Correspondence -Bulletin - Nov. 8, 1942 - Dr. Bernard W. Spilman

Correspondence from Mary S. Vail, church historian of Spilman Memorial Baptist Church. A collection of First Baptist Church Shelby bulletins from the personal paper of Dr. Bernard W. Spilman.https://digitalcommons.gardner-webb.edu/first-baptist-shelby-zeno-wall/1010/thumbnail.jp

Short Communication Bcl-2 Expression Inhibits Liver Carcinogenesis and Delays the Development of Proliferating Foci

Tumor development is thought to require both increased proliferation and inhibition of apoptosis. However , the relationship between cell replication and cell death in liver tumorigenesis is complex because both proliferation and apoptosis increase during hepatocarcinogenesis. To investigate the effect of the anti-apoptotic gene Bcl-2 in liver carcinogenesis, we established a line of double transgenic mice that express transforming growth factor-␣ (TGF-␣) , a liver mitogen , and Bcl-2. Double transgenic mice , TGF-␣ and Bcl-2 single transgenics , and wild type received an injection of diethylnitrosamine at 15 days of age. This alkylating agent induces liver carcinogenesis and its effect is greatly enhanced by TGF-␣. We report that Bcl-2 expression inhibited diethylnitrosamine-induced liver carcinogenesis and counteracted the enhancing effect of TGF-␣. Bcl-2 delayed the growth of proliferative foci at the early stages of carcinogenesis and inhibited cell proliferation in these foci. The effect of Bcl-2 on liver carcinogenesis is consistent with its reported ability to interfere with cell replication. The data demonstrate that the expression of an antiapoptotic gene during liver carcinogenesis causes a delay rather than an increase in tumorigenesis. The discovery that overexpression of Bcl-2 in follicular lymphomas, caused by a chromosomal translocation, inhibits apoptosis without increasing cell proliferation established a new mode of action for oncogenes

Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose

The found down patient

BackgroundUnconscious patients who present after being "found down" represent a unique triage challenge. These patients are selected for either trauma or medical evaluation based on limited information and have been shown in a single-center study to have significant occult injuries and/or missed medical diagnoses. We sought to further characterize this population in a multicenter study and to identify predictors of mistriage.MethodsThe Western Trauma Association Multicenter Trials Committee conducted a retrospective study of patients categorized as found down by emergency department triage diagnosis at seven major trauma centers. Demographic, clinical, and outcome data were collected. Mistriage was defined as patients being admitted to a non-triage-activated service. Logistic regression was used to assess predictors of specified outcomes.ResultsOf 661 patients, 33% were triaged to trauma evaluations, and 67% were triaged to medical evaluations; 56% of all patients had traumatic injuries. Trauma-triaged patients had significantly higher rates of combined injury and a medical diagnosis and underwent more computed tomographic imaging; they had lower rates of intoxication and homelessness. Among the 432 admitted patients, 17% of them were initially mistriaged. Even among properly triaged patients, 23% required cross-consultation from the non-triage-activated service after admission. Age was an independent predictor of mistriage, with a doubling of the rate for groups older than 70 years. Combined medical diagnosis and injury was also predictive of mistriage. Mistriaged patients had a trend toward increased late-identified injuries, but mistriage was not associated with increased length of stay or mortality.ConclusionPatients who are found down experience significant rates of mistriage and triage discordance requiring cross-consultation. Although the majority of found down patients are triaged to nontrauma evaluation, more than half have traumatic injuries. Characteristics associated with increased rates of mistriage, including advanced age, may be used to improve resource use and minimize missed injury in this vulnerable patient population.Level of evidenceEpidemiologic study, level III