potential in Different Varieties of Shisham (Dalbergia sissoo Roxb.)

Nine phenotypically different varieties of Shisham (Dalbergia sissoo Roxb.) were identified from Punjab University, Quaid-e-Azam Lahore, Pakistan and adjacent areas, on the basis of physical appearance of the plant, branching pattern, pod characters, leaf and leaflet size and shape, branching and leaf density and stem surface characteristics. On the basis of their relative resistance to dieback disease, the different varieties were named as Resistant 1, Susceptible 1‑4, Unspecified 1‑4. The Resistant 1 variety is characterized with dense, and long branches, which grow outward and downward forming a canopy. Generally plants do not attain much height. Leaves are large up to 16 cm in length, with four or five leaflets per leaf. Leaflets broad, globose or subglobose, young leaflets glaucous, mature leaflets glabrous, leaflet apex apiculate. Pods small, generally one rarely two seeded. Susceptible 1 and Susceptible 2 varieties were found to be highly susceptible to dieback showing 20% or more dieback incidence. These two varieties have been commonly cultivated in Punjab. Susceptible 3 and Susceptible 4 varieties were least susceptible showing dieback incidence not more than 2 %. The unspecified varieties 1 – 4 were named so because they did not show any disease symptoms but number of plants of these varieties was not large enough to decide their resistant potential. Shisham forestation can be revived by planting Resistant 1 and less susceptible varieties viz., Susceptible 3 and Susceptible 4 on suitable, well-drained sandy loam soils

Thiopurine monotherapy is effective in ulcerative colitis but significantly less so in Crohn’s disease: long-term outcomes for 11 928 patients in the UK inflammatory bowel disease bioresource

Objective: Thiopurines are widely used as maintenance therapy in inflammatory bowel disease (IBD) but the evidence base for their use is sparse and their role increasingly questioned. Using the largest series reported to date, we assessed the long-term effectiveness of thiopurines in ulcerative colitis (UC) and Crohn’s disease (CD), including their impact on need for surgery. Design: Outcomes were assessed in 11 928 patients (4968 UC, 6960 CD) in the UK IBD BioResource initiated on thiopurine monotherapy with the intention of maintaining medically induced remission. Effectiveness was assessed retrospectively using patient-level data and a definition that required avoidance of escalation to biological therapy or surgery while on thiopurines. Analyses included overall effectiveness, time-to-event analysis for treatment escalation and comparison of surgery rates in patients tolerant or intolerant of thiopurines. Results: Using 68 132 patient-years of exposure, thiopurine monotherapy appeared effective for the duration of treatment in 2617/4968 (52.7%) patients with UC compared with 2378/6960 (34.2%) patients with CD (p<0.0001). This difference was corroborated in a multivariable analysis: after adjusting for variables including treatment era, thiopurine monotherapy was less effective in CD than UC (OR 0.47, 95% CI 0.43 to 0.51, p<0.0001). Thiopurine intolerance was associated with increased risk of surgery in UC (HR 2.44, p<0.0001); with a more modest impact on need for surgery in CD (HR=1.23, p=0.0015). Conclusion: Thiopurine monotherapy is an effective long-term treatment for UC but significantly less effective in CD

Targeting the MAPK7/MMP9 axis for metastasis in primary bone cancer

Metastasis is the leading cause of cancer related death. This multistage process involves contribution from both tumour cells and the tumour stroma to release metastatic cells into the circulation. Circulating tumour cells (CTCs) survive circulatory cytotoxicity, extravasate and colonise secondary sites effecting metastatic outcome. Reprogramming the transcriptomic landscape is a metastatic hallmark but detecting underlying master regulators that drive pathological gene expression is a key challenge, especially in childhood cancer. Here we used whole tumour plus single cell RNA sequencing in primary bone cancer and CTCs to perform weighted gene co-expression network analysis to systematically detect coordinated changes in metastatic transcript expression. This approach with comparisons applied to data collected from cell line models, clinical samples and xenograft mouse models revealed MAPK7/MMP9 signalling as a driver for primary bone cancer metastasis. RNAi knockdown of MAPK7 reduces proliferation, colony formation, migration, tumour growth, macrophage residency/polarisation and lung metastasis. Parallel to these observations were reduction of activated interleukins IL1B, IL6, IL8 plus mesenchymal markers VIM and VEGF in response to MAPK7 loss. Our results implicate a newly discovered, multidimensional MAPK7/MMP9 signalling hub in primary bone cancer metastasis that is clinically actionable

COVID-19 breakthrough infections in type 1 diabetes mellitus: a cross-sectional study by the COVID-19 Vaccination in Autoimmune Diseases (COVAD) Group

To investigate the frequency, profile, and severity of COVID-19 breakthrough infections (BI) in patients with type I diabetes mellitus (T1DM) compared to healthy controls (HC) after vaccination. The second COVID-19 Vaccination in Autoimmune Diseases (COVAD-2) survey is a multinational cross-sectional electronic survey which has collected data on patients suffering from various autoimmune diseases including T1DM. We performed a subgroup analysis on this cohort to investigate COVID-19 BI characteristics in patients with T1DM. Logistic regression with propensity score matching analysis was performed. A total of 9595 individuals were included in the analysis, with 100 patients having T1DM. Among the fully vaccinated cohort, 16 (16%) T1DM patients had one BI and 2 (2%) had two BIs. No morbidities or deaths were reported, except for one patient who required hospitalization with oxygen without admission to intensive care. The frequency, clinical features, and severity of BIs were not significantly different between T1DM patients and HCs after adjustment for confounding factors. Our study did not show any statistically significant differences in the frequency, symptoms, duration, or critical care requirements between T1DM and HCs after COVID-19 vaccination. Further research is needed to identify factors associated with inadequate vaccine response in patients with BIs, especially in patients with autoimmune diseases