Molecular Characterization and Human T-Cell Responses to a Member of a Novel Mycobacterium tuberculosis mtb39 Gene Family

We have used expression screening of a genomic Mycobacterium tuberculosis library with tuberculosis (TB) patient sera to identify novel genes that may be used diagnostically or in the development of a TB vaccine. Using this strategy, we have cloned a novel gene, termed mtb39a, that encodes a 39-kDa protein. Molecular characterization revealed that mtb39a is a member of a family of three highly related genes that are conserved among strains of M. tuberculosis and Mycobacterium bovis BCG but not in other mycobacterial species tested. Immunoblot analysis demonstrated the presence of Mtb39A in M. tuberculosis lysate but not in culture filtrate proteins (CFP), indicating that it is not a secreted antigen. This conclusion is strengthened by the observation that a human T-cell clone specific for purified recombinant Mtb39A protein recognized autologous dendritic cells infected with TB or pulsed with purified protein derivative (PPD) but did not respond to M. tuberculosis CFP. Purified recombinant Mtb39A elicited strong T-cell proliferative and gamma interferon responses in peripheral blood mononuclear cells from 9 of 12 PPD-positive individuals tested, and overlapping peptides were used to identify a minimum of 10 distinct T-cell epitopes. Additionally, mice immunized with mtb39a DNA have shown increased protection from M. tuberculosis challenge, as indicated by a reduction of bacterial load. The human T-cell responses and initial animal studies provide support for further evaluation of this antigen as a possible component of a subunit vaccine for M.tuberculosis.     

Cognitive-behavioral treatment of adolescent depression: efficacy of acute group treatment and booster sessions

OBJECTIVE: This trial examined the effects of both acute and maintenance cognitive-behavioral therapy (CBT) for depressed adolescents. METHOD: Adolescents with major depression or dysthymia (N = 123) were randomly assigned to 1 of 3 eight-week acute conditions: adolescent group CBT (16 two-hour sessions); adolescent group CBT with a separate parent group; or waitlist control. Subsequently, participants completing the acute CBT groups were randomly reassigned to 1 of 3 conditions for the 24-month follow-up period: assessments every 4 months with booster sessions; assessments only every 4 months; or assessments only every 12 months. RESULTS: Acute CBT groups yielded higher depression recovery rates (66.7%) than the waitlist (48.1%), and greater reduction in self-reported depression. Outcomes for the adolescent-only and adolescent + parent conditions were not significantly different. Rates of recurrence during the 2-year follow-up were lower than found with treated adult depression. The booster sessions did not reduce the rate of recurrence in the follow-up period but appeared to accelerate recovery among participants who were still depressed at the end of the acute phase. CONCLUSIONS: The findings, which replicate and expand upon a previous study, support the growing evidence that CBT is an effective intervention for adolescent depression.     

Trends and cyclic variation in the incidence of childhood type 1 diabetes in two Italian regions over 33 years and during the COVID-19 pandemic

Aim

There is conflicting evidence about the impact of the COVID-19 pandemic on the incidence of type 1 diabetes. Here, we analysed long-term trends in the incidence of type 1 diabetes in Italian children and adolescents from 1989 to 2019 and compared the incidence observed during the COVID-19 pandemic with that estimated from long-term data.

Materials and Methods

This was a population-based incidence study using longitudinal data from two diabetes registries in mainland Italy. Trends in the incidence of type 1 diabetes from 1 January 1989 to 31 December 2019 were estimated using Poisson and segmented regression models.

Results

There was a significant increasing trend in the incidence of type 1 diabetes of 3.6% per year [95% confidence interval (CI): 2.4-4.8] between 1989 and 2003, a breakpoint in 2003, and then a constant incidence until 2019 (0.5%, 95% CI: -1.3 to 2.4). There was a significant 4-year cycle in incidence over the entire study period. The rate observed in 2021 (26.7, 95% CI: 23.0-30.9) was significantly higher than expected (19.5, 95% CI: 17.6-21.4; p = .010).

Conclusion

Long-term incidence analysis showed an unexpected increase in new cases of type 1 diabetes in 2021. The incidence of type 1 diabetes now needs continuous monitoring using population registries to understand better the impact of COVID-19 on new-onset type 1 diabetes in children.