Activity

For disease modeling, we used hiPSC-derived cardiomyocytes from a patient with arrhythmogenic cardiomyopathy due to mutations in the desmoplakin gene. HCQ inhibitor manufacturer We demonstrated that manifestation of this desmosome-linked disease state required dyn-EHT conditioning and that it could not be induced using 2D or standard 3D EHT approaches. Thus, a dynamic loading strategy is necessary to provoke the disease phenotype of diastolic lengthening, reduction of desmosome counts, and reduced contractility, which are related to primary end points of clinical disease, such as chamber thinning and reduced cardiac output.Metastatic estrogen receptor α (ERα)-positive breast cancer is presently incurable. Seeking to target these drug-resistant cancers, we report the discovery of a compound, called ErSO, that activates the anticipatory unfolded protein response (a-UPR) and induces rapid and selective necrosis of ERα-positive breast cancer cell lines in vitro. We then tested ErSO in vivo in several preclinical orthotopic and metastasis mouse models carrying different xenografts of human breast cancer lines or patient-derived breast tumors. In multiple orthotopic models, ErSO treatment given either orally or intraperitoneally for 14 to 21 days induced tumor regression without recurrence. In a cell line tail vein metastasis model, ErSO was also effective at inducing regression of most lung, bone, and liver metastases. ErSO treatment induced almost complete regression of brain metastases in mice carrying intracranial human breast cancer cell line xenografts. Tumors that did not undergo complete regression and regrew remained sensitive to retreatment with ErSO. ErSO was well tolerated in mice, rats, and dogs at doses above those needed for therapeutic responses and had little or no effect on normal ERα-expressing murine tissues. ErSO mediated its anticancer effects through activation of the a-UPR, suggesting that activation of a tumor protective pathway could induce tumor regression.

Childhood vaccine delivery services in the low- and middle-income countries (LMIC) are struggling to reach every child with lifesaving vaccines. Short message service (SMS) reminders have demonstrated positive impact on a number of attrition-prone healthcare delivery services. We aimed to evaluate the effectiveness of SMS reminders in improving immunisation coverage and timeliness in LMICs.

PubMed, Embase, Scopus, Cochrane CENTRAL, CINAHL, CNKI, PsycINFO and Web of Science including grey literatures and Google Scholar were systematically searched for randomised controlled trials (RCTs) and non-RCTs that evaluated the effect of SMS reminders on childhood immunisation and timeliness in LMICs. Risk of bias was assessed using the Cochrane Risk of Bias 2.0 assessment tool for RCTs and Cochrane Risk of Bias in Non-randomised Studies of Interventions tool for non-RCTs. Meta-analysis was conducted using random-effects models to generate pooled estimates of risk ratio (RR).

18 studies, 13 RCTs and 5 non-RCTs involving 32 712 infants (17 135 in intervention groups and 15 577 in control groups) from 11 LMICs met inclusion criteria. Pooled estimates showed that SMS reminders significantly improved childhood immunisation coverage (RR=1.16; 95% CI 1.10 to 1.21; I

=90.4%). Meta-analysis of 12 included studies involving 25 257 infants showed that SMS reminders significantly improved timely receipt of childhood vaccines (RR=1.21; 95% CI 1.12 to 1.30; I

=87.3%). Subgroup analysis showed that SMS reminders are significantly more effective in raising childhood immunisation coverage in lower middle-income and low-income countries than in upper middle-income countries (p<0.001) and sending more than two SMS reminders significantly improves timely receipt of childhood vaccines than one or two SMS reminders (p=0.040).

Current evidence from LMICs, although with significant heterogeneity, suggests that SMS reminders can contribute to achieving high and timely childhood immunisation coverage.

CRD42021225843.

CRD42021225843.Chimeric antigen receptor (CAR) T-cell therapies that target either CD19 or CD22 alone have potent antilymphoma effects. However, antigen escape-mediated relapse often occurs. CAR T cells targeting both CD19 and CD22 may overcome this limitation. In this study, we developed bispecific CAR T cells simultaneously recognizing CD19- and CD22-expressing targets and assessed their safety and efficacy profiles in patients with relapsed/refractory aggressive B-cell lymphoma. Twenty-four patients were screened, and 16 were found eligible for the study. CAR T-cell-associated toxicities were recorded. Responses, overall survival (OS), and progression-free survival (PFS) were assessed. Of the 16 eligible patients, 14 (87.5%) achieved objective response and 10 (62.5%) achieved complete response (CR). The 2-year OS and PFS rates were 77.3% and 40.2%, respectively. Achieving CR (P = 0.046) and the number of prior chemotherapy lines (n = 2; P = 0.047) were independent prognostic factors associated with favorable PFS. The 2-year OS and PFS among patients who achieved CR were higher than among those who did not (P = 0.015 and P less then 0.001, respectively). The 2-year PFS among patients who received two prior lines of chemotherapy was higher than that among patients who received more than two lines of chemotherapy (P = 0.049); OS did not differ between the groups. Severe grade 4 cytokine-release syndrome (CRS) was observed in 1 patient; 4 and 11 patients had grades 1 and 2 CRS, respectively. No patients developed neurotoxicity. CD19/CD22 dual-targeted CAR T cells may be a safe, potent antilymphoma cell-based targeted immunotherapy.In this issue, Ruf and colleagues show that antigen stimulation of mucosal-associated invariant T (MAIT) cells in the presence of the TLR9 ligand CpG decreases intrahepatic tumor growth, suggesting that MAIT cells could be used as an antitumor tool.See related article by Ruf et al., p. 1024 (3).

This prospective study aimed to determine the effectiveness of prophylactic subcutaneous retention sutures in the prevention of superficial wound separation in women with a confirmed or suspected cancer who had gynecological surgery by midline laparotomy.

This was a non-randomized, controlled intervention study including patients who underwent cancer surgery between May 2018 and August 2019. Patients who underwent midline laparotomy with confirmed or suspected cancer were included and patients who had an early post-operative complication or who underwent surgery again before the removal of stitches were excluded. The independent variables that might predict the superficial wound site dehiscence and prolongation of the hospitalization period were analyzed using logistical regression analysis.

A total of 208 patients were included in the study. Age, presence of comorbid diseases, low pre-operative hemoglobin, low pre-operative albumin, higher weight, higher body mass index (BMI), pre- and post-operative blood transfusion, and absence of retention sutures were associated with higher risk of superficial wound separation.